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Tigermed Group
www.tigermedgrp.com

V.2021.03
ARCoV-005 Endpoint case training
Protective Efficacy Follow-up
Protocol flow chart
Screening Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Visit 10 EOS
Treatment Treatment Follow-up Cross-vaccination End of study
Randomization

D-7 D0 D28 D42 6 months after 2nd dose

Endpoint case reporting

Weekly Protective Efficacy Follow-up Bi-Weekly Follow-up

Note:
• All participants will have efficacy follow-up weekly, subjects will be followed once a week from the first vaccination to at least 6
months after the second vaccination. The protective efficacy will be followed up biweekly from cross-vaccination (the third dose) to 6
months after the fourth dose by telephone and E-mail etc.
• The purpose of the follow-up is to ask if the participant has any symptoms related to COVID-19, regardless of severity.
• The visit window for Efficacy follow-up is varied from 5~30 days in different visits based on the flowchart.

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How to ask questions during weekly efficacy follow-up?
Self introduction
• Hello, this is XX from XX hospital. Thank you for participating in the Walvax COVID-19 vaccine clinical study. You are valuable to us
as part of the clinical trial conducted in this country. Your health is our main priority and we would want to follow up clos ely with
you to ensure you are doing well. If you experience any medicinal condition, please do not hesitate to reach out to us. We ha ve
well experienced doctors that are able to help you and take care of your concern.
Q1: Ask for COVID-19 symptoms
(a) Have you had any of the following discomfort since last contact?
⑴Fever (Oral temperature≥ 37.5℃/ ⑹Nasal obstruction/Rhinorrhea ⑾Headache
Axillary temperature≥37.3 ℃) ⑺Raw throat ⑿Shortness of breath or dyspnea
⑵Muscle pain ⑻Chills ⒀General weakness/ Fatigue
⑶Newly occurred parosmia/dysgeusia ⑼Diarrhea
⑷Mental status change ⑽Anorexia/ Nausea /Vomiting
⑸Cough

(b) Have you had any other discomfort since last contact? Have you been hospitalized since the last contact?
Q2: (a) Have you received a COVID-19 test since last contact? (b) What's the date and the result?
Q3: Has anyone around you been diagnosed with COVID-19 recently (especially in the past 28 days)?
Q4: Any updated for the AEs/SAEs reported previously?
Q5: Is there anything else I can help you? Have you been vaccinated with other COVID-19 vaccines since the last contact?
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Efficacy follow-up weekly routine process
Weekly Phone contact

Answered the phone Not answered the phone

• Re-contact via phone calls, text

The answers of Q1, Q2 and Q3 are all “no" Any answer of Q1, Q2 or Q3 is "yes" messages, or emails

• Documented in SD and EDC • Documented in SD and EDC

• Phone contact next week • Fill in Suspected case test tracker
• Important Subject Follow-up Process

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 Important subject efficacy follow-up process
If any answer of question 1, question 2 or question 3 is "yes", will comes to the "Important Subject Follow-up Process".
Q1: Q2: Q3:
Meets the criteria symptoms of
COVID-19 (refer to Appendix 1 of
Without any symptom of COVID-19 A symptomatic, without a PCR(+) result, but
protocol) but with a positive PCR test with COVID-19 contact history recently

• Ask the subject returning to site • Keep in touch, and track whether the subjects have symptoms
• Have a lab testing for SARS-CoV-2 in the follow-up
1) laboratory of study institution • If meets any of the signs or symptoms of COVID-19, go back to
2) central laboratory of local country Q1.
• Meet Q2: Keep in touch, and track whether the subjects have • If there is no symptom after 4 weeks of continuous follow up,
symptoms in the follow-up the routine follow-up procedure will be adopted.
✓ If the test result for SARS-
CoV-2 nucleic acid is
positive with laboratory of
study institution,
repeated sampling should PCR(+) PCR(-)
be performed and sent to
central laboratory for
testing and confirmation, At least 1 retest in 3 days after the prior testing day
which will be regarded as
the final result.
• Report the case to EAC mailbox

• FU subject based on the local requirements, or every 7-10 days until RT-PCR is negative(2 consecutive negative results taken at least 24 hours apart)
• Ask if any relatives and friends who entered the study at the same time also had discomfort or illness. If yes, contact as soon as possible.
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 Weekly/Biweekly Follow up---Worksheet V1.1 20Dec 2021
If COVID-19 status
Type: Has SAE status Has AESI status been
checked, is any Did participant take any
1 onsite been checked with checked with
Remote visit Has Covid-19 status symptoms? Please new medication in past week or
Date 2 phone call Completed by subject? (If any subject? (If any
after V1（D0） been checked with specify. And if take any medication to
completed 3 email (Name of staff) SAE, please AESI, please
(once a week) subject? confirmed an endpoint treat an SAE or AESI or
4 message complete a SAE complete a AESI
case, please report it receive any other vaccination?
5 other form per SOP) form per SOP)
ASAP.

□Yes, specify □No

□Fever
□cough
D7/W1 □Yes □No □Fatigue □Yes □No □Yes □No □Yes ,pls fill CM log □No
□Sputum production
□Shortness of breath
□other:
□Yes, specify □No
□Fever
□cough
D14/W2 □Yes □No □Fatigue □Yes □No □Yes □No □Yes ,pls fill CM log □No
□Sputum production
□Shortness of breath
□other:
□Yes, specify □No
□Fever
□cough
D21/W3 □Yes □No □Fatigue □Yes □No □Yes □No □Yes ,pls fill CM log □No
□Sputum production
□Shortness of breath
□other:

✓ Worksheet is source documents, please directly record the weekly efficacy follow up contents in
worksheet!
Telephone Contact Report

If the investigator should

follow up subject in addition
to weekly follow-up, please
use telephone contact report
of worksheet as source
documents
 Two and more COVID-19 related symptoms(the
Sample testing procedure symptoms other than fever and/or respiratory
tract symptoms persist for ≥48 hours)
Or One and more respiratory related
Suspected symptoms(persisting for any time)
COVID-19
PCR testing Or Clinical or imaging evidence
suggests pneumonia

Study Local central

institution lab lab
Collect two swab Collect one swab

PCR negative PCR positive PCR positive PCR negative

Repeat within Send swab B Confirmed Repeat within

Collect two swab 3 days to central lab case 3 days

PCR negative PCR positive PCR positive PCR negative

No more PCR Send swab B Confirmed No more PCR

testing to central lab case testing

Please send the “COVID-19 case data collection form” to EAC

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Suspected COVID-19 Case follow up Tracker
1) Routine weekly follow up- if Q1 or Q2 or Q3 is/are yes, please enter the below form, and escalation to
Important Subject Follow-up Process

Q1: collect Q2: have the PCR Q3: close contact

suspected testing with with COVID-19
COVID-19 positive result patients
symptoms
Suspected COVID-19 Case follow up Tracker
2) Focused subjects information collection

Focused following up
Contact
RT-PCR Next Action Any Other
Person -
RT-PCR Testing if column O is sampling Local lab National for the Close Contact
Sampling Name & Contact
scheduled?(Y/N No, please list method (In- testing reference Lab subject (use subjects with Comments
date Position of Date
) the reason home/In- result/date result/ date dropdown this subject in
Site
hospital) list) the study
Personnel
1) report
endpoint case;
2) repeat PCR
testing;
3) keep in
focused
subject follow
up;
4) return to
routine weekly
follow up;
Suspected COVID-19 Case follow up Tracker
3) Report

Suspected Endpoint case report

Endpoint Case Illness visit
Illness Visit
Email Report EDC Entry Report Person Comments
Date
Date Date

This tracker is designed for supporting site to manage suspected endpoint case subject.
Training on Endpoint Case Reporting
Lab testing workflow

COVID-19 related symptoms or Imaging

✓EDC Entry

✓ laboratory of study
institution SARS-CoV2 PCR test
✓ central laboratory of local
country

✓ If the test result for

SARS-CoV-2 nucleic
Negative
acid is positive,
*At least 1 retest repeated sampling
should be performed
Positive Positive and sent to central
laboratory for testing
and confirmation,
Repeat in 3 days after the which will be regarded
prior testing day as the final result.

Report to EAC

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 What kind of cases need to be submitted to EAC?
✓ SARS-CoV2 PCR test (+）no
matter the lab

Subjects with COVID-19 related

Death cases
symptoms and/or imaging + a
(Due to COVID-19)
positive PCR

Report to EAC

Note:
• Sites should report the endpoint cases within 24 hours after the cases are learned.
• PCR positive, regardless of time frame and testing lab.
• COVID-19 related symptoms are described in the study protocol, the duration matters as well.
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Reporting timing

Initial report

The investigator/study coordinator should send the documents to the EAC mailbox within 24 hours
once above cases are diagnosed/occurred.

Follow-up report

The investigator should monitor the subjects with COVID-19 closely.

If the condition deteriorates, a follow-up report is required to be submitted to EAC mailbox within 24
hours.

Supplementary documents
and reply to queries

The investigator/study coordinator should provide requested documents and reply the queries
around the case within 3 calendar days from the receipt of the request from Tigermed MM.

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 What documents need to be submitted to EAC?

01 Essential:
 PCR report
 COVID-19 Illness Visit Form (Initial Report )

02 Essential if done:
 Imaging report
 COVID-19 Illness Visit Form ((follow-up Report )

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Documents to be reported

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Documents to be reported
Document name Is it necessary Document type Transmission medium

COVID-19 Illness Visit Form- Initial Report Necessary

COVID-19 Illness Visit Form- Follow-up Report Necessary if the subjects have this report

Report of SARS-CoV-2 RT-PCR test Necessary

Report of imaging Necessary if the subjects have this report

Diary card If applicable

Redacted scanned copy of medical records If applicable Electronic document

Pertinent laboratory results If applicable (PDF format) Via E-mail

SAE report
If applicable
(if applicable）

Autopsy report If applicable

Others:
If applicable
______________

Note:
1. The participant identifier should be redacted, and the source document should be translated to English if it is in local lang uage in the first place. In addition, the following
information are considered necessary to be recorded in the source documents.
2. when a COVID-19 case meets the criteria of a SAE, a SAE report to the pharmacovigilance of Tigermed is needed. Meanwhile, this SAE report is required to submit to the EAC public
mailbox along with other documents mentioned above as well.
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Sample management for suspected/confirmed
Covid-19 cases

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Sample type
Suspected case during Surveillance
• Suspected case first and repeat visit: Pharyngeal swabs
For participants with suspicious symptoms reported proactively or verified by study staff.
And those with a negative result on their first test will have a second nucleic acid test within 3
days.
Confirmed case during Surveillance

• Confirmed case repeat visit : Pharyngeal swabs and Serum sample

After the last nucleic acid test shows positive results for confirmation COVID-19.
• Confirmed case recovery visit : Serum sample

After negative conversion of nucleic acid test.

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Kits used for samples
1. For serum sample —Confirmed case repeat and recovery visit

Test A Test B Tube Labels *5

Test C Back up
Cryogenic storage
Red cap blood collection Disposable pipette, box, 9*9, 3
tube, 10ml/vials *1 3ml/vials *1 Cryogenic storage tube, (centralized at country
2ml/vials *4 central lab)

2. For pharyngeal /nasopharyngeal swabs—For PCR test and confirmed case exploratory study
For one PCR test
Cryogenic storage box 7*7 , 1
IF for exploratory (storage or ship to reference lab)
study:
Swabs *1 Virus sampling tube is
Virus sampling tube, non-inactivated.
Medium color is Biohazard bag, 1
inactivated for PCR test Tube Labels *1
different. (sampling tube or box
3ml/vials *1 package when shipment)
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Sample Collection
1. Steps for Virus sample collection—PCR test and confirmed case exploratory study(NGS)

Nasopharyngeal swabs：
Nasopharyngeal
(Option 1, more preferred. If the first swab is a pharyngeal swab, swabs collection
position
a nasopharyngeal swab must be used for retesting)
• Insert the swab into the nasal cavity in the direction
Oropharyngeal
perpendicular to the nose (face) until the finger touches the swabs collection
tip of the nose (the depth of the swab should reach at least position
half the length from the earlobe to the tip of the nose).
• Leave the swab in the nose for seconds and gently rotate it
for 3-5 times.
• Quickly place the swab into the collection tube containing 3
mL of preservation solution. Oropharyngeal swabs: (Option 2)
• After insertion of the swab, break the sterile swab rod near • Use a sterile swab to smear the back wall and both sides of
the top, tighten the tubular cover and seal for testing. the tonsil using moderate force.
• Take out of the portions, and avoid touching the tongue and
Note: 2 swabs need to be taken for per subject per visit for PCR test. quickly immerse the test strip in the tube containing 3 ml
When the testing laboratory is a reference lab of the region/country, sampling liquid.
there will be no need to collect the second sample. Only 1 swab need • Discard the tail, tighten the tubular cover and seal for testing.
to be taken for exploratory study.
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Sample Collection
2. Steps for serum sample collection—Confirmed case (repeat and recovery visit)

x2
Put in different boxes

(Minimum 1h)

Tips: ✓ Totally collect 10ml blood and transfer the serum to 4 cryogenic vials for 1ml (the remaining serum go to the
backup tube and may be less than 1ml).

✓ For confirmed cases: 4 tubes go to 3 storage boxes Primary 1 and Primary 2 tubes go to the same storage box
while Primary 3 tube and the backup tube go to different storage boxes. (Waiting to be sent to the testing lab)

✓ Serum samples should be stored ideally in a -80 oC(+20/-10) freezer or -20 oC(±5) temporary storage.
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 Sample Shipment
1. Sample storage and shipment condition
Sample type Sample format Storage condition Shipment condition
-20 oC for 4 weeks Dry ice with temperature
Serum vials in boxes
-80 oC for long-term monitoring (-60 C to -90 oC)
o

2~8 oC for 24 h by default 2~8 oC, within 24 h by default

Pharyngeal swab for PCR -20 oC for 2 weeks For more than 24 h, dry ice with
Sampling tube
test temperature monitoring (-60 oC to
-80 oC for long-term -90 oC)
Nasopharyngeal or -20 oC for 2 weeks
opharyngeal swab for NGS Dry ice with temperature
Sampling tube
test (confirmed case) -80 oC for long-term monitoring (-60 oC to -90 oC)

For temporary storage of samples, set the freezer -20 oC and range ±5 oC. For long term storage, set the freezer -80 oC or -70 oC to ensure storage condition,
acceptable for temperature range from -90 oC to -60 oC, record temperature changes during storage and provide necessary report.
Tips:
• Storage time means the time from sample collection to sample testing, including shipment time (if any).
• If country’s central lab (for PCR test) completed the validation and has an SOP for longer storage at 2~8 oC like 48h or
72h, the lab should provide the related document and follow their SOP after approved. When -80 oC freezer is not
available, swab samples may be stored in a freezer -20 oC for 2 weeks. However, if the swab for NGS test could not
be put into -80 oC freezer within 24h, it should be put in -20 oC freezer after collection then be shipped to country’s
central lab within 2 weeks.
• Serum samples should be stored ideally at -80 oC but acceptable at -20 oC for max 4 weeks. Notify Country Project
Manager to arrange storage/shipping solution.
• Samples should always be shipped together with a copy of their corresponding Sample Record and shipping list Form.
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• The frequency of sample transportation is in accordance with the situation of Site. 27
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Tigermed Group
www.tigermedgrp.com

Headquarters
F18, Building A – Shengda Science Park
No.19 Jugong Road, Binjiang District, Hangzhou, China 310051
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