Pro Ncov 3002 Report

Report of Phase Ⅲ Clinical Trial of Inactivated COVID-19 Vaccine in Children and Adolescents
2 SYNOPSIS
Name of Sponsor/Company: (For National Authority Use Only)

Individual Study Table
Sinovac Life Sciences Co., Ltd.
Referring to Part of the Dossier
Name of Finished Product:
COVID-19 Vaccine (Vero Cell), Volume:
Inactivated Page:
Name of Active Ingredient:
Inactivated SARS-CoV-2 virus
Antigen
Title of Study: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase Ⅲ Clinical Trial to
Evaluate the Efficacy, Immunogenicity and Safety of COVID-19 Vaccine (Vero Cell), Inactivated
(CoronaVac®) in Children and Adolescents Aged 6 Months to 17 Years
CT.gov identifier: NCT04992260
Countries of Study Centers: South Africa, Malaysia, Philippines and Chile
Studied period (years):

(date of first enrolment) Phase of the study: Phase Ⅲ
(date of last completed)
Sep 2021 - Ongoing
Objectives and Endpoints:
Objectives Endpoints
Primary
To evaluate the efficacy of two dose of Incidence of RT-PCR confirmed symptomatic
CoronaVac® against RT-PCR confirmed COVID-19 cases with onset at least 14 days after
symptomatic COVID-19 cases in participants the second dose
aged 6 months to 17 years
Secondary
Efficacy
To evaluate the efficacy of at least one dose of Incidence of RT-PCR confirmed symptomatic
CoronaVac® against RT-PCR confirmed COVID-19 cases with onset at least 14 days after
symptomatic COVID-19 cases the first dose
To assess the effect of a two dose of Incidence of RT-PCR confirmed, symptomatic
CoronaVac® against RT-PCR confirmed COVID-19, with onset at least 14 days after the
symptomatic COVID-19 cases in baseline second dose in SARS-CoV-2 uninfected
SARS-CoV-2 uninfected participants (serologically or molecularly confirmed)
participants at baseline
To evaluate the efficacy of two dose of Incidence of hospitalization/severe/death caused
CoronaVac® on hospitalization/severe/death by COVID-19 with onset at least 14 days after the
caused by COVID-19 second dose
Safety
To evaluate the safety of CoronaVac® in terms Occurrence, intensity, duration, and relationship
of solicited local and systemic adverse events of solicited local and systemic AEs during 7 days
(AEs) during 7 days after each dose following each dose vaccination and of
vaccination, and in terms of unsolicited AEs unsolicited AEs during 28 days post-vaccination
during 28 days postvaccination (Subgroup)
To evaluate safety in terms of serious adverse Occurrence and relationship of SAEs (from first
events (SAEs) dose to 12 months after the last dose)
To evaluate safety in terms of adverse events Occurrence and relationship of AESI (from first
of special interest (AESI) dose to 12 months after the last dose)
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Name of Sponsor/Company:
Individual Study Table (For National Authority Use Only)
Inactivated Page:
Antigen
Immunogenicity (Subgroup)
To evaluate the immunogenicity of Analysis of SARS-CoV-2 neutralizing antibody
CoronaVac® in a subgroup of participants, as titers by micro-cytopathic method;
compared to placebo Analysis of Anti-SARS-CoV-2 S by
electrochemiluminescence immunoassay.
Exploratory
To evaluate the vaccine enhanced disease The difference of the presence, severity and
(VED) of CoronaVac® duration of COVID-19 signs and symptoms, and
the incidence of severe disease between the
vaccine and placebo groups
To evaluate cell mediated immunity against Analysis of cytokine secreting SARS-CoV-2
SARS-CoV-2 in a subset of vaccinated specific T cells by ELISPOT;
participants, as compared to placebo (Only for Analysis of activated/memory SARS-CoV-2
Chile) specific T cells by flow cytometry.
To characterize the immune response of Characterization of total and neutralizing anti-
eventual cases of COVID-19 or MIS-C in SARS-CoV-2 antibodies;
participants (Only for Chile) Characterization of cell mediated immunity.
Methodology
This is a global multi-centre study, and the enrolment plan will be specified by each country. For this case-
driven, randomized, double-blinded, and placebo-controlled phase Ⅲ trial, adaptive design will be adopted,
and 14,000 healthy participants aged 6 months to 17 years will be enrolled and randomly assigned into 2
groups at a ratio of 1:1 to receive 2 doses of vaccine (600SU) or placebo with an interval of 28 days.
The duration of individual participation, including screening, will be maximum 13 month. The end-of-study
is considered as the completion of the last visit for the last participant in the study.
In this trial, efficacy assessments include the surveillance for COVID-19-like symptoms, the laboratory
confirmation of SARS-CoV-2 infection by RT-PCR, recording of COVID-19-related hospitalizations. Safety
assessments include two parts. For all participants, the immediate reactions within 30 minutes after each
dose will be monitored, and diary cards will be distributed to participants in safety evaluation sub-group to
record the adverse events. The local and systemic solicited adverse events within 7 days and the unsolicited
adverse events within 28 days will also be monitored after each dose in safety evaluation sub-group. For all
participants, the collection of adverse events of special interest (AESI), and serious adverse events (SAEs)
will be monitored to 12 months after full-course inoculation.
Immunogenicity assessments with emphasis on neutralizing and S-protein antibodies will also be performed
in sub-group participants.
Any confirmed COVID-19 patients will be followed by the investigator until resolution. For the variant
concern, the whole viral genome sequencing to detect outstanding mutations among all the confirmed
COVID-19 cases in this trial will be done in local lab of each country.
Number of subjects (Planned and actual number for analysis): Planned to enroll 14,000 subjects; and actually
enrolled 11349 subjects.
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Inactivated Page:
Antigen
Inclusion/Exclusion criteria:
Inclusion criteria:
In order to be eligible to participate in this study, any individual must meet the following criteria:
1. Healthy children and adolescents aged 6 months to 17 years;
2. The participants and/or their guardians are able to understand and sign the informed consent voluntarily
(in accordance with the local regulations);
3. Able to comply with study procedures based on the assessment of the Investigator;
4. Female participants of childbearing potential (post-menarche girls or in accordance with the local
standard of care) may be enrolled in the study if the participant fulfills all the following criteria:
• Has a negative pregnancy test on the day of the first dose (Day 0).
• Has practiced adequate contraception or has abstained from all activities that could result in
pregnancy for at least 28 days prior to the first dose (Day 0).
• Has agreed to continue adequate contraception through 3 months following the second dose (Day 28).
• Is not currently breastfeeding.
5. Must be willing to provide verifiable identification (in accordance with the local regulations), has means
to be contacted and to contact the investigator during the study.
Exclusion criteria:
Participants are excluded from the study if any of the following criteria apply:
- History of confirmed infection of SARS CoV-2 prior to randomization;
- Close contact with a confirmed COVID-19 within 14 days prior to randomization;
- Prior administration of an investigational coronavirus vaccine or current/planned simultaneous
participation in another interventional study to prevent or treat COVID-19;
- Allergy to vaccines or vaccine/placebo ingredients, and serious adverse reactions to vaccines, such as
urticaria, dyspnea, angioneuroedema;
- Personal or first-grade relative (siblings) history of multisystem inflammatory disease in children
(MIS-C);
- Significant chronic illnesses that, in the opinion of the investigator, is at a stage where it might
interfere with trial conduct or completion (may include, but are not limited to cardiovascular disease,
liver or kidney disorders, respiratory illnesses)
- Significant chronic central nervous system diseases or neuromuscular disorders, psychosis or severe
cognitive behavioral disorder, in the opinion of the investigator, including epilepsy, autism spectrum
disorder, intellectual disabilities (excluding Down Syndrome);
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Inactivated Page:
Antigen
- Acute central nervous system diseases such as encephalitis/myelitis, acute disseminating
encephalomyelitis, and related disorders;
- History of autoimmune and/or haematological diseases (including but not limited to systemic lupus
erythematosus, thyroidectomy, autoimmune thyroid disease, any form of malignant tumor, asplenia,
functional asplenia, or splenectomy resulting from any condition); well controlled type I diabetes
mellitus is allowed;
- History of bleeding disorders (e.g. factor deficiency, coagulopathy or platelet disorder), or prior
history of significant bleeding or bruising following IM injections or venipuncture;
- Immunosuppressive therapy (systemic corticoid therapy, e.g. prednisone ≥2 mg/Kg/d or ≥20 mg/day
for >14 days), cytotoxic therapy (antineoplastic chemotherapy, radiation therapy), (excluding topical
or aerosol corticosteroid therapy) in the past 6 months;
- Receipt of blood products or immunoglobulins in the past 3 months;
- Receipt of other investigational drugs in the past 30 days;
- Receipt of attenuated live vaccines in the past 14 days;
- Receipt of inactivated or subunit vaccines in the past 7 days;
- Acute exacerbation or presentation of stable chronic diseases (including but not limited to asthma,
migraine, gastrointestinal disorder, etc;
- Acute febrile illness with oral temperature >37.7°C or axillary temperature >37.5°C on the day of
vaccination (refer to section 7.1 Delay/Discontinuation of Study Vaccination); enrollment could be
considered if the fever is absent for 72 hours;
- Any confirmed or suspected human immunodeficiency virus (HIV) infection;
- Children in care or under a court order;
- According to the investigator's judgment, the subject has any other factors that might interfere with
the results of the clinical trial or pose additional risk to the subject due to participation in the study.
Test product, dose and mode of administration, batch number:
The test products used in this trial are the COVID-19 vaccine and placebo produced by Sinovac. The product
information is as follows:
Antigen Batch Expiration
Group Name Package
content number date
COVID-19 Vaccine Pre-filled

Vaccine 600SU/0.5ml D202104004 April 5th 2023
(Vero Cell), Inactivated syringe
Placebo Aluminum hydroxide Pre-filled April 15th

0SU/0.5ml 2020041602
control diluent syringe 2023
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Inactivated Page:
Antigen
Dose and Administration: Intramuscularly inject to the deltoid of the upper arm, with a single dose of 0.5mL
investigational vaccine or placebo. The vaccine should be shaken well before inoculation.
Duration of treatment:
Immunization schedule is two-dose vaccinated on day 0 and day 28 respectively, subjects are expected to
participate in the trial for a maximum of 13 months.
Prespecified Criteria for Suspected COVID-19
The criteria for suspected COVID-19 are prespecified as follows, which triggers to proceed the collection of
respiratory tract sample (eg, nasopharyngeal swab, throat swab or saliva).
• Fever or chills
• Cough
• Nasal congestion or runny nose
• New loss of taste or smell
• Sore throat
• Shortness of breath or difficulty breathing
• Diarrhea
• Nausea or vomiting
• Stomachache
• Tiredness
• Headache
• Muscle pain
Case Definition for primary endpoint
Definition of RT-PCR confirmed symptomatic COVID-19 (adapted from NMPA standard):
Individuals with at least two type A symptoms, or at least one type B symptom, or chest imaging
characteristics, and with a positive RT-PCR test of COVID-19.
1) Clinical symptom
Symptom A (for at least 2 days): Fever, chills, sore throat, tiredness, nasal congestion or running nose, muscle
pain, stomachache, headache, nausea or vomiting, diarrhea.
Symptom B: Cough (for at least 2 days), new loss of taste or smell (for at least 2 days), shortness of breath
or difficulty breathing (any duration).
2) Chest imaging characteristics of COVID-19: In the early stage, there were multiple small patches and
interstitial changes, especially in the lung periphery. Furthermore, it develops into multiple ground glass
shadows and infiltrating shadows in both lungs. In severe cases, lung consolidation may occur, and rarely
pleural effusion. In MIS-C, heart shadow enlargement and pulmonary edema can be observed in patients
with cardiac insufficiency.
Regarding the RT-PCR test, respiratory tract sample (eg, nasopharyngeal swab, throat swab or saliva) will
be collected.
Severe COVID-19 cases (adapted from China standard):
Refers to a laboratory confirmed case of SARS-CoV-2 infection that has one or more of the following
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Inactivated Page:
Antigen
conditions:
• High fever (≥39.5℃) lasts for more than 3 days;
• Shortness of breath (6-11 months old: RR≥50 times/min; 1-5 years old: RR≥40 times/min; >5 years
old, RR≥30 times/min), except for the effects of fever and crying;
• In the resting state, when inhaling air, the oxygen saturation is ≤93%;
• Assisted breathing (nasal flaring, chest wall recessions);
• Drowsiness, convulsions;
• Poor feeding or feeding difficulties, with signs of dehydration.
Regarding the criteria of severe COVID-19 cases also could be defined by specific guidelines for children
in country.
Method of statistics:
Statistical Hypotheses
The null hypothesis and alternative hypothesis of the main analysis are as follows:
H0: the lower limit of 95% confidence interval of the protective efficacy of the test vaccine on confirmed
COVID-19 cases is less than or equal to 0% (i.e., VE ≤ 0%)
H1: the lower limit of 95% confidence interval of the protective efficacy of the test vaccine on confirmed
COVID-19 cases is greater than 0% (i.e., VE > 0%)
Sample Size Determination
The sample size calculation is based on following factors.
• Type I error equal to 0.05 (2-sided)；
• Type II error equal to 10%, therefore, power of the trial equals to 90%；
• Expected vaccine efficacy is 50%；
• The lower limit of the 95% confidence interval (95% CI) for the expected vaccine efficacy is above 0;
• Participants will be randomly assigned into 2 groups at a ratio of 1:1;
• Expected incidence rate of participants in placebo group= 1%；
• 10% loss to follow up;
• Interim analysis would be introduced when 1/2 expected cases are observed.
It is assumed that the incidence rate of COVID-19 in Children and adolescents be 1% in placebo arm. An
interim analysis is planned when 50% of confirmed COVID-19 cases are observed, and O’Brien-Fleming
spending function will be employed to control familywise type I error rate within 5%. In order to detect 50%
vaccine efficacy (lower bound of 95% CI > 0), a total of 93 confirmed COVID-19 cases and at least12,593
participants are required to achieve 90% power with two-sided significance level of 5%. The number-of-
events calculation is based on an exact conditional method under large sample Poisson distribution
assumption proposed by Chan and Bohidar. Considering 10% loss of follow up, approximately 14,000
participants will be needed to recruit in total and 7,000 participants in each arm.
The sample size is set to accumulate enough cases for protective efficacy analysis.
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Inactivated Page:
Antigen
Abstract - Conclusion
Efficacy results
Results of interim efficacy analysis indicated that, the efficacy of CoronaVac ® on moderate (VE 40.31%,
with fever) or hospitalized cases (75.22%) was higher than that of against mild cases (17.23%). The long-
term efficacy analysis also showed the same trend, that the efficacy against hospitalization was 84.19% and
against severe cases was 100.00%, while the efficacy on confirmed COVID-19 cases was 20.27%.
In terms of efficacy, the protection of CoronaVac® against hospitalized COVID-19 case caused by Omicron
was favorable, however, the protection of CoronaVac ® against mild COVID-19 case caused by Omicron was
relatively low, which is supporting the rationality of booster immunization to counter the emerging variants.
About half of the subjects had previous SARS-CoV-2 exposure, and incidence density of COVID-19 in this
population is much lower than that of population without previous exposure, indicating a protection triggered
by previous infection. The efficacy results indicated that receiving COVID-19 vaccine may not be able to
provide additional protection based on the previous infection.
From the perspectives of public health and aim to reduce the burden of disease, if the usage of vaccine could
decrease the required medical intervention and incidence rate of severe cases, this could obviously reduce
the economic burden at national and individual level, leading significant social and economic benefits.
Safety and immunogenicity results for children aged 6-35 months
Safety: The safety profile subjects aged 6-35 months was favorable, with or without previous exposure to
SARS-CoV-2. The overall incidence rate of ARs within 28 days of each vaccination was 31.68% (64/202),
34.65% in vaccine group and 28.71% in placebo group, respectively, without significant difference. The most
common AR was fever, vaccination site pain, vaccination site swelling, vaccination site erythema and
injection site induration, without significant difference between the groups. Adverse reactions were mainly
of Grade 1, two Grade 3 and above adverse reactions was reported during study period. No SAE related with
vaccine was reported.
Immunogenicity: A high seropositive rate was observed, 116 (65.91%) participants were seropositive before
vaccination, indicating a very high prevalence of COVID-19 in South Africa for this population. 28 days
after two doses of vaccination, the GMT of neutralizing antibody in vaccine group and placebo group were
743.55 and 43.45, respectively. Stratified by baseline neutralizing antibody (positive/negative), the GMT of
neutralizing antibody in seronegative subjects and seropositive subjects were 234.38 and 1138.79,
respectively, suggesting that investigational vaccine has good immunogenicity in eliciting both priming
immune response and anamnestic immune response.
Safety and immunogenicity results for children and adolescents aged 3-17 years
Safety: For the participants aged 3-17 years, the overall incidence rate of ARs within 28 days of each
vaccination, was 35.71% (vaccine group 39.34% vs. placebo group 27.46%, P=0.0001), 31.10% (vaccine
group 36.09% vs. placebo group 24.11%, P<0.0001) and 21.29% (vaccine group 22.71% vs. placebo group
19.63%, P=0.4185) in the 3-5 years group, 6-11 years group and 12-17 years group, respectively. In all the
three age groups, the most common AR was vaccination site pain, and normally followed by vaccination site
erythema, fever, injection site induration and fatigue. The adverse reactions were mainly of Grade 1. No SAE
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Inactivated Page:
Antigen
related with vaccine was reported.
Immunogenicity: The immunogenicity results of the participants aged 3-17 years were similar with that of
the 6-35 months, which had 62.62% seropositive participants at baseline. For seronegative participants at
baseline, 28 days after two doses of vaccination, the neutralizing antibody seroconversion rates in the vaccine
group and the placebo group were 100.00% and 19.30%, the GMT was 204.73 and 3.28, and the GMI was
100.31 and 1.54, respectively. For seropositive participants at baseline, the seroconversion rates 28 days after
two doses of vaccination in vaccine group and placebo group were 55.85% and 28.46%, the GMT were
507.48 and 218.03, and the GMI were 3.75 and 1.39, respectively. These results indicated a high prevalence
of COVID-19 before and during the clinical trial in this age group, and immunogenicity analysis stratified
by countries should be conducted for results adjustment.
Conclusion:
In conclusion, this study showed satisfactory safety and immunogenicity of CoronaVac ® in children and
adolescents aged 6 months to 17 years using a 0,28 days immunization schedule, regardless for immune-
naïve children or previously infected children. In terms of efficacy, the protection of CoronaVac ® against
hospitalized COVID-19 case caused by Omicron was favorable, and the booster immunization needs to be
introduced to counter the emerging variants.
Date of report: February 2023
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3 TABLE OF CONTENTS FOR THE INDIVIDUAL CLINICAL STUDY REPORT
1 TITLE PAGE ...................................................................................................................... 1

2 SYNOPSIS.......................................................................................................................... 1
3 TABLE OF CONTENTS FOR THE INDIVIDUAL CLINICAL STUDY REPORT ............ 9
4 LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ......................................... 11
5 ETHICS ............................................................................................................................ 12
5.1 INDEPENDENT ETHICS COMMITTEE (IEC) OR INSTITUTIONAL REVIEW
BOARD (IRB) ........................................................................................................................ 12
5.2 ETHICAL CONDUCT OF THE STUDY ............................................................ 12
5.3 PATIENT INFORMATION AND CONSENT ...................................................... 12
6 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ............................. 12
7 INTRODUCTION ............................................................................................................. 12
8 STUDY OBJECTIVES AND ENDPOINTS ...................................................................... 13
9 INVESTIGATIONAL PLAN............................................................................................. 14
9.1 OVERALL STUDY DESIGN AND PLAN DESCRIPTION ................................ 14
9.2 DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF CONTROL
GROUPS 15
9.3 SELECTION OF STUDY POPULATION ........................................................... 15
9.4 TREATMENT ..................................................................................................... 17
9.5 EFFICACY AND SAFETY VARIBLES .............................................................. 20
9.6 DATA QUALITY ASSURANCE ......................................................................... 30
9.7 STATISTICAL METHODS PLANNED IN THE PROTOCOL AND
DETERMINATION OF SAMPLE SIZE ................................................................................. 31
10 STUDY PATIENTS ........................................................................................................... 35
10.1 DISPOSITION OF PATIENTS ............................................................................ 35
11 EFFICACY EVALUATION .............................................................................................. 35
11.1 DATA SETS ANALYSED.................................................................................... 36
11.2 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS .................. 36
11.3 MEASUREMENTS OF CLINICAL FEATURES ................................................ 36
11.4 EFFICACY RESULTS AND TABULATIONS OF INDIVIDUAL PATIENT DATA
37
12 SAFETY EVALUATION .................................................................................................. 57
12.1 Safety analysis in aged 6-35 months..................................................................... 57
12.2 Safety analysis in aged 3-5 years .......................................................................... 65
12.3 Safety analysis in aged 6-11 years ........................................................................ 74
12.4 Safety analysis in aged 12-17 years ...................................................................... 84
12.5 Safety analysis in all age groups........................................................................... 92
12.6 Serious Adverse Events in 6 months-17 years ...................................................... 94
13 DISCUSSION AND OVERALL CONCLUSIONS ........................................................... 96
13.1 EFFICACY EVALUATION ................................................................................. 96
13.2 IMMUNOGENICITY EVALUATION ................................................................. 97
13.3 SAFETY EVALUATION ..................................................................................... 98
13.4 CONCLUSION.................................................................................................... 98
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14 TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN THE

TEXT 99
15 REFERENCES.................................................................................................................. 99
16 ADDPENDICES ............................................................................................................... 99
16.1 STUDY INFORMATION .................................................................................... 99
16.2 PATIENT DATA LISTINGS .............................................................................. 100
16.3 CASE REPORT FORMS ................................................................................... 101
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4 LIST OF ABBREVIATIONS AND DEFINITION OF TERMS

ADE Antibody Dependent Enhancement
AE Adverse Event
CDC Center for Disease Control and Prevention
CDE Center for Drug Evaluation
CFDA China Food and Drug Administration
COVID-19 Corona Virus Disease 2019
CFDI Center for Food and Drug Inspection
CRF Case Report Form
eCRF Electronic Case Report Form
ELISA Enzyme-Linked Immune-sorbent Assay
EDC Electronic Data Capture
FAS Full Analysis Set
GCP Good Clinical Practice
GMT Geometric Mean Titer
GMI Geometric Mean Increase
IEC Independent Ethics Committee
ITT Intention-to-Treat
MedDRA Medical Dictionary for Regulatory Activities
NMPA National Medical Products Administration
PI Principal Investigator
PPS Per Protocol Set
PT Preferred Term
SAE Serious Adverse Event
SARS Severe Acute Respiratory Syndrome
SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2
SOC System Organ Class
SOP Standard Operation Procedure
SS Safety Set
SUSAR Suspected Unexpected Serious Adverse Reaction
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5 ETHICS
5.1 INDEPENDENT ETHICS COMMITTEE (IEC) OR INSTITUTIONAL REVIEW BOARD

(IRB)
The clinical trial protocol, informed consent form and all the tables containing subjects’ information
were reviewed and approved by the Ethics Committee of all study sites.
5.2 ETHICAL CONDUCT OF THE STUDY

The clinical trial was conducted in accordance with the ethical principles of Ethics Review Committee
and Declaration of Helsinki. In addition, this trial was conducted in accordance with standards of Good
Clinical Practice (GCP). Any problems related to safety of the clinical study in the process of the
clinical study such as change of the clinical study protocol or participant information page and serious
adverse events (SAEs) in the clinical study were timely reported to the ethics committee.
5.3 PATIENT INFORMATION AND CONSENT

The principal investigator and team must follow the applicable regulatory standards and regulatory
requirements, GCP and ethics principles to draft and document the informed consent form. The
informed consent form shall be approved by the Ethics Committee before its use. Under the conditions
of voluntary participation, the participants and/or guardians will have the opportunity to read, ask and
clarify their questions before confirming their intention to participate in the study and the participants
will receive a copy of the signed informed consent form. The the participants and/or guardians may
withdraw the consent at any time (even after the beginning of the study procedures). Participants’ rights
and well-being will be protected and will be emphasized that their quality of medical service will not
be affected if they do not accept to participate in the study.
6 INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
Statistician: Zhiwei Jiang from Beijing Key Tech Statistical Technology Co., Ltd.
Monitoring Institute: IQVIA
7 INTRODUCTION
The COVID-19 vaccine (Vero cell), Inactivated developed by Sinovac could induce active immunity
to prevent disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the
pre-clinical studies, the vaccine demonstrated preliminary efficacy and safety in animals [1]. The
vaccine was approved by the National Medical Products Administration (NMPA) on April 13, 2020
for clinical trials. The phase I/II clinical trial in healthy adults aged 18-59 years old was launched in
Jiangsu Province, China on April 16, 2020. The Phase I/II clinical trial in elderly aged 60 years and
above was launched in Hebei Province, China on May 22, 2020, and the Phase I/II clinical trial in
children and adolescents aged 3-17 years was launched in Hebei Province, China on October 31, 2020.
The results showed good safety and immunogenicity in adults, elderly and children and adolescents [2-
4]
. Three phase Ⅲ clinical trials of the COVID-19 vaccine were carried out in Brazil (18 years old and
above), Indonesia (18-59 years old) and Turkey (18-59 years old), which adopted the randomized,
double-blind, placebo-controlled study design to evaluate the efficacy of the vaccine [5-7]. The results
in Brazil showed good efficacy and safety of the vaccine, and it was approved for conditional
marketing in China on February 5, 2021 (approval number: 2021S00156, 2021S00157). In addition,
CoronaVac® was approved by WHO for emergency use in adults on June 01, 2021 [8].
To further evaluate the efficacy and safety of the COVID-19 vaccine in children and adolescents, this
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clinical trial is formulated.

8 STUDY OBJECTIVES AND ENDPOINTS
Objectives Endpoints
Primary
To evaluate the efficacy of two dose of Incidence of RT-PCR confirmed symptomatic

CoronaVac® against RT-PCR confirmed COVID-19 casesa with onset at least 14 days
symptomatic COVID-19 cases in participants after the second dose
aged 6 months to 17 years
Secondary
Efficacy
To evaluate the efficacy of at least one dose of Incidence of RT-PCR confirmed symptomatic
CoronaVac® against RT-PCR confirmed COVID-19 casesa with onset at least 14 days
symptomatic COVID-19 cases after the first dose
To assess the effect of a two dose of CoronaVac® Incidence of RT-PCR confirmed, symptomatic
against RT-PCR confirmed symptomatic COVID-19a, with onset at least 14 days after the
COVID-19 cases in baseline SARS-CoV-2 second dose in SARS-CoV-2 uninfected
uninfected participants (serologically or molecularly confirmed)
participants at baseline
To evaluate the efficacy of two dose of Incidence of hospitalization/severeb/death

CoronaVac® on hospitalization/severeb/death caused by COVID-19 with onset at least 14 days
caused by COVID-19 after the second dose
Safety
To evaluate the safety of CoronaVac® in terms of Occurrence, intensity, duration, and relationship
solicited local and systemic adverse events (AEs) of solicited local and systemic AEs during 7
during 7 days after each dose vaccination, and in days following each dose vaccination and of
terms of unsolicited AEs during 28 days unsolicited AEs during 28 days post-vaccination
postvaccination (Subgroup)
To evaluate safety in terms of serious adverse Occurrence and relationship of SAEs (from first
events (SAEs) dose to 12 months after the last dose)
To evaluate safety in terms of adverse events of Occurrence and relationship of AESI (from first
special interest (AESI) dose to 12 months after the last dose)
Immunogenicity (Subgroup)
To evaluate the immunogenicity of CoronaVac® Analysis of SARS-CoV-2 neutralizing antibody

in a subgroup of participants, as compared to titers by micro-cytopathic method;
placebo
Analysis of Anti-SARS-CoV-2 S by
electrochemiluminescence immunoassay.
Exploratory
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To evaluate the vaccine enhanced disease (VED) The difference of the presence, severity and
of CoronaVac® duration of COVID-19 signs and symptoms, and
the incidence of severe disease between the
vaccine and placebo groups
To evaluate cell mediated immunity against Analysis of cytokine secreting SARS-CoV-2

SARS-CoV-2 in a subset of vaccinated specific T cells by ELISPOT;
participants, as compared to placebo (Only for
Chile) Analysis of activated/memory SARS-CoV-2
specific T cells by flow cytometry.
To characterize the immune response of eventual Characterization of total and neutralizing anti-
cases of COVID-19 or MIS-C in participants SARS-CoV-2 antibodies;
(Only for Chile)
Characterization of cell mediated immunity.
a
Per case definition for RT-PCR confirmed symptomatic COVID-19 (see below).
b
Per case definition for Severe COVID-19 cases (see below).
9 INVESTIGATIONAL PLAN
9.1 OVERALL STUDY DESIGN AND PLAN DESCRIPTION

This is a global multi-center study, and the enrollment plan will be specified by each country. The
study protocol will be adjusted based on local conditions and requests from local IRB.
The study aims to evaluate the efficacy, safety and immunogenicity of CoronaVac®. For this case-
driven, randomized, double-blinded, and placebo-controlled phase Ⅲ trial, adaptive design is adopted,
and 14,000 healthy participants aged 6 months to 17 years will be enrolled and randomly assigned into
2 groups at a ratio of 1:1 to receive 2 doses of vaccine (600SU) or placebo with an interval of 28 days.
This study is designed as double-blind to prevent the introduction of biases in the assessment of
efficacy, adverse events and immunogenicity. The clinical care team, the healthcare professional
responsible for the vaccination and the participant will not know which investigational product will be
administered. The operational team of the sponsor will also remain blinded.
The duration of individual participation, including screening, will be maximum 13 months. The end-
of-study is considered as the completion of the last visit for the last participant in the study.
In this trial, efficacy assessments include the surveillance for COVID-19-like symptoms, the
laboratory confirmation of SARS-CoV-2 infection by RT-PCR, recording of COVID-19-related
hospitalizations.
Safety assessments include two parts: for all participants, the immediate reactions within 30 minutes
after each dose will be monitored, and diary cards will be distributed to participants in safety evaluation
sub-group to record the adverse events. The local and systemic solicited adverse events within 7 days
and the unsolicited adverse events within 28 days will also be monitored after each dose in safety
evaluation sub-group.
For all participants, the collection of adverse events of special interest (AESI), and serious adverse
events (SAEs) will be monitored to 12 months after full-course inoculation.
Immunogenicity assessments with emphasis on neutralizing and anti-SARS-CoV-2 S antibodies will
also be performed.
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Any confirmed COVID-19 patients will be followed by the investigator until resolution. For the variant
concern, the whole viral genome sequencing to detect outstanding mutations among all the confirmed
COVID-19 cases in this trial will be done in local lab of each country.
Table 1 Clinical study design
Age group
Country
6-35 months* 3-5 years 6-11 years 12-17 years
Vaccine group 100 1900 2500 2500

Placebo group 100 1900 2500 2500
Total 200 3800 5000 5000
Immunogenicity 200 460 600 600
Safety 200 760 1000 1000
*The participants in this age group will be enrolled in South Africa.
9.2 DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF CONTROL

GROUPS
This study is designed to evaluate the efficacy and safety of CoronaVac® among children aged 6
months to 17 years. Placebo is used as the control to compare the frequency and magnitude of changes
in clinical and immunological endpoints.
Additionally, randomization is used to minimize bias in the assignment of participants into the two
groups. Blinding is used to reduce the potential bias during data collection and evaluation of study
endpoints.
Additional surveillance for COVID-19 is conducted as part of the study, given the potential risk of
disease enhancement. If a participant experiences symptom, a COVID-19 illness visit will occur. As
part of these visits, respiratory tract samples will be taken for antigen assessment as well as recording
of COVID-19-related clinical and laboratory information.
9.3 SELECTION OF STUDY POPULATION
9.3.1 Inclusion Criteria

- Healthy children and adolescents aged 6 months to 17 years;
- The participants and/or their guardians are able to understand and sign the informed consent
voluntarily (in accordance with the local regulations);
- Able to comply with study procedures based on the assessment of the Investigator;
- Female participants of childbearing potential (post-menarche girls or in accordance with the
local standard of care) may be enrolled in the study if the participant fulfills all the following
criteria:
• Has a negative pregnancy test on the day of the first dose (Day 0).
• Has practiced adequate contraception or has abstained from all activities that could result in
pregnancy for at least 28 days prior to the first dose (Day 0).
• Has agreed to continue adequate contraception through 3 months following the second dose
(Day 28).
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• Is not currently breastfeeding.

- Must be willing to provide verifiable identification (in accordance with the local regulations),
has means to be contacted and to contact the investigator during the study.
9.3.2 Exclusion Criteria

- History of confirmed infection of SARS CoV-2 prior to randomization;
- Close contact with a confirmed COVID-19 within 14 days prior to randomization;
- Prior administration of an investigational coronavirus vaccine or current/planned simultaneous
participation in another interventional study to prevent or treat COVID-19;
- Allergy to vaccines or vaccine/placebo ingredients, and serious adverse reactions to vaccines,
such as urticaria, dyspnea, angioneuroedema;
- Personal or first-grade relative (siblings) history of multisystem inflammatory disease in children
(MIS-C);
- Significant chronic illnesses that, in the opinion of the investigator, is at a stage where it might
interfere with trial conduct or completion (may include, but are not limited to cardiovascular
disease, liver or kidney disorders, respiratory illnesses)
- Significant chronic central nervous system diseases or neuromuscular disorders, psychosis or
severe cognitive behavioral disorder, in the opinion of the investigator, including epilepsy,
autism spectrum disorder, intellectual disabilities (excluding Down Syndrome);
- Acute central nervous system diseases such as encephalitis/myelitis, acute disseminating
encephalomyelitis, and related disorders;
- History of autoimmune and/or haematological diseases (including but not limited to systemic
lupus erythematosus, thyroidectomy, autoimmune thyroid disease, any form of malignant tumor,
asplenia, functional asplenia, or splenectomy resulting from any condition); well controlled type
I diabetes mellitus is allowed;
- History of bleeding disorders (e.g. factor deficiency, coagulopathy or platelet disorder), or prior
history of significant bleeding or bruising following IM injections or venipuncture;
- Immunosuppressive therapy (systemic corticoid therapy, e.g. prednisone ≥2 mg/Kg/d or ≥20
mg/day for >14 days), cytotoxic therapy (antineoplastic chemotherapy, radiation therapy),
(excluding topical or aerosol corticosteroid therapy) in the past 6 months;
- Receipt of blood products or immunoglobulins in the past 3 months;
- Receipt of other investigational drugs in the past 30 days;
- Receipt of attenuated live vaccines in the past 14 days;
- Receipt of inactivated or subunit vaccines in the past 7 days;
- Acute exacerbation or presentation of stable chronic diseases (including but not limited to
asthma, migraine, gastrointestinal disorder, etc;
- Acute febrile illness with oral temperature >37.7°C or axillary temperature >37.5°C on the day
of vaccination (refer to section 7.1 Delay/Discontinuation of Study Vaccination); enrollment
could be considered if the fever is absent for 72 hours;
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- Any confirmed or suspected human immunodeficiency virus (HIV) infection;

- Children in care or under a court order;
- According to the investigator's judgment, the subject has any other factors that might interfere
with the results of the clinical trial or pose additional risk to the subject due to participation in
the study.
9.4 TREATMENT
9.4.1 Treatments Administered

The routine immunization procedure is two doses given on Day 0 and Day 28, and each dose is 0.5 ml.
The recommended site of administration is deltoid of upper arm by intramuscular injection.
9.4.2 Identity of Investigational Product
9.4.2.1 Characteristics of the Investigational Vaccine

COVID-19 Vaccine (Vero Cell), Inactivated is produced with a series of procedures: inoculate SARS-
CoV-2 (strain CZ02) onto African green monkey kidney cells (Vero cells), followed by cultivation,
harvest, inactivation, concentration, purification and aluminum hydroxide adsorption. It is milky white
suspension, can be layered through precipitation, easy to shake well. Its main ingredient is inactivated
SARS-CoV-2, and excipients are aluminum hydroxide, disodium hydrogen phosphate, sodium
dihydrogen phosphate, sodium chloride, etc., without preservatives. It’s packaged in vial or pre-filled
syringe, 0.5 ml/vial (syringe). After vaccination, the vaccine can induce the body to produce antibodies
against SARS-CoV-2, and is used to prevent the disease caused by SARS-CoV-2 infection.
The investigational vaccine was produced by Sinovac Life Sciences, and verified by National Institutes
for Food and Drug Control to meet the requirements of Standard for Manufacturing and Testing of
COVID-19 Vaccine (Vero Cell), Inactivated. The vaccine is injection of 0.5 mL/dose, containing 600
SU/0.5 ml of SARS-CoV-2 antigen.
9.4.2.2 Stability of the Vaccine

The stability study plan of the bulk and finished product of the COVID-19 Vaccine (Vero Cell),
Inactivated was formulated, and the stability study is being carried out according to the study plan.
The accelerated thermal stability studies at 25±1°C for 56 days and 37±1°C for 42 days had been
completed in six batches of vaccine finished products. When stored at 25±1°C, the antigen content
after dissociation at each time point including 42 days met the quality standard. After dissociation at
56 days, the antigen content was lower than the quality standard, and the test was terminated. When
stored at 37±1°C, the antigen content at each time point including 28 days after dissociation met the
quality standard. The antigen content of some batches was less than 50% of the labeled amount after
dissociation at the monitoring point 42 days, and the test was terminated.
Of the 9 finished product batches, 3 batches have completed the long-term stability observation for 6
months, and no significant change have been found in the data of each test item. The other 6 batches
have completed the long-term stability observation for 3 months, and the antigen content of each batch
of finished products of COVID-19 Vaccine (Vero Cell), Inactivated has not decreased significantly
after dissociation.
According to the results of accelerated stability study, the period of validity of the vaccine was
tentatively determined to be 3 years at 2-8°C. Each batch of finished products of COVID-19 Vaccine
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(Vero Cell), Inactivated will continue to be monitored in accordance with the stability study plan.
9.4.2.3 Control Vaccine

The study was controlled with placebo containing aluminum hydroxide, disodium hydrogen phosphate,
sodium dihydrogen phosphate, and sodium chloride. The placebo was packaged in the same way as
the investigational vaccine, using a prefilled syringe package of 0.5 ml/ dose. Placebo should be stored
at 2 to 8°C. Dosage was 0.5 ml. The recommended use is intramuscular injection into the deltoid region
of the upper arm. The immunization procedure was 2 doses at 4-week interval.
9.4.2.4 Storage and Transportation of the Vaccine

The vaccine should be stored and transported at 2 to 8°C, keep in dark place.
9.4.2.5 Information on the Investigational Product

Information of the investigational product is shown in the following table:
Table 2 Information on the investigational product
Grouping Vaccine name Packaging Antigen content Manufacturer Batch No. Expiry date
Investigational COVID-19 Vaccine (Vero Pre-filled Sinovac Life

600SU/0.5ml D202104004 April 5th 2023
vaccine Cell), Inactivated Syringe Sciences
Aluminum hydroxide Pre-filled Sinovac Life

Placebo 0SU/0.5ml 2020041602 April 15th 2023
diluent Syringe Sciences
9.4.3 Method of Assigning Patients to Treatment Groups

Central randomization will be implemented in this study. The participants will be randomly assigned
to the vaccine group or placebo group according to a 1:1 ratio. The randomization will be balanced by
using randomly permuted blocks and will be stratified by site and age groups. The randomization
statistician uses SAS software to generate a random list, which will be imported into the IWRS system.
9.4.4 Selection of the Doses in the Study

The dose selected for this study (600SU/0.5ml) is based on assessment of available safety and
immunogenicity data from Phase I/II studies of CoronaVac® in children and adolescents
(NCT04551547), Phase I/II clinical trial in healthy adults (NCT04352608), and the Phase III clinical
trial in adults and elderly (NCT04456595). The dose selected for this study is proved safe, effective
and immunogenic in these studies.
9.4.5 Selection and Timing of Dose for each Patient

Subjects received two doses of the investigational vaccine (600SU/0.5ml) or placebo (0SU/0.5ml)
according to the 0, 28-day immunization schedule.
9.4.6 Blinding Method
9.4.6.1 Blinded Personnel

In this study, a double-blind design is adopted. The clinical medical team, vaccinating doctors, subjects
and sponsors are all blinded to the vaccination.
Results of subject immunological and virological monitoring may only be published with the Sponsor's
written authorization. Where necessary, independent scientists not involved in clinical and laboratory
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evaluations may review unblinded data from laboratory results.
9.4.6.2 Blinding
Investigators will log in to the IWRS system, enter the key information of the participants to obtain
the random numbers when they are enrolled. Before each vaccination, an authorized pharmacist will
log in to the IWRS system and obtain the vaccine number.
9.4.6.3 Emergency Unblinding Procedure

If an emergency medical issue and/or legal and/or regulatory requirements require unblinding ahead
of schedule, the investigator or his/her medical representative should inform the sponsor first. The
unblinding will carry out through the IWRS system. The date and reason that the blind was broken
must be recorded in the source documentation and eCRF.
9.4.7 Prior and Concomitant Treatment
9.4.7.1 Prior Treatment

According to the protocol, participants who meet the following criteria are not eligible for inclusion:
a. Prior administration of an investigational coronavirus vaccine to prevent or treat COVID-19;
b. Immunosuppressive therapy (systemic corticoid therapy, e.g. prednisone ≥2 mg/Kg/d or ≥20 mg/day
for >14 days), cytotoxic therapy (antineoplastic chemotherapy, radiation therapy), (excluding topical
or aerosol corticosteroid therapy) in the past 6 months;
c. Receipt of blood products or immunoglobulins in the past 3 months; receipt of other investigational
drugs in the past 30 days; receipt of inactivated or subunit vaccines in the past 7 days;
9.4.7.2 Concomitant Treatment

Permitted during the study:
a. If an AE occurs during the study period, necessary drug therapy and medical treatment are allowed;
b. If severe allergic reaction or life-threatening reaction occur, first aid measures should be taken
immediately;
c. There should be at least 7 days interval between an inactivated or sub-unit vaccine, and at least 14
days between a live vaccinated and the study vaccine, respectively;
d. Participants could be vaccinated in case of emergency, such as rabies, tetanus vaccine;
Prohibited during the study:
a. The use of any coronavirus vaccine (licensed or investigational) other than CoronaVac ® is
disallowed at any time prior to vaccination and during the study.
b. Refer to Exclusion Criteria for further details of prohibited therapy.
9.4.8 Treatment Compliance

Study vaccines will be administered by investigator or designee, and the date and time of vaccine
administration will be recorded in the eCRF.
Participants who miss the second dose of investigational product due to noncompliance with the visit
schedule and not due to a safety pause will still be required to follow the original visit and testing
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schedule as described in the protocol. Unless consent is withdrawn, a participant who withdraws or is
withheld from receiving the second dose of study vaccine will remain in the study and complete all
efficacy, safety and immunogenicity assessments required through the participant’s scheduled end of
study.
The study site is responsible for ensuring that participants comply with the study windows allowed. If
a participant misses a visit, the site must attempt to contact the participant and reschedule the missed
visit as soon as possible. Every effort should be made to contact the participant and complete a visit
within the defined visit window. If a participant does not complete a visit within the time window, the
visit should be conducted and will be classified as a protocol deviation. All information of this visit
will be captured and included into eCRF.
9.5 EFFICACY AND SAFETY VARIBLES
9.5.1 Efficacy and Safety Measurement Assessed and Flow Chart
9.5.1.1 Study Procedures Diagram

Table 3 Diagram of visit procedures
Procedure Screening V1 V2 V3 V4 V5 V6 V7
V3+6 V3+12
V1+8 D28 V3+8 V3+28
Date of Visit D-28～D0 D0 months months
(+3) (+10) (+3) (+10)
(+30) (+30)
Preliminary notification, participant
X
enrolment
Informed consent and assent X
Demographic information X
Physical examination X
Pregnancy examination (post-
menarche girls or in accordance X X
with the local standard of care)
Inclusion/exclusion criteria
X X
screening
Sample collection and detection of
SARS-CoV-2 (IgG/IgM rapid test, X
antigen rapid test)
HIV infection test (Only South
X
Africa)
Vaccination X X
Efficacy assessments
Weekly telephone/ text contacts for
8 weeks, and then at least every 2
weeks telephone/ text contacts Active and passive
during the rest monitoring for
COVID-19
Immunogenicity assessments
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(Sub-group)
Blood collection X X X X
Humoral immunogenicity (blood),
3.0 3.0 3.0 3.0
mL
Cell immunogenicity (blood), mL
TBD TBD TBD TBD
(Only Chile)
Safety assessments
Participant self-recording of the
safety observation on diary cards X X X X X
(Sub-group)
Monitoring of AESI/SAE,
information of concomitant use of X X X X X X X
drug/vaccine
9.5.1.2 Efficacy Evaluation

Primary efficacy analysis will be based on the cumulative incidence of all symptomatic RT-PCR
confirmed COVID-19 cases occurring 14 days after the second vaccination. The analysis included the
combined efficacy of the vaccine in all populations 14 days after the second dose.
9.5.1.2.1 Efficacy Endpoints
1) The cumulative incidence of symptomatic cases of RT-PCR confirmed COVID-19 at least 14 days
after the second vaccination.
2) The cumulative incidence of symptomatic cases of RT-PCR confirmed COVID-19 at least 14 days
after the first vaccination.
3) The cumulative incidence of hospitalization/severe/death caused by COVID-19 with onset at least 14
days after the second dose.
9.5.1.2.2 Relative Definition of Efficacy Endpoints
➢ Prespecified Criteria for Suspected COVID-19
The criteria for suspected COVID-19 are prespecified as follows, which triggers to proceed the
collection of respiratory tract sample (eg, nasopharyngeal swab, throat swab or saliva).
• Fever or chills
• Cough
• Nasal congestion or runny nose
• New loss of taste or smell
• Sore throat
• Shortness of breath or difficulty breathing
• Diarrhea
• Nausea or vomiting
• Stomachache
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• Tiredness
• Headache
• Muscle pain
➢ Case Definition for primary endpoint
Definition of RT-PCR confirmed symptomatic COVID-19 (adapted from NMPA standard):
Individuals with at least two type A symptoms, or at least one type B symptom, or chest imaging
characteristics, and with a positive RT-PCR test of COVID-19.
1) Clinical symptom
Symptom A (for at least 2 days): Fever, chills, sore throat, tiredness, nasal congestion or running nose,
muscle pain, stomachache, headache, nausea or vomiting, diarrhea.
Symptom B: Cough (for at least 2 days), new loss of taste or smell (for at least 2 days), shortness of
breath or difficulty breathing (any duration).
2) Chest imaging characteristics of COVID-19: In the early stage, there were multiple small patches
and interstitial changes, especially in the lung periphery. Furthermore, it develops into multiple ground
glass shadows and infiltrating shadows in both lungs. In severe cases, lung consolidation may occur,
and rarely pleural effusion. In MIS-C, heart shadow enlargement and pulmonary edema can be
observed in patients with cardiac insufficiency.
Regarding the RT-PCR test, respiratory tract sample (eg, nasopharyngeal swab, throat swab or saliva)
will be collected.
Regarding the sensitivity analysis, country specific local case definition also will be adopted.
➢ Determination criteria for severe COVID-19 cases (adapted from China standard)
Refers to a laboratory confirmed case of SARS-CoV-2 infection that has one or more of the following
conditions:
• High fever(≥39.5℃) lasts for more than 3 days;
• Shortness of breath (6-11 months old: RR≥50 times/min; 1-5 years old: RR≥40 times/min; >5
years old, RR≥30 times/min), except for the effects of fever and crying;
• In the resting state, when inhaling air, the oxygen saturation is ≤93%;
• Assisted breathing (nasal flaring, chest wall recessions);
• Drowsiness, convulsions;
• Poor feeding or feeding difficulties, with signs of dehydration.
Regarding the criteria of severe COVID-19 cases also could be defined by specific guidelines for
children in country.
➢ SARS-CoV-2 Infection at Baseline
SARS-CoV-2 infection is defined by seropositivity due to infection measured by rapid test of SARS-
CoV-2 IgG/IgM of the baseline blood sample, or has a SARS-CoV-2 positive antigen test result with
a respiratory tract sample (eg, nasopharyngeal swab, throat swab or saliva).
9.5.1.2.3 Clinical Endpoint Adjudication Committee (CEAC)
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The objective of the Clinical Endpoint Adjudication Committee is for the judgement of primary
endpoint events by experts in the COVID-19 vaccine research field, to make sure each event included
in the analysis meets the definition of the clinical trial protocol. Committee members do not participate
as principal or co-investigators, and their review needs to ensure that the reports are adequate and
unbiased, and that clinical endpoints are reviewed in a blind manner. The primary function of the
CEAC is to review in detail each case reported by the investigator as a possible study endpoint and to
determine whether the case meets the definition in the clinical trial protocol or the definition finally
determined by the CEAC.
9.5.1.3 Immunogenicity Evaluation

Serum samples of the participants in the immunogenicity subgroup will be obtained for
immunogenicity testing at the visits specified in the SoA. The following assays will be performed:
• SARS-CoV-2 neutralization assay
• Anti-SARS-CoV-2 S antibody level assay
Note that for the immunogenicity analyses, all the serum samples will be sent to China, and National
Institutes for Food and Drug Control (NIFDC) will conduct the analysis. SARS-CoV-2 neutralization
assay will be performed using the method of micro-cytopathic test, and the Anti-SARS-CoV-2 S
antibody test will be performed using the electrochemiluminescence immunoassay.
Further antibody assays to evaluate reactivity to additional SARS-CoV-2 antigens or variants will be
evaluated as an exploratory aim in a subset of volunteers in each age group in Chile. (Only for Chile)
As an exploratory aim, cell mediated immunity against specific SARS-CoV-2 will be evaluated in a
subset of the volunteers in each age group in Chile. Evaluations will be performed by ELISPOT to
detect cytokine secreting T cells and flow cytometry to detect activation and memory markers on
SARS-CoV-2 specific T cells. (Only for Chile)
As other exploratory aim, immunological assays will be performed in COVID-19 cases and eventual
cases of MIS-C. (Only for Chile)
9.5.1.3.1 Immunogenicity Endpoints
1) Seropositive rates, seroconversion rates of neutralizing antibody at 28 days, 6 and 12 months after
second dose vaccination.
2) GMT, GMI of neutralizing antibody at 28 days, 6 and 12 months after second dose vaccination.
3) GMC of anti-SARS-CoV-2 S antibody at 28 days, 6 and 12 months after second dose vaccination.
4) The cell-mediated immune response before each vaccination and after the second vaccination. (Only
for Chile)
9.5.1.3.2 Relative Definition of Immunogenicity Endpoints
1) Evaluation criteria for serum neutralizing antibody
The determination criteria for positivity of serum antibodies are as follows:
- The antibody titer ≥1:8 is positive.
The determination criteria for seroconversion of antibodies are as follows:
- If the titer of neutralizing antibody is less than 1:8 before immunization, the titer of neutralizing
antibody ≥1:8 after immunization is positive. For neutralizing antibody ≥1:8 before immunization,
neutralizing antibody titer increased by 4 times or more after immunization is positive.
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- GMT refers to geometric mean titer, GMI refers to geometric mean increase of post-immunization
antibody titer relative to baseline antibody titer. For the calculation of GMT and GMI, the value of
antibody titer <1:8 is assigned to 1:4.
9.5.1.4 Safety Evaluation

Planned time points for all safety assessments are provided in the SoA. Any clinically relevant changes
occurring during the study must be recorded on the AE section of the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
9.5.1.4.1 Safety Endpoints
1) The incidence rate of solicited local and systemic adverse reactions within 7 days after each dose
vaccination.
2) The incidence rate of unsolicited adverse events within 28 days after each dose vaccination.
3) The incidence rate of SAEs and the relationship to the vaccine within the period of 12 months after
4) The incidence rate of AESIs and the relationship to the vaccine within the period of 12 months after
9.5.1.4.2 Observation Indicators for Safety
Solicited local adverse events: Pain, induration, swelling, redness, rash, pruritus.
Solicited systemic adverse events (including vital signs): Acute allergic reaction, skin and mucosa
abnormality, diarrhea, anorexia, vomiting, nausea, muscle pain (non-inoculated site), headache, cough,
fatigue, fever.
9.5.1.4.3 Definition of Adverse Events/reactions
The safety of vaccines will be evaluated according to the extent, intensity and correlation with
vaccination of local adverse events, systemic adverse events and other adverse events.
All adverse medical events occurring during the trial (since signing of the informed consent form)
should be collected and recorded.
(1) Adverse events (AE): Adverse medical events that occur after vaccination, but are not necessarily
causally related with the trial vaccine;
(2) Adverse reactions: adverse events that demonstrate a reasonable causal relationship with the
investigational product will be considered as adverse reactions.
(3) Serious adverse event (SAE): It refers to adverse events that results in following serious
outcomes: death, life-threatening event, persistent or significant disability or incapacity, need
hospitalization treatment, prolong hospitalization time, important medical event, cause congenital
anomaly or birth defect, etc.;
(4) Suspected unexpected serious adverse reaction (SUSAR): defined as a SAR, the nature and
severity of which is not consistent with the information about the medicinal product in question set
out in the Investigational Brochure (IB).
(5) Solicited/unsolicited adverse events: In this trial, the solicited period is 0-7 days after each dose
of vaccination, and the unsolicited period is 8-28 days. The solicited adverse events refer to the
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solicited symptoms reported within the solicited period, and the unsolicited adverse events refer to
the unsolicited symptoms reported within the solicited period, or any symptoms reported within the
non-solicited period.
(6) Adverse Events of Special Interest (AESI):
The Priority List of Adverse Events of Special Interest in CoronaVac® is included in events of
special interest. In this study, the following should be reported expeditiously:
• SAEs;
• Pregnancy in the first 4 weeks after the last vaccination;
• Bell palsy;
• Generalized seizure;
• Guillain-Barrésyndrome;
• Acute disseminated encephalomyelitis;
• Hematological thrombocytopenia;
• Immune anaphylaxis;
• Vasculitis;
• MIS-C;
• Other serious local or systemic adverse events after immunization.
9.5.1.4.4 Safety Observation Time
After each dose of vaccine, participants are observed on site for 30 minutes, record the corresponding
adverse events on the diary card, and confirm that there is no acute allergic reaction before leaving.
Systematic safety observations are conducted within 28 days after each dose, and subjects are required
to record the occurrence of adverse events in a diary card. Doctors should explain the judgment,
measurement, recording, precautions and reporting method of adverse events. Solicited observation is
carried out within 7 days after each vaccination. Participants and/or their guardians are required to
closely observe symptoms and temperature and fill in the diary card every day. The investigators verify
the adverse events on the 8th days after vaccination (through face-to-face interviews or by telephone).
The investigators verify the adverse events on the 28th days after each vaccination.
For all participants, the collection of adverse events of special interest (AESI), and serious adverse
events (SAEs) will be monitored to 12 months after full-course inoculation.
9.5.1.4.5 Safety Evaluation Criteria
The severity of adverse events is classified according to Table 4 (local adverse events), Table 5
(systemic adverse events) and Table 6 (unsolicited adverse events, fever and other suspected symptoms
of COVID-19), created based on the “Guidelines for grading scale of adverse events in vaccine clinical
trials, 2019” of the National Medical Products Administration, China.
Table 4 Classification of the severity of the solicited local clinical adverse reactions
Grade 1 Grade 2 Grade 3 Grade 4
Pain Not affecting or Affecting physical Affecting daily life Loss of basic self-care
slightly affecting activity ability, or
physical activity hospitalization
Induration#,
Swelling #
>14 years Diameter 2.5 to <5 cm 5 to <10 cm in diameter Diameter ≥10 cm or Abscess, exfoliative
2 2 2
or area 6.25 to <25 cm or 25 to <100 cm in area ≥ 100 cm or dermatitis, dermal or
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without affecting or area or affecting daily ulceration or secondary deep tissue necrosis
slightly affecting daily life infection or phlebitis or
life aseptic abscess or
wound drainage or
seriously affecting
daily life
≤14 years Diameter <2.5 cm ≥2.5 cm in diameter or ≥ 50% area of Abscess, exfoliative
< 50% area of the the inoculated limb or dermatitis, dermal or
inoculated limb ulceration or secondary deep tissue necrosis
(anatomically, the limb infection or phlebitis or
where the inoculation wound drainage or
site is located, such as seriously affecting
the upper arm or thigh) daily life
Redness#, Rash#
>14 years Diameter 2.5 to <5 cm 5 to <10 cm in diameter Diameter ≥10 cm or Abscess, exfoliative
2 2 2
or area 6.25 to <25 cm or 25 to <100 cm in area ≥ 100 cm or dermatitis, dermal or
without affecting or area or affecting daily ulceration or secondary deep tissue necrosis
slightly affecting daily life infection or phlebitis or
life aseptic abscess or
wound drainage or
seriously affecting
daily life
≤14 years Diameter <2.5 cm ≥2.5 cm in diameter or ≥ 50% area of the Abscess, exfoliative
< 50% area of the inoculated limb or dermatitis, dermal or
inoculated limb ulceration or secondary deep tissue necrosis
(anatomically, the limb infection or phlebitis or
where the inoculation wound drainage or
site is located, such as seriously affecting
the upper arm or thigh) daily life
Pruritus Itching at injection site, Itching at injection site, Affecting daily life NA
relieved within 48 did not alleviate within
hours 48 h after treatment
# The maximum measured diameter or area should be used for induration and swelling, rash and redness; evaluation and
grading should be based on functional grade and actual measurement results, and higher grading indicators should be
selected.
Table 5 Classification of severity of the solicited systemic clinical adverse events and of the signs and
symptoms in case of fever and suspicion of COVID-19
Acute Local urticaria, no Local urticaria need Extensive urticaria or Anaphylactic shock or life-
allergic treatment required treatment or mild angioedema treated or mild threatening bronchospasm or
reaction* angioedema, no treatment bronchospasm laryngeal edema
required
Skin and Erythema/pruritus/color Diffuse Massive Exfoliative dermatitis
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mucosa change rash/maculopapular blisters/exudation/desquamation/ involving mucosa, erythema
abnormality rash/dryness/desquamation ulcer multiforme, or suspected
Stevens-Johnsons syndrome
Diarrhea Mild or transient, 3-4 Moderate or persistent, 5-7 >7 times/day, abnormal stool, or Hypotensive shock,
times/day, abnormal times/day, abnormal stool, hemorrhagic diarrhea, orthostatic hospitalization
stool, or mild diarrhea or diarrhea >1 week hypotension, electrolyte
lasting less than 1 week imbalance, requiring intravenous
infusion >2L
Anorexia Decreased appetite, not Decreased appetite, Decreased appetite, and Need intervention (such as
affecting food intake reduced food intake, not significantly reduced body gastric tube feeding,
affecting body weight weight parenteral nutrition)
Vomiting 1-2 times/24 hours 3-5 times/24 hours or >6 times within 24 hours or Hospitalization or other
without affecting affecting activity requiring intravenous fluid nutrition routes due to
activity infusion hypotensive shock
Nausea Transient (<24 hours) or Persistent nausea leads to Persistent nausea leads to almost Life threatening (e.g.,
intermittent and reduced food intake (24-48 no food intake (>48 hours) or hypotensive shock)
basically normal food hours) requires intravenous fluids
intake
Muscle pain Does not affect daily Slightly affects daily Severe muscle pain, seriously Emergency or hospitalization
(non- activities activities affects daily activities
inoculated
site)
Headache Not affecting daily Transient, slightly Seriously affecting daily Intractability, need
activities, no treatment affecting daily activities, activities, need treatment or emergency or hospitalization
required may need treatment or intervention
intervention
Cough Transient, no treatment Persistent cough, Paroxysmal cough, no Emergency or hospitalization
required effectively controlled with improvement after treatment
treatment
Fatigue No interference with Some interference with Significant prevents daily Emergency or hospitalization
activity activity activity
Vital Signs
Fever, 37.5-37.9℃ 38.0-39.4℃ ≥39.5℃ Sustained Fever: ≥ 39.5 ℃
axillary for longer than 5 days
temperature†
* Refers to type I hypersensitivity
†Oral temperature = axillary temperature +0.2℃.
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Table 6 Classification of the severity of unsolicited clinical Adverse Events and of other signs and
symptoms in case of fever and suspicion of COVID-19
GRADE 1 (Mild) Transient (< 48 hours) or mild discomfort; no medical intervention/therapy required
GRADE 2 (Moderate) Mild to moderate limitation in activity - some assistance may be needed; no or minimal
medical intervention/therapy required
GRADE 3 (Severe) Marked limitation in activity, some assistance usually required; medical
intervention/therapy required, hospitalizations possible
GRADE 4 (Life- Extreme limitation in activity, significant assistance required; significant medical
threatening) intervention/therapy required, hospitalization or hospice care probable
GRADE 5 Death
9.5.1.4.6 Classification of the Causal Relationship

All adverse events should be classified by the principal investigator or his medical representative as to
their causal relationship with the product under investigation, according to the classification adapted
from the “Uppsala Monitoring Center” of the World Health Organization (WHO-UMC), described in
Table 7.
The sponsor may request additional clarifications from the principal investigator to justify the causal
relationship attributed to the event. The causal relationship may also be reviewed at the request of the
Independent Data and Safety Monitoring Committee upon written justification. All local reactions after
administration of the product under investigation will be considered as adverse events with a certain
causal relationship to vaccination.
Table 7 Classification of causal relationship of Adverse Events with the investigational product
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Reasonable causal relationship Causal relationship NOT reasonable

Adverse Event considered as Adverse Reaction Adverse Event cannot be considered as
Adverse Reaction.
Certain Probable Possible Unlikely Not related
Event or change A clinical event, A clinical event, A clinical event, A clinical event,
(abnormal value) in a including a change including a change including a change including a change
laboratory test, with (abnormal value) in (abnormal value) in (abnormal value) in (abnormal value)
plausible temporal a laboratory test, a laboratory test, a laboratory test, in a laboratory test,
relationship with with a reasonable with a reasonable which, due to the which, due to the
regarding the temporal temporal time of the time of the
administration of the relationship relationship administration of administration of
intervention; regarding the regarding the the intervention, the intervention,
administration of administration of gives cause to an gives cause to a
the intervention; the intervention; unlikely, but not non-existing
impossible, relationship;
relationship;
It cannot be explained It is unlikely to be It can also be Another disease or Another disease or
by a concurrent disease caused by a explained by another drug another drug
or another intervention concomitant illness concurrent disease provide a plausible provide a plausible
or medication; or by another or other explanation explanation
The event is defined intervention or interventions or
pharmacologically or medication; medications;
phenomenologically
(i.e., a specific and
objective disorder or a
pharmacologically
recognized
phenomenon);
The response to The response to Lack of
discontinuation or discontinuation or information or lack
withdrawal is plausible withdrawal is of clarity about
(pharmacologically, clinically withdrawal or
pathologically); reasonable; treatment
discontinuation
Re-exposure is Re-exposure is not
satisfactory, if required required
9.5.1.4.7 Outcome of Adverse Events
Outcome of Adverse Events includes: 1) recovered; 2) unrecovered; 3) recovered with sequela; 4)
death; 5) loss of follow up or unknown.
9.5.2 Appropriateness of Measurements

The primary objective of this study is to evaluate the efficacy, immunogenicity and safety of the
vaccine. In terms of efficacy evaluation, the incidence density of clinically symptomatic COVID-19
cases with positive SARS-CoV-2 RT-PCR test result is used as the endpoint to evaluate the efficacy of
the vaccine, vaccinated per 0, 28-day schedule.
As for evaluating the immunogenicity of the vaccine, considering that the immunogenicity caused by
inactivated vaccines is mainly humoral immunity, thus, humoral immunity is mainly evaluated in this
study, and the seroconversion rate and GMT of neutralizing antibody is taken as the main indicator for
evaluating the immunogenicity. At the same time, to explore the cellular immune response induced by
the vaccine.
As for the safety evaluation of the vaccine, the safety indicators set in this study include: the incidence
of adverse events after vaccination, the incidence of SAE, and the occurrence of AESI.
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9.5.3 Primary Efficacy Variables

In this clinical trial, the primary endpoint is the incidence of symptomatic COVID-19 cases confirmed
by RT-PCR from 14 days after the second dose vacciantion.
9.5.4 Drug Concentration Measurements

Not applicable.
9.6 DATA QUALITY ASSURANCE
9.6.1 General Consideration

Quality Assurance (QA) oversight will be implemented at all stages of the trial process per ICH E6
(R2) section 5.0 and/or local government GCP requirements.
Quality Control (QC) procedures will be implemented beginning with the data entry system and data
QC checks that will be run on the database will be generated. Any missing data or data anomalies will
be communicated to the site(s) for clarification/resolution.
The site will also develop routine operational checks to verify that critical protocol requirements and
procedures are executed correctly and completely at the time the work is being performed.
The investigational site will provide direct access to all study related documents, source
data/documents, and reports for the purpose of monitoring and auditing by the Sponsor, and inspection
by local and regulatory authorities.
9.6.2 Clinical Monitoring

The CRO, on behalf of the Sponsor of this study, is responsible for ensuring that the study is conducted
in accordance with ICH GCP and regulatory requirements. For this purpose, monitors will provide
external monitoring for this study. A site initiation visit will be conducted prior to beginning the
study, and monitoring will be conducted at initiation, during, and at closeout of the study. During the
course of the study monitors will visit (virtual visit permissible) the clinical site at intervals to verify
compliance to the protocol; completeness, accuracy, and consistency of the data and study product
accountability; and adherence to ICH GCP and applicable regulations. As needed and when appropriate,
the monitors will also provide clarifications and additional training to help the site resolve issues
identified during the monitoring visit.
Investigators and/or their study staff will be trained on the study protocol and all applicable study
procedures prior to study initiation.
Study progress will be monitored by sponsor study team or representative (e.g., a contract research
organization) as frequently as necessary to ensure the rights and well-being of study participants are
protected; to verify adequate, accurate and complete data collection; protocol compliance and to
determine that the study is being conducted in conformance with applicable regulatory requirements.
Arrangements for monitoring visits will be made in advance in accordance with the monitoring plan.
9.6.3 Data and Safety Monitoring Board (DSMB)

A DSMB will be established will be established to periodically review cumulative data, as needed.
DSMB members will include infectious disease experts, vaccine experts, as well as a biostatistician.
The responsibilities and procedures of DSMB will be defined in the DSMB Charters.
DSMB charters shall be also aligned with regards to review and stopping rules as much as possible
to avoid huge differences and biases, except for local regulatory rules that might be imposed.
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The DSMB will be responsible for safeguarding the interests of trial participants, assessing safety
during the trial, and for monitoring the overall conduct of the clinical trial. The DSMB will provide
recommendations about continuing, modifying or stopping the trial.
9.7 STATISTICAL METHODS PLANNED IN THE PROTOCOL AND DETERMINATION

OF SAMPLE SIZE
9.7.1 Statistical and Analysis Plans
9.7.1.1 Definition of the Population for Analysis

9.7.1.1.1 Enrolled Population
All the participants who signed the informed consent and are screened to meet the inclusion criteria of
this study, regardless of whether they are randomized, are defined as enrolled population.
9.7.1.1.2 Population for Efficacy Analysis
E-FAS (Full Analysis Set for Efficacy): includes all randomized participants who follows intent to treat
(ITT) principle, receive at least 1 dose of vaccine or placebo, and have any follow-up for case
surveillance after the first dose vaccination. The participant who takes the vaccine erroneously will be
included in the efficacy analysis according to randomized group.
E-mFAS 1 (modified Full Analysis Set 1 for Efficacy): includes all randomized participants who
receive at least 1 dose of vaccine or placebo, have any follow-up for case surveillance 14 days
following the first dose vaccination, and are RT-PCR negative at baseline. The participant who takes
the vaccine erroneously will be included in the efficacy analysis according to randomized group.
E-mFAS 2 (modified Full Analysis Set 2 for Efficacy): It is a subset of E-mFAS1, includes all
participants who complete 2 doses of vaccination, have any follow-up for case surveillance 14 days
after first dose vaccination, and are RT-PCR negative at baseline.
E-PPS (Per-Protocol Set for Efficacy): includes the randomized participants who meet inclusion
criteria, unmeet exclusion criteria, and complete 2 doses of vaccination, have any follow-up for case
surveillance 14 days after first dose vaccination, and are RT-PCR negative at baseline. The participant
who meets any one of following conditions will be excluded from E-PPS:
• No follow-up records after 14 days following the second dose;
• Major protocol deviations/violations.
• Any conditions which may affect the evaluation of vaccine efficacy.
9.7.1.1.3 Population for Safety Analysis
SS (Safety Set): includes all participants who receive at least 1 dose of vaccine or placebo. The
participant who takes the vaccine erroneously will be included in the safety analysis as treated.
In addition to SS, safety set after the first dose (SS1) and safety set after the second dose (SS2) will be
defined as well. SS1 includes all participants who take the first vaccination and is to analyze safety
data after the first dose, and SS2 includes the participants who take the second vaccination and is to
analyze safety data after the second dose.
9.7.1.1.4 Population for Immunogenicity Analysis
I-FAS (Full Analysis Set for Immunogenicity): includes all randomized participants who follows ITT
principle, receive at least 1 dose of vaccine or placebo, and have valid immunogenicity data before the
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first dose. The participant who takes the vaccine erroneously will be included in the immunogenicity
analysis as randomized.
I-PPS (Per-Protocol Set for Immunogenicity): includes the randomized participants who meet
inclusion criteria, unmeet exclusion criteria, complete 2 doses of vaccination, have both valid pre-
vaccination immunogenicity data and the values 28 days after the second dose. The participant who
meets any one of following conditions will be excluded from I-PPS.
• No valid immunogenicity data at baseline and 28 days after the second dose;
• Major protocol deviations/violations;
• Concomitant medications and vaccines which may affect immunogenicity analysis;
• Any conditions which may affect the evaluation of immunogenicity.
9.7.1.2 Descriptive Analysis

Baseline demographic and anthropometric data, including age, age group, weight, height, waist
circumference, gender and race/ethnicity are analyzed descriptively. The baseline exposure history of
SARS-COV-2 is descriptively analyzed in terms of virological diagnosis, serological diagnosis, and
total. Data on racial or ethnic ancestry are collected using self-report method. Chi-square test /Fisher
exact probability test is used for binary variables, and Student t test or ANOVA is used for continuous
variables. Carrying out analysis per different study sites and of total population respectively.
MedDRA is used to encode the subjects' medical history. All diseases and current diseases of the
subjects are listed by study group and age group, respectively, according to SOC and PT.
The distribution of subjects is described by research center and total subjects respectively, including
the number of subjects screened, the number of people per dose of vaccination, the incidence of
subjects’ withdrawal and discontinuing the study, and the reasons for withdrawal and discontinuing
are described. CONSORT flow chart is adopted to depict the distribution of subjects. Subjects who
failed screening and who discontinued the study will be listed.
List the protocol deviations in detail.
9.7.1.3 Efficacy Analysis

The person-year incidence rate of confirmed COVID-19 case in each group will be calculated from
(the number of confirmed COVID-19 cases/person-years at risk) × 100%. Their 95% Cis will be
estimated as well. Poisson regression model will be employed to estimate the vaccine efficacy and 95%
confidence interval (CI). The model will include the number of confirmed COVID-19 cases as
dependent variable, groups assignment as fixed effect and the person year at risk as the offset.
E-mFAS2 and E-PPS population are used for the primary population to evaluate vaccine efficacy.
9.7.1.4 Safety Analysis

Treatment-emergent adverse events (TEAEs) are defined as any AEs that occurred on or after first
dose date or worsening of existing events. Adverse events will be coded using the Medical Dictionary
for Regulatory Activities (MedDRA), version 21.0 or later version.
TEAEs are summarized by frequency and percentage of patients, frequency of occurrences, and
tabulated by system organ class (SOC) and preferred term (PT). Serious adverse events (SAEs) will
be summarized as well.
The following summary tables and patient level listings will be presented for TEAE data:
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Overall Summary of Adverse Events

• TEAEs by SOC and PT
• TEAEs by SOC and PT, Related to Vaccination
• TEAEs by SOC and PT, Unrelated to Vaccination
• TEAEs by SOC, PT and Severity
• TEAEs by SOC, PT and Severity, Related to Vaccination
• TEAEs by SOC, PT and Severity, Unrelated to Vaccination
• TEAEs by SOC, PT and Doses
• TEAEs by SOC, PT and Doses, Related to Vaccination
• TEAEs by SOC, PT and Doses, Unrelated to Vaccination
• TESAEs by SOC and PT
• TESAEs by SOC and PT, Related to Vaccination
• TESAEs by SOC and PT, Unrelated to Vaccination
• Listing of Serious Adverse Events
• Listing of Related Serious Adverse Events
• Listing of AEs
All AEs including both treatment-emergent and non-treatment-emergent events will be presented in
listings.
9.7.1.5 Immunogenicity Analysis

The seropositive rates, seroconversion rates in seronegative participants at baseline, 4-fold increase
rates in seropositive participants at baseline, seroconversion/4-fold increase rates 28 days after two
doses in both vaccine and placebo groups will be estimated, and the corresponding 95% CIs will be
derived from Clopper-Pearson method. Their differences between two groups are compared by using
Chi-square tests/Fisher Exact test.
The descriptive statistics, including geometric mean and corresponding 95% CI, are employed to
summarize GMT and GMI after 28 days following the second dose in all population, seronegative
population at baseline and seropositive population at baseline, respectively. The t-tests after log
transformation will be compared between the two groups.
The reverse cumulative distribution plot is to depict the pre- and post-vaccination antibody data in the
vaccine and placebo groups.
The seropositive rates and GMTs at Month 12 in the vaccine and placebo groups will be estimated in
IPS population.
9.7.1.6 Processing of missing data

In the evaluation of vaccine efficacy, the actual exposure time of the subjects is taken as the
denominator, and the cases observed during the exposure time is taken as the numerator to calculate
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the incidence and vaccine efficacy.
9.7.2 Determination of Sample Size
9.7.2.1 Efficacy
The sample size calculation for efficacy is based on following factors.
• Type I error equal to 0.05 (2-sided)；
• Type II error equal to 10%, therefore, power of the trial equals to 90%；
• Expected vaccine efficacy is 50%；
• The lower limit of the 95% confidence interval (95% CI) for the expected vaccine efficacy is
above 0;
• Participants will be randomly assigned into 2 groups at a ratio of 1:1;
• Expected incidence rate of participants in placebo group= 1%；
• 10% loss to follow up;
• Interim analysis would be introduced when 1/2 expected cases are observed.
It is assumed that the incidence rate of COVID-19 in Children and adolescents be 1% in placebo arm.
An interim analysis is planned when 50% of confirmed COVID-19 cases are observed, and O’Brien-
Fleming spending function will be employed to control familywise type I error rate within 5%. In order
to detect 50% vaccine efficacy (lower bound of 95% CI > 0), a total of 93 confirmed COVID-19 cases
and at least 12,593 participants are required to achieve 90% power with two-sided significance level
of 5%. The number-of-events calculation is based on an exact conditional method under large sample
Poisson distribution assumption proposed by Chan and Bohidar. Considering 10% loss of follow up,
approximately 14,000 participants will be needed to recruit in total and 7,000 participants in each arm.
9.7.2.2 Safety
The sample size calculation for safety was based on the denominator needed to determine the
maximum risk of an adverse vaccine reaction occurring if the reaction is not reported in the study as
described by Hanley and Lippman-Hand.
Formula:
𝑙𝑛 𝛼
𝑁𝑖 =
ln(1 − 𝑀)
Where: Ni is the sample size of vaccinees for each age group, N1 = Adults (18-59 years) and N2 =
Elderly (60 years or more) and α is the type I error
For this calculation, the following parameters were used in the age group of Adults (18-59 years):
• Type I error equal to 5% (two-tailed)
• Maximum risk of 1 in 500, equal to 0.002
Substituting these values in Formula, we obtain N≅1497
Following the 1:1 vaccine: placebo ratio, 1497 participants will be on the placebo arm, out of a total
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of participants N = 2994. The minimum sample size by 8% to predict loss of follow-up 2994 / 0.92≅
6280 as the minimum number of participants in the study.
10 STUDY PATIENTS
10.1 DISPOSITION OF PATIENTS

As of August 31st, 2022, a total of 11,349 subjects were enrolled (Vaccine group: 6,073; Placebo group:
5,276), in which 11,343 have received 1st dose of COVID-19 vaccine (Vaccine group: 6,071; Placebo
group: 5,272), and 11,037 have received the 2nd dose (Vaccine group: 5,972; Placebo group: 5,065).
For efficacy analysis, a total of 9,859 subjects were included in the E-mFAS 2 set (Vaccine group:
4,933; Placebo group: 4,926), 9,678 subjects were included into the E-PPS set (Vaccine group: 4,841;
Placebo group: 4,837).
For safety analysis in the total participants, 11,343 subjects were included in the SS, including 11,343
in the SS1 and 11,037 in the SS2. As in the safety subgroup, 202 aged 6-35 months, 1134 aged 3-5
years, 1016 aged 6-11 years and 587 aged 12-17 years were included in the safety analysis.
Analysis of subject enrollment and distribution is shown in the table below.
Table 8 Subjects enrollment and distribution
Vaccine group Placebo group Total
N (%) N (%) N (%)
Screened Subjects 11744
Screened Failure 395
Enrolled 6073 5276 11349
Received Dose 1 6071 (99.97) 5272 (99.92) 11343 (99.95)
Received Dose 2 5972 (98.34) 5065 (96.00) 11037 (97.25)
Ongoing 4690 (77.23) 4608 (87.34) 9298 (81.93)
Completed 632 (10.41) 2 (0.04) 634 (5.59)
Study Discontinued 751 (12.37) 666 (12.62) 1417 (12.49)
Efficacy Analysis Population
E-mFAS 2 4933 (81.23) 4926 (93.37) 9859 (86.87)
E-PPS 4841 (79.71) 4837 (91.68) 9678 (85.28)
Safety Analysis Population
(all participants)
SS 6078 5265 11343 (99.95)
SS1 6072 5271 11343 (99.95)
SS2 5975 5062 11037 (97.25)
Safety Analysis Population
(safety subgroup)
6-35 months 101 101 202
3-5 years 788 346 1134
6-11 years 593 423 1016
12-17 years 317 270 587
(1) Data analysis cut-off date was 2022-08-31.
11 EFFICACY EVALUATION
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11.1 DATA SETS ANALYSED

E-mFAS2 and E-PPS, in which COVID-19 cases are collected from 14 days after the second dose, are
for primary efficacy evaluation. In this report, we presented all the results of E-mFAS2 and E-PPS.
In current version of report, the immunogenicity were analyzed from I-PPS (Per-Protocol Set for
Immunogenicity), which includes the randomized participants who meet inclusion criteria, unmeet
exclusion criteria, complete 2 doses of vaccination, have both valid pre-vaccination immunogenicity
data and the values 28 days after the second dose.
11.2 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS

As of August 31st, 2022, a total of 9,859 subjects was included in the E-mFAS 2 analysis set. The
subjects were divided into two groups, 4,933 in the vaccine group and 4,926 in the placebo group.
Among them, 52.61% were Asian, and 40.41% were Black or African American. There was no
significant difference of demographic and other baseline characteristics of the subject between the
vaccine and placebo group.
Analysis of demographic and other baseline characteristics is shown in the table below.
Table 9 Demographic and other baseline characteristics (E-mFAS 2)
Variables P value
(N=4933) (N=4926) (N=9859)
Age (years)
Mean (SD) 10.70 (4.06) 10.70 (4.05) 10.70 (4.06) 0.9968
Median 11.21 11.21 11.21
Age group
6-35 months n(%) 100 (2.03) 101 (2.05) 201 (2.04) 0.9996
3-5 years n(%) 733 (14.86) 732 (14.86) 1465 (14.86)
6-11 years n(%) 1925 (39.02) 1925 (39.09) 3850 (39.05)
12-17 years n(%) 2175 (44.09) 2167 (44.00) 4342 (44.05)
Gender
Male n(%) 2532 (51.33) 2526 (51.28) 5058 (51.30) 0.9613
Female n(%) 2401 (48.67) 2400 (48.72) 4801 (48.70)
Transgender n(%) 0 (0.00) 0 (0.00) 0 (0.00)
Race
Hispanic n(%) 96 (1.95) 105 (2.13) 201 (2.04) 0.9213
Chilean native n(%) 1 (0.02) 2 (0.04) 3 (0.03)
Asian n(%) 2595 (52.60) 2592 (52.62) 5187 (52.61)
Black or African American n(%) 1997 (40.48) 1987 (40.34) 3984 (40.41)
White n(%) 10 (0.20) 8 (0.16) 18 (0.18)
Other n(%) 233 (4.72) 232 (4.71) 465 (4.72)
Unknown n(%) 1 (0.02) 0 (0.00) 1 (0.01)
Height (cm) Mean (SD) 136.32 (22.07) 136.61 (22.11) 136.47 (22.09) 0.5101
Weight (kg) Mean (SD) 35.14 (16.20) 35.05 (15.83) 35.10 (16.01) 0.7981
2
BMI (kg/m ) Mean (SD) 17.87 (4.36) 17.78 (4.43) 17.82 (4.39) 0.3241
11.3 MEASUREMENTS OF CLINICAL FEATURES
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Clinical features of subjects included in the E-mFAS 2 analysis set was analyzed (analysis with data
cut-off date August 31st, 2022). Among the 9,856 subjects with baseline IgG/IgM test results, 48.77%
were with positive baseline IgG, 0.85% were with positive baseline IgM. No subject was infected with
HIV or pregnant at baseline. There was no significant difference between clinical features of subjects
between vaccine and placebo group.
The case monitoring time (from 14 days after full vaccination) of subjects was 173.71 days for vaccine
group and 171.15 days for placebo group, without significant difference between vaccine and placebo
group.
Analysis of clinical features is shown in the table below.
Table 10 Clinical features of subjects (E-mFAS 2)
Variables P value
(N=4933) (N=4926) (N=9859)
Baseline IgG
Positive n(%) 2427 (49.22) 2380 (48.32) 4807 (48.77) 0.8060
Negative n(%) 2495 (50.60) 2534 (51.45) 5029 (51.02)
Invalid n(%) 8 (0.16) 10 (0.20) 18 (0.18)
Not done n(%) 1 (0.02) 1 (0.02) 2 (0.02)
Total (Missing) 4931 (2) 4925 (1) 9856 (3)
Baseline IgM
Positive n(%) 34 (0.69) 50 (1.02) 84 (0.85) 0.0480
Negative n(%) 4894 (99.25) 4864 (98.76) 9758 (99.01)
Invalid n(%) 3 (0.06) 10 (0.20) 13 (0.13)
Not done n(%) 0 (0.00) 1 (0.02) 1 (0.01)
Total (Missing) 4931 (2) 4925 (1) 9856 (3)
HIV test
Negative n(%) 2209 (99.77) 2203 (99.73) 4412 (99.75) 0.7599
Positive n(%) 0 (0.00) 0 (0.00) 0 (0.00)
Uncertain n(%) 5 (0.23) 6 (0.27) 11 (0.25)
Total (Missing) 2214 (8) 2209 (9) 4423 (17)
Pregnancy
Negative n(%) 1053 (43.86) 1066 (44.42) 2119 (44.14) 0.6960
Positive n(%) 0 (0.00) 0 (0.00) 0 (0.00)
Not done n(%) 1348 (56.14) 1334 (55.58) 2682 (55.86)
Total (Missing) 2401 (0) 2400 (0) 4801 (0)
Case monitoring time (from 14
days after full vaccination) (days)
Mean (SD) 173.71 (65.88) 171.15 (66.94) 172.43 (66.42) 0.0557
Median 168.00 167.00 167.00
Follow-up time (from 14 days after
full vaccination) (days)
Mean (SD) 188.52 (58.21) 183.27 (63.93) 185.90 (61.19) <0.0001
Median 177.00 174.00 176.00
11.4 EFFICACY RESULTS AND TABULATIONS OF INDIVIDUAL PATIENT DATA

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11.4.1 Analysis of Efficacy

The cut-off date of interim efficacy analysis is March 10th, 2022, and of the long-term efficacy analysis
is August 31st, 2022.
In addition, immunogenicity analysis results of participants aged 6-35 months and 3-17 years are
displayed in this section.
11.4.1.1 Interim Analysis of Protective Efficacy

11.4.1.1.1 Primary Efficacy Analysis
The primary efficacy analysis was conducted based on all confirmed COVID-19 cases according to
case definition, in both E-mFAS 2 set and E-PPS set, which showed consistent results. The following
description is based on the results of E-mFAS 2 set.
The interim analysis results showed that among 5,041 subjects, a total of 125 confirmed cases were
reported in the case monitoring period, including 57 cases in the vaccine group (incidence density (ID):
16.19/100 person-years) and 68 cases in the placebo group (ID: 19.64/100 person-years). The efficacy
of the vaccine against confirmed COVID-19 cases is 17.23% (95%CI: -19.45, 42.83).
The analysis results are shown in table below.
Table 11 Efficacy against COVID-19 cases of any severity 14 days after second dose vaccination
(Interim analysis)
Vaccine group Placebo group

Analysis No. of cases/ No. of cases/
Efficacy and 95%CI
sets Sample Person-years Sample Person-years (%)
Incidence density Incidence density
size of exposure size of exposure
(100 person-year) (100 person-year)
E-mFAS 2 2538 352.1 57 (16.19) 2503 346.2 68 (19.64) 17.23 (-19.45, 42.83)
E-PPS 2511 347.3 55 (15.84) 2479 342.1 68 (19.88) 20.19 (-15.57, 45.11)
11.4.1.1.2 Efficacy Analysis by Severity

The efficacy of COVID-19 vaccine against COVID-19 cases with different severity, in the E-mFAS 2
set and the E-PPS set, which showed consistent results. The efficacy against hospitalization COVID-
19 cases, sever COVID-19 cases, and death COVID-19 cases were analyzed accordingly. Besides, the
efficacy against COVID-19 cases (meet case defination) with fever symptom (lasting at least for 2
days) was also analyzed, given that fever is a typical symptom of COVID-19 in pediatric population.
The following description is based on the results of E-mFAS 2 set.
The results in the interim analysis showed that among 5,041 subjects, a total of 77 confirmed cases
with fever were reported in the case monitoring period, including 29 cases in the vaccine group (ID:
8.24/100 person-years) and 48 cases in the placebo group (ID: 13.87/100 person-years). The efficacy
of the vaccine against cases with fever is 40.31% (95%CI: 3.39, 63.71); a total of 5 hospitalization
cases were reported, including 1 case in vaccine group (ID: 0.28/100 person-years) and 4 cases in
placebo group (ID: 1.16/100 person-years). The efficacy of the vaccine against hospitalization cases is
75.22% (95%CI: -150.39, 99.50). No sever case or death case was reported during study period.
See table below for details.
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Table 12 Efficacy against COVID-19 cases 14 days after second dose vaccination by severity (Interim
analysis)
Analysis Person- No. of cases/ Person- No. of cases/ Efficacy and 95%CI
Severity
Sets years of Incidence density years of Incidence density (%)
exposure (100 person-year) exposure (100 person-year)
Total sample size N=2538 N=2503

Cases with fever 352.1 29 (8.24) 346.2 48 (13.87) 40.31 (3.39, 63.71)
E-mFAS
Hospitalization cases 352.1 1 (0.28) 346.2 4 (1.16) 75.22 (-150.39, 99.50)
2
Severe cases 352.1 0 (0.00) 346.2 0 (0.00) NE
Death cases 352.1 0 (0.00) 346.2 0 (0.00) NE
Cases with fever 347.3 28 (8.06) 342.1 48 (14.03) 42.45 (6.39, 65.23)
E-PPS Hospitalization cases 347.3 1 (0.29) 342.1 4 (1.17) 75.29 (-149.70, 99.50)
Severe cases 347.3 0 (0.00) 342.1 0 (0.00) NE
Death cases 347.3 0 (0.00) 342.1 0 (0.00) NE
11.4.1.1.3 Efficacy Analysis by Different Variants

Respiratory tract specimens of confirmed COVID-19 cases in this study were sequenced to detect
variants. In E-mFAS 2 set, a total of 89 respiratory tract specimens were sequenced, and results showed
that all of them are Omicron variant, including 34 BA.1 subtype, 51 BA.2 subtype, and 4 unspecified.
The efficacy against COVID-19 cases caused by different Omicron subtype was analyzed based on the
cases with sequencing result, in both E-mFAS 2 set and the E-PPS set, which showed consistent results.
The results of E-mFAS 2 set showed that COVID-19 vaccine has a better efficacy against Omicron
BA.1 (45.97%, 95%CI: -14.03, 75.63) than that of Omicron BA.2 (18.48%, 95%CI: -46.77, 55.14).
Table 13 Efficacy against COVID-19 cases caused by different variants 14 days after second dose
vaccination (Interim analysis)

Analysis Person- No. of cases/ Person- No. of cases/ Efficacy and 95%CI
Variants
Sets years of Incidence density years of Incidence density (%)
E-mFAS B.1.1.529/OMICRON BA.1 352.1 12 (3.41) 346.2 22 (6.36) 45.97 (-14.03, 75.63)
2 B.1.1.529/OMICRON BA.2 352.1 23 (6.53) 346.2 28 (8.09) 18.48 (-46.77, 55.14)
B.1.1.529/OMICRON (unspecified) 352.1 2 (0.57) 346.2 2 (0.58) 0.77 (-1268.93, 92.81)
E-PPS Total sample size N=2511 N=2479
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B.1.1.529/OMICRON BA.1 347.3 11 (3.17) 342.1 22 (6.43) 50.40 (-6.72, 78.28)

B.1.1.529/OMICRON BA.2 347.3 22 (6.34) 342.1 28 (8.18) 22.20 (-41.00, 57.58)
B.1.1.529/OMICRON (unspecified) 347.3 2 (0.58) 342.1 2 (0.58) 0.78 (-1268.83, 92.81)
11.4.1.1.4 Efficacy Analysis by Age-groups

The efficacy against COVID-19 cases in different age-groups was analyzed in both E-mFAS 2 set and
the E-PPS set, which showed consistent results.
In E-mFAS 2 set, there are 195 subjects in 6-35 months age-group, 960 subjects in 3-5 years age-group,
2179 subjects in 6-11 years age-group, and 1707 subjects in 12-17 years age-group.
The results of E-mFAS 2 set showed that, for subjects aged 3-17 years, the efficacy against confirmed
COVID-19 cases is 24.24% (95%CI: -113.19, 74.02) in 3-5 years age-group; 22.05% (95%CI: -26.85,
52.48) in 6-11 years age-group, and 7.64% (95%CI: -99.49, 57.47) in 12-17 years age-group. For 6-
35 months age-group, the sample size is relatively low, and a high baseline seropositive rate (see more
details in 11.4.1.2), results showed that the efficacy against confirmed COVID-19 cases is -96.84%
(95%CI: -11512.91, 89.75) in 6-35 months age-group.
Table 14 Efficacy against COVID-19 cases 14 days after second dose vaccination by age-groups (Interim
analysis)
Analysis Person- No. of cases/ No. of cases/

Age group Person-years Efficacy and 95%CI (%)
Sets N years of Incidence density N Incidence density
of exposure
exposure (100 person-year) (100 person-year)

6-35 months 97 11.4 2 (17.50) 98 11.2 1 (8.89) -96.84 (-11512.91, 89.75)
E-mFAS
3-5 years 484 52.8 8 (15.15) 476 50.9 10 (19.65) 24.24 (-113.19, 74.02)
2
6-11 years 1096 139.5 32 (22.93) 1083 138.1 41 (29.68) 22.05 (-26.85, 52.48)
12-17 years 861 148.4 15 (10.11) 846 145.9 16 (10.97) 7.64 (-99.49, 57.47)
6-35 months 93 11.1 2 (17.97) 93 10.8 1 (9.28) -93.75 (-11330.80, 89.91)
E-PPS 3-5 years 481 52.3 8 (15.31) 474 50.6 10 (19.75) 24.16 (-113.42, 73.99)
6-11 years 1088 138 32 (23.18) 1077 137.2 41 (29.88) 22.11 (-26.74, 52.52)
12-17 years 849 145.8 13 (8.91) 835 143.4 16 (11.15) 19.97 (-77.45, 64.59)
11.4.1.1.5 Efficacy Analysis by Baseline Exposure Status

This multicenter study is conducted in countries/sites with high-level SARS-CoV-2 prevalance. In this
case, IgG, IgM and antigen test were conducted during enrollment to assess the baseline exposure
status of subjects, and subjects with any positive result of IgG, IgM or antigen test will be taken as
with previous exposure of SARS-CoV-2. It was found that more than one-third of subjects enrolled in
this study was exposed to SARS-CoV-2 before enrollment.
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The efficacy against COVID-19 cases in population with different baseline exposure status was
analyzed in both E-mFAS 2 set and the E-PPS set, which showed consistent results.
The results showed that, the incidence density of COVID-19 in population with previous exposure is
lower than that of population without previous exposure (12.38/100 person-year vs. 18.00/100 person-
year in vaccine group and 10.21/100 person-year vs. 23.91/100 person-year in placebo group), the
efficacy against confirmed COVID-19 cases in population without previous exposure is 24.53%
(95%CI: -14.14, 50.42), while efficacy against confirmed COVID-19 cases in population with
previous exposure is -21.58 (95%CI: -196.26, 48.78).
Table 15 Efficacy against COVID-19 cases 14 days after second dose vaccination by baseline exposure
(Interim analysis)

Analysis Efficacy and 95%CI
Baseline exposure
Sets Person- No. of cases/ Person- No. of cases/ (%)
N years of Incidence density N years of Incidence density

E-mFAS Without previous
1599 238.9 43 (18.00) 1603 238.4 57 (23.91) 24.53 (-14.14, 50.42)
2 exposure
With previous exposure 938 113.1 14 (12.38) 900 107.7 11 (10.21) -21.58 (-196.26, 48.78)

Without previous
E-PPS 1585 236.2 43 (18.21) 1587 236.1 57 (24.14) 24.58 (-14.05, 50.45)
exposure
With previous exposure 925 110.9 12 (10.82) 892 106.0 11 (10.38) -4.32 (-161.24, 57.91)
* One subject in vaccine group with missing baseline exposure information was excluded from this analysis.
11.4.1.2 Long-term Analysis of Protective Efficacy

11.4.1.2.1 Primary Efficacy Analysis
The primary efficacy analysis was conducted based on all confirmed COVID-19 cases according to
case definition, in both E-mFAS 2 set and E-PPS set, which showed consistent results. The following
description is based on the results of E-mFAS 2 set.
In the long-term efficacy analysis, 346 confirmed cases were reported in a total sample size of 9,859
subjects, which included 156 cases in the vaccine group (ID: 6.65/100 person-years) and 190 cases in
the placebo group (ID: 8.23/100 person-years). The efficacy of the vaccine against confirmed COVID-
19 cases is 20.27% (95%CI: 0.95, 35.91).
Table 16 Efficacy against COVID-19 cases of any severity 14 days after second dose vaccination (Long-
term analysis)
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No. of cases/ No. of cases/

Analysis Sample Person-years Sample Person-years Efficacy and 95%CI
Incidence density Incidence density
sets size of exposure size of exposure (%)
(100 person-year) (100 person-year)
E-mFAS 2 4933 2346.1 156(6.65) 4926 2308.2 190(8.23) 20.27(0.95, 35.91)

E-PPS 4841 2305.2 152(6.59) 4837 2269.8 187(8.24) 21.02(1.65, 36.67)
11.4.1.2.2 Efficacy Analysis by Severity

The efficacy of COVID-19 vaccine against COVID-19 cases with different severity, in the E-mFAS 2
set and the E-PPS set, which showed consistent results. The efficacy against hospitalization COVID-
19 cases, sever COVID-19 cases, and death COVID-19 cases were analyzed accordingly. The
following description is based on the results of E-mFAS 2 set.
The results in the interim analysis showed that among 9,859 subjects, a total of 7 hospitalization cases
were reported, including 1 case in vaccine group (ID: 0.04/100 person-years) and 6 cases in placebo
group (ID: 0.26/100 person-years). The efficacy of the vaccine against hospitalization cases is 84.19%
(95%CI: -30.30, 99.66). None of a severe case was reported in the vaccine group and 2 were reported
in the placebo group (ID: 0.09/100 person-years), the efficacy against severe cases is 100% (95%CI: -
423.87, 100.00). No death case was reported during study period.
Table 17 Efficacy against COVID-19 cases 14 days after second dose vaccination by severity (Long-term
analysis)
No. of cases/
Analysis Person- No. of cases/ Person- Efficacy and 95%CI
Severity Incidence
Sets years of Incidence density years of (%)
density (100
exposure (100 person-year) exposure
person-year)
E-mFAS Hospitalization cases 2346.1 1 (0.04) 2308.2 6 (0.26) 84.19(-30.30, 99.66)

2 Severe cases 2346.1 0 (0.00) 2308.2 2 (0.09) 100.00(-423.87, 100.00)
Death cases 2346.1 0 (0.00) 2308.2 0 (0.00) NE
Hospitalization cases 2305.2 1 (0.04) 2269.8 6 (0.26) 84.19(-30.34, 99.66)
E-PPS
Severe cases 2305.2 0 (0.00) 2269.8 2 (0.09) 100.00(-424.27, 100.00)
Death cases 2305.2 0 (0.00) 2269.8 0 (0.00) NE
11.4.1.2.3 Efficacy Analysis by Age-groups

The efficacy against COVID-19 cases in different age-groups was analyzed in both E-mFAS 2 set and
In E-mFAS 2 set, there are 200 subjects in 6-35 months age-group, 1,466 subjects in 3-5 years age-
group, 3,852 subjects in 6-11 years age-group, and 4,341 subjects in 12-17 years age-group.
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The results of E-mFAS 2 set showed that, for subjects aged 3-17 years, the efficacy against confirmed
COVID-19 cases is 33.65% (95%CI: -14.09, 61.94) in 3-5 years age-group; 15.16% (95%CI: -13.87,
36.88) in 6-11 years age-group, and 23.82% (95%CI: -17.88, 51.12) in 12-17 years age-group. For 6-
35 months age-group with the relatively small sample size, results showed that the efficacy against
confirmed COVID-19 cases is -48.82% (95%CI: -1681.84, 82.95) in 6-35 months age-group.
Table 18 Efficacy against COVID-19 cases 14 days after second dose vaccination by age-groups (Long-
term analysis)

Age group Person-years Incidence Person-years Incidence
Sets N N (%)
of exposure density (100 of exposure density (100
person-year) person-year)
Total sample
N=4933 N=4926
size
E-mFAS 6-35 months 100 58.0 3 (5.18) 100 57.5 2 (3.48) -48.82(-1681.84, 82.95)
2 3-5 years 733 302.4 25 (8.27) 733 290.6 35 (12.05) 33.65(-14.09, 61.94)
6-11 years 1927 933.8 89 (9.53) 1925 915.0 102 (11.15) 15.16(-13.87, 36.88)
12-17 years 2173 1051.9 39 (3.71) 2168 1045.1 51 (4.88) 23.82(-17.88, 51.12)
Total sample
N=4841 N=4837
size
6-35 months 95 55.3 3(5.42) 95 54.7 2 (3.66) -48.21(-1674.50, 83.02)

E-PPS
3-5 years 726 298.8 25 (8.37) 728 288.1 35 (12.15) 33.54(-14.27, 61.88)
6-11 years 1896 919.6 87 (9.46) 1893 902.5 101 (11.19) 16.15(-12.81, 37.78)
12-17 years 2124 1031.4 37 (3.59) 2121 1024.5 49 (4.78) 24.76(-17.69, 52.27)
11.4.1.2.4 Efficacy Analysis by Baseline Exposure Status

The efficacy against COVID-19 cases in population with different baseline exposure status was
analyzed in both E-mFAS 2 set and the E-PPS set, which showed consistent results.
The results showed that, the incidence density of COVID-19 in population with previous exposure is
lower than that of population without previous exposure (4.01/100 person-year vs. 9.17/100 person-
year in vaccine group and 3.75/100 person-year vs. 12.47/100 person-year in placebo group), the
efficacy against confirmed COVID-19 cases in population without previous exposure is 26.82%
(95%CI: 5.70, 43.35), while efficacy against confirmed COVID-19 cases in population with previous
exposure is -5.10 (95%CI: -63.71, 32.37).
Table 19 Efficacy against COVID-19 cases 14 days after second dose vaccination by baseline exposure
(Long-term analysis)
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Analysis Efficacy and

Baseline exposure No. of cases/ No. of cases/
Sets 95%CI (%)
Person-years Incidence Person-years Incidence
N[1] N[1]

E-mFAS Without previous
2496 1199.6 110 (9.17) 2533 1186.8 148 (12.47) 26.82(5.70, 43.35)
2 exposure
With previous exposure 2436 1145.9 46 (4.01) 2393 1121.4 42 (3.75) -5.10(-63.71, 32.37)

Without previous
E-PPS 2456 1180.3 108 (9.15) 2484 1166.1 145 (12.43) 26.72(5.33, 43.42)
exposure
With previous exposure 2384 1124.4 44 (3.91) 2353 1103.7 42 (3.81) -0.85(-57.78, 35.47)
[1]
Number of cases can be evaluated.
11.4.1.2.5 Efficacy Analysis by Countries

The efficacy against COVID-19 cases in different countries was analyzed in both E-mFAS 2 set and
In E-mFAS 2 set, there are 251 subjects from Chile, 4,440 subjects from South Africa, 1,514 subjects
from Malaysia, and 3,654 subjects from the Philippines. Due to the regulatory requirements, all the
subjects were earlier unblinded after the EUA approval, thus the efficacy result in Chile is unavailable.
The results of E-mFAS 2 set showed that, the efficacy against confirmed COVID-19 cases is 16.89%
(95%CI: -17.75, 41.51) in subjects from South Africa; 21.77% (95%CI: -7.60, 43.28) in subjects from
Malaysia, and 24.89% (95%CI: -42.02, 60.90) in subjects from the Philippines.
Table 20 Efficacy against COVID-19 cases 14 days after second dose vaccination by countries (Long-
term analysis)

Countries Person-years Incidence Person-years Incidence
Sets [1] [1] (%)
N N

Chile 125 2.7 0 (0.00) 126 2.7 0 (0.00) -
E-mFAS
South Africa 2222 1184.2 63 (5.32) 2218 1172.3 75 (6.40) 16.89(-17.75, 41.51)
2
Malaysia 750 329.3 74 (22.47) 764 312.8 90 (28.77) 21.77(-7.60, 43.28)
Philippines 1836 829.9 19 (2.29) 1818 820.4 25 (3.05) 24.89(-42.02, 60.90)
E-PPS
Chile 125 2.7 0(0.00) 126 2.7 0(0.00) -
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South Africa 2155 1153.5 61 (5.29) 2153 1143.8 72 (6.29) 16.06(-19.73, 41.31)
Malaysia 746 327.7 72 (21.97) 761 311.3 90 (28.91) 23.88(-4.95, 44.95)
Philippines 1815 821.4 19 (2.31) 1797 812.0 25 (3.08) 24.84(-42.12, 60.87)
[1]
Number of cases can be evaluated.
11.4.1.3 Immunogenicity analysis

11.4.1.3.1 Immunogenicity in children aged 6-35 months
The immunogenicity analysis of Per-Protocol Set for Immunogenicity (I-PPS) showed that a total of
176 participants aged 6~35 months enrolled at five sites in South Africa received two dose
investigational vaccine or placebo and had blood tests before and 28 days after 2-dose of vaccination.
Results showed that 116 (65.91%) participants were seropositive before vaccination, and the
seropositive rates of neutralizing antibodies before vaccination in vaccine group and placebo group
were 73.03% and 58.62%, respectively, and the GMT was 59.3 and 22.9, respectively. There was
significant difference of neutralizing antibodies between groups at baseline, with the vaccine group
higher than that of the placebo group.
28 days after two doses of vaccination, the seropositive rates in vaccine group and placebo group were
100.00% and 68.97%, the seroconversion rates were 79.78% and 25.29%, and the GMT were 743.55
and 43.45, respectively. All these immunogenicity indicators of the vaccine group were higher than
that of the placebo group, and there was statistically significant difference between two groups.
Stratified by baseline neutralizing antibody (positive/negative), similar immunogenicity results were
observed between two comparison groups. All the immunogenicity indicators mentioned above of the
vaccine group were higher than those of placebo group and the differences were statistically significant
between two groups, suggesting that investigational vaccine has good immunogenicity in eliciting both
priming immune response and anamnestic immune response. For seronegative participants at baseline
(n=60), the neutralizing antibody seroconversion rates in the vaccine group and the placebo group were
100.00% and 33.33%, the GMT was 234.38 and 5.38, and the GMI was 101.43 and 2.49, respectively.
For seropositive participants at baseline (n=116), the seroconversion rates 28 days after two doses of
vaccination in vaccine group and placebo group were 72.31% and 19.61%, the GMT was 1138.79 and
189.75, and the GMI was 5.79 and 1.56, respectively. In immune naïve participants, all subjects had
seroconverted but elicited low neutralizing antibodies, while in previously infected participants,
investigational vaccine elicited very high neutralizing antibody GMT but relatively low GMI.
Table 21 Overview of neutralizing antibodies between CoronaVac® and placebo groups in children 6~35
months
Neutralizing antibody
Timepoints Indicators P-value
（n=89） (n=87)
no. of participants 89 87
Seropositive rate, n (%) 65 (73.03) 51 (58.62) 0.0437
Before vaccination (95%CI) 62.58, 81.90 47.55, 69.08
GMT 59.3 22.9 0.0048
(95%CI) 37.1, 94.9 14.4, 36.6
Seropositive before
GMT 196.7 121.3 0.0308
vaccination
(95%CI) 146.7, 263.9 87.1, 168.9
28 days after second dose # no. of participants 89 87
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（n=89） (n=87)
Seropositive rate, n (%) 89 (100.00) 60 (68.97) <0.0001
(95%CI) 95.94, 100.00 58.14, 78.45
Seroconversion rate, n (%) 71 (79.78) 22 (25.29) <0.0001
(95%CI) 69.93, 87.55 16.58, 35.75
GMT 743.55 43.45 <0.0001
(95%CI) 571.10, 968.08 26.88, 70.23
GMI 12.53 1.9 <0.0001
(95%CI) 8.63, 18.19 1.45, 2.48
28 days after second dose (95%CI) 85.75, 100.00 18.56, 50.97
with seronegative results GMT 234.38 5.38 <0.0001
before vaccination # (95%CI) 138.70, 396.06 3.61, 8.03
GMI 101.43 2.49 <0.0001
(95%CI) 58.55, 175.72 1.69, 3.68
with seropositive results GMT 1138.79 189.75 <0.0001
GMI 5.79 1.56 <0.0001
(95%CI) 4.29, 7.80 1.08, 2.26
Note: GMT=geometric mean titer; GMI=geometric mean fold increase; 95%CI=95% confidence interval; RT-PCR=reverse transcription-
polymerase chain reaction.
# I-PPS (Per-Protocol Set for Immunogenicity) was used for the analysis, including all the randomized participants who meet inclusion criteria, unmeet
exclusion criteria, complete 2 doses of vaccination, have both valid pre-vaccination immunogenicity data and the values 28 days after the second dose.
11.4.1.3.2 Immunogenicity in children and adolescents aged 3-17 years

General Analysis
A total of 816 participants aged 3-17 years was included in I-PPS for immunogenicity analysis. Results
showed that 511 (62.62%) participants were seropositive before vaccination, and the seropositive rates
of neutralizing antibodies before vaccination in vaccine group and placebo group were 58.11% and
68.33%, respectively, and the GMT of the were 23.3 and 40.2, respectively. There was significant
difference of neutralizing antibodies between groups at baseline, with the placebo group higher than
that of the vaccine group.
28 days after two doses of vaccination, the seropositive rates in vaccine group and placebo group were
100.00% and 73.89%, the seroconversion rates were 100% and 19.30%, and the GMT were 346.97
and 57.75, respectively. All these immunogenicity indicators of the vaccine group were higher than
that of the placebo group, and there was statistically significant difference between two groups.
Stratified by baseline neutralizing antibody (positive/negative), similar immunogenicity results were
observed between two comparison groups. For seronegative participants at baseline (n=305), the
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neutralizing antibody seroconversion rates in the vaccine group and the placebo group were 100.00%
and 19.30%, the GMT was 204.73 and 3.28, and the GMI was 100.31 and 1.54, respectively. For
seropositive participants at baseline (n=511), the seroconversion rates 28 days after two doses of
vaccination in vaccine group and placebo group were 55.85% and 28.46%, the GMT were 507.48 and
218.03, and the GMI were 3.75 and 1.39, respectively. In immune naïve participants, all the subjects
had seroconverted but elicited low neutralizing antibodies, while in previously infected participants,
investigational vaccine elicited higher neutralizing antibody GMT but with a relatively low GMI. All
the immunogenicity indicators mentioned above of the vaccine group were higher than those of
placebo group and the differences were statistically significant between two groups, suggesting that
investigational vaccine has good immunogenicity in eliciting both priming immune response and
anamnestic immune response.
Table 22 Overview of neutralizing antibodies between CoronaVac ® and placebo groups in children 3-17
years
（n=456） (n=360)
GMT 23.3 40.2 0.0012
(95%CI) 18.8, 29.0 31.3, 51.5
Seropositive before
GMT 135.2 156.6 0.2785
vaccination
(95%CI) 113.3, 161.4 128.2, 191.3
(95%CI) 99.19, 100.00 69.03, 78.35
28 days after second dose # (95%CI) 98.09, 100.00 12.51, 27.75
GMT 346.97 57.75 <0.0001
(95%CI) 310.43, 387.81 45.32, 73.59
GMI 14.86 1.44 <0.0001
(95%CI) 12.14, 18.19 1.22, 1.69
GMI 100.31 1.54 <0.0001
(95%CI) 84.79, 118.67 1.30, 1.82
28 days after second dose Seroconversion rate, n (%) 148 (55.85) 70 (28.46) <0.0001
with seropositive results (95%CI) 49.64, 61.92 22.90, 34.53
before vaccination # GMT 507.48 218.03 <0.0001
(95%CI) 445.05, 578.67 182.80, 260.06
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（n=456） (n=360)
GMI 3.75 1.39 <0.0001
(95%CI) 3.07, 4.59 1.12, 1.74
Stratified by age groups

3-5 years group
A total of 155 participants aged 3-5 years was included for immunogenicity analysis. Results showed
that the seropositive rates of neutralizing antibodies before vaccination in vaccine group and placebo
group were 43.48% and 46.03%, respectively.
28 days after two doses of vaccination, the neutralizing antibody seroconversion rates of seronegative
participants at baseline in the vaccine group and the placebo group were 100.00% and 17.65%, the
GMT was 330.71 and 3.04, and the GMI was 163.16 and 1.38, respectively. For seropositive
participants at baseline, the seroconversion rates 28 days after two doses of vaccination in vaccine
group and placebo group were 60.00% and 24.14%, the GMT were 585.84 and 203.31, and the GMI
were 5.52 and 0.93, respectively.
years
（n=92） (n=63)
GMT 11.3 18.2 0.2102
(95%CI) 7.2, 17.8 9.7, 34.3
Seropositive before
GMT 106.2 218.4 0.0387
vaccination
(95%CI) 68.2, 165.2 126.8, 376.2
(95%CI) 96.07, 100.00 40.94, 66.61
GMT 424.05 21.04 <0.0001
(95%CI) 331.24, 542.86 11.48, 38.54
GMI 37.42 1.15 <0.0001
(95%CI) 23.68, 59.15 0.81, 1.64
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（n=92） (n=63)
(95%CI) 93.15, 100.00 6.76, 34.53
28 days after second dose
GMT 330.71 3.04 <0.0001
with seronegative results
(95%CI) 241.85, 452.21 2.23, 4.14
before vaccination #
GMI 163.16 1.38 <0.0001
(95%CI) 119.08, 223.56 1.04, 1.84
Seroconversion rate, n (%) 24 (60.00) 7 (24.14) 0.0031
with seropositive results GMT 585.84 203.31 0.0014
GMI 5.52 0.93 0.0001
(95%CI) 3.15, 9.67 0.46, 1.89
6-11 years group

GMT was 162.16 and 2.94, and the GMI was 79.32 and 1.39, respectively. For seropositive participants
at baseline, the seroconversion rates 28 days after two doses of vaccination in vaccine group and
placebo group were 50.00% and 22.33%, the GMT were 445.07 and 174.82, and the GMI were 3.02
and 1.03, respectively.
years
（n=203） (n=162)
GMT 19.9 34.5 0.0339
(95%CI) 14.3, 27.7 23.3, 51.0
Seropositive before
GMT 147.3 170.5 0.5027
vaccination
(95%CI) 112.0, 193.6 121.7, 238.9
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（n=203） (n=162)
(95%CI) 98.20, 100.00 59.48, 74.44
GMT 277.47 39.48 <0.0001
(95%CI) 233.19, 330.17 27.23, 57.24
GMI 13.95 1.15 <0.0001
(95%CI) 10.30, 18.88 0.90, 1.45
GMI 79.32 1.39 <0.0001
(95%CI) 62.15, 101.23 1.09, 1.77
GMI 3.02 1.03 <0.0001
(95%CI) 2.20, 4.15 0.73, 1.45
12-17 years group

years
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（n=161） (n=135)
GMT 43.2 69.9 0.0585
(95%CI) 30.3, 61.5 49.3, 99.0
Seropositive before
GMT 135.8 133.2 0.9248
vaccination
(95%CI) 102.8, 179.2 100.8, 176.0
(95%CI) 97.73, 100.00 84.99, 95.32
GMT 410.11 146.04 <0.0001
(95%CI) 344.84, 487.73 105.88, 201.45
GMI 9.50 2.09 <0.0001
(95%CI) 6.91, 13.07 1.59, 2.74
GMI 93.71 2.42 <0.0001
(95%CI) 68.48, 128.24 1.59, 3.69
GMI 4.02 2.03 0.0020
(95%CI) 2.98, 5.41 1.49, 2.78
Stratified by countries
Chile
A total of 110 participants in Chile was included for immunogenicity analysis, all of them were in the
vaccine group. Results showed that the seropositive rates of neutralizing antibodies before vaccination
was 19.09%.
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participants at baseline was 100.00%, the GMT was 264.61, and the GMI was 131.28. For seropositive
participants at baseline, the seroconversion rates 28 days after two doses of vaccination was 80.95%,
the GMT was 1195.04, and the GMI was 7.32.
years in Chile
（n=110） (n=0)
Seropositive rate, n (%) 21 (19.09) - -
Before vaccination (95%CI) 12.22, 27.69
GMT 4.7 - -
(95%CI) 3.3, 6.5
Seropositive before
GMT 163.2 - -
vaccination
(95%CI) 109.1, 244.1
Seropositive rate, n (%) 110 (100.00) - -
(95%CI) 96.70, 100.00
Seroconversion rate, n (%) 106 (96.36) - -
28 days after second dose # (95%CI) 90.95, 99.00
GMT 352.87 - -
(95%CI) 277.37, 448.92
GMI 75.66 - -
(95%CI) 55.38, 103.39
28 days after second dose (95%CI) 95.94, 100.00
with seronegative results GMT 264.61 - -
before vaccination # (95%CI) 206.72, 338.72
GMI 131.28 - -
(95%CI) 102.81, 167.64
28 days after second dose (95%CI) 58.09, 94.55
with seropositive results GMT 1195.04 - -
before vaccination # (95%CI) 781.75, 1826.82
GMI 7.32 - -
(95%CI) 3.93, 13.64
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South Africa
A total of 197 participants in South Africa was included for immunogenicity analysis. Results showed
GMT was 275.19 and 4.31, and the GMI was 122.24 and 1.92, respectively. For seropositive
participants at baseline, the seroconversion rates 28 days after two doses of vaccination in vaccine
group and placebo group were 74.36% and 35.53%, the GMT were 652.16 and 233.29, and the GMI
were 6.71 and 2.33, respectively.
years in South Africa
（n=99） (n=98)
GMT 43.7 42.7 0.9285
(95%CI) 30.0, 63.8 29.6, 61.7
Seropositive before
GMT 97.2 100.3 0.8660
vaccination
(95%CI) 73.8, 128.2 79.3, 126.7
(95%CI) 96.34, 100.00 76.01, 91.17
GMT 543.08 95.21 <0.0001
(95%CI) 445.79, 661.61 61.58, 147.20
GMI 12.42 2.23 <0.0001
(95%CI) 8.72, 17.67 1.70, 2.92
GMI 122.24 1.92 <0.0001
(95%CI) 73.43, 203.49 1.18, 3.12
with seropositive results
(95%CI) 63.21, 83.58 24.88, 47.34
GMT 652.16 233.29 <0.0001
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（n=99） (n=98)
(95%CI) 533.65, 796.99 166.86, 326.17
GMI 6.71 2.33 <0.0001
(95%CI) 4.94, 9.11 1.68, 3.21
Malaysia
A total of 206 participants in Malaysia was included for immunogenicity analysis. Results showed that
the seropositive rates of neutralizing antibodies before vaccination in vaccine group and placebo group
were 31.07% and 26.21%, respectively.
participants at baseline in the vaccine group and the placebo group were 100.00% and 5.26%, the GMT
was 152.68 and 2.40, and the GMI was 76.34 and 1.17, respectively. For seropositive participants at
baseline, the seroconversion rates 28 days after two doses of vaccination in vaccine group and placebo
group were 50.00% and 7.41%, the GMT were 248.38 and 61.75, and the GMI were 3.27 and 1.09,
respectively.
years in Malaysia
（n=103） (n=103)
GMT 6.2 4.9 0.3173
(95%CI) 4.4, 8.7 3.6, 6.6
Seropositive before
GMT 76.0 56.8 0.2255
vaccination
(95%CI) 55.0, 105.1 39.4, 81.9
(95%CI) 96.48, 100.00 20.59, 38.90
GMT 177.60 5.63 <0.0001
(95%CI) 143.90, 219.19 4.02, 7.88
GMI 28.68 1.15 <0.0001
(95%CI) 20.02, 41.08 0.99, 1.32
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（n=103） (n=103)
(95%CI) 94.94, 100.00 1.45, 12.93
GMT 152.68 2.40 <0.0001
with seronegative results
(95%CI) 116.19, 200.63 2.02, 2.86
GMI 76.34 1.17 <0.0001
(95%CI) 58.09, 100.32 1.01, 1.35
GMI 3.27 1.09 <0.0001
(95%CI) 2.26, 4.73 0.74, 1.59
The Philippines
A total of 303 participants in the Philippines was included for immunogenicity analysis. Results
showed that the seropositive rates of neutralizing antibodies before vaccination in vaccine group and
placebo group were 93.06% and 89.94%, respectively.
years in the Philippines
（n=144） (n=159)
GMT 134.1 151.1 0.6192
(95%CI) 96.7, 185.8 107.2, 213.1
Seropositive before
GMT 182.5 240.3 0.1890
vaccination
(95%CI) 136.9, 243.4 178.9, 322.8
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（n=144） (n=159)
(95%CI) 97.47, 100.00 91.97, 98.60
GMT 406.42 191.74 <0.0001
(95%CI) 333.79, 494.85 149.83, 245.37
GMI 3.03 1.27 0.0001
(95%CI) 2.20, 4.18 0.93, 1.72
GMI 42.00 4.16 <0.0001
(95%CI) 22.80, 77.38 2.37, 7.31
with seropositive results GMT 454.80 266.91 0.0003
GMI 2.49 1.11 0.0006
(95%CI) 1.81, 3.43 0.80, 1.54
11.4.2 Statistical/Analytical Issues
11.4.2.1 Adjustments for Covariates

Not applicable.
11.4.2.2 Handling of Dropouts or Missing Data

In the efficacy evaluation, take the actual exposure time of the subjects as the denominator and
observed cases during the exposure time as numerator to calculate the incidence rate and vaccine
efficacy. In the statistical analysis of the full immunogenicity analysis set, those with missing serum
neutralizing antibody test results after immunization were filled in by the method of Last Observation
Carried Forward (LOCF). For those with missing serum results before immunization, the maximum
value of the serum antibody before immunization of all subjects was used to fill in the pre-immunity
antibody value, and the corresponding immunogenicity endpoint was further derived and calculated.
Missing data in other immunogenicity and safety endpoints were not processed in this trial.
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11.4.2.3 Interim Analysis and Data Monitoring

No formal interim analysis was performed in this study, so no type I error control was required. In the
safety and immunogenicity evaluation results, the calculated P value is only the nominal P value
(nominal P value), which is mainly used to describe the strength of the association between the
evaluation endpoint and the treatment group, not as a formal basis for statistical inferences.
12 SAFETY EVALUATION
12.1 Safety analysis in aged 6-35 months
12.1.1 Overall Safety analysis in 6-35 months of safety subgroup

In the phase III clinical trial, 202 children aged 6~35 months in the safety subgroup received at least
one dose of investigational vaccine/placebo were included into safety analysis. The overall incidence
rate of AEs was 67.33% (136/202) in the safety analysis period. The incidence rates of AEs were 71.29%
(72/101) and 63.37% (64/101) in vaccine and placebo group, respectively. The incidence rate of AEs
in the vaccine group was not statistically different from that of placebo group (P=0.2937). The overall
incidence rate of adverse events related to vaccine (adverse reactions, ARs) within 28 days of each
vaccination, was 31.68% (64/202). The incidence rates of ARs were 34.65% (35/101) and 28.71%
(29/101) in vaccine and placebo group, respectively. The incidence rate of ARs in the vaccine group
not statistically different from that of placebo group (P=0.4497).
The incidence rates of systemic and local adverse reactions were 29.70% and 9.90%, respectively. The
incidence rate of systemic adverse reactions in the vaccine group was not statistically different from
that of placebo group (33.66% vs 25.74%, P=0.2811). The incidence of local adverse reactions was
either not statistically different between the vaccine group and placebo group (8.91% vs 10.89%,
P=0.8144).
Most of the ARs were solicited adverse reactions, with an overall incidence rate of 31.68%. The
incidence rates of solicited ARs in the vaccine and placebo group were 34.65% and 28.71%,
respectively. The incidence of solicited ARs in the vaccine group was not statistically different from
that of placebo group (P=0.4497). The overall incidence rate of unsolicited ARs was 1.49%. The
incidence rates of unsolicited ARs in the vaccine group and placebo group were 0.99% and 1.98%,
respectively. No difference was found in the incidence of unsolicited ARs between groups.
Adverse reactions mainly occurred within 7 days after vaccination. The overall incidence of adverse
reactions within 7 days after vaccination was 31.68%, and the incidence of adverse reactions in the
vaccine group (34.65%) was not statistically different from that of placebo group (28.71%) (P=0.4497).
The incidence rate of adverse reactions occurred within 30 min was 0.50%. There was no adverse
reactions occurred within 8~28 days after vaccination.
The adverse reactions were mainly of Grade 1. The overall incidence rates of Grade 1 and 2 adverse
reactions were 23.76% (vaccine group 28.71% vs placebo group 18.81%, P=0.1363) and 15.84%
(vaccine group 13.86% vs placebo group 17.82%, P=0.5637), respectively. The incidence of Grade 3
adverse reactions was 0.99%, there was no significant statistical difference between groups.
Table 30 Difference of adverse events occurrence between participants receiving CoronaVac® and placebo
in children 6~35 months (safety subgroup)
(n=101) (n=101) (n=202) P-value
Category
no. of no. of no. of no. of no. of no. of [1]
events subjects (%) events subjects (%) events subjects (%)
Total AEs # 255 72(71.29) 235 64(63.37) 490 136(67.33) 0.2937
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(n=101) (n=101) (n=202) P-value
Category
AEs within 28 days of each dose 156 56(55.45) 133 48(47.52) 289 104(51.49) 0.3244
AEs related to vaccine 91 35(34.65) 89 29(28.71) 180 64(31.68) 0.4497
Systemic AEs 75 34(33.66) 61 26(25.74) 136 60(29.70) 0.2811
Local AEs 16 9(8.91) 28 11(10.89) 44 20(9.90) 0.8144
Solicited AEs 90 35(34.65) 87 29(28.71) 177 64(31.68) 0.4497
Unsolicited AEs 1 1(0.99) 2 2(1.98) 3 3(1.49) 1.0000
Within 0~30 min 0 0(0.00) 4 1(0.99) 4 1(0.50) 1.0000
Within 0~7 days 91 35(34.65) 89 29(28.71) 180 64(31.68) 0.4497
Within 8~28days 0 0(0.00) 0 0(0.00) 0 0(0.00) 1.0000
Grade 1 AEs 72 29(28.71) 60 19(18.81) 132 48(23.76) 0.1363
Grade 2 AEs 18 14(13.86) 28 18(17.82) 46 32(15.84) 0.5637
Grade 3 AEs 1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000
First dose vaccination 67 26(25.74) 58 23(22.77) 125 49(24.26) 0.7429
Second dose vaccination 24 14(14.00) 31 14(14.00) 55 28(14.00) 1.0000
AEs unrelated to vaccine 65 33(32.67) 44 29(28.71) 109 62(30.69) 0.6474
AEs after 28 days of each dose 99 45(44.55) 102 35(34.65) 201 80(39.60) 0.1953
[1] The P value is calculated using Fisher's exact probability method.
(1) Adverse events were categorized according to the Medical Dictionary for Regulatory Activities (MedDRA) 24.0.
(2) Solicited adverse events are analyzed according to the event names pre-specified in the study protocol.
(3) Related to the vaccine means that the relationship between the adverse event and the research vaccine is "possibly related, likely
related, and definitely related".
(4) Unrelated to the vaccine means that the relationship between the adverse event and the research vaccine is "may be unrelated,
certainly unrelated".
(5) # SS (Safety Set) were used for the analysis, including all participants who receive at least 1 dose of vaccine or placebo, collected
following the period from the first dose inoculation to the time of this report generated.
12.1.2 Display and analysis of Adverse Events in 6-35 months of safety subgroup
According to SOC classification statistics, adverse reactions are mainly general disorders and
administration site conditions, with an overall incidence of 22.77%. The most common AR was fever,
with incidence rates of 13.86% and 15.84% in the vaccine group and placebo group, respectively;
followed by diarrhoea (12.87% in vaccine group and 9.90% in placebo group), cough (13.86% in
vaccine group and 7.92% in placebo group) and vaccination site pain (7.92% in vaccine group and
8.91% in placebo group). For above AR symptoms, there was no significant difference between two
groups. See Table below for details.
Table 31 Occurrence of adverse reactions after vaccination in children 6~35 months of safety subgroup
(classified by SOC and PT)
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Vaccine group (N=101) Placebo group (N=101) Total (N=202)
Category no. of no. of no. of P-value

no. of no. of no. of
subjects subjects subjects
events events events
(%) (%) (%)
Total ARs 91 35(34.65) 89 29(28.71) 180 64(31.68) 0.4497
Grade 1 72 29(28.71) 60 19(18.81) 132 48(23.76) 0.1363
Grade 2 18 14(13.86) 28 18(17.82) 46 32(15.84) 0.5637
Grade 3 1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000
General disorders and
34 21(20.79) 48 25(24.75) 82 46(22.77) 0.6150
administration site conditions
Grade 1 22 14(13.86) 31 13(12.87) 53 27(13.37) 1.0000
Grade 2 11 9(8.91) 16 14(13.86) 27 23(11.39) 0.3760
Grade 3 1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000
Fever 17 14(13.86) 18 16(15.84) 35 30(14.85) 0.8435
Grade 1 8 7(6.93) 2 2(1.98) 10 9(4.46) 0.1698
Grade 2 8 8(7.92) 15 14(13.86) 23 22(10.89) 0.2585
Grade 3 1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000
Vaccination site pain 8 8(7.92) 13 9(8.91) 21 17(8.42) 1.0000
Grade 1 6 6(5.94) 12 8(7.92) 18 14(6.93) 0.7829

Grade 2 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
Vaccination site swelling 2 2(1.98) 5 4(3.96) 7 6(2.97) 0.6828
Grade 1 2 2(1.98) 5 4(3.96) 7 6(2.97) 0.6828
Vaccination site erythema 2 2(1.98) 4 2(1.98) 6 4(1.98) 1.0000
Grade 1 1 1(0.99) 4 2(1.98) 5 3(1.49) 1.0000

Grade 2 1 1(0.99) 0 0(0.00) 1 1(0.50) 1.0000
Injection site induration 2 2(1.98) 2 1(0.99) 4 3(1.49) 1.0000
Grade 1 2 2(1.98) 2 1(0.99) 4 3(1.49) 1.0000

Fatigue 1 1(0.99) 2 2(1.98) 3 3(1.49) 1.0000
Grade 1 1 1(0.99) 2 2(1.98) 3 3(1.49) 1.0000
Vaccination site pruritus 1 1(0.99) 2 1(0.99) 3 2(0.99) 1.0000
Grade 1 1 1(0.99) 2 1(0.99) 3 2(0.99) 1.0000
Vaccination site rash 1 1(0.99) 2 1(0.99) 3 2(0.99) 1.0000
Grade 1 1 1(0.99) 2 1(0.99) 3 2(0.99) 1.0000
Gastrointestinal disorders 23 16(15.84) 25 14(13.86) 48 30(14.85) 0.8435
Grade 1 21 15(14.85) 20 11(10.89) 41 26(12.87) 0.5292

Grade 2 2 2(1.98) 5 4(3.96) 7 6(2.97) 0.6828
Diarrhoea 16 13(12.87) 12 10(9.90) 28 23(11.39) 0.6586
Grade 1 14 12(11.88) 9 7(6.93) 23 19(9.41) 0.3353
Grade 2 2 2(1.98) 3 3(2.97) 5 5(2.48) 1.0000
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(%) (%) (%)
Vomiting 6 6(5.94) 6 6(5.94) 12 12(5.94) 1.0000
Grade 1 6 6(5.94) 5 5(4.95) 11 11(5.45) 1.0000
Grade 2 0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000
Nausea 1 1(0.99) 7 5(4.95) 8 6(2.97) 0.2117
Grade 1 1 1(0.99) 6 5(4.95) 7 6(2.97) 0.2117
Grade 2 0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000
Respiratory, thoracic and
17 14(13.86) 9 8(7.92) 26 22(10.89) 0.2585
mediastinal disorders
Grade 1 14 13(12.87) 6 5(4.95) 20 18(8.91) 0.0815
Grade 2 3 3(2.97) 3 3(2.97) 6 6(2.97) 1.0000
Cough 17 14(13.86) 9 8(7.92) 26 22(10.89) 0.2585
Grade 1 14 13(12.87) 6 5(4.95) 20 18(8.91) 0.0815
Grade 2 3 3(2.97) 3 3(2.97) 6 6(2.97) 1.0000
Nervous system disorders 7 7(6.93) 1 1(0.99) 8 8(3.96) 0.0649
Grade 1 5 5(4.95) 0 0(0.00) 5 5(2.48) 0.0594

Grade 2 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
Headache 7 7(6.93) 1 1(0.99) 8 8(3.96) 0.0649
Grade 1 5 5(4.95) 0 0(0.00) 5 5(2.48) 0.0594
Grade 2 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
Musculoskeletal and
4 4(3.96) 3 3(2.97) 7 7(3.47) 1.0000
connective tissue disorders
Grade 1 4 4(3.96) 1 1(0.99) 5 5(2.48) 0.3687
Grade 2 0 0(0.00) 2 2(1.98) 2 2(0.99) 0.4975
Myalgia 4 4(3.96) 3 3(2.97) 7 7(3.47) 1.0000
Grade 1 4 4(3.96) 1 1(0.99) 5 5(2.48) 0.3687
Grade 2 0 0(0.00) 2 2(1.98) 2 2(0.99) 0.4975
Skin and subcutaneous
2 2(1.98) 2 2(1.98) 4 4(1.98) 1.0000
tissue disorders
Grade 1 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
Grade 2 0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000
Mucocutaneous rash 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
Grade 1 2 2(1.98) 0 0(0.00) 2 2(0.99) 0.4975

Grade 2 0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000
Rash 0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000
Grade 1 0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000
Metabolism and nutrition
2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
disorders
Grade 1 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
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(%) (%) (%)
Decreased appetite 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
Grade 1 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000
Immune system disorders 2 2(1.98) 0 0(0.00) 2 2(0.99) 0.4975
Grade 1 2 2(1.98) 0 0(0.00) 2 2(0.99) 0.4975

Hypersensitivity 2 2(1.98) 0 0(0.00) 2 2(0.99) 0.4975
Grade 1 2 2(1.98) 0 0(0.00) 2 2(0.99) 0.4975
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Table 32 Occurrence of adverse reactions within 28 days after vaccination of first and second dose in 6-35 months of safety subgroup (classified by SOC
and PT)
First dose vaccination Second dose vaccination
Vaccine group (N=101) Placebo group (N=101) Total (N=202) Vaccine group (N=100) Placebo group (N=100) Total (N=200)
Category no. of no. of no. of P-value no. of no. of no. of P-value

no. of no. of no. of no. of no. of no. of
subjects subjects subjects subjects subjects subjects
events events events events events events
(%) (%) (%) (%) (%) (%)
Total ARs 67 26(25.74) 58 23(22.77) 125 49(24.26) 0.7429 24 14(14.00) 31 14(14.00) 55 28(14.00) 1.0000
General
disorders and
27 16(15.84) 28 19(18.81) 55 35(17.33) 0.7105 7 7(7.00) 20 12(12.00) 27 19(9.50) 0.3350
administration site
conditions
Fever 12 10(9.90) 12 11(10.89) 24 21(10.40) 1.0000 5 5(5.00) 6 6(6.00) 11 11(5.50) 1.0000
Vaccination
8 8(7.92) 7 7(6.93) 15 15(7.43) 1.0000 0 0(0.00) 6 6(6.00) 6 6(3.00) 0.0289
site pain
Vaccination
2 2(1.98) 3 3(2.97) 5 5(2.48) 1.0000 0 0(0.00) 2 2(2.00) 2 2(1.00) 0.4975
site swelling
Injection site
2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000 0 0(0.00) 1 1(1.00) 1 1(0.50) 1.0000
induration
Vaccination
1 1(0.99) 2 2(1.98) 3 3(1.49) 1.0000 1 1(1.00) 2 2(2.00) 3 3(1.50) 1.0000
site erythema
Vaccination
1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000 0 0(0.00) 1 1(1.00) 1 1(0.50) 1.0000
site pruritus
Fatigue 1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000 0 0(0.00) 1 1(1.00) 1 1(0.50) 1.0000
Vaccination
0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000 1 1(1.00) 1 1(1.00) 2 2(1.00) 1.0000
site rash
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(%) (%) (%) (%) (%) (%)
Gastrointestinal
16 10(9.90) 17 9(8.91) 33 19(9.41) 1.0000 7 6(6.00) 8 6(6.00) 15 12(6.00) 1.0000
disorders
Diarrhoea 12 9(8.91) 8 7(6.93) 20 16(7.92) 0.7954 4 4(4.00) 4 4(4.00) 8 8(4.00) 1.0000
Vomiting 3 3(2.97) 3 3(2.97) 6 6(2.97) 1.0000 3 3(3.00) 3 3(3.00) 6 6(3.00) 1.0000
Nausea 1 1(0.99) 6 4(3.96) 7 5(2.48) 0.3687 0 0(0.00) 1 1(1.00) 1 1(0.50) 1.0000
Respiratory,
thoracic and
12 11(10.89) 6 6(5.94) 18 17(8.42) 0.3108 5 5(5.00) 3 3(3.00) 8 8(4.00) 0.7209
mediastinal
disorders
Cough 12 11(10.89) 6 6(5.94) 18 17(8.42) 0.3108 5 5(5.00) 3 3(3.00) 8 8(4.00) 0.7209
Musculoskeletal
and connective 3 3(2.97) 3 3(2.97) 6 6(2.97) 1.0000 1 1(1.00) 0 0(0.00) 1 1(0.50) 1.0000
tissue disorders
Myalgia 3 3(2.97) 3 3(2.97) 6 6(2.97) 1.0000 1 1(1.00) 0 0(0.00) 1 1(0.50) 1.0000
Nervous system
5 5(4.95) 1 1(0.99) 6 6(2.97) 0.2117 2 2(2.00) 0 0(0.00) 2 2(1.00) 0.4975
disorders
Headache 5 5(4.95) 1 1(0.99) 6 6(2.97) 0.2117 2 2(2.00) 0 0(0.00) 2 2(1.00) 0.4975
Skin and
subcutaneous 2 2(1.98) 2 2(1.98) 4 4(1.98) 1.0000 - - - - - - -
tissue disorders
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(%) (%) (%) (%) (%) (%)
Mucocutaneous 2 2(1.98) 1 1(0.99) 3 3(1.49) 1.0000 - - - - - - -

rash
Rash 0 0(0.00) 1 1(0.99) 1 1(0.50) 1.0000 - - - - - - -
Metabolism and
1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000 1 1(1.00) 0 0(0.00) 1 1(0.50) 1.0000
nutrition disorders
Decreased
1 1(0.99) 1 1(0.99) 2 2(0.99) 1.0000 1 1(1.00) 0 0(0.00) 1 1(0.50) 1.0000
appetite
Immune system
1 1(0.99) 0 0(0.00) 1 1(0.50) 1.0000 1 1(1.00) 0 0(0.00) 1 1(0.50) 1.0000
disorders
Hypersensitivity 1 1(0.99) 0 0(0.00) 1 1(0.50) 1.0000 1 1(1.00) 0 0(0.00) 1 1(0.50) 1.0000
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12.2 Safety analysis in aged 3-5 years
12.2.1 Overall Safety analysis in 3-5 years of safety subgroup

A total of 1134 participants aged 3-5 years in the safety subgroup received at least one dose of
investigational vaccine/placebo were included into safety analysis. The overall incidence rate of AEs
was 59.96% (680/1134) in the safety analysis period. The incidence rates of AEs were 63.96%
in the vaccine group was statistically different from that of placebo group (P<0.0001). The overall
incidence rate of ARs within 28 days of each vaccination, was 35.71% (405/1134). The incidence rates
of ARs were 39.34% (310/788) and 27.46% (95/346) in vaccine and placebo group, respectively. The
incidence rate of ARs in the vaccine group was statistically different from that of placebo group
(P=0.0001).
The incidence rates of systemic and local adverse reactions were 20.55% and 25.31%, respectively.
The incidence rate of systemic adverse reactions in the vaccine group was not statistically different
from that of placebo group (21.70% vs 17.92%, P=0.1517). The incidence of local adverse reactions
was statistically different between the vaccine group and placebo group (28.55% vs 17.92%,
P=0.0001).
respectively. The incidence of solicited ARs in the vaccine group was statistically different from that
of placebo group (P=0.0002). The overall incidence rate of unsolicited ARs was 5.03%. The incidence
rates of unsolicited ARs in the vaccine group and placebo group were 5.30% and 4.62%, respectively.
No difference was found in the incidence of unsolicited ARs between groups.
vaccine group (39.34%) was statistically different from that of placebo group (27.46%) (P=0.0001).
The incidence rate of adverse reactions occurred within 30 min was 9.52%, without statistically
different between the groups (vaccine group 10.15% vs placebo group 8.09%, P=0.3229). There was
no adverse reactions occurred within 8~28 days after vaccination.
reactions were 32.72% (vaccine group 36.42% vs placebo group 24.28%, P<0.0001) and 10.23%
in children and adolescents aged 3-5 years (safety subgroup)
(n=788) (n=346) (n=1134) P-value
Category
Total AEs # 1996 504(63.96) 523 176(50.87) 2519 680(59.96) <0.0001
Systemic AEs 377 171(21.70) 138 62(17.92) 515 233(20.55) 0.1517
Local AEs 442 225(28.55) 117 62(17.92) 559 287(25.31) 0.0001
Solicited AEs 769 304(38.58) 235 94(27.17) 1004 398(35.10) 0.0002
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(n=788) (n=346) (n=1134) P-value
Category
Unsolicited AEs 50 41(5.20) 20 16(4.62) 70 57(5.03) 0.7687
Within 0~30 min 103 80(10.15) 43 28(8.09) 146 108(9.52) 0.3229
Within 0~7 days 819 310(39.34) 255 95(27.46) 1074 405(35.71) 0.0001
Within 8~28days 0 0(0.00) 0 0(0.00) 0 0(0.00) 1.0000
Grade 1 AEs 689 287(36.42) 224 84(24.28) 913 371(32.72) <0.0001
Grade 2 AEs 125 92(11.68) 31 24(6.94) 156 116(10.23) 0.0145
Grade 3 AEs 5 5(0.63) 0 0(0.00) 5 5(0.44) 0.3308
AEs after 28 days of each dose 562 230(29.19) 49 34(9.83) 611 264(23.28) <0.0001
AEs unrelated to vaccine 562 230(29.19) 49 34(9.83) 611 264(23.28) <0.0001
following the period from the first dose inoculation to the time of August 31st, 2022.
12.2.2 Display and analysis of Adverse Events in 3-5 years of safety subgroup
administration site conditions, with an overall incidence of 30.95%. The most common AR was
vaccination site pain, with an incidence rate of 21.32% in the vaccine group and 13.58% in the placebo
group (P=0.0023); followed by vaccination site erythema (11.55% in vaccine group and 6.65% in
placebo group, P=0.0133), fever (6.47% in vaccine group and 5.49% in placebo group, P=0.5932) and
fatigue (5.20% in vaccine group and 5.49% in placebo group, P=0.8856). See Table below for details.
Table 34 Occurrence of adverse reactions within 28 days after vaccination in 3-5 years of safety subgroup

(%) (%) (%)
Total ARs 819 310(39.34) 255 95(27.46) 1074 405(35.71) 0.0001
Grade 1 689 287(36.42) 224 84(24.28) 913 371(32.72) <0.0001
Grade 2 125 92(11.68) 31 24(6.94) 156 116(10.23) 0.0145
Grade 3 5 5(0.63) 0 0(0.00) 5 5(0.44) 0.3308
544 268(34.01) 157 83(23.99) 701 351(30.95) 0.0008
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(%) (%) (%)
Grade 1 474 236(29.95) 134 70(20.23) 608 306(26.98) 0.0006
Grade 2 65 60(7.61) 23 20(5.78) 88 80(7.05) 0.3140
Grade 3 5 5(0.63) 0 0(0.00) 5 5(0.44) 0.3308
Grade 1 207 163(20.69) 57 47(13.58) 264 210(18.52) 0.0047

Grade 2 8 8(1.02) 0 0(0.00) 8 8(0.71) 0.1151
Grade 1 103 89(11.29) 22 19(5.49) 125 108(9.52) 0.0020

Grade 2 5 5(0.63) 4 4(1.16) 9 9(0.79) 0.4675
Fever 54 51(6.47) 19 19(5.49) 73 70(6.17) 0.5932
Grade 1 13 11(1.40) 4 4(1.16) 17 15(1.32) 1.0000
Grade 2 37 36(4.57) 15 15(4.34) 52 51(4.50) 1.0000
Grade 3 4 4(0.51) 0 0(0.00) 4 4(0.35) 0.3199
Fatigue 48 41(5.20) 21 19(5.49) 69 60(5.29) 0.8856
Grade 1 39 33(4.19) 19 17(4.91) 58 50(4.41) 0.6377
Grade 2 8 8(1.02) 2 2(0.58) 10 10(0.88) 0.7322
Grade 3 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 44 44(5.58) 11 11(3.18) 55 55(4.85) 0.0983

Grade 2 2 2(0.25) 1 1(0.29) 3 3(0.26) 1.0000
Grade 1 35 32(4.06) 8 8(2.31) 43 40(3.53) 0.1638

Grade 2 3 3(0.38) 0 0(0.00) 3 3(0.26) 0.5574
Grade 1 25 19(2.41) 8 8(2.31) 33 27(2.38) 1.0000

Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 8 8(1.02) 1 1(0.29) 9 9(0.79) 0.2903

Grade 2 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
Injection site haematoma 0 0(0.00) 3 2(0.58) 3 2(0.18) 0.0929
Grade 1 0 0(0.00) 3 2(0.58) 3 2(0.18) 0.0929
Injection site panniculitis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000

Vaccination site
0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
haematoma
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(%) (%) (%)
Grade 1 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
Grade 1 69 56(7.11) 19 15(4.34) 88 71(6.26) 0.0838

Grade 2 8 8(1.02) 3 2(0.58) 11 10(0.88) 0.7322
Diarrhoea 36 32(4.06) 10 9(2.60) 46 41(3.62) 0.2996
Grade 1 35 32(4.06) 8 7(2.02) 43 39(3.44) 0.1098
Grade 2 1 1(0.13) 2 2(0.58) 3 3(0.26) 0.2223
Vomiting 24 24(3.05) 8 8(2.31) 32 32(2.82) 0.5638
Grade 1 20 20(2.54) 7 7(2.02) 27 27(2.38) 0.6777
Grade 2 4 4(0.51) 1 1(0.29) 5 5(0.44) 1.0000
Nausea 9 9(1.14) 1 1(0.29) 10 10(0.88) 0.2986
Grade 1 9 9(1.14) 1 1(0.29) 10 10(0.88) 0.2986
Abdominal pain 5 5(0.63) 2 2(0.58) 7 7(0.62) 1.0000
Grade 1 4 4(0.51) 2 2(0.58) 6 6(0.53) 1.0000
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Odynophagia 1 1(0.13) 1 1(0.29) 2 2(0.18) 0.5173
Grade 1 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Abdominal pain upper 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Gastritis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
71 53(6.73) 25 18(5.20) 96 71(6.26) 0.3548
Grade 1 49 40(5.08) 22 17(4.91) 71 57(5.03) 1.0000
Grade 2 22 19(2.41) 3 2(0.58) 25 21(1.85) 0.0328
Cough 42 38(4.82) 17 15(4.34) 59 53(4.67) 0.8786
Grade 1 28 27(3.43) 16 15(4.34) 44 42(3.70) 0.4951
Grade 2 14 12(1.52) 1 1(0.29) 15 13(1.15) 0.1247
Nasal congestion 11 10(1.27) 6 6(1.73) 17 16(1.41) 0.5869
Grade 1 8 8(1.02) 5 5(1.45) 13 13(1.15) 0.5507
Grade 2 3 3(0.38) 1 1(0.29) 4 4(0.35) 1.0000
Rhinorrhoea 11 10(1.27) 1 1(0.29) 12 11(0.97) 0.1883
Grade 1 8 8(1.02) 1 1(0.29) 9 9(0.79) 0.2903
Grade 2 3 3(0.38) 0 0(0.00) 3 3(0.26) 0.5574
Sneezing 3 3(0.38) 1 1(0.29) 4 4(0.35) 1.0000
Grade 1 3 3(0.38) 0 0(0.00) 3 3(0.26) 0.5574
Grade 2 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
Oropharyngeal pain 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
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(%) (%) (%)
Grade 1 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Rhinitis allergic 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000

Nasal pruritus 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Epistaxis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 26 22(2.79) 13 12(3.47) 39 34(3.00) 0.5717

Grade 2 7 7(0.89) 1 1(0.29) 8 8(0.71) 0.4471
Headache 32 28(3.55) 13 12(3.47) 45 40(3.53) 1.0000
Grade 1 25 21(2.66) 12 11(3.18) 37 32(2.82) 0.6973
Grade 2 7 7(0.89) 1 1(0.29) 8 8(0.71) 0.4471
Somnolence 1 1(0.13) 1 1(0.29) 2 2(0.18) 0.5173
Grade 1 1 1(0.13) 1 1(0.29) 2 2(0.18) 0.5173
32 29(3.68) 11 10(2.89) 43 39(3.44) 0.5972
disorders
Grade 1 26 24(3.05) 11 10(2.89) 37 34(3.00) 1.0000
Grade 2 6 6(0.76) 0 0(0.00) 6 6(0.53) 0.1860
Grade 1 26 24(3.05) 11 10(2.89) 37 34(3.00) 1.0000
Grade 2 6 6(0.76) 0 0(0.00) 6 6(0.53) 0.1860
Musculoskeletal and
26 22(2.79) 16 15(4.34) 42 37(3.26) 0.2037
Grade 1 20 18(2.28) 16 15(4.34) 36 33(2.91) 0.0820
Grade 2 6 5(0.63) 0 0(0.00) 6 5(0.44) 0.3308
Myalgia 25 21(2.66) 16 15(4.34) 41 36(3.17) 0.1444
Grade 1 20 18(2.28) 16 15(4.34) 36 33(2.91) 0.0820
Grade 2 5 4(0.51) 0 0(0.00) 5 4(0.35) 0.3199
Arthralgia 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
25 24(3.05) 8 8(2.31) 33 32(2.82) 0.5638
tissue disorders
Grade 1 16 16(2.03) 7 7(2.02) 23 23(2.03) 1.0000
Grade 2 9 9(1.14) 1 1(0.29) 10 10(0.88) 0.2986
Grade 1 13 13(1.65) 5 5(1.45) 18 18(1.59) 1.0000
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(%) (%) (%)
Grade 2 8 8(1.02) 1 1(0.29) 9 9(0.79) 0.2903
Pruritus 0 0(0.00) 2 2(0.58) 2 2(0.18) 0.0929
Grade 1 0 0(0.00) 2 2(0.58) 2 2(0.18) 0.0929
Rash 2 2(0.25) 0 0(0.00) 2 2(0.18) 1.0000
Grade 1 2 2(0.25) 0 0(0.00) 2 2(0.18) 1.0000
Urticaria 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 2 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Dermatitis allergic 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 4 4(0.51) 0 0(0.00) 4 4(0.35) 0.3199

Grade 2 2 2(0.25) 0 0(0.00) 2 2(0.18) 1.0000
Grade 1 4 4(0.51) 0 0(0.00) 4 4(0.35) 0.3199
Grade 2 2 2(0.25) 0 0(0.00) 2 2(0.18) 1.0000
Infections and infestations 5 5(0.63) 1 1(0.29) 6 6(0.53) 0.6735
Grade 1 5 5(0.63) 1 1(0.29) 6 6(0.53) 0.6735

Rhinitis 2 2(0.25) 1 1(0.29) 3 3(0.26) 1.0000
Grade 1 2 2(0.25) 1 1(0.29) 3 3(0.26) 1.0000
Upper respiratory tract
1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
infection
Grade 1 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Bronchitis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Nasopharyngitis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Grade 1 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000
Psychiatric disorders 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
Grade 1 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
Insomnia 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
Grade 1 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051
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Table 35 Occurrence of adverse reactions within 28 days after vaccination of first and second dose in 3-5 years of safety subgroup (classified by SOC
and PT)
Vaccine group Placebo group Vaccine group Placebo group
Total (N=1134) Total (N=1038)
(N=788) (N=346) (N=754) (N=284)
P- P-
Category no. of no. of no. of no. of no. of no. of
no. of no. of no. of value no. of no. of no. of value
(%) (%) (%) (%) (%) (%)
Total ARs 527 252(31.98) 187 80(23.12) 714 332(29.28) 0.0029 292 148(19.63) 68 41(14.44) 360 189(18.21) 0.0581
351 217(27.54) 114 69(19.94) 465 286(25.22) 0.0074 193 122(16.18) 43 34(11.97) 236 156(15.03) 0.0980
Vaccination site pain 136 134(17.01) 41 41(11.85) 177 175(15.43) 0.0319 79 79(10.48) 16 16(5.63) 95 95(9.15) 0.0155
Vaccination site erythema 70 69(8.76) 16 16(4.62) 86 85(7.50) 0.0142 38 38(5.04) 10 10(3.52) 48 48(4.62) 0.4067
Fever 39 37(4.70) 11 11(3.18) 50 48(4.23) 0.2666 15 15(1.99) 8 8(2.82) 23 23(2.22) 0.4778

Fatigue 32 31(3.93) 17 17(4.91) 49 48(4.23) 0.5217 16 16(2.12) 4 4(1.41) 20 20(1.93) 0.6147
Injection site induration 29 29(3.68) 11 11(3.18) 40 40(3.53) 0.7302 17 17(2.25) 1 1(0.35) 18 18(1.73) 0.0339
Vaccination site swelling 22 22(2.79) 7 7(2.02) 29 29(2.56) 0.5433 16 16(2.12) 1 1(0.35) 17 17(1.64) 0.0529
Vaccination site pruritus 16 16(2.03) 8 8(2.31) 24 24(2.12) 0.8232 10 10(1.33) 0 0(0.00) 10 10(0.96) 0.0702
Vaccination site rash 6 6(0.76) 1 1(0.29) 7 7(0.62) 0.6823 2 2(0.27) 1 1(0.35) 3 3(0.29) 1.0000
Injection site haematoma 0 0(0.00) 2 2(0.58) 2 2(0.18) 0.0929 0 0(0.00) 1 1(0.35) 1 1(0.10) 0.2736
Injection site panniculitis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
Vaccination site haematoma - - - - - - - 0 0(0.00) 1 1(0.35) 1 1(0.10) 0.2736
Gastrointestinal disorders 50 40(5.08) 17 14(4.05) 67 54(4.76) 0.5453 27 22(2.92) 5 4(1.41) 32 26(2.50) 0.1886
Diarrhoea 24 22(2.79) 7 7(2.02) 31 29(2.56) 0.5433 0 0(0.00) 1 1(0.07) 1 1(0.05) 1.0000

Vomiting 14 14(1.78) 7 7(2.02) 21 21(1.85) 0.8122 1 1(0.12) 0 0(0.00) 1 1(0.05) 0.3731
Nausea 7 7(0.89) 0 0(0.00) 7 7(0.62) 0.1082 2 2(0.27) 1 1(0.35) 3 3(0.29) 1.0000
Abdominal pain 2 2(0.25) 2 2(0.58) 4 4(0.35) 0.5899 3 3(0.40) 0 0(0.00) 3 3(0.29) 0.5662
Odynophagia 1 1(0.13) 1 1(0.29) 2 2(0.18) 0.5173 - - - - - - -
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(N=788) (N=346) (N=754) (N=284)
P- P-
(%) (%) (%) (%) (%) (%)
Abdominal pain upper 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
Gastritis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
41 33(4.19) 14 12(3.47) 55 45(3.97) 0.6239 30 28(3.71) 11 8(2.82) 41 36(3.47) 0.5711
Cough 25 24(3.05) 11 11(3.18) 36 35(3.09) 0.8547 17 17(2.25) 6 6(2.11) 23 23(2.22) 1.0000
Rhinorrhoea 7 7(0.89) 1 1(0.29) 8 8(0.71) 0.4471 4 4(0.53) 0 0(0.00) 4 4(0.39) 0.5798
Nasal congestion 6 6(0.76) 2 2(0.58) 8 8(0.71) 1.0000 0 0(0.00) 1 1(0.07) 1 1(0.05) 1.0000
Oropharyngeal pain 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
Sneezing 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 2 2(0.27) 1 1(0.35) 3 3(0.29) 1.0000
Epistaxis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
Rhinitis allergic - - - - - - - 1 1(0.13) 0 0(0.00) 1 1(0.10) 1.0000

Nasal pruritus - - - - - - - 1 1(0.13) 0 0(0.00) 1 1(0.10) 1.0000
Nervous system disorders 24 24(3.05) 11 11(3.18) 35 35(3.09) 0.8547 9 7(0.93) 3 3(1.06) 12 10(0.96) 1.0000
Headache 23 23(2.92) 10 10(2.89) 33 33(2.91) 1.0000 9 7(0.93) 3 3(1.06) 12 10(0.96) 1.0000
Somnolence 1 1(0.13) 1 1(0.29) 2 2(0.18) 0.5173 - - - - - - -
Musculoskeletal and connective
17 17(2.16) 13 13(3.76) 30 30(2.65) 0.1577 9 9(1.19) 3 3(1.06) 12 12(1.16) 1.0000
tissue disorders
Myalgia 16 16(2.03) 13 13(3.76) 29 29(2.56) 0.1027 9 9(1.19) 3 3(1.06) 12 12(1.16) 1.0000
Arthralgia 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 0 0(0.00) 1 1(0.07) 1 1(0.05) 1.0000
20 20(2.54) 8 8(2.31) 28 28(2.47) 1.0000 0 0(0.00) 1 1(0.07) 1 1(0.05) 1.0000
disorders
Decreased appetite 20 20(2.54) 8 8(2.31) 28 28(2.47) 1.0000 12 11(1.46) 3 3(1.06) 15 14(1.35) 0.7690
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(N=788) (N=346) (N=754) (N=284)
P- P-
(%) (%) (%) (%) (%) (%)
Skin and subcutaneous tissue
16 16(2.03) 8 8(2.31) 24 24(2.12) 0.8232 9 9(1.19) 0 0(0.00) 9 9(0.87) 0.1244
disorders
Mucocutaneous rash 13 13(1.65) 6 6(1.73) 19 19(1.68) 1.0000 8 8(1.06) 0 0(0.00) 8 8(0.77) 0.1159
Pruritus 0 0(0.00) 2 2(0.58) 2 2(0.18) 0.0929 - - - - - - -
Rash 2 2(0.25) 0 0(0.00) 2 2(0.18) 1.0000 - - - - - - -
Dermatitis allergic 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
Infections and infestations 4 4(0.51) 1 1(0.29) 5 5(0.44) 1.0000 1 1(0.13) 0 0(0.00) 1 1(0.10) 1.0000
Rhinitis 2 2(0.25) 1 1(0.29) 3 3(0.26) 1.0000 - - - - - - -
Bronchitis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
Nasopharyngitis 1 1(0.13) 0 0(0.00) 1 1(0.09) 1.0000 - - - - - - -
Upper respiratory tract infection - - - - - - - 1 1(0.13) 0 0(0.00) 1 1(0.10) 1.0000
Immune system disorders 4 4(0.51) 0 0(0.00) 4 4(0.35) 0.3199 2 2(0.27) 0 0(0.00) 2 2(0.19) 1.0000
Psychiatric disorders 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051 - - - - - - -
Insomnia 0 0(0.00) 1 1(0.29) 1 1(0.09) 0.3051 - - - - - - -
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was 47.34% (481/1016) in the safety analysis period. The incidence rates of AEs were 52.28%
in the vaccine group was statistically different from that of placebo group (P=0.0002). The overall
of ARs were 36.09% (214/593) and 24.11% (102/423) in vaccine and placebo group, respectively. The
incidence rate of ARs in the vaccine group was statistically different from that of placebo group
(P<0.0001).
was statistically different between the vaccine group and placebo group (26.31% vs 13.71%,
P<0.0001).
respectively. The incidence of solicited ARs in the vaccine group was statistically different from that
of placebo group (P<0.0001). The overall incidence rate of unsolicited ARs was 3.74%. The incidence
rates of unsolicited ARs in the vaccine group and placebo group were 3.71% and 3.78%, respectively.
No difference was found in the incidence of unsolicited ARs between groups.
vaccine group (36.09%) was statistically different from that of placebo group (23.88%) (P<0.0001).
The incidence rate of adverse reactions occurred within 30 min was 9.74%, without statistically
different between the groups (vaccine group 11.30% vs placebo group 7.57%, P=0.0533). There was
only 3 adverse reactions occurred within 8~28 days after vaccination.
reactions were 28.74% (vaccine group 33.73% vs placebo group 21.75%, P<0.0001) and 6.00%
(n=593) (n=423) (n=1016) P-value
Category
Total AEs # 1004 310(52.28) 524 171(40.43) 1528 481(47.34) 0.0002
AEs within 28 days of each dose 777 270(45.53) 413 141(33.33) 1190 411(40.45) <0.0001
AEs related to vaccine 540 214(36.09) 290 102(24.11) 830 316(31.10) <0.0001
Systemic AEs 232 119(20.07) 153 71(16.78) 385 190(18.70) 0.1926
Local AEs 308 156(26.31) 137 58(13.71) 445 214(21.06) <0.0001
Solicited AEs 516 208(35.08) 271 95(22.46) 787 303(29.82) <0.0001
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(n=593) (n=423) (n=1016) P-value
Category
Unsolicited AEs 24 22(3.71) 19 16(3.78) 43 38(3.74) 1.0000
Within 0~30 min 117 67(11.30) 73 32(7.57) 190 99(9.74) 0.0533
Within 0~7 days 540 214(36.09) 287 101(23.88) 827 315(31.00) <0.0001
Within 8~28days 0 0(0.00) 3 3(0.71) 3 3(0.30) 0.0719
Grade 1 AEs 487 200(33.73) 252 92(21.75) 739 292(28.74) <0.0001
Grade 2 AEs 49 39(6.58) 36 22(5.20) 85 61(6.00) 0.4221
Grade 3 AEs 4 4(0.67) 2 2(0.47) 6 6(0.59) 1.0000
(4) Unrelated to the vaccine means that the relationship between the adverse event and the research vaccine is "may be unrela ted,
group (P<0.0001); followed by headache (9.27% in vaccine group and 5.44% in placebo group,
P=0.0235), vaccination site erythema (9.27% in vaccine group and 5.20% in placebo group, P=0.0161),
fever (4.72% in vaccine group and 4.73% in placebo group, P=1.0000) and injection site induration
(4.89% in vaccine group and 3.31% in placebo group, P=0.2688). See Table below for details.
Table 37 Occurrence of adverse reactions within 28 days after vaccination in 6-11 years of safety subgroup
Category no. of no. of no. of no. of no. of no. of P-value

Total ARs 540 214(36.09) 290 102(24.11) 830 316(31.10) <0.0001
Grade 1 487 200(33.73) 252 92(21.75) 739 292(28.74) <0.0001
Grade 2 49 39(6.58) 36 22(5.20) 85 61(6.00) 0.4221
Grade 3 4 4(0.67) 2 2(0.47) 6 6(0.59) 1.0000
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364 184(31.03) 178 77(18.20) 542 261(25.69) <0.0001
Grade 1 338 173(29.17) 161 67(15.84) 499 240(23.62) <0.0001
Grade 2 22 19(3.20) 15 13(3.07) 37 32(3.15) 1.0000
Grade 3 4 4(0.67) 2 2(0.47) 6 6(0.59) 1.0000
Vaccination site pain 164 125(21.08) 65 49(11.58) 229 174(17.13) <0.0001
Grade 1 161 123(20.74) 63 47(11.11) 224 170(16.73) <0.0001

Grade 2 3 3(0.51) 2 2(0.47) 5 5(0.49) 1.0000
Grade 1 63 54(9.11) 27 22(5.20) 90 76(7.48) 0.0213

Grade 2 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Fever 29 28(4.72) 21 20(4.73) 50 48(4.72) 1.0000
Grade 1 17 17(2.87) 9 9(2.13) 26 26(2.56) 0.5481
Grade 2 9 9(1.52) 10 9(2.13) 19 18(1.77) 0.4792
Grade 3 3 3(0.51) 2 2(0.47) 5 5(0.49) 1.0000
Grade 1 30 27(4.55) 15 13(3.07) 45 40(3.94) 0.2555

Grade 2 3 3(0.51) 1 1(0.24) 4 4(0.39) 0.6450
Fatigue 25 21(3.54) 20 17(4.02) 45 38(3.74) 0.7386
Grade 1 22 19(3.20) 19 16(3.78) 41 35(3.44) 0.7276
Grade 2 2 2(0.34) 1 1(0.24) 3 3(0.30) 1.0000
Grade 3 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 15 14(2.36) 15 13(3.07) 30 27(2.66) 0.5544

Grade 2 2 2(0.34) 1 1(0.24) 3 3(0.30) 1.0000
Grade 1 16 16(2.70) 9 7(1.65) 25 23(2.26) 0.2943

Grade 2 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 10 10(1.69) 4 4(0.95) 14 14(1.38) 0.4175
Injection site haemorrhage 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Grade 1 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Injection site hypoaesthesia 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000

Vaccination site
1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
discolouration
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Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 53 46(7.76) 29 24(5.67) 82 70(6.89) 0.2109

Grade 2 12 11(1.85) 3 3(0.71) 15 14(1.38) 0.1727
Headache 63 55(9.27) 28 23(5.44) 91 78(7.68) 0.0235
Grade 1 51 44(7.42) 26 21(4.96) 77 65(6.40) 0.1206
Grade 2 12 11(1.85) 2 2(0.47) 14 13(1.28) 0.0856
Somnolence 0 0(0.00) 3 3(0.71) 3 3(0.30) 0.0719
Grade 1 0 0(0.00) 3 3(0.71) 3 3(0.30) 0.0719
Dizziness 2 2(0.34) 1 1(0.24) 3 3(0.30) 1.0000
Grade 1 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 1 25 21(3.54) 31 21(4.96) 56 42(4.13) 0.2676

Grade 2 0 0(0.00) 5 4(0.95) 5 4(0.39) 0.0298
Diarrhoea 12 12(2.02) 15 14(3.31) 27 26(2.56) 0.2288
Grade 1 12 12(2.02) 12 11(2.60) 24 23(2.26) 0.6696
Grade 2 0 0(0.00) 3 3(0.71) 3 3(0.30) 0.0719
Vomiting 4 4(0.67) 11 11(2.60) 15 15(1.48) 0.0161
Grade 1 4 4(0.67) 10 10(2.36) 14 14(1.38) 0.0287
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Nausea 6 6(1.01) 10 9(2.13) 16 15(1.48) 0.1878
Grade 1 6 6(1.01) 9 8(1.89) 15 14(1.38) 0.2796
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Abdominal pain upper 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Grade 1 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Odynophagia 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
24 22(3.71) 19 16(3.78) 43 38(3.74) 1.0000
Grade 1 19 18(3.04) 10 9(2.13) 29 27(2.66) 0.4328
Grade 2 5 4(0.67) 9 7(1.65) 14 11(1.08) 0.2169
Cough 20 19(3.20) 14 14(3.31) 34 33(3.25) 1.0000
Grade 1 16 15(2.53) 9 9(2.13) 25 24(2.36) 0.8346
Grade 2 4 4(0.67) 5 5(1.18) 9 9(0.89) 0.5021
Rhinorrhoea 1 1(0.17) 2 2(0.47) 3 3(0.30) 0.5740
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 2 0 0(0.00) 2 2(0.47) 2 2(0.20) 0.1731
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Grade 1 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 2 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Nasal obstruction 1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Oropharyngeal pain 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Sneezing 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Musculoskeletal and
34 25(4.22) 15 12(2.84) 49 37(3.64) 0.3086
Grade 1 28 22(3.71) 14 11(2.60) 42 33(3.25) 0.3727
Grade 2 6 5(0.84) 1 1(0.24) 7 6(0.59) 0.4098
Myalgia 33 24(4.05) 14 11(2.60) 47 35(3.44) 0.2275
Grade 1 27 21(3.54) 13 10(2.36) 40 31(3.05) 0.3557
Grade 2 6 5(0.84) 1 1(0.24) 7 6(0.59) 0.4098
Muscular weakness 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Limb discomfort 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 1 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
11 11(1.85) 2 2(0.47) 13 13(1.28) 0.0856
disorders
Grade 1 10 10(1.69) 2 2(0.47) 12 12(1.18) 0.1374
Grade 2 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 8 8(1.35) 2 2(0.47) 10 10(0.98) 0.2081
Grade 2 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Increased appetite 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Grade 1 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
8 7(1.18) 3 3(0.71) 11 10(0.98) 0.5350
disorders
Grade 1 8 7(1.18) 2 2(0.47) 10 9(0.89) 0.3188
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 1 5 5(0.84) 1 1(0.24) 6 6(0.59) 0.4098

Rash 1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000
Grade 1 1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000
Rash papular 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
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Rash pruritic 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000

Pruritus 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 4 4(0.67) 0 0(0.00) 4 4(0.39) 0.1454

Grade 2 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Grade 1 4 4(0.67) 0 0(0.00) 4 4(0.39) 0.1454
Grade 2 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135
Grade 1 0 0(0.00) 2 2(0.47) 2 2(0.20) 0.1731

Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
0 0(0.00) 2 2(0.47) 2 2(0.20) 0.1731
infection
Grade 1 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 2 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Rhinitis 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 1 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Blood and lymphatic system
1 1(0.17) 2 2(0.47) 3 3(0.30) 0.5740
disorders
Grade 1 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 2 1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000
Lymphadenopathy 1 1(0.17) 2 2(0.47) 3 3(0.30) 0.5740
Grade 1 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163
Grade 2 1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000
Investigations 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Body temperature increased 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Eye disorders 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000

Periorbital swelling 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Grade 1 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
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and PT)
(N=593) (N=423) (N=589) (N=416)
P- P-
(%) (%) (%) (%) (%) (%)
Total ARs 329 170(28.67) 188 83(19.62) 517 253(24.90) 0.0012 211 111(18.85) 102 55(13.22) 313 166(16.52) 0.0198
administration site 215 144(24.28) 110 63(14.89) 325 207(20.37) 0.0003 149 98(16.64) 68 42(10.10) 217 140(13.93) 0.0031
conditions
Vaccination site
44 43(7.25) 17 17(4.02) 61 60(5.91) 0.0314 21 21(3.57) 10 10(2.40) 31 31(3.08) 0.3562
erythema
Fatigue 14 14(2.36) 15 15(3.55) 29 29(2.85) 0.3394 11 11(1.87) 5 5(1.20) 16 16(1.59) 0.4552
Fever 14 14(2.36) 13 13(3.07) 27 27(2.66) 0.5544 15 15(2.55) 8 8(1.92) 23 23(2.29) 0.6694
Injection site
17 17(2.87) 11 10(2.36) 28 27(2.66) 0.6955 16 16(2.72) 5 5(1.20) 21 21(2.09) 0.1188
induration
Vaccination site
12 12(2.02) 6 6(1.42) 18 18(1.77) 0.6309 5 5(0.85) 3 3(0.72) 8 8(0.80) 1.0000
pruritus
Vaccination site
9 9(1.52) 9 9(2.13) 18 18(1.77) 0.4792 8 8(1.36) 7 7(1.68) 15 15(1.49) 0.7931
swelling
Vaccination site rash 5 5(0.84) 3 3(0.71) 8 8(0.79) 1.0000 5 5(0.85) 1 1(0.24) 6 6(0.60) 0.4098
Injection site
1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
haemorrhage
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(N=593) (N=423) (N=589) (N=416)
P- P-
(%) (%) (%) (%) (%) (%)
Injection site
1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 - - - - - - -
hypoaesthesia
Vaccination site
1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 - - - - - - -
discolouration
Nervous system
41 40(6.75) 24 22(5.20) 65 62(6.10) 0.3531 24 23(3.90) 8 8(1.92) 32 31(3.08) 0.0946
disorders
Headache 41 40(6.75) 20 18(4.26) 61 58(5.71) 0.1006 22 22(3.74) 8 8(1.92) 30 30(2.99) 0.1311
Somnolence 0 0(0.00) 3 3(0.71) 3 3(0.30) 0.0719 0 0(0.00) 1 1(0.05) 1 1(0.02) 0.4708

Dizziness 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5143
Gastrointestinal
21 17(2.87) 23 18(4.26) 44 35(3.44) 0.2950 4 4(0.68) 13 11(2.64) 17 15(1.49) 0.0157
disorders
Diarrhoea 10 10(1.69) 10 10(2.36) 20 20(1.97) 0.4957 2 2(0.34) 5 5(1.20) 7 7(0.70) 0.1330
Vomiting 4 4(0.67) 7 7(1.65) 11 11(1.08) 0.2169 0 0(0.00) 4 4(0.96) 4 4(0.40) 0.0291
Nausea 4 4(0.67) 6 6(1.42) 10 10(0.98) 0.3348 2 2(0.34) 4 4(0.96) 6 6(0.60) 0.2384
Abdominal pain
2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135 - - - - - - -
upper
Odynophagia 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 - - - - - - -
Musculoskeletal and
connective tissue 19 18(3.04) 8 8(1.89) 27 26(2.56) 0.3156 15 14(2.38) 7 7(1.68) 22 21(2.09) 0.5086
disorders
Myalgia 18 17(2.87) 8 8(1.89) 26 25(2.46) 0.4126 15 14(2.38) 6 6(1.44) 21 20(1.99) 0.3632
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(N=593) (N=423) (N=589) (N=416)
P- P-
(%) (%) (%) (%) (%) (%)
Muscular weakness 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 - - - - - - -
Limb discomfort - - - - - - - 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4139
Respiratory, thoracic
and mediastinal 11 10(1.69) 16 14(3.31) 27 24(2.36) 0.0984 13 13(2.21) 3 2(0.48) 16 15(1.49) 0.0325
disorders
Cough 10 10(1.69) 12 12(2.84) 22 22(2.17) 0.2744 10 10(1.70) 2 2(0.48) 12 12(1.19) 0.1372
Rhinorrhoea 0 0(0.00) 2 2(0.47) 2 2(0.20) 0.1731 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000

Oropharyngeal pain 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163 - - - - - - -
Nasal congestion 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4139
Nasal obstruction 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Sneezing - - - - - - - 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Metabolism and
9 9(1.52) 2 2(0.47) 11 11(1.08) 0.1343 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5143
nutrition disorders
Decreased appetite 7 7(1.18) 2 2(0.47) 9 9(0.89) 0.3188 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5143
Increased appetite 2 2(0.34) 0 0(0.00) 2 2(0.20) 0.5135 - - - - - - -
Skin and
subcutaneous tissue 6 5(0.84) 2 2(0.47) 8 7(0.69) 0.7059 2 2(0.34) 1 1(0.24) 3 3(0.30) 1.0000
disorders
Mucocutaneous rash 4 4(0.67) 0 0(0.00) 4 4(0.39) 0.1454 1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000
Rash papular 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163 - - - - - - -
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(N=593) (N=423) (N=589) (N=416)
P- P-
(%) (%) (%) (%) (%) (%)
Rash pruritic 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 1 1(0.05) 0 0(0.00) 1 1(0.02) 1.0000
Pruritus 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 1 1(0.05) 0 0(0.00) 1 1(0.02) 1.0000

Rash 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4163 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Immune system
5 5(0.84) 0 0(0.00) 5 5(0.49) 0.0796 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
disorders
Infections and
0 0(0.00) 2 2(0.47) 2 2(0.20) 0.1731 0 0(0.00) 1 1(0.05) 1 1(0.02) 0.4708
infestations
Upper respiratory
0 0(0.00) 2 2(0.47) 2 2(0.20) 0.1731 - - - - - - -
tract infection
Rhinitis - - - - - - - 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4139
Blood and lymphatic
1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4139
system disorders
Lymphadenopathy 1 1(0.17) 1 1(0.24) 2 2(0.20) 1.0000 0 0(0.00) 1 1(0.24) 1 1(0.10) 0.4139
Investigations 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 - - - - - - -
Body temperature
1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000 - - - - - - -
increased
Eye disorders - - - - - - - 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
Orbital swelling - - - - - - - 1 1(0.17) 0 0(0.00) 1 1(0.10) 1.0000
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was 32.71% (192/587) in the safety analysis period. The incidence rates of AEs were 33.12% (105/317)
and 32.22% (87/270) in vaccine and placebo group, respectively. The incidence rate of AEs in the
vaccine group was not statistically different from that of placebo group (P=0.8600). The overall
of ARs were 22.71% (72/317) and 19.63% (53/270) in vaccine and placebo group, respectively.
was either not statistically different between the vaccine group and placebo group (14.51% vs 10.37%,
P=0.1367).
respectively. The incidence of solicited ARs in the vaccine group was not statistically different from
that of placebo group (P=0.4750). The overall incidence rate of unsolicited ARs was 1.87%. The
incidence rates of unsolicited ARs in the vaccine group and placebo group were 1.58% and 2.22%,
respectively. No difference was found in the incidence of unsolicited ARs between groups.
vaccine group (22.71%) was not statistically different from that of placebo group (19.63%) (P=0.4185).
The incidence rate of adverse reactions occurred within 30 min was 2.56% (vaccine group 2.52% vs
placebo group 2.59%). There was only 1 adverse reaction occurred within 8~28 days after vaccination.
reactions were 19.08% (vaccine group 20.82% vs placebo group 17.04%, P=0.2489) and 5.45%
(n=317) (n=270) (n=587) P-value
Category
Total AEs # 319 105(33.12) 172 87(32.22) 491 192(32.71) 0.8600
Systemic AEs 117 53(16.72) 65 37(13.70) 182 90(15.33) 0.3581
Local AEs 89 46(14.51) 35 28(10.37) 124 74(12.61) 0.1367
Solicited AEs 201 69(21.77) 94 52(19.26) 295 121(20.61) 0.4750
Unsolicited AEs 5 5(1.58) 6 6(2.22) 11 11(1.87) 0.7618
Within 0~30 min 15 8(2.52) 7 7(2.59) 22 15(2.56) 1.0000
Within 0~7 days 206 72(22.71) 99 53(19.63) 305 125(21.29) 0.4185
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(n=317) (n=270) (n=587) P-value
Category
Within 8~28days 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
Grade 1 AEs 173 66(20.82) 82 46(17.04) 255 112(19.08) 0.2489
Grade 2 AEs 32 20(6.31) 16 12(4.44) 48 32(5.45) 0.3650
Grade 3 AEs 1 1(0.32) 2 2(0.74) 3 3(0.51) 0.5968
group (P=0.0814); followed by headache (8.52% in vaccine group and 6.67% in placebo group,
P=0.4391), fever (2.84% in vaccine group and 5.56% in placebo group, P=0.1418) and myalgia (6.31%
in vaccine group and 1.48% in placebo group, P=0.0030). See Table below for details.
Table 40 Occurrence of adverse reactions within 28 days after vaccination in 12-17 years of safety
subgroup (classified by SOC and PT)
Category P-value
Total ARs 206 72(22.71) 100 53(19.63) 306 125(21.29) 0.4185
Grade 1 173 66(20.82) 82 46(17.04) 255 112(19.08) 0.2489
Grade 2 32 20(6.31) 16 12(4.44) 48 32(5.45) 0.3650
Grade 3 1 1(0.32) 2 2(0.74) 3 3(0.51) 0.5968
110 56(17.67) 52 40(14.81) 162 96(16.35) 0.3721
Grade 1 92 50(15.77) 44 34(12.59) 136 84(14.31) 0.2891
Grade 2 17 15(4.73) 6 6(2.22) 23 21(3.58) 0.1212
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Grade 3 1 1(0.32) 2 2(0.74) 3 3(0.51) 0.5968
Grade 1 47 38(11.99) 24 22(8.15) 71 60(10.22) 0.1346

Grade 2 8 8(2.52) 0 0(0.00) 8 8(1.36) 0.0088
Fever 10 9(2.84) 16 15(5.56) 26 24(4.09) 0.1418
Grade 1 4 4(1.26) 8 7(2.59) 12 11(1.87) 0.3606
Grade 2 5 5(1.58) 6 6(2.22) 11 11(1.87) 0.7618
Grade 3 1 1(0.32) 2 2(0.74) 3 3(0.51) 0.5968
Grade 1 7 6(1.89) 4 4(1.48) 11 10(1.70) 0.7597
Grade 1 9 8(2.52) 2 2(0.74) 11 10(1.70) 0.1177

Fatigue 10 9(2.84) 1 1(0.37) 11 10(1.70) 0.0244
Grade 1 6 6(1.89) 1 1(0.37) 7 7(1.19) 0.1312
Grade 2 4 4(1.26) 0 0(0.00) 4 4(0.68) 0.1285
Grade 1 9 8(2.52) 1 1(0.37) 10 9(1.53) 0.0430
Grade 1 6 5(1.58) 2 2(0.74) 8 7(1.19) 0.4609
Grade 1 3 3(0.95) 2 2(0.74) 5 5(0.85) 1.0000

Pain 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Grade 1 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Grade 1 22 20(6.31) 16 14(5.19) 38 34(5.79) 0.5990

Grade 2 11 10(3.15) 6 6(2.22) 17 16(2.73) 0.6138
Headache 31 27(8.52) 22 18(6.67) 53 45(7.67) 0.4391
Grade 1 21 20(6.31) 16 14(5.19) 37 34(5.79) 0.5990
Grade 2 10 9(2.84) 6 6(2.22) 16 15(2.56) 0.7946
Dizziness 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Grade 1 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Tremor 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Grade 2 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Musculoskeletal and
24 20(6.31) 6 5(1.85) 30 25(4.26) 0.0075
Grade 1 23 19(5.99) 6 5(1.85) 29 24(4.09) 0.0119
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Grade 2 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Myalgia 24 20(6.31) 5 4(1.48) 29 24(4.09) 0.0030
Grade 1 23 19(5.99) 5 4(1.48) 28 23(3.92) 0.0050
Grade 2 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Limb discomfort 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
Grade 1 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
13 12(3.79) 13 12(4.44) 26 24(4.09) 0.8349
Grade 1 12 11(3.47) 11 10(3.70) 23 21(3.58) 1.0000
Grade 2 1 1(0.32) 2 2(0.74) 3 3(0.51) 0.5968
Cough 12 11(3.47) 12 12(4.44) 24 23(3.92) 0.6705
Grade 1 11 10(3.15) 10 10(3.70) 21 20(3.41) 0.8206
Grade 2 1 1(0.32) 2 2(0.74) 3 3(0.51) 0.5968
Rhinorrhoea 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Grade 1 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Grade 1 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
Grade 1 22 16(5.05) 3 3(1.11) 25 19(3.24) 0.0086

Grade 2 1 1(0.32) 1 1(0.37) 2 2(0.34) 1.0000
Diarrhoea 11 11(3.47) 1 1(0.37) 12 12(2.04) 0.0077
Grade 1 11 11(3.47) 1 1(0.37) 12 12(2.04) 0.0077
Vomiting 6 6(1.89) 1 1(0.37) 7 7(1.19) 0.1312
Grade 1 5 5(1.58) 1 1(0.37) 6 6(1.02) 0.2254
Grade 2 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Nausea 6 6(1.89) 1 1(0.37) 7 7(1.19) 0.1312
Grade 1 6 6(1.89) 1 1(0.37) 7 7(1.19) 0.1312
Gastritis 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
Grade 2 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
1 1(0.32) 3 2(0.74) 4 3(0.51) 0.5968
disorders
Grade 1 0 0(0.00) 2 1(0.37) 2 1(0.17) 0.4600
Grade 2 1 1(0.32) 1 1(0.37) 2 2(0.34) 1.0000
Rash 0 0(0.00) 2 2(0.74) 2 2(0.34) 0.2111
Grade 1 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
Grade 2 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600
Grade 1 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4600

Grade 2 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
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2 2(0.63) 0 0(0.00) 2 2(0.34) 0.5024
disorders
Grade 1 2 2(0.63) 0 0(0.00) 2 2(0.34) 0.5024
Grade 1 2 2(0.63) 0 0(0.00) 2 2(0.34) 0.5024
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and PT)

(N=316) (N=271) (N=313) (N=264)
P- P-
(%) (%) (%) (%) (%) (%)
Total ARs 150 66(20.89) 71 41(15.13) 221 107(18.23) 0.086 56 31(9.90) 29 18(6.82) 85 49(8.49) 0.2304
administration site 83 51(16.14) 40 32(11.81) 123 83(14.14) 0.1541 27 21(6.71) 12 11(4.17) 39 32(5.55) 0.2049
conditions
Fever 5 5(1.58) 12 12(4.43) 17 17(2.90) 0.0488 5 4(1.28) 4 4(1.52) 9 8(1.39) 1.0000

Vaccination site
6 6(1.90) 4 4(1.48) 10 10(1.70) 0.7591 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
erythema
Vaccination site
8 7(2.22) 2 2(0.74) 10 9(1.53) 0.1879 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
pruritus
Injection site induration 7 7(2.22) 1 1(0.37) 8 8(1.36) 0.0749 2 2(0.64) 0 0(0.00) 2 2(0.35) 0.5027
Fatigue 8 8(2.53) 0 0(0.00) 8 8(1.36) 0.0087 2 2(0.64) 1 1(0.38) 3 3(0.52) 1.0000
Vaccination site
5 5(1.58) 2 2(0.74) 7 7(1.19) 0.4600 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
swelling
Vaccination site rash 3 3(0.95) 2 2(0.74) 5 5(0.85) 1.0000 - - - - - - -
Pain 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000 - - - - - - -
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(N=316) (N=271) (N=313) (N=264)
P- P-
(%) (%) (%) (%) (%) (%)
Nervous system
22 22(6.96) 14 11(4.06) 36 33(5.62) 0.1515 11 9(2.88) 8 8(3.03) 19 17(2.95) 1.0000
disorders
Headache 21 21(6.65) 14 11(4.06) 35 32(5.45) 0.2029 10 9(2.88) 8 8(3.03) 18 17(2.95) 1.0000
Tremor 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000 - - - - - - -

Dizziness - - - - - - - 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000
Gastrointestinal
19 14(4.43) 4 4(1.48) 23 18(3.07) 0.0527 4 3(0.96) 0 0(0.00) 4 3(0.52) 0.2541
disorders
Diarrhoea 9 9(2.85) 1 1(0.37) 10 10(1.70) 0.0240 2 2(0.64) 0 0(0.00) 2 2(0.35) 0.5027
Nausea 6 6(1.90) 1 1(0.37) 7 7(1.19) 0.1305 - - - - - - -

Vomiting 4 4(1.27) 1 1(0.37) 5 5(0.85) 0.3802 2 2(0.64) 0 0(0.00) 2 2(0.35) 0.5027
Gastritis 0 0(0.00) 1 1(0.37) 1 1(0.17) 0.4617 - - - - - - -
Respiratory, thoracic
9 8(2.53) 8 8(2.95) 17 16(2.73) 0.8033 4 4(1.28) 5 4(1.52) 9 8(1.39) 1.0000
and mediastinal disorders
Cough 8 7(2.22) 8 8(2.95) 16 15(2.56) 0.6087 4 4(1.28) 4 4(1.52) 8 8(1.39) 1.0000
Rhinorrhoea 1 1(0.32) 0 0(0.00) 1 1(0.17) 1.0000 - - - - - - -
Nasal congestion - - - - - - - 0 0(0.00) 1 1(0.38) 1 1(0.17) 0.4575
Musculoskeletal and
14 13(4.11) 2 2(0.74) 16 15(2.56) 0.0153 10 10(3.19) 4 4(1.52) 14 14(2.43) 0.2781
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(N=316) (N=271) (N=313) (N=264)
P- P-
(%) (%) (%) (%) (%) (%)
Myalgia 14 13(4.11) 2 2(0.74) 16 15(2.56) 0.0153 10 10(3.19) 3 3(1.14) 13 13(2.25) 0.1571
Limb discomfort - - - - - - - 0 0(0.00) 1 1(0.38) 1 1(0.17) 0.4575
1 1(0.32) 3 2(0.74) 4 3(0.51) 0.5978 1 1(0.04) 0 0(0.00) 1 1(0.02) 1.0000
tissue disorders
Rash 0 0(0.00) 2 2(0.74) 2 2(0.34) 0.2127 0 0(0.00) 1 1(0.05) 1 1(0.02) 0.4875
Mucocutaneous rash 1 1(0.32) 1 1(0.37) 2 2(0.34) 1.0000 - - - - - - -
Metabolism and
2 2(0.63) 0 0(0.00) 2 2(0.34) 0.5021 - - - - - - -
nutrition disorders
Decreased appetite 2 2(0.63) 0 0(0.00) 2 2(0.34) 0.5021 - - - - - - -
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12.5 Safety analysis in all age groups

Except of safety subgroup participants, all the participants spontaneously reported the adverse events during the study period, see below table for
the overview of safety analysis in all age groups in SS set.
Table 42 Difference of adverse events occurrence between participants receiving CoronaVac® and placebo in children and adolescents aged 6 months-17 years
6-35 months 3-5 years 6-11 years 12-17 years
Placebo Placebo Placebo Placebo
Vaccine group P-value Vaccine group P-value Vaccine group P-value Vaccine group P-value
Category group group group group
[1] [1] [1] [1]
(n=101) (n=102) (n=1433) (n=982) (n=2243) (n=1987) (n=2301) (n=2193)
Total AEs # 72(71.29) 65(63.73) 0.2948 778(54.29) 394(40.12) <0.0001 750(33.44) 589(29.64) 0.0089 525(22.82) 479(21.84) 0.4519
AEs within 28 days of each dose 56(55.45) 49(48.04) 0.3266 648(45.22) 323(32.89) <0.0001 554(24.70) 416(20.94) 0.0038 372(16.17) 310(14.14) 0.0613
AEs related to vaccine 35(34.65) 29(28.43) 0.3674 386(26.94) 159(16.19) <0.0001 339(15.11) 222(11.17) 0.0002 179(7.78) 143(6.52) 0.1054
Systemic AEs 34(33.66) 26(25.49) 0.2210 227(15.84) 99(10.08) <0.0001 200(8.92) 154(7.75) 0.1819 136(5.91) 111(5.06) 0.2143
Local AEs 9(8.91) 11(10.78) 0.8145 254(17.73) 92(9.37) <0.0001 212(9.45) 104(5.23) <0.0001 83(3.61) 51(2.33) 0.0138
Within 0~30 min 0(0.00) 1(0.98) 1.0000 93(6.49) 39(3.97) 0.0080 91(4.06) 50(2.52) 0.0059 24(1.04) 12(0.55) 0.0670
Within 0~7 days 35(34.65) 29(28.43) 0.3674 386(26.94) 159(16.19) <0.0001 339(15.11) 221(11.12) 0.0001 179(7.78) 142(6.48) 0.0931
Within 8~28days 0(0.00) 0(0.00) 1.0000 0(0.00) 0(0.00) 1.0000 0(0.00) 3(0.15) 0.1036 0(0.00) 3(0.14) 0.1161
Grade 1 AEs 29(28.71) 19(18.63) 0.1007 343(23.94) 138(14.05) <0.0001 301(13.42) 185(9.31) <0.0001 141(6.13) 105(4.79) 0.0493
Grade 2 AEs 14(13.86) 18(17.65) 0.5641 123(8.58) 40(4.07) <0.0001 69(3.08) 61(3.07) 1.0000 67(2.91) 58(2.64) 0.6502
Grade 3 AEs 1(0.99) 1(0.98) 1.0000 6(0.42) 0(0.00) 0.0874 5(0.22) 2(0.10) 0.4587 1(0.04) 2(0.09) 0.6161
Grade 4 AEs 0(0.00) 0(0.00) 1.0000 0(0.00) 0(0.00) 1.0000 0(0.00) 1(0.05) 0.4697 0(0.00) 0(0.00) 1.0000
First dose vaccination 26(25.74) 23(22.55) 0.6256 308(21.49) 129(13.14) <0.0001 257(11.47) 176(8.85) 0.0052 128(5.57) 104(4.73) 0.2248
Second dose vaccination 14(14.00) 14(13.86) 1.0000 174(12.58) 60(7.29) <0.0001 161(7.29) 92(4.68) 0.0004 81(3.55) 53(2.44) 0.0349
AEs unrelated to vaccine 33(32.67) 30(29.41) 0.6510 453(31.61) 234(23.83) <0.0001 315(14.04) 271(13.64) 0.7214 259(11.26) 210(9.58) 0.0709
AEs after 28 days of each dose 45(44.55) 36(35.29) 0.1986 404(28.19) 138(14.05) <0.0001 398(17.74) 325(16.36) 0.2356 283(12.30) 274(12.49) 0.8563
AEs related to vaccine 0(0.00) 0(0.00) 1.0000 0(0.00) 0(0.00) 1.0000 0(0.00) 0(0.00) 1.0000 0(0.00) 0(0.00) 1.0000
AEs unrelated to vaccine 45(44.55) 36(35.29) 0.1986 404(28.19) 138(14.05) <0.0001 398(17.74) 325(16.36) 0.2356 283(12.30) 274(12.49) 0.8563
[1] The P-value is calculated using Fisher's exact probability method.
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(2) Related to the vaccine means that the relationship between the adverse event and the research vaccine is "possibly related, likely related, and definitely related".
(3) Unrelated to the vaccine means that the relationship between the adverse event and the research vaccine is "may be unrelated, certainly unrelated".
(4) # SS (Safety Set) were used for the analysis, including all participants who receive at least 1 dose of vaccine or placebo, collected following the period from the first dose inoculation to
the time of this report generated.
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12.6 Serious Adverse Events in 6 months-17 years

As of August 31st, 2022, a total of 135 SAEs were reported in 120 children and adolescents aged 6
months-17 years (72 SAEs in vaccine group and 63 SAEs in placebo group). All the SAEs were
determined unrelated to vaccine.
Table 43 List of Serious Adverse Events after vaccination in children and adolescents 6 months-17 years
Vaccine group
Placebo group (N=5265) Total (N=11343)
(N=6078)
(%) (%) (%)
Total SAEs 72 63(1.04) 63 57(1.08) 135 120(1.06) 0.8542
Gastroenteritis 9 9(0.15) 6 6(0.11) 15 15(0.13) 0.7969
COVID-19 pneumonia 3 3(0.05) 9 9(0.17) 12 12(0.11) 0.0781
Pneumonia 6 6(0.10) 4 4(0.08) 10 10(0.09) 0.7601
Pneumonia viral 2 2(0.03) 3 3(0.06) 5 5(0.04) 0.6685
Urinary tract infection 1 1(0.02) 3 3(0.06) 4 4(0.04) 0.3431
Dengue fever 1 1(0.02) 2 2(0.04) 3 3(0.03) 0.6001
Otitis media 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
Tuberculosis 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
Appendicitis 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
COVID-19 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
1 1(0.02) 0 0(0.00) 1 1(0.01) 1
infection
Lower respiratory tract
1 1(0.02) 0 0(0.00) 1 1(0.01) 1
infection
Joint abscess 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Parasitic gastroenteritis 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Septic shock 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Diarrhoea infectious 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Tonsillitis 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Influenza 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Eczema herpeticum 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Meningitis viral 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Pneumonia bacterial 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Meningitis bacterial 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Bacterial sepsis 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Abscess limb 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Pulmonary tuberculosis 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Meningitis 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Impetigo 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Cellulitis 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
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Vaccine group
(N=6078)
(%) (%) (%)
Toxic shock syndrome
1 1(0.02) 0 0(0.00) 1 1(0.01) 1
streptococcal
Atypical pneumonia 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Injury, poisoning and
13 12(0.20) 5 5(0.09) 18 17(0.15) 0.2236
procedural complications
Upper limb fracture 3 2(0.03) 0 0(0.00) 3 2(0.02) 0.5025
Lower limb fracture 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
Animal bite 2 2(0.03) 0 0(0.00) 2 2(0.02) 0.5025
Skin laceration 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
Traumatic haemothorax 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Head injury 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Injury 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Foreign body in ear 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Arthropod sting 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Soft tissue injury 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Near drowning 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Scrotal injury 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Skull fractured base 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
7 6(0.10) 5 5(0.09) 12 11(0.10) 1
Asthma 3 3(0.05) 3 3(0.06) 6 6(0.05) 1
Wheezing 2 1(0.02) 1 1(0.02) 3 2(0.02) 1
Bronchospasm 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
Dyspnoea 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Seizure 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
Headache 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Guillain-Barre syndrome 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Fever convulsions 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Epilepsy 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Status epilepticus 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Retrograde amnesia 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
administration site 3 3(0.05) 5 4(0.08) 8 7(0.06) 0.7114
conditions
Fever 3 3(0.05) 4 3(0.06) 7 6(0.05) 1
Electrocution 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Faecaloma 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
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Vaccine group
(N=6078)
(%) (%) (%)
Enteritis 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Gastritis 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Blood and lymphatic
2 2(0.03) 1 1(0.02) 3 3(0.03) 1
system disorders
Lymphadenitis 1 1(0.02) 1 1(0.02) 2 2(0.02) 1
Lymphadenopathy 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
1 1(0.02) 0 0(0.00) 1 1(0.01) 1
disorders
Dehydration 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Pregnancy, puerperium
0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
and perinatal conditions
Pregnancy 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Reproductive system and
1 1(0.02) 0 0(0.00) 1 1(0.01) 1
breast disorders
Testicular torsion 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
1 1(0.02) 0 0(0.00) 1 1(0.01) 1
tissue disorders
Decubitus ulcer 1 1(0.02) 0 0(0.00) 1 1(0.01) 1
Psychiatric disorders 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Intentional self-injury 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Renal and urinary
0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
disorders
Glomerulonephritis acute 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
Neoplasms benign,
malignant and unspecified 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
(incl cysts and polyps)
Brain neoplasm 0 0(0.00) 1 1(0.02) 1 1(0.01) 0.4642
13 DISCUSSION AND OVERALL CONCLUSIONS
13.1 EFFICACY EVALUATION

In this report, efficacy analysis was conducted based on data from all 4 countries, taking March 10th,
2022 as the cut-off date of interim analysis and August 31st, 2022 as the cut-off date of long-term
analysis.
During the study period, the large vaccination campaign was launched in Chile for children aged 3-17
years due to the EUA approval of CoronaVac® in 2021. Hence, all the enrolled subjects in Chile have
been unblinded since 2nd December 2021 due to the requirements from ethical committee, and all the
participants I placebo have been vaccinated with 2 doses of CoronaVac®. Under this scenario, the data
of unblinded subjects were censored in efficacy analysis after unblinding.
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Results of interim efficacy analysis indicated that, the efficacy of CoronaVac® on moderate (VE
40.31%, with fever) or hospitalized cases (75.22%) was higher than that of against mild cases (17.23%).
The long-term efficacy analysis also showed the same trend, that the efficacy against hospitalization
was 84.19% and against severe cases was 100.00%, while the efficacy on confirmed COVID-19 cases
was 20.27%. Possible reasons for the relatively low efficacy against mild COVID-19 cases were listed
below.
Firstly, the efficacy analysis in this clinical trial was conducted under the COVID-19 pandemic. In all
countries of this trial, the COVID-19 pandemic increased after enrollment. In addition, new variant,
the Omicron emerged and became the dominated variant in all these countries since Dec 2021, which
made the efficacy evaluation more conservative. Based on the sequencing results obtained before
interim analysis (accounting for 71% of cases included in interim efficacy analysis), all of them are
Omicron variant. Thus, the results mainly showed the efficacy against Omicron variant in pediatric
population. In addition, studies in other COVID-19 vaccines, such as Moderna and Pfizer showed that
the efficacy against Omicron decreased rapidly as well.
Secondly, the majority of confirmed COVID-19 cases were with mild symptoms. Among 346
confirmed cases, 7 of them were hospitalized (2%), lower compared to the results in Brazil phase Ⅲ
clinical trial (6%) and in Turkey (14%), which could underestimate the vaccine efficacy.
Besides, our interim analysis results showed that vaccine efficacy was also affected by different
Omicron subtype (BA.1 and BA.2). A better efficacy against Omicron BA.1 (45.97%) than Omicron
BA.2 (18.48%) was observed, suggesting a cross protection of between prototype and Omicron BA.1.
About half of the subjects had previous SARS-CoV-2 exposure, and incidence density of COVID-19
in this population is much lower than that of population without previous exposure, indicating a
protection triggered by previous infection. The efficacy results indicated that receiving COVID-19
vaccine may not be able to provide additional protection based on the previous infection.
In terms of long-term efficacy evaluation, the protection of CoronaVac® against hospitalized or severe
COVID-19 case caused by Omicron was favorable, however, the protection of CoronaVac® against
mild COVID-19 case caused by Omicron was relatively low, and the same trend was also observed in
the interim analysis.
From the perspectives of public health and aim to reduce the burden of disease, if the usage of vaccine
could decrease the required medical intervention and incidence rate of severe cases, this could
obviously reduce the economic burden at national and individual level, leading significant social and
economic benefits.
13.2 IMMUNOGENICITY EVALUATION

This is our first study enrolled 6-35 months subjects and provided immunogenicity data for this
population. For this aged group subjects, a high seropositive rate was observed, 116 (65.91%)
participants were seropositive before vaccination, indicating a very high prevalence of COVID-19 in
South Africa for this population. 28 days after two doses of vaccination, the GMT of neutralizing
antibody in vaccine group and placebo group were 743.55 and 43.45, respectively. Stratified by
baseline neutralizing antibody (positive/negative), the GMT of neutralizing antibody in seronegative
subjects and seropositive subjects were 234.38 and 1138.79, respectively.
The immunogenicity results of the participants aged 3-17 years were similar with that of the 6-35
months, which had 62.62% seropositive participants at baseline. For seronegative participants at
baseline, 28 days after two doses of vaccination, the neutralizing antibody seroconversion rates in the
vaccine group and the placebo group were 100.00% and 19.30%, the GMT was 204.73 and 3.28, and
the GMI was 100.31 and 1.54, respectively. For seropositive participants at baseline, the
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seroconversion rates 28 days after two doses of vaccination in vaccine group and placebo group were
55.85% and 28.46%, the GMT were 507.48 and 218.03, and the GMI were 3.75 and 1.39, respectively.
These results indicated a high prevalence of COVID-19 before and during the clinical trial in this age
group.
Stratified analysis by the age group, the participants aged 12-17 years had the highest baseline
seropositive rates with 72.67% and 84.44% in the vaccine group and placebo group, respectively. In
the baseline seronegative participants, the children aged 3-5 years had the strongest immune response
compared to the other two age groups, 28 days after two doses of vaccination, the GMT were 330.71
(GMI 163.16) and 3.04 (GMI 1.38) in the vaccine group and placebo group, respectively. Among all
the age groups, participants with seropositive neutralizing antibody at baseline were all elicited a high
level of antibody after receiving 2 doses of vaccination. Thus, it can be suggested that investigational
vaccine has good immunogenicity in eliciting both priming immune response and anamnestic immune
response.
Stratified analysis by countries, the participants in South Africa and the Philippines had the most
significant seropositive rates at baseline (South Africa: vaccine group 78.79% and placebo group
77.55%, the Philippines: vaccine group 93.06% and placebo group 89.94%). In the baseline
seropositive participants, the seroconversion rates at 28 days after two doses of vaccination in vaccine
group and placebo group were 74.36% and 35.53% in South Africa, and 42.54% and 28.67% in the
Philippines, respectively. All these results indicated a very high prevalence of COVID-19 in these two
countries before and during the clinical trial.
13.3 SAFETY EVALUATION

This study also provided safety data in subjects aged 6-35 months for the very first time. The overall
incidence rate of ARs within 28 days of each vaccination was 31.68% (64/202), 34.65% in vaccine
group and 28.71% in placebo group, respectively, without significant difference. The most common
AR was fever, vaccination site pain, vaccination site swelling, vaccination site erythema and injection
site induration, without significant difference between the groups. Adverse reactions were mainly of
Grade 1, two Grade 3 and above adverse reactions was reported during study period. No SAE related
with vaccine was reported.
For the participants aged 3-17 years, the overall incidence rate of ARs within 28 days of each
vaccination, was 35.71% (vaccine group 39.34% vs. placebo group 27.46%, P=0.0001), 31.10%
(vaccine group 36.09% vs. placebo group 24.11%, P<0.0001) and 21.29% (vaccine group 22.71% vs.
placebo group 19.63%, P=0.4185) in the 3-5 years group, 6-11 years group and 12-17 years group,
respectively. In all the three age groups, the most common AR was vaccination site pain, and normally
followed by vaccination site erythema, fever, injection site induration and fatigue. The adverse
reactions were mainly of Grade 1. No SAE related with vaccine was reported.
The safety profile of the participants aged 6-35 months and 3-17 years was favorable, with or without
previous exposure to SARS-CoV-2.
13.4 CONCLUSION
In conclusion, this study showed satisfactory safety and immunogenicity of CoronaVac® in children
and adolescents aged 6 months to 17 years using a 0,28 days immunization schedule, regardless for
immune-naïve children or previously infected children. In terms of efficacy, the protection of
CoronaVac® against hospitalized COVID-19 case caused by Omicron was favorable, and the booster
immunization needs to be introduced to counter the emerging variants.
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14 TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN THE

TEXT
None.
15 REFERENCES
1. Gao Q, Bao L, Mao H, Wang L, Qin C. Rapid development of an inactivated vaccine candidate
for SARS-CoV-2. Science 2020: eabc1932.
2. Yanjun Zhang, Gang Zeng, Hongxing Pan, et al. Safety, tolerability, and immunogenicity of an
inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-
blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021 Feb;21(2):181-192.
3. Zhiwei Wu, Yaling Hu, Miao Xu, et al. Safety, tolerability, and immunogenicity of an
inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a
randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021
Feb 3;S1473-3099(20)30987-7. Online ahead of print.
4. Bihua Han, Yufei Song, Changgui Li, et al. Safety, Tolerability and Immunogenicity of an
Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Children and Adolescents: A
Randomised, Double-Blind, and Placebo-Controlled, Phase 1/2 Clinical Trial. Available at
SSRN: https://ssrn.com/abstract=3820545 or http://dx.doi.org/10.2139/ssrn.3820545.
5. Final Clinical Study Report of A Randomized, Double-blind, Placebo-controlled Phase Ⅲ
clinical trial to evaluate the efficacy and safety of the COVID-19 Vaccine (Vero Cell),
Inactivated developed and manufactured by Sinovac in healthcare professionals in Brazil, Feb
2021
6. Interim Clinical Study Report of A Phase III, Observer-blind, Randomized, Placebo-controlled
Study of the Efficacy, Safety and Immunogenicity of SARS-CoV-2 Inactivated Vaccine in
Healthy Adults Aged 18-59 Years in Indonesia, Jan 2021
7. Interim Clinical Study Report of Efficacy and Safety Evaluation of COVID-19 Vaccine (Vero
cell), Inactivated Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial in
Turkey, Dec 2020.
8. https://extranet.who.int/pqweb/vaccines/who-recommendation-sinovac-covid-19-vaccine-vero-
cell-inactivated-coronavac
9. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-
19/pfizer-biontech-covid-19-vaccine
16 ADDPENDICES
16.1 STUDY INFORMATION
16.1.1 Protocol and protocol amendments

See attachment 16.1.1.
16.1.2 Sample case report form

16.1.3 List of IECs or IRBs-Representative written information for patient and sample consent
forms
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16.1.4 List of description of investigators and other important participants in the study,
including brief CVs or equivalent summaries of training and experience relevant to the
performance of the clinical study
16.1.5 Signature of principal or coordinating investigator (s) or sponsor’s responsible medical

officer, depending on the regulatory authority’s requirement
16.1.6 Listing of patients receiving test drug(s)/investigational product(s) from specific batches,
where more than one batch was used
Not applicable.
16.1.7 Randomization scheme and codes (patient identification and treatment assigned)
Not applicable.
16.1.8 Audit certificates (if available)

Not applicable.
16.1.9 Documentation of statistical methods

16.1.10 Documentation of inter-laboratory standardisation methods and quality assurance

procedures if used
Not applicable.
16.1.11 Publication based on the study

Not applicable.
16.1.12 Important publications referenced in the report

Not applicable.
16.2 PATIENT DATA LISTINGS
16.2.1 Discontinued patients

16.2.2 Protocol deviations

16.2.3 Patients excluded from the efficacy analysis
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Not applicable.
16.2.4 Demographic data

16.2.5 Compliance and/or drug concentration data (if available)

Not applicable.
16.2.6 Individual efficacy response data

Not applicable.
16.2.7 Adverse events listings (each patient)

16.2.8 Listing of individual laboratory measurements by patient, when required by regulatory

authorities
Not applicable.
16.3 CASE REPORT FORMS
16.3.1 CRFs for deaths, other serious adverse events and withdrawals for AE
Not applicable.
16.3.2 Other CRFs submitted

Not applicable.
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Report of Phase Ⅲ Clinical Trial of Inactivated COVID-19 Vaccine in Children and Adolescents

Name of Sponsor/Company: (For National Authority Use Only)

Countries of Study Centers: South Africa, Malaysia, Philippines and Chile

Studied period (years):

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COVID-19 Vaccine Pre-filled

Placebo Aluminum hydroxide Pre-filled April 15th

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Date of report: February 2023

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3 TABLE OF CONTENTS FOR THE INDIVIDUAL CLINICAL STUDY REPORT

1 TITLE PAGE ...................................................................................................................... 1

14 TABLES, FIGURES AND GRAPHS REFERRED TO BUT NOT INCLUDED IN THE

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4 LIST OF ABBREVIATIONS AND DEFINITION OF TERMS

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5.1 INDEPENDENT ETHICS COMMITTEE (IEC) OR INSTITUTIONAL REVIEW BOARD

5.2 ETHICAL CONDUCT OF THE STUDY

5.3 PATIENT INFORMATION AND CONSENT

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clinical trial is formulated.

To evaluate the efficacy of two dose of Incidence of RT-PCR confirmed symptomatic

To evaluate the efficacy of two dose of Incidence of hospitalization/severeb/death

To evaluate the immunogenicity of CoronaVac® Analysis of SARS-CoV-2 neutralizing antibody

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To evaluate cell mediated immunity against Analysis of cytokine secreting SARS-CoV-2

9.1 OVERALL STUDY DESIGN AND PLAN DESCRIPTION

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Vaccine group 100 1900 2500 2500

9.2 DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF CONTROL

9.3 SELECTION OF STUDY POPULATION

9.3.1 Inclusion Criteria

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• Is not currently breastfeeding.

9.3.2 Exclusion Criteria

- Any confirmed or suspected human immunodeficiency virus (HIV) infection;

9.4.1 Treatments Administered

9.4.2 Identity of Investigational Product

9.4.2.1 Characteristics of the Investigational Vaccine

9.4.2.2 Stability of the Vaccine

9.4.2.3 Control Vaccine

9.4.2.4 Storage and Transportation of the Vaccine

9.4.2.5 Information on the Investigational Product

Investigational COVID-19 Vaccine (Vero Pre-filled Sinovac Life

Aluminum hydroxide Pre-filled Sinovac Life

9.4.3 Method of Assigning Patients to Treatment Groups

9.4.4 Selection of the Doses in the Study

9.4.5 Selection and Timing of Dose for each Patient

9.4.6 Blinding Method

9.4.6.1 Blinded Personnel

evaluations may review unblinded data from laboratory results.

9.4.6.3 Emergency Unblinding Procedure

9.4.7 Prior and Concomitant Treatment

9.4.7.1 Prior Treatment

9.4.7.2 Concomitant Treatment

9.4.8 Treatment Compliance

9.5 EFFICACY AND SAFETY VARIBLES

9.5.1 Efficacy and Safety Measurement Assessed and Flow Chart

9.5.1.1 Study Procedures Diagram

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