Clinical trial NCT04869982
Conditions: Herpes Zoster
Sponsor: GlaxoSmithKline
Start date: 2021-05-14; Completion date: 2023-04-20
Enrollment: 6138 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to assess vaccine efficacy (VE), ability to generate immune response and safety of two doses of the recombinant subunit zoster vaccine (RZV) for prevention of Herpes Zoster (HZ) in Chinese adults aged 50 years and older.

Detailed description:

Arms: arm 1: Participants randomized to the RZV Group were scheduled to receive two doses of RZV, one at Day 1 and one at Month 2. arm 2: Participants randomized to the Placebo Group were scheduled to receive two doses of placebo, one at Day 1 and one at Month 2.
Interventions: intervention 1: RZV intervention 2: Placebo
Intervention descriptions: intervention 1: 2 doses of RZV in 0, 2 months schedule, administered intramuscularly in the deltoid region of the non-dominant arm intervention 2: 2 doses of placebo in 0, 2 months schedule, administered intramuscularly in the deltoid region of the non-dominant arm

Protocol documents:
Prot_000.pdf: 
Protocol Amendment 2
Study ID:  212884 
Official Title of Study: A phase IV, randomized, observer-blind, placebo-controlled, 
multi-center study to assess the prophylactic efficacy against Herpes Zoster, 
immunogenicity and safety of Shingrix when administered intramuscularly on a 2-dose 
schedule in Chinese adults aged 50 years and older. 
NCT number: NCT04869982
Date of Document: 23 Nov 2020 


CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
1 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’institut 89, 
1330 Rixensart, Belgium
Primary Study vaccine 
and number 
GlaxoSmithKline Biologicals SA (GSK) lyophilized 
formulation of the Recombinant Zoster Vaccine (RZV) 
(GSK1437173A) 
Other Study vaccine 
Placebo (Lyophilized sucrose reconstituted with saline 
[NaCl] solution) 
eTrack study number 
and abbreviated title 
212884 (ZOSTER-076) 
Date of protocol 
Final: 26 February 2020 
Date of protocol 
amendment 
Amendment 1 Final: 23 April 2020 
Amendment 2 Final: 23 November 2020 
Short Title 
Efficacy, immunogenicity and safety study of GSK's 
Recombinant Zoster Vaccine Shingrix (GSK1437173A) in 
Chinese adults aged 50 years. 
Detailed title 
A phase IV, randomized, observer-blind, placebo-
controlled, multi-center study to assess the prophylactic 
efficacy against Herpes Zoster, immunogenicity and safety 
of Shingrix when administered intramuscularly on a 2-dose 
schedule in Chinese adults aged 50 years and older. 
Co-ordinating author 
(Amended, 23 
November 2020) 
 and 
 
(4Clinics for GSK), Scientific Writers 
Contributing authors 
(Amended, 23 
November 2020) 
•
, Clinical Research and Development
Lead
•
, Expert Statistician
•
, Lead Statistician
•
, Study Delivery Lead
•
 and 
, Safety
Evaluation & Risk Management (SERM) Safety
physicians
•
, deputy Qualified Person
for Pharmacovigilance (dQPPV) and 
,
Belgium
•
 and 
 Oversight
Data Manager
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CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
2 
eTrack study number 
and abbreviated title 
212884 (ZOSTER-076) 
Detailed title 
A phase IV, randomized, observer-blind, placebo-
controlled, multi-center study to assess the prophylactic 
efficacy against Herpes Zoster, immunogenicity and safety 
of Shingrix when administered intramuscularly on a 2-dose 
schedule in Chinese adults aged 50 years and older. 
Contributing authors 
(Cont.) (Amended, 23 
November 2020) 
•
 and 
, Global Regulatory
Affairs
•
 and 
Clinical Trial Supply Managers
•
 and 
, Global Patents
•
 and 
, Clinical
Laboratory Science Readout Team Leaders
•
 and 
, Clinical
Laboratory Science Study Managers
•
, 
,
China/Hong Kong
•
, Cluster Medical Lead
•
, Local Medical Lead, China
•
 and 
, Local Delivery Lead
•
 and 
, Clinical and
Epidemiology Project Lead (CEPL) for ZOSTER,
Clinical R&D.
GSK Protocol WS v 16.0.1 
©2020 GSK group of companies or its licensor. 
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CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
3 
Protocol Amendment 2 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
212884 (ZOSTER-076) 
Date of protocol amendment 
Amendment 2 Final: 23 November 2020 
Detailed Title  
A phase IV, randomized, observer-blind, placebo-
controlled, multi-center study to assess the 
prophylactic efficacy against Herpes Zoster, 
immunogenicity and safety of Shingrix when 
administered intramuscularly on a 2-dose schedule 
in Chinese adults aged 50 years and older. 
Sponsor signatory 
Jasur Danier,  
Clinical and Epidemiology Project Lead (CEPL) for 
ZOSTER, Clinical R&D 
Signature 
Date 


CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
4 
Protocol Amendment 2 Investigator Agreement 
I agree: 
•
To conduct the study in compliance with this protocol, any future protocol
amendments or protocol administrative changes, with the terms of the clinical trial
agreement and with any other study conduct procedures and/or study conduct
documents provided by GlaxoSmithKline Biologicals SA (GSK).
•
To assume responsibility for the proper conduct of the study at this site.
•
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all
applicable regulatory requirements.
•
To ensure that all persons assisting me with the study are adequately informed about
the GSK study vaccine and other study-related duties and functions as described in
the protocol.
•
To supervise any individual or party to whom I have delegated trial-related duties
and functions conducted at the trial site.
•
To ensure that any individual or party to whom I have delegated trial-related duties
and functions conducted at the trial site are qualified to perform those trial-related
duties and functions.
•
To acquire the reference ranges for laboratory tests performed locally and, if required
by local regulations, obtain the laboratory’s current certification or Quality
Assurance procedure manual.
•
To ensure that no clinical samples (including serum samples) are retained onsite or
elsewhere without the approval of GSK and the express written informed consent of
the subject and/or the subject’s legally acceptable representative.
•
To perform no other biological assays on the clinical samples except those described
in the protocol or its amendment(s).
•
To co-operate with a representative of GSK in the monitoring process of the study
and in resolution of queries about the data.
•
To have control of all essential documents and records generated under my
responsibility before, during, and after the trial.
•
That I have been informed that certain regulatory authorities require the sponsor to
obtain and supply, as necessary, details about the investigator’s ownership interest in
the sponsor or the investigational vaccine, and more generally about his/her financial
ties with the sponsor. GSK will use and disclose the information solely for the
purpose of complying with regulatory requirements.
Hence, I: 
•
Agree to supply GSK with any necessary information regarding ownership interest
and financial ties (including those of my spouse and dependent children).
•
Agree to promptly update this information if any relevant changes occur during the
course of the study and for 1 year following completion of the study.
•
Agree that GSK may disclose any information about such ownership interests and
financial ties to regulatory authorities.
•
Agree to provide GSK with an updated Curriculum Vitae and other documents
required by regulatory agencies for this study.


CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
5 
eTrack study number and 
Abbreviated Title 
212884 (ZOSTER-076) 
Date of protocol amendment 
Amendment 2 Final: 23 November 2020 
Detailed Title 
A phase IV, randomized, observer-blind, placebo-
controlled, multi-center study to assess the 
prophylactic efficacy against Herpes Zoster, 
immunogenicity and safety of Shingrix when 
administered intramuscularly on a 2-dose schedule 
in Chinese adults aged 50 years and older. 
Investigator name 
Signature 
Date 


CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
6 
SPONSOR INFORMATION 
1.
Sponsor
GlaxoSmithKline Biologicals SA 
Rue de l’Institut 89, 1330 Rixensart, Belgium 
2.
Sponsor Medical Expert for the Study
Refer to the local study contact information document. 
3.
Sponsor Study Monitor
Refer to the local study contact information document. 
4.
Sponsor Study Contact for Reporting of a Serious Adverse Event
GSK Central Back-up Study Contact for Reporting SAEs: refer to protocol Section 
12.5.9.3  
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
5.
GSK Contact information for Emergency Unblinding
GSK helpdesk contact: refer to Table 13. 


CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
7 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Table 1 
Document history 
Document 
Date 
Amendment 2 
23-NOV-2020
Amendment 1 
23-APR-2020
Final Protocol 
26-FEB-2020
Amendment 2 (23-NOV-2020) 
Overall Rationale for the Amendment: 
Based on feedback of the Center for Drug Evaluation (CDE) in China, interim analysis 
that was originally planned to support license renewal will not be performed. 
Additionally, wording regarding a secondary endpoint of potential immune-medicated 
diseases (pIMDs) prior or planned concomitant administration of corticosteroids, and 
pregnancy reporting was clarified and/or corrected. Study procedures for special 
circumstances were updated. The definition of the Enrolled Set was modified. Minor 
edits were made for clarity and consistency (see Section 12.8). 
Table 2 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Section 10.3.6 (Interim 
analyses); Section 10.4 
(Sequence of analyses) 
No interim analyses will be 
performed. Information regarding 
the requirement for an interim 
report of demography and safety 
for license renewal requirements 
has been removed. 
Based on feedback of the Center 
for Drug Evaluation (CDE), an 
interim analysis will not be 
performed. 
Section 6.2.2 (Prior/Concomitant 
therapy); Section 7.5.2 
(Concomitant 
medications/products/vaccines 
that may lead to the elimination 
of a subject from analyses) 
Correction of the corticosteroids 
dose, considered an exclusion 
criterion for study participation 
when administered or planned to 
be administered during the 
period starting 3 months prior to 
the first vaccine, and possibly 
determining a subject’s 
evaluability in the per-protocol 
analysis when administered 
during the study. It is detailed 
that prednisone 20 mg/day, or 
equivalent, is not allowed 
(previously stated that 
prednisone 5 mg/day, or 
equivalent, is allowed). 
A correction was made in 
alignment with the dose detailed 
in GSK’s current document 
standard. 


CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
8 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4, Table 5 (Study 
objectives and endpoints); 
Section 3.3.1 (Risk assessment); 
Section 8.5.2 Table 19 
(Reporting periods for collecting 
safety information); Section 
10.3.5 (Safety analyses); Section 
12.5.8.1 (Time period for 
detecting and recording adverse 
events, serious adverse events 
and pregnancies); Section 
12.5.9.5 (Reporting of pIMD to 
GSK) 
 
Modification of a secondary 
endpoint: occurrence of related# 
serious pIMDs after 12 months 
post last vaccination up to study 
end (instead of occurrence of all 
pIMDs from Day 1 to study end). 
Clarification that all pIMDs are to 
be reported up to 12 months 
post last vaccination. Beyond 
this time period, only related 
serious adverse events (SAEs) 
(including related serious pIMDs 
as per investigator assessment) 
are to be reported. 
A modification was made to 
clarify that only related serious 
pIMDs, are to be reported 
beyond 12 months post last 
vaccination. 
Section 2, Table 3 (Schedule of 
Activities); Section 8.5.2, Table 
19 (Reporting periods for 
collecting safety information); 
Section 8.5.4 Table 20 
(Timeframes for submitting 
serious adverse event, 
pregnancy and other events 
reports to GSK); Section 8.5.4.1, 
Table 21 (Contact information for 
reporting of serious adverse 
events (SAEs), pIMDs and 
pregnancies); Section 12.5.8.1 
(Time period for detecting and 
recording adverse events, 
serious adverse events and 
pregnancies)  
Note on pregnancy reporting:  
Pregnancies are to be reported 
and timing of exposure to the 
study treatment (i.e., RZV or 
placebo) is considered. 
Previously only exposure to 
Shingrix was detailed in the note. 
A note on reporting of 
pregnancies was corrected, 
because applicable in case of 
vaccination with either RZV or 
placebo.  
Section 8.4 (Study procedures 
during special circumstances) 
Clarification that COVID-19 
cases identified during the study 
(as per standard of care) will be 
captured and reported using 
standard AE, medically-attended 
AE or SAE criteria, and should 
be reported in the eCRF 
according to the World Health 
Organization (WHO) Case 
Definition.  
Study procedures for special 
circumstances were updated to 
clarify the recording in the eCRF 
of information on COVID-19 
cases. 
Section 10.2 (Populations for 
analyses); Section 10.3.1 
(Subjects disposition) 
The definition of the Enrolled Set 
was modified to include eligible 
subjects who have signed an 
informed consent and were 
randomized or undergone an 
invasive procedure; a 
Randomized Set will not be 
applicable for analyses. 
A modification was made to 
better define the subject 
disposition and the cohorts for 
statistical analyses.  
# In the protocol, AEs causally related to the study vaccine as per investigator agreement are also 
referred to as ‘related AEs’. 


CONFIDENTIAL 
212884 (ZOSTER-076) 
Protocol Amendment 2 Final 
23 November 2020 
9 
TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
1.
SYNOPSIS ............................................................................................................. 16 
2.
SCHEDULE OF ACTIVITIES (SOA) ....................................................................... 16 
3.
INTRODUCTION .................................................................................................... 21 
3.1. 
Study rationale ............................................................................................ 21 
3.2. 
Background (Amended, 23 November 2020) .............................................. 22 
3.3. 
Benefit/Risk assessment ............................................................................. 22 
3.3.1. 
Risk assessment (Amended, 23 November 2020) ....................... 23 
3.3.2. 
Benefit assessment ..................................................................... 25 
3.3.3. 
Overall Benefit: Risk conclusion ................................................... 25 
4.
OBJECTIVES AND ENDPOINTS ........................................................................... 25 
5.
STUDY DESIGN .................................................................................................... 26 
5.1. 
Scientific rationale for study design ............................................................. 26 
5.2. 
Overall design (Amended, 23 November 2020) .......................................... 27 
5.3. 
Number of subjects (Amended, 23 November 2020)................................... 29 
5.4. 
Subject and study completion ..................................................................... 30 
6.
STUDY POPULATION ........................................................................................... 30 
6.1. 
Inclusion criteria for enrolment .................................................................... 30 
6.2. 
Exclusion criteria for enrolment ................................................................... 31 
6.2.1. 
Medical conditions ....................................................................... 31 
6.2.2. 
Prior/Concomitant therapy (Amended, 23 November 2020) ......... 31 
6.2.3. 
Prior/Concurrent clinical study experience ................................... 32 
6.2.4. 
Other exclusions .......................................................................... 32 
6.3. 
Criteria for temporary delay for enrolment and vaccination ......................... 32 
7.
TREATMENTS ....................................................................................................... 32 
7.1. 
Treatments administered ............................................................................ 33 
7.2. 
Method of treatment assignment ................................................................. 34 
7.2.1. 
Subject identification .................................................................... 34 
7.2.2. 
Randomization of treatment ......................................................... 34 
7.2.2.1. 
Randomization of supplies .......................................... 34 
7.2.2.2. 
Treatment allocation to the subject ............................. 34 
7.2.2.2.1. 
Study group and treatment 
number allocation ................................... 34 
7.2.2.2.2. 
Treatment number allocation for 
subsequent dose .................................... 35 
7.2.3. 
Allocation of subjects to assay subsets (Amended, 23 
November 2020) .......................................................................... 35 
7.3. 
Blinding and unblinding ............................................................................... 36 
7.3.1. 
Emergency unblinding ................................................................. 36 
7.4. 
Handling, storage and replacement of study vaccine .................................. 37 
7.4.1. 
Storage and handling of study vaccine ........................................ 37 
7.4.2. 
Replacement of unusable vaccine doses ..................................... 37 
7.5. 
Concomitant medication(s)/product(s) and concomitant vaccinations ......... 37 


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7.5.1. 
Recording of concomitant medications/products and 
concomitant vaccinations ............................................................. 37 
7.5.2. 
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from analyses (Amended, 
23 November 2020) ..................................................................... 38 
7.6. 
Intercurrent medical conditions that may lead to elimination of a 
subject from analyses ................................................................................. 39 
7.7. 
Contraindications to subsequent vaccine administration ............................. 40 
7.8. 
Warnings and precautions .......................................................................... 40 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 40 
8.1. 
General study aspects ................................................................................ 41 
8.1.1. 
Data Collection ............................................................................ 41 
8.1.2. 
Monthly contacts .......................................................................... 42 
8.2. 
Pre-vaccination procedures ........................................................................ 42 
8.2.1. 
Informed Consent ........................................................................ 42 
8.2.2. 
Collection of demographic data .................................................... 42 
8.2.3. 
Medical and vaccination history ................................................... 42 
8.2.4. 
History directed physical examination .......................................... 42 
8.2.5. 
Pregnancy test ............................................................................. 43 
8.2.6. 
Check contraindications, warnings and precautions to 
vaccination ................................................................................... 43 
8.2.7. 
Pre-vaccination body temperature ............................................... 43 
8.2.8. 
Record any concomitant medications/vaccinations and 
any intercurrent medical conditions .............................................. 43 
8.3. 
Efficacy assessments ................................................................................. 43 
8.3.1. 
Case Definitions ........................................................................... 43 
8.3.1.1. 
Suspected Herpes Zoster ........................................... 43 
8.3.1.2. 
Confirmed HZ ............................................................. 44 
8.3.2. 
Evaluation of suspected HZ cases ............................................... 45 
8.3.3. 
Follow up of suspected HZ cases (Amended, 23 
November 2020) .......................................................................... 46 
8.3.4. 
Use of specified study materials .................................................. 46 
8.3.5. 
Biological samples (Amended, 23 November 2020) ..................... 47 
8.3.6. 
Laboratory assays ....................................................................... 48 
8.3.6.1. 
Herpes Zoster lesion samples (Amended, 23 
November 2020) ......................................................... 48 
8.3.7. 
Biological Sample Evaluation ....................................................... 49 
8.3.8. 
Immunological correlates of protection ......................................... 49 
8.4. 
Study procedures during special circumstances (Amended, 23 
November 2020) ......................................................................................... 49 
8.5. 
Safety Assessments ................................................................................... 51 
8.5.1. 
Safety definitions ......................................................................... 51 
8.5.2. 
Time period and frequency for collecting AE and serious 
adverse event (SAE) information ................................................. 52 
8.5.3. 
Method of detecting AEs and SAEs ............................................. 53 
8.5.4. 
Reporting of serious adverse events, pregnancies, and 
other events ................................................................................. 53 
8.5.4.1. 
Contact information for reporting of SAEs, 
pIMDs and pregnancies .............................................. 54 
8.5.4.2. 
Regulatory reporting requirements for SAEs............... 54 
8.5.5. 
Follow-up of AEs, SAEs, pIMDs and pregnancies ........................ 54 


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8.5.6. 
Treatment of adverse events ....................................................... 55 
8.5.7. 
Subject card ................................................................................. 55 
8.6. 
Genetic Research (Pharmacogenetics)....................................................... 55 
9. 
DISCONTINUATION CRITERIA ............................................................................. 55 
9.1. 
Discontinuation from the study .................................................................... 55 
9.2. 
Discontinuation of study vaccine ................................................................. 56 
9.3. 
Lost to follow-up .......................................................................................... 57 
10. STATISTICAL CONSIDERATIONS ........................................................................ 57 
10.1. 
Sample size determination .......................................................................... 57 
10.1.1. 
Hypotheses related to primary and secondary objectives ............ 57 
10.1.2. 
Sample size calculation ............................................................... 58 
10.1.3. 
10.2. 
Populations for analyses (Amended, 23 November 2020) .......................... 59 
10.3. 
Statistical analyses ..................................................................................... 59 
10.3.1. 
Subjects disposition (Amended, 23 November 2020) ................... 59 
10.3.2. 
Demography and baseline characteristics analyses ..................... 59 
10.3.3. 
Efficacy analyses ......................................................................... 60 
10.3.3.1. Case accountability (Amended, 23 November 
2020) .......................................................................... 60 
10.3.4. 
 
10.3.5. 
Safety analyses (Amended, 23 November 2020) ......................... 62 
10.3.6. 
Interim analyses (Amended, 23 November 2020) ........................ 63 
10.4. 
Sequence of analyses (Amended, 23 November 2020) .............................. 63 
11. REFERENCES ....................................................................................................... 64 
12. APPENDICES ........................................................................................................ 66 
12.1. 
Appendix 1: Abbreviations, glossary of terms and trademarks .................... 66 
12.1.1. 
List of abbreviations ..................................................................... 66 
12.1.2. 
Glossary of terms ......................................................................... 69 
12.1.3. 
Trademarks ................................................................................. 73 
12.2. 
Appendix 2: Clinical laboratory tests ........................................................... 73 
12.3. 
Appendix 3: Clinical laboratories ................................................................. 76 
12.4. 
Appendix 4: Study governance considerations............................................ 77 
12.4.1. 
Regulatory and ethical considerations ......................................... 77 
12.4.2. 
Financial disclosure ..................................................................... 77 
12.4.3. 
Informed consent process ............................................................ 78 
12.4.4. 
Data protection ............................................................................ 78 
12.4.5. 
Publication policy ......................................................................... 78 
12.4.6. 
Dissemination of clinical study data ............................................. 79 
12.4.7. 
Data quality assurance ................................................................ 79 
12.4.8. 
Source documents ....................................................................... 80 
12.4.9. 
Study and site closure .................................................................. 80 
12.5. 
Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 81 
12.5.1. 
Definition of AE ............................................................................ 81 
12.5.1.1. AE Definition ............................................................... 81 
12.5.1.2. Events Meeting the AE Definition ............................... 81 
12.5.1.3. Events NOT Meeting the AE Definition ....................... 82 
12.5.2. 
Definition of SAE .......................................................................... 82 
CCI
CCI


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12.5.3. 
Solicited adverse events .............................................................. 84 
12.5.4. 
Unsolicited adverse events .......................................................... 85 
12.5.5. 
Adverse events of special interest (AESIs) .................................. 86 
12.5.5.1. Potential immune-mediated diseases ......................... 86 
12.5.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................ 90 
12.5.7. 
Events or outcomes not qualifying as adverse events or 
serious adverse events ................................................................ 90 
12.5.7.1. Pregnancy .................................................................. 90 
12.5.8. 
Detecting and recording adverse events, serious adverse 
events and pregnancies ............................................................... 91 
12.5.8.1. Time period for detecting and recording 
adverse events, serious adverse events and 
pregnancies (Amended, 23 November 2020) ............. 92 
12.5.8.2. Evaluation of adverse events and serious 
adverse events ........................................................... 93 
12.5.8.2.1. Active questioning to detect 
adverse events and serious 
adverse events ....................................... 93 
12.5.8.2.2. Assessment of adverse events ............... 93 
12.5.8.2.3. Medically attended visits ......................... 97 
12.5.9. 
Reporting of serious adverse events, pregnancies, and 
other events ................................................................................. 98 
12.5.9.1. Prompt reporting of serious adverse events, 
pregnancies, and other events to GSK ....................... 98 
12.5.9.2. SAEs requiring expedited reporting to GSK ................ 98 
12.5.9.3. Back-up system in case the electronic reporting 
system does not work ................................................. 98 
12.5.9.4. Completion and transmission of pregnancy 
reports to GSK ............................................................ 99 
12.5.9.5. Reporting of pIMD to GSK (Amended, 23 
November 2020) ......................................................... 99 
12.5.10. Updating of SAE, pregnancy, and pIMD information after 
removal of write access to the subject’s eCRF ............................. 99 
12.5.11. Follow-up of adverse events, serious adverse events, 
pIMDs and pregnancies ............................................................. 100 
12.5.11.1. Follow-up during the study ........................................ 100 
12.5.11.2. Follow-up after the subject is discharged from 
the study ................................................................... 100 
12.5.11.3. Follow-up of pregnancies .......................................... 100 
12.6. 
Appendix 6: Contraceptive guidance and collection of pregnancy 
information ................................................................................................ 101 
12.6.1. 
Definitions .................................................................................. 101 
12.6.1.1. Woman of Childbearing Potential (WOCBP) ............. 101 
12.6.1.1.1. Women in the following categories 
are not considered WOCBP .................. 101 
12.6.2. 
Contraception guidance ............................................................. 101 
12.6.3. 
Collection of pregnancy information ........................................... 103 
12.6.3.1. Female Subjects who become pregnant ................... 103 
12.7. 
Appendix 7: Country-specific requirements ............................................... 103 
12.8. 
Appendix 8: Protocol Amendment History ................................................. 104 


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212884 (ZOSTER-076) 
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13 
LIST OF TABLES 
PAGE 
Table 1 
Document history ..................................................................................... 7 
Table 2 
List of main changes in the protocol and their rationale ............................ 7 
Table 3 
Schedule of Activities (Amended, 23 November 2020) ........................... 17 
Table 4 
Study procedures to be performed during the follow-up period for 
each suspected HZ case ........................................................................ 19 
Table 5 
Intervals between study visits (Amended, 23 November 2020) .............. 20 
Table 6 
Intervals between visits/contacts for subjects in case of 
suspected HZ ......................................................................................... 20 
Table 7 
Study objectives and endpoints (Amended, 23 November 2020) ........... 25 
Table 8 
Study groups, treatment and epochs foreseen in the study .................... 28 
Table 9 
Study groups and treatment foreseen in the study ................................. 28 
Table 10 
Blinding of study epochs ........................................................................ 29 
Table 11 
Treatments administered ........................................................................ 33 
Table 12 
Number of subjects required for enrolment ............................................. 35 
Table 13 
Contact information for emergency unblinding ....................................... 36 
Table 14 
Biological samples ................................................................................. 47 
Table 16 
Molecular Biology ................................................................................... 48 
Table 17 
Immunological read—outs ...................................................................... 49 
Table 18 
Intervals between study visits during special circumstances 
(Amended, 23 November 2020) ............................................................. 50 
Table 19 
Reporting periods for collecting safety information (Amended, 23 
November 2020) .................................................................................... 52 
Table 20 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK (Amended, 23 November 2020) ................. 53 
Table 21 
Contact information for reporting of serious adverse events 
(SAEs), pIMDs and pregnancies (Amended, 23 November 2020) .......... 54 
Table 22 
Sample size and expected number of cases in ZOSTER-076 ................ 58 
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Table 23 
Solicited local adverse events ................................................................ 84 
Table 24 
Solicited general adverse events ............................................................ 85 
Table 25 
List of potential immune-mediated diseases (pIMDs) ............................. 87 
Table 26 
Intensity scales for solicited symptoms in adults ..................................... 94 
Table 27 
Highly Effective Contraceptive Methods ............................................... 102 
 


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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview (Amended, 23 November 2020) ......................... 27 
Figure 2 
Algorithm for HZ case definition by GSK PCR ........................................ 76 
 


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1. 
SYNOPSIS 
Indication:  
Shingrix is indicated in China for the prevention of Herpes Zoster (HZ) in adults 50 years 
of age (YOA) or older. 
Rationale: 
As per requirement of Chinese regulatory authorities, ZOSTER-076 will evaluate the 
vaccine efficacy (VE), cellular immunogenicity and safety of 2 doses of 
GlaxoSmithKline Biologicals SA’s [GSK’s] Recombinant Zoster Vaccine (RZV) vaccine 
for the prevention of HZ in Chinese adults ≥ 50 YOA. 
Objectives and Endpoints:  
Refer to Table 7. 
Overall Design (Amended, 23 November 2020): 
 
BS= Blood sampling; N= number of subjects planned to be enrolled; Vacc= Vaccination 
Note: 
  
‡ All subjects will be followed-up until last enrolled subject has completed 1 year of follow-up post last vaccination. In 
case criteria for vaccine efficacy analyses are not met during this period, the follow-up will be extended. 
2. 
SCHEDULE OF ACTIVITIES (SOA) 
Table 3 outlines study procedures and Table 4 presents procedures to be performed for 
each suspected HZ case. 
RZV Group (N=3069)
Randomization (1:1)
Visit 1
Day 1
Vacc 1
BS
Visit 2
Month 2
Vacc 2
Visit 3
Month 3
BS
Monthly Contact Until 
Study End ‡
Epoch 001 (Vaccination phase)
Epoch 002 (Follow-up phase)
Placebo Group (N=3069)
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Table 3 
Schedule of Activities (Amended, 23 November 2020) 
Epoch 
Primary (Epoch 001)  
Long-term follow-up 
(Epoch-002) 
Notes 
Type of contact 
Visit 1 
Visit 2  
Visit 3  
Monthly Contacts† 
 
Timepoints 
Day 1 
Month 2 
Month 3 
Month 4 to Study End * 
 
Sampling Timepoints 
Pre-Vacc 
 
Post-Vacc 
 
 
Informed consent 
● 
 
 
 
See Section 12.4.3  
Check inclusion/exclusion criteria 
● 
 
 
 
See Sections 6.1 and 6.2 for Inclusion and Exclusion criteria 
Record demographic data 
● 
 
 
 
Refer to Section 8.2.2  
Record medical and vaccination history 
● 
 
 
 
Refer to Section 8.2.3  
History directed physical examination 
O 
O 
 
 
Refer to Section 8.2.4  
Pregnancy test (If applicable) 
● 
● 
 
 
Refer to Section 8.2.5 
Check contraindications to vaccination 
O 
O 
 
 
Refer to Sections 7.7 and 7.8 
Pre-vaccination body temperature 
● 
● 
 
 
Refer to Section 8.2.7  
Study group and treatment number allocation 
O 
 
 
 
Refer to Section 7.2.2.2.1 
Treatment number allocation for subsequent dose 
 
O 
 
 
Refer to Section 7.2.2.2.2 
Record administered treatment number 
● 
● 
 
 
Refer to Section 7.2.2 
Vaccine administration 
● 
● 
 
 
Refer to Section 7.1 for more information  
Any subject with a clinically diagnosed suspected HZ episode 
between Visit 1 (Day 1) and Visit 2 (Month 2) is not to receive 
the second dose (See Section 7.7 for details). 
Post-vaccination observation (30 mins) 
O 
O 
 
 
 
Distribute diary cards and train subjects on 
completion of diary cards 
O 
O 
 
 
Diary card will be provided to record solicited local and 
general AEs, unsolicited AEs and concomitant medication 
after each vaccination. 
Additional HZ-specific diary card will be provided to all 
subjects 
Train subjects on signs/symptoms of HZ 
O 
O 
O 
O 
 
Recording solicited AEs (Days 1–7) post-vaccination 
by subjects on diary cards 
O 
O 
 
 
Refer to Section 12.5.8 
Recording unsolicited AEs including cellulitis (Days 1-
30) post-vaccination by subjects on diary cards 
O 
O 
 
 
Refer to Section 12.5.8 
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Epoch 
Primary (Epoch 001)  
Long-term follow-up 
(Epoch-002) 
Notes 
Type of contact 
Visit 1 
Visit 2  
Visit 3  
Monthly Contacts† 
 
Timepoints 
Day 1 
Month 2 
Month 3 
Month 4 to Study End * 
 
Sampling Timepoints 
Pre-Vacc 
 
Post-Vacc 
 
 
Record medically attended visits (Days1-30) post 
vaccination  
● 
● 
 
 
 
Return Diary card 
 
O 
O 
 
 
Diary card transcription 
 
● 
● 
 
 
Record and follow-up of HZ cases 
● 
● 
● 
● 
Refer to Section 8.3.3 
Record any concomitant medications/vaccinations 
● 
● 
● 
● 
Refer to Section 7.5  
Record intercurrent medical conditions 
● 
● 
● 
● 
Refer to Section 7.6 
Record SAEs, pIMDs and pregnancies 
● 
● 
● 
● 
Refer to Section 12.5.8 
Record SAEs related to study participation, or to a 
concurrent GlaxoSmithKline medication/vaccine 
● 
● 
● 
● 
 
Record AE/SAEs leading to withdrawal 
● 
● 
● 
● 
 
Study Conclusion 
 
 
 
● 
Refer to Section 5.4  
AE: Adverse Event; 
; HZ: Herpes Zoster; pIMD: potential Immune Mediated Disease; SAE: Serious Adverse Event; 
● is used to indicate a study procedure that requires documentation in the individual eCRF 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
†The duration of the study will vary for each subject. Study conclusion will be scheduled based on the projected date of the last contact of the last enrolled subject, that is 14 months 
(approximately 430 days) from the enrolment date. In case criteria for vaccine efficacy analyses are not met during this period, the follow-up will be extended. The study conclusion 
visit/ contact for subjects with an ongoing episode of HZ will occur after the resolution of the rash OR when Day HZ-29 follow-up has been completed. The investigator is to record all 
ongoing HZ-associated symptoms in the eCRF. 
 This applies to pregnancy cases with exposure to the study treatment at any age of gestation. The timing of exposure to the study treatment during pregnancy is estimated in 
relation to the first day of the last menstrual period, ultrasound or known date of fertilization (e.g., assisted reproductive technology). 
*All subjects will be followed-up until last enrolled subject has completed 1 year of follow-up post last vaccination. In case criteria for vaccine efficacy analyses are not met during this 
period, the follow-up will be extended.  
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Table 4 
Study procedures to be performed during the follow-up period for each suspected HZ case 
Type of contact 
Visit HZ-1 
Visit HZ-2 
Contact HZ-3 
Contact HZ-4 
Visit HZ-5 
Timepoints 
Day HZ-1 
Day HZ-8 
Day HZ-15 
Day HZ-22 
Day HZ-29** 
Perform targeted clinical examination 
O 
 
 
 
 
Return HZ-specific diary cards to study staff/investigator 
O 
 
 
 
 
Perform the checks below in the event of clinically diagnosed suspected HZ cases only 
Transcription of the HZ-specific diary card by study staff/investigator 
● 
 
 
 
 
Take digital photographs of HZ rash 
● 
 
 
 
 
Collect HZ lesion samples (3 replicate samples) for confirmation by PCR* 
● 
 
 
 
 
Record relevant information regarding HZ in eCRF 
● 
● 
● 
● 
● 
Record concomitant medication/vaccination  
● 
● 
● 
● 
● 
Record any other intercurrent medical conditions 
● 
● 
● 
● 
● 
Record any medical attention received for HZ 
● 
● 
● 
● 
● 
eCRF = electronic Case Report Form; HZ = Herpes Zoster; PCR = Polymerase Chain Reaction 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
 Additional photographs of HZ lesions may be taken after Visit HZ-1 to help note the progression of the rash. 
* If during clinical evaluation at Visit HZ-1, the investigator determines that adequate rash samples are not present (that is <3 lesions present or only papules), the investigator has the 
option of collecting 3 additional samples prior to or at Visit HZ-2 (preferably within 7 days).  
** If the HZ rash has not resolved by Day HZ-29, the subject will be seen weekly until the rash resolves. At the time of LSLV, if a subject has an ongoing HZ case, they will be followed 
up till Day HZ-29.  


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The investigator should arrange study visits within the intervals described in Table 5. 
Table 5 
Intervals between study visits (Amended, 23 November 2020) 
Interval 
Optimal length of interval 
Allowed interval  
Visit 1 → Visit 2 
60 days (2 months) 
49 days - 83 days#  
Visit 2 → Visit 3 
30 days (1 month) 
28 days- 48 days# 
Between Monthly Contacts* 
30 days (1 month) 
20 – 40 days 
Visit 2 → Month 14 Contact (for the 
last enrolled subject only)**  
365 days (12 months) 
344 – 395 days 
*including first contact post Visit 3 (Month 3).  
** All subjects will be followed-up until last enrolled subject has completed 1 year of follow-up post last vaccination. In 
case criteria for vaccine efficacy analyses are not met during this period, the follow-up will be extended. 
# Subjects may not be eligible for inclusion in the per protocol set (PPS) for 
 if study visits 
occur outside the allowed interval. 
Time intervals between study visits/contacts to be performed for follow-up of clinically 
confirmed suspected HZ are presented in Table 6. If the HZ rash has not resolved by Day 
HZ-29, the subject will be seen weekly until the rash resolves. At the time of LSLV, if a 
subject has an ongoing HZ case, they will be followed up till Day HZ-29. 
Table 6 
Intervals between visits/contacts for subjects in case of suspected 
HZ 
Interval between Visits/ Contacts 
Length of 
interval 
Optimal Timing of contact 
(range of days) 
Visit HZ-1 (Day HZ-1) → Visit HZ-2 (Day HZ-8) 
7 days 
Day HZ-8 (+/- 3 days)* 
Visit HZ-2 (Day HZ-8) → Contact HZ-3 (Day HZ-15) 
7 days 
Day HZ-15 (+/- 3 days)* 
Contact HZ-3 (Day HZ-15) → Contact HZ-4 (Day HZ-22) 
7 days 
Day HZ-22 (+/- 3 days)* 
Contact HZ-4 (Day HZ-22) → Visit HZ-5 (Day HZ-29)  
7 days 
Day HZ-29 (+/- 3 days)* 
Note: The date of the previous visit/contact is used as reference date to define the interval between the subsequent 
study visits/contacts. 
* If contacted early in the window, then remaining days in the interval will need to be captured with the next contact. 
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3. 
INTRODUCTION 
3.1. 
Study rationale 
GlaxoSmithKline Biologicals SA (GSK) vaccine for the prevention of HZ is a 
recombinant subunit (su) vaccine consisting of Varicella Zoster Virus (VZV) 
glycoprotein E (gE) as antigen and the adjuvant system AS01B. The vaccine, referred to 
as recombinant zoster vaccine (RZV) or Shingrix has been evaluated in several studies in 
healthy elderly adults (≥ 50 YOA) and immunocompromised (IC) adults (≥18 YOA). In 
these studies, it was shown to be efficacious and elicit strong cellular and humoral 
immune responses. Furthermore, the safety and reactogenicity profile of the vaccine was 
acceptable [Leroux-Roels, 2012; Chlibek, 2013; Chlibek, 2014; Stadtmauer, 2014; 
Berkowitz, 2015; Lecrenier, 2018; Lal, 2015; Cunningham, 2016; López-Fauqued, 2019; 
Vink, 2019(a); Vink, 2019(b); Bastidas, 2019; Dagnew, 2019].  
Two large pivotal Phase III trials, ZOSTER-006 [also referred to as ZOE-50] that 
enrolled subjects ≥ 50 YOA and ZOSTER-022 [also referred to as ZOE-70] that enrolled 
subjects ≥ 70 YOA, evaluated the vaccine efficacy (VE), immunogenicity and safety of 
RZV. The combined enrollment in these studies was more than 30 000 subjects who 
either received RZV or placebo on a 0 and 2 month schedule. Results from ZOSTER-006 
and ZOSTER-022 showed a VE of 97.2% and 89.8% against HZ in adults ≥ 50 YOA and 
≥ 70 YOA, respectively. In addition, the co-primary objective of a pre-specified pooled 
analysis of ZOSTER-006 and ZOSTER-022 demonstrated that RZV effectively prevents 
post-herpetic neuralgia (PHN) with an efficacy of 88.8% in people ≥ 70 YOA. No safety 
concerns have been raised [Lal, 2015; Cunningham, 2016; López-Fauqued, 2019]. 
Upon request from Chinese regulatory authorities, the results of these pivotal studies 
were analyzed in an Asian sub-population. A total of 5 196 subjects were enrolled from 
Asia; specifically, from China (Taiwan Province and Hong-Kong Special Administrative 
Region), South Korea and Japan. Despite the fact that ZOSTER-006 and ZOSTER-022 
studies were not powered to perform inferential analyses on sub-populations, results from 
the Asian sub-population analysis showed a VE of 95.55% and 95.26% against HZ in 
adults ≥ 50 YOA and ≥ 70 YOA, respectively. 
 
 
 
 
 
 
 
 
. Further, the reactogenicity and 
safety profiles of RZV in the Asian sub-population were comparable to the reactogenicity 
and safety profile in the entire populations of both studies. Please refer to the local 
prescribing information of RZV for further details. 
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Shingrix is approved in Canada, the United States, the European Economic Area (EEA) 
countries, Japan, Australia and China for prevention of HZ in adults ≥50 YOA. In 
addition, in the EEA and Australia, Shingrix is also indicated for prevention of HZ related 
complications, such as PHN in adults ≥50 YOA. 
3.2. 
Background (Amended, 23 November 2020) 
VZV causes 2 distinct diseases. Varicella (chickenpox) occurs shortly after primary VZV 
infection and is characterized by systemic illness and a widely disseminated rash. HZ, 
commonly called shingles, occurs when VZV reactivates from latency and typically 
manifests as a localized pain and dermatomal rash. 
The typical HZ rash usually lasts 2 to 4 weeks and is typically accompanied by acute 
neuritis presented as pain that is often described as burning, shooting, or stabbing. In 
some patients, even touching the affected area lightly may cause pain, a phenomenon 
known as allodynia. This HZ-associated pain may be severe, and pruritus, which can also 
be severe, may be as common as pain. 
The most common complication of HZ is PHN, which is defined as pain that persists 
after the resolution of the HZ rash. Affected patients typically report constant burning, 
throbbing, intermittent sharp or electric shock-like pain, or allodynia [Dworkin, 2007]. 
Other complications of HZ include ophthalmologic, neurological, cutaneous and visceral 
disease, which can result in severe disability. (Amended, 23 November 2020) 
The incidence of HZ increases with age due to immune-senescence and waning of VZV 
immunity over time following primary varicella infection. While few epidemiological 
studies have directly assessed the burden of HZ in China, these studies indicate that the 
risk of HZ in Chinese adults ≥50 YOA is comparable to the risk observed in the Asian 
regions and the rest of the world. HZ incidence increases with age and is more common 
in females than in males. Overall, risk of HZ in Chinese adults > 50 YOA ranged from 
3.2 per 1000 person years to 8.6 per 1000 person years, which is similar to the rest of the 
world [Zhu, 2015; Li, 2016; Lu, 2018]. 
Shingrix is the first shingles vaccine licensed for use in China and is indicated for the 
prevention of HZ in adults ≥50 YOA. Please refer to the local prescribing information for 
further details. As per requirement of the Chinese regulatory authorities, this post-
licensure study will evaluate VE, cellular immunogenicity and safety of Shingrix in 
adults ≥50 YOA in China. 
3.3. 
Benefit/Risk assessment 
The following section outlines the risk assessment and mitigation strategy for this study 
protocol. 
Please refer to the Prescribing Information and the current Investigator’s Brochure (IB) 
for information regarding the summary potential risks and benefits of Shingrix. 


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3.3.1. 
Risk assessment (Amended, 23 November 2020) 
Important Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
Study vaccine: RZV 
Risk of potential immune mediated diseases (pIMDs) 
following the RZV vaccination 
Based on the theoretical concern that vaccination with 
an adjuvanted vaccine containing potent 
immunostimulants may interfere with immunological 
self-tolerance, pIMDs are adverse events of special 
interest (AESI) undergoing special safety monitoring for 
all GSK vaccines containing Adjuvant Systems. pIMDs 
are a subset of adverse events (AEs) that include 
autoimmune diseases and other inflammatory and/or 
neurological disorders of interest which may or may not 
have an autoimmune etiology. Up to date, there is no 
evidence of an increased risk of pIMDs following 
vaccination with RZV in the populations evaluated 
adults 50 YOA or older [López-Fauqued, 2019] 
Close monitoring of pIMDs as per study protocol and analysis 
of safety data generated through clinical trials and other 
sources. The potential risk of events of possible autoimmune 
etiology to occur is mentioned in the Informed Consent Form 
(ICF). In addition, the ICF advises subjects to contact the 
study doctor or the study staff immediately, should they get 
any symptoms that they feel may be serious. pIMDs will be 
collected up to 12 months after administration of the last dose 
of study vaccine, and pIMDs considered serious and 
related to study vaccine will be collected from 12 months 
after administration of the last dose of study vaccine until 
study end. (Amended, 23 November 2020) 
Hypersensitivity reactions (including anaphylaxis) 
Hypersensitivity reactions may occur following exposure 
to allergens from a variety of sources including food, 
aeroallergens, venom, drugs and immunizations. 
Vaccines are a mixture of compounds and allergic 
sensitization can occur to any component. While 
cutaneous reactions, such as rash or urticaria, are 
common, anaphylactic reactions are very 
rare.[Ruggerberg, 2007]  
Administration of the study vaccination is to be preceded by a 
review of the subjects’ medical history (especially with regard 
to previous vaccination and possible occurrence of 
undesirable events) and a history-directed clinical 
examination. 
Anaphylaxis following vaccine administration is a 
contraindication to subsequent vaccination. 
As with all injectable vaccines, appropriate medical treatment 
and supervision should always be readily available in case of 
an anaphylactic event following the administration of the 
vaccine. The onset of serious vaccine-related allergic 
symptoms is typically immediate. In order to assess and 
adequately treat subjects who may have allergic reaction to 
vaccination, all subjects will need to remain under observation 
(i.e. visibly followed; no specific procedure) at the vaccination 
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Important Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
Study Procedures 
Risk from lesion sampling. 
Swab/needle sampling of lesions/crusts associated risk 
of secondary infection, and discomfort related to the 
procedure. 
Lesion samples will be obtained by a trained professional 
under aseptic conditions to minimize the potential for 
secondary infection. 
The potential risk of some temporary discomfort during the 
sampling procedure and the risk of infection are mentioned in 
the ICF. 
 
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3.3.2. 
Benefit assessment 
Benefits include: 
• 
Subjects receiving RZV during the study are very likely to have a reduced risk of HZ 
since RZV is shown to be efficacious. 
• 
Medical evaluation/assessments associated with study procedures (e.g. physical 
examination, HZ case ascertainment).  
3.3.3. 
Overall Benefit: Risk conclusion 
Taking into account the measures to minimize risk to subjects participating in this study, 
the potential or identified risks in association with RZV and study procedures are offset 
by the anticipated benefits to subjects receiving RZV. 
The benefit-risk profile of Shingrix for the prevention of HZ in adults 50 YOA 
continues to be favorable. 
4. 
OBJECTIVES AND ENDPOINTS 
Table 7 
Study objectives and endpoints (Amended, 23 November 2020) 
Objectives 
Endpoints 
Primary 
To evaluate VE in the prevention of HZ compared 
to placebo in Chinese adults  50 YOA, as 
measured by the reduction in HZ risk. 
Criterion: The objective is met if the lower limit (LL) 
of the 2-sided 95% confidence interval (CI) of VE is 
above 25%. 
Confirmed HZ cases in the modified Exposed Set (mES). 
Refer to Section 10.2 for description of mES. 
Secondary 
To evaluate VE in the prevention of HZ compared 
to placebo in subjects within each of the following 
age ranges: 50-69 YOA and  70 YOA, as 
measured by the reduction in HZ risk 
Confirmed HZ cases within each of the following age ranges: 
50-69 YOA and  70 YOA in the mES. 
To evaluate vaccine reactogenicity and safety 
Solicited local and general adverse events (AEs) (Amended, 
23 November 2020) 
− 
Occurrence, intensity and resulting in medically 
attended visit of each solicited local AE within 7 
days (Days 1 - 7) after each vaccination  
− 
Occurrence, intensity, resulting in medically 
attended visit and relationship to vaccination of 
each solicited general AE within 7 days (Days 1 - 
7) after each vaccination.  
Unsolicited AEs 
− 
Occurrence, intensity, resulting in a medically-
attended visit, and relationship to vaccination of 
unsolicited AEs (including cellulitis) within 30 
days (Days 1 - 30) post-vaccination period, 
according to the Medical Dictionary for 
Regulatory Activities (MedDRA) classification. 


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Objectives 
Endpoints 
Serious Adverse Events (SAEs) (Amended, 23 November 
2020) 
− 
Occurrence and relationship to vaccination of 
SAEs from Day 1 up to 30 days post last 
vaccination.  
− 
Occurrence and relationship to vaccination of 
SAEs from Day 1 up to 12 months post last 
vaccination. 
− 
Occurrence of SAEs related to study vaccine, 
from Day 1 up to end of study. 
− 
Occurrence of SAEs related to study participation 
or to GlaxoSmithKline concomitant 
medication/vaccine during the entire study 
period.  
− 
Occurrence and relationship to vaccination of 
fatal SAEs from Day 1 up to 30 days post last 
vaccination. 
− 
 Occurrence and relationship to vaccination of 
fatal SAEs from Day 1 up to 12 months post last 
vaccination.  
− 
Occurrence of related-fatal SAEs from Day 1 up 
to end of study. 
pIMDs (Amended, 23 November 2020) 
− 
Occurrence and relationship to vaccination of 
pIMDs from Day 1 up to 30 days post last 
vaccination. 
− 
Occurrence and relationship to vaccination of 
pIMDs from Day 1 up to 12 months post last 
vaccination. 
− 
Occurrence of related serious pIMDs after 12 
months post last vaccination up to study end.  
Exploratory 
5. 
STUDY DESIGN 
5.1. 
Scientific rationale for study design 
Study ZOSTER-076 will be conducted to evaluate VE, cellular immunogenicity and 
reactogenicity/safety of RZV in subjects ≥ 50 YOA in China. Subjects will be 
randomized 1:1 to the RZV or Placebo arm and will be followed in an observer-blind 
design. Recruitment will be stratified by age, including a minimum of subjects in each 
age category to ensure recruitment of a broad age range of adults ≥ 50 YOA. Additional 
minimization factors include center, age (50-59, 60-69, 70-79 and ≥ 80 years - to ensure a 
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comparable age spectrum in each treatment group), gender and presence of significant 
medical conditions, for example, diabetes mellitus. 
A lyophilized sucrose cake reconstituted with saline (NaCl) solution is included as a 
control (placebo) in this study evaluating the VE, cellular immunogenicity and 
reactogenicity/safety of RZV in this population. The use of placebo control and the 
observer-blind, randomized study design aim to minimize the potential biases in study 
results. 
5.2. 
Overall design (Amended, 23 November 2020) 
Figure 1 
Study design overview (Amended, 23 November 2020) 
 
; N= number of subjects planned to be enrolled; Vacc= Vaccination 
. 
‡ All subjects will be followed-up until last enrolled subject has completed 1 year of follow-up post last vaccination. In 
case criteria for vaccine efficacy analyses are not met during this period, the follow-up will be extended. 
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. Therefore, adherence to the study design requirements, 
including those specified in the schedule of activities (Section 2), are essential and 
required for study conduct.  
• 
Type of study: self-contained 
• 
Experimental design: Phase IV, randomized, observer-blind, placebo-controlled, 
multi-centric, single-country study with 2 parallel groups. 
• 
Duration of the study: The duration of the study will vary for each subject. The 
duration of the study will be up to the study conclusion contact that occurs within 
30 days of the projected study conclusion date of the last enrolled subject, that is, 
14 months (approximately 430 days) from the enrolment date. Therefore, subjects 
enrolled early in the trial will be followed for longer duration than the subjects who 
enrol later in the trial. In case criteria for VE analyses are not met during this period, 
the follow-up will be extended. 
RZV Group (N=3069)
Randomization (1:1)
Visit 1
Day 1
Vacc 1
BS
Visit 2
Month 2
Vacc 2
Visit 3
Month 3
BS
Monthly Contact Until 
Study End ‡
Epoch 001 (Vaccination phase)
Epoch 002 (Follow-up phase)
Placebo Group (N=3069)
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The study conclusion visit/ contact for subjects with an ongoing episode of HZ at the 
time of last subject last contact will occur at Visit HZ-5 (Day HZ-29).  
− 
Epoch 001 (Vaccination phase): 
 
 
− 
Epoch 002 (Follow-up phase): Starting with the first monthly contact after Visit 
3 (Month 3) and ending at the monthly contact that occurs within 30 days of the 
projected study conclusion date of the last enrolled subject, that is, 14 months 
(approximately 430 days) from the enrolment date of the last enrolled subject. 
(Amended, 23 November 2020) 
• 
Primary completion Date (PCD): The primary completion date will be when the last 
subject completes his/her study conclusion contact (within 30 days of the projected 
study conclusion date of the last enrolled subject, that is, 14 months (approximately 
430 days) from the enrolment date. In case criteria for VE analyses are not met 
during this period, the follow-up will be extended. 
Refer to glossary of terms for the definition of PCD. 
• 
End of Study (EoS): 1) After all the subjects complete their study conclusion contact, 
occurring within 30 days of the projected study conclusion date of the last enrolled 
subject, that is, 14 months (approximately 430 days) from the enrolment date of the 
last subject; In case criteria for VE analyses are not met during this period, the 
follow-up will be extended and 2) the release of all polymerase chain reaction (PCR) 
test results for the HZ rash lesion samples. 
Refer to glossary of terms for the definition of EoS. 
• 
Study groups: 
Table 8 
Study groups, treatment and epochs foreseen in the study  
Study groups 
Targeted number of 
eligible subjects 
Age (years) 
Epochs 
Epoch 001  
Epoch-002  
RZV group 
3069 
50 years  
●  
● 
Placebo group 
3069  
50 years  
●  
●  
Table 9 
Study groups and treatment foreseen in the study 
Treatment name 
Vaccine/Product name 
Study Groups 
RZV 
Placebo 
RZV 
VZV gE  
● 
 
AS01B  
● 
 
Placebo 
Lyophilized sucrose  
 
● 
Saline (NaCl) solution for reconstitution 
 
● 
• 
Control: Placebo-controlled  
• 
Vaccination schedule: 0 and 2 months 
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• 
Treatment allocation: Eligible subjects will be randomized (1:1) to RZV group or 
Placebo group. The randomization algorithm will use a stratification procedure 
accounting for age (50-69 YOA and  70 YOA). 
• 
Blinding:  
Table 10 
Blinding of study epochs 
Study Epochs 
Blinding 
Epoch 001 
observer-blind 
Epoch-002 
observer-blind 
• 
Sampling schedule: 
− 
 
 
 
− 
Clinical specimens of HZ lesions will be collected from all subjects who are 
clinically diagnosed with a suspected case of HZ (Section 8.3.2). 
− 
A urine specimen will be collected from all female subjects of child-bearing 
potential (see glossary of terms for definition of woman of child bearing 
potential) at Visit 1 (Day 1) and Visit 2 (Month 2). 
Note: The result of the pregnancy test must be obtained before any study vaccination 
and must be negative. 
• 
Data collection: standardized Electronic Case Report Form (eCRF). Solicited and 
unsolicited AEs will be collected using a subject Diary (paper Diary [pDiary]). In the 
event of suspected HZ, the HZ clinical course will be collected using a HZ-specific 
diary card.  
• 
Safety monitoring: An internal GSK Safety Review Team (SRT) will oversee the 
safety of the ZOSTER-076 study. All safety data, i.e. suspected HZ cases, AEs, 
SAEs, fatal SAEs, pIMDs and cellulitis will be reviewed in a blinded manner by the 
SRT at regular intervals together with data from other ongoing ZOSTER vaccine 
studies. Any potential safety concern related to conduct of the study will be escalated 
to higher governing bodies as per internal GSK process. (Amended, 23 November 
2020) 
5.3. 
Number of subjects (Amended, 23 November 2020) 
Approximately 6138 subjects will be randomized leading to approximately 5524 
evaluable subjects for an estimated total of 2762 evaluable subjects per treatment group. 
 
 
Withdrawals will not be replaced. 
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5.4. 
Subject and study completion 
A subject is considered to have completed the study if he/she is available for the 
concluding contact. This corresponds to the last monthly contact that occurs within 30 
days of the projected study conclusion date of the last enrolled subject, that is, 14 months 
(approximately 430 days) from the enrolment date of the last subject. In case criteria for 
vaccine efficacy analyses are not met during this period, the follow-up will be extended. 
6. 
STUDY POPULATION 
6.1. 
Inclusion criteria for enrolment 
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity, regulatory acceptability of the study or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
All subjects must satisfy ALL the following criteria at study entry: 
• 
Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary cards, return for follow-up 
visits) or/and subjects’ Legally Acceptable Representative(s) [LAR(s)] who, in the 
opinion of the investigator, can and will comply, with the requirements of the 
protocol (e.g. completion of the diary cards, return for follow-up visits). 
• 
Written or witnessed/thumb printed informed consent obtained from the 
subject/subject’s LAR prior to performance of any study specific procedure.  
• 
A male or female aged 50 years or older at the time of the first vaccination. 
• 
Medically stable subjects as established by medical history and history-directed 
clinical examination before entering into the study. 
• 
Female subjects of non-childbearing potential may be enrolled in the study. Non-
childbearing potential is defined as current bilateral tubal ligation or occlusion, 
hysterectomy, bilateral ovariectomy or post-menopause. Please refer to Section 
12.6.1 for definitions of menopause. 
• 
Female subjects of childbearing potential may be enrolled in the study, if the subject  
− 
has practiced adequate contraception for 30 days prior to vaccination, and 
− 
has a negative pregnancy test on the day of vaccination, and 
− 
has agreed to continue adequate contraception during the entire treatment period 
and for 2 months after completion of the vaccination series. 
Refer to Section 12.6.1.1 for definitions of woman of child bearing potential and 
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6.2. 
Exclusion criteria for enrolment 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study. 
6.2.1. 
Medical conditions 
• 
Any other condition (e.g., extensive psoriasis, chronic pain syndrome, cognitive 
impairment, severe hearing loss) that, in the opinion of the investigator, might 
interfere with the evaluations required by the study. 
• 
History of HZ 
• 
Significant underlying illness that in the opinion of the investigator would be 
expected to prevent completion of the study (e.g., life-threatening disease likely to 
limit survival to less than 4 years). 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine or study materials and equipment. 
• 
Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional 
abnormality as determined by physical examination or laboratory screening tests. 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition 
resulting from disease (e.g., malignancy, Human Immunodeficiency Virus [HIV] 
infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during 
cancer chemotherapy, organ transplantation or to treat autoimmune disorders)  
6.2.2. 
Prior/Concomitant therapy (Amended, 23 November 2020) 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study vaccine during the period starting 30 days before the 
first dose of study vaccine (Day -29 to Day 1), or planned use during the study 
period. 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 30 days before each dose and ending 30 days after the 
last dose of vaccine administration. However, licensed pneumococcal vaccines and 
inactivated and subunit influenza vaccines (without adjuvant for seasonal or 
pandemic flu) may be co- administered with any dose of study vaccine. 
• 
Previous vaccination against varicella or HZ. 
• 
Administration of long-acting immune-modifying drugs at any time during the study 
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• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the first dose of study vaccine up to one 
month post dose 2 (Month 3). 
• 
Planned or chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 3 
months prior to the first vaccine. For corticosteroids, this will mean prednisone 
20 mg/day, or equivalent, is not allowed. Inhaled, intra-articular and topical 
steroids are allowed. (Amended, 23 November 2020) 
6.2.3. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the subject has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or medical device). 
6.2.4. 
Other exclusions 
• 
Pregnant or lactating female. 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions within 2 months of last vaccination. 
• 
History of current/chronic alcohol consumption and/or drug abuse. 
6.3. 
Criteria for temporary delay for enrolment and vaccination 
Vaccination may be postponed within the allowed time interval until transient 
circumstances cited below have been resolved: 
• 
Acute disease and/or fever at the time of enrolment. For this study, fever is defined 
as temperature 37.3°C as per guidelines from Chinese authorities for axillary 
measurement. The preferred location for measuring temperature in this study will be 
the axillary route.  
• 
Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever maybe enrolled at the discretion of the investigator.  
7. 
TREATMENTS 
Study treatment is defined as a set of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject. 
 


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7.1. 
Treatments administered  
Table 11 
Treatments administered 
Study Treatment Name: 
RZV 
Placebo 
Vaccine/Product name * 
VZV gE  
AS01B  
Lyophilised sucrose 
Sucrose=20mg 
Saline (NaCl ) solution 
Presentation 
Lyophilized pellet in a monodose 
vial  
Liquid in a monodose vial  
Lyophilized pellet in a 
monodose vial  
Liquid in a syringe  
Vaccine formulation: 
gE=50µg per 0.5 ml of 
reconstituted vaccine 
MPL=50µg; QS21=50µg; 
Liposomes per 0.5 ml of 
reconstituted vaccine 
Sucrose=20mg per 0.5 mL of 
reconstituted placebo 
NaCl=150mM (water for 
injection) 
Route of Administration  
IM  
IM  
Location 
Deltoid  
Deltoid  
Laterality ** 
Non-dominant  
Non-dominant  
Number of doses to be administered: 
2 
2 
Volume to be administered *** 
0.5 mL  
0.5 mL  
Packaging and Labelling 
Refer to SPM for more details  
Refer to SPM for more details  
Manufacturer 
GSK  
GSK 
AS01B= Adjuvant System 01B; gE= recombinant purified Glycoprotein E; IM= intramuscular MPL= 3-O-desacyl-4’-monophosphoryl lipid A; NaCl= Sodium Chloride; SPM= Study 
Procedures Manual  
* QS-21= Quillaja saponaria Molina, fraction 21 (Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of Agenus Inc., a Delaware, USA corporation)  
** The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the vaccine in the non-dominant arm, an injection in the dominant arm may be 
performed 
*** Refer to the SPM for the volume after reconstitution. 


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After completing all prerequisite procedures prior to vaccination (refer to Section 7.7 
regarding the contraindications to subsequent vaccination), 1 dose of study vaccine will 
be administered intramuscularly preferably in the deltoid of the non-dominant arm (refer 
to Table 11 for details regarding the treatment administered). 
If the investigator or delegate determines that the subject’s health on the day of 
administration temporarily precludes vaccine administration, the visit will be rescheduled 
within the allowed interval for this visit (refer to Table 5). 
The subjects will be observed closely for at least 30 minutes following the administration 
of the vaccine, with appropriate medical treatment readily available in case of 
anaphylaxis and syncope. 
7.2. 
Method of treatment assignment 
7.2.1. 
Subject identification 
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification 
numbers allocated to each study center. 
7.2.2. 
Randomization of treatment 
7.2.2.1. 
Randomization of supplies 
The randomization of supplies within blocks will be performed at GSK, using MATerial 
EXcellence (MatEx), a program developed for use in Statistical Analysis System (SAS) 
(Cary, NC, USA) by GSK. Entire blocks will be shipped to the study 
centres/warehouse(s). 
To allow GSK to take advantage of greater rates of recruitment in this multi-centre study 
and to thus reduce the overall study recruitment period, an over-randomization of 
supplies will be prepared.  
7.2.2.2. 
Treatment allocation to the subject 
The treatment numbers will be allocated by component. 
7.2.2.2.1. Study group and treatment number allocation 
The target will be to enrol approximately 6138 eligible subjects who will be randomly 
assigned to 2 study groups in a (1:1) ratio (approximately 3069 subjects in each group). 
The enrolment will be performed to ensure distribution of the population across the 2 age 
strata (50-69 YOA and >70 YOA). Approximately 75-80% and 20-25% subject should 
be enrolled in 50-69 YOA and >70 YOA, respectively. The expected distribution of 
subjects within these 2 age strata is as shown in Table 12. 
To ensure that the collection of date of birth will not jeopardize the privacy of Personally 
Identifiable Information (PII), only year of birth (YYYY) will be collected. 


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Table 12 
Number of subjects required for enrolment 
Age Stratum 
Vaccine 
Targeted number (%) of subjects 
50-69 YOA 
RZV 
4604-4910 (75-80%) 
Placebo 
≥ 70 YOA 
RZV 
1228-1534 (20-25%) 
Placebo 
Allocation of the subject to a study group at the investigator site will be performed using 
a randomization system on internet (SBIR). Within each age stratum, the randomization 
algorithm will use a minimization procedure accounting for center, gender, age (50-59, 
60-69 for 50-69 YOA stratum, 70-79 and ≥80 YOA for ≥ 70 YOA stratum) and a 
combined minimization factor to reflect the presence of any of the following conditions: 
type 2 diabetes mellitus, asthma, chronic obstructive pulmonary disease, chronic kidney 
disease and depression. Minimization factors will have equal weight in the minimization 
algorithm. 
After obtaining the signed and dated ICF from the subject/subject’s LAR and having 
checked the eligibility of the subject, the study staff in charge of the vaccine 
administration will access SBIR. Upon the subject identification number, the 
randomization system will determine the study group and will provide the treatment 
number to be used for the first dose. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions. 
7.2.2.2.2. Treatment number allocation for subsequent dose 
For the second dose, the study staff in charge of vaccine administration will access SBIR, 
provide the subject identification number and the system will provide a treatment number 
consistent with the allocated study group. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
7.2.3. 
Allocation of subjects to assay subsets (Amended, 23 November 
2020) 
 
 
 
 
 
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7.3. 
Blinding and unblinding 
This study will be conducted in an observer-blind manner. By observer-blind, it is meant 
that during the course of the study, the vaccine(s) recipient and those responsible for the 
evaluation of any study endpoint (e.g. safety, reactogenicity and efficacy) will all be 
unaware of which vaccine was administered. To do so, vaccine preparation and 
administration will be done by authorized medical personnel who will not participate in 
any of the study outcomes. 
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the subject and study (without any link to the treatment 
attributed to the subject) to each sample. 
7.3.1. 
Emergency unblinding 
Unblinding of a subject’s individual treatment code should occur only in the case of a 
medical emergency when knowledge of the treatment is essential for the clinical 
management or welfare of the subject. 
The emergency unblinding process consists of the automated Internet-based system 
(SBIR) that allows the investigator to have unrestricted, immediate and direct access to 
the subject’s individual study treatment. 
As a back-up process, the investigator has the option of contacting a GSK Helpdesk 
(refer to Table 13) if he/she needs support to perform the unblinding (i.e. he/she cannot 
access the automated Internet-based system). 
A non-investigator physician (e.g. physician from emergency room) or subject/care 
giver/family member can also request emergency unblinding either via the investigator 
(preferred option) or via the GSK Helpdesk (back up process). Contact details of 
investigator and GSK Helpdesk are available in the patient/subject card. 
Table 13 
Contact information for emergency unblinding 
GSK Helpdesk 
24/24 hour and 7/7 day availability 
The Helpdesk is available by phone, fax and email 
Phone: +32.2.656.68.04 
Fax: +32.2.401.25.75 
email: rix.ugrdehelpdesk@gsk.com 
A subject will be withdrawn from analysis of efficacy if the subject’s treatment code is 
unblinded by the investigator or treating physician but will still be followed-up for safety. 
The relevant event or condition will be recorded in the eCRF. 
GSK Vaccines Clinical Safety and Pharmacovigilance (VCSP) staff may unblind the 
treatment assignment for any subject in case of Suspected Unexpected Serious Adverse 
Reaction (SUSAR) as well as in case of fatal or life-threatening cases. If the SAE 
requires that an expedited regulatory report be sent to a regulatory agency, a copy of the 
report, identifying the subject’s treatment assignment, may be sent to investigators in 
accordance with local regulations and/or GSK policy. 


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7.4. 
Handling, storage and replacement of study vaccine 
7.4.1. 
Storage and handling of study vaccine 
The study vaccines must be stored at the respective label storage temperature conditions 
in a safe and locked place. Access to the storage space should be limited to authorised 
study personnel. The storage conditions will be assessed during pre-study activities under 
the responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccine. 
A temperature excursion is any temperature that is not in range of the label storage 
temperature conditions. Temperatures outside the range of label storage temperature 
conditions must be reported and/or documented. Temperature excursion impacting study 
vaccines must be reported and/or documented. 
In the frame of the reporting, the lack/absence of temperature monitoring documentation 
from a device meeting GSK requirements has to be considered as a temperature 
excursion. 
Study vaccine that are impacted by a temperature excursion will not be used and must be 
quarantined at label storage conditions until usage approval has been obtained from/via 
the local study contact (e.g. Site Monitor). 
Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on 
the temperature excursion reporting and usage decision process, packaging and 
accountability of the study vaccine. 
7.4.2. 
Replacement of unusable vaccine doses 
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomization when applicable), at least 5% additional vaccine doses will be 
supplied to replace those that are unusable.  
7.5. 
Concomitant medication(s)/product(s) and concomitant 
vaccinations 
7.5.1. 
Recording of concomitant medications/products and 
concomitant vaccinations 
At each study visit/contact, the investigator or delegate should question the subject and/or 
subject’s LAR about any medications/products taken and vaccinations received by the 
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The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF. 
• 
All concomitant medications/products, except vitamins and dietary supplements, 
administered during the period of 30 days following each dose of study vaccine. 
• 
Any concomitant vaccination administered in the period starting 30 days before the 
first dose of study vaccine until study end. 
• 
Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination) within 24 hours of each 
dose of study vaccine administration. 
An anti-pyretic is considered to be prophylactic when it is given in the absence of fever 
and any other symptom, to prevent fever from occurring. 
• 
Any medication used during the assessment or treatment of HZ or its complications 
during the study. 
• 
Any concomitant medications/products/vaccines leading to the withdrawal or non-
eligibility of the subject from the study (See section 7.5.2). 
• 
Any concomitant medications/products/vaccines relevant to an SAE/pIMD to be 
reported as per protocol or administered at any time during the study period for the 
treatment of a SAE/pIMD. In addition, concomitant medications relevant to SAEs 
and pIMDs need to be recorded on the expedited Adverse Event report. 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7.5.2. 
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from analyses (Amended, 23 November 
2020) 
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
per-protocol analysis. See Section 10.2 for definition for populations to be analyzed. 
• 
Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine during the study period; 
• 
Administration of a vaccine not foreseen by the study protocol within 30 days prior 
to dose 2 of vaccine and/or within 30 days after any dose. However, licensed non-
replicating vaccines against pneumococcus, seasonal or pandemic flu (without 
adjuvant) may be co-administered with either dose of study vaccine. 
In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a 
pandemic) is organized by the public health authorities, outside the routine 
immunization program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to its Summary of Product 
Characteristics (SmPC) or Prescribing Information and according to the local 
governmental recommendations and provided a written approval of the Sponsor is 
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• 
Receipt of a vaccine against HZ other than the study vaccine during the study period; 
• 
Prolonged use (> 14 consecutive days) of oral and/or parenteral antiviral agents that 
are active against VZV (acyclovir, valacyclovir, famciclovir etc.) during the study 
period for an indication other than to treat suspected or confirmed HZ or an HZ-
related complication (topical use of these antiviral agents is allowed); 
• 
Chronic administration (i.e. more than 14 days in total) of immunosuppressants or 
other immune-modifying drugs during the study period. For corticosteroids, this will 
mean prednisone 20 mg/day or equivalent is not allowed. Inhaled, intra-articular 
and topical steroids are allowed. (Amended, 23 November 2020) 
• 
Immunoglobulins and/or any blood products or plasma derivatives during the period 
starting 3 months before the first dose of study vaccine up to one month post dose 2 
(Month 3). 
• 
Administration of cytotoxic chemotherapy at any time during the study period. 
• 
Drug and/or alcohol abuse. 
A detailed, comprehensive list of reasons for elimination from analyses will be 
established at the time of data cleaning. 
7.6. 
Intercurrent medical conditions that may lead to elimination 
of a subject from analyses 
At each study visit subsequent to the first vaccination/the vaccination visit, it must be 
verified if the subject has experienced or is experiencing any intercurrent medical 
condition (IMC) that may lead to elimination from per protocol analysis. If it is the case, 
the condition(s) must be recorded in the eCRF. 
Subjects may be eliminated from the modified exposed set (mES) and/or per protocol set 
(PPS) for 
 if, during the study, they incur a condition that 
has the potential to impact the effect of the vaccine e.g. they have any confirmed or 
suspected immunosuppressive or immunodeficient condition resulting from disease (e.g. 
malignancy, HIV infection).  
 
 
 
 
 
Intercurrent conditions should be reported in the AE section of the eCRF. 
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7.7. 
Contraindications to subsequent vaccine administration 
Prior to receipt of additional study vaccination, subjects must be evaluated to confirm that 
they are eligible for subsequent vaccination.  
If subjects meet any of the original exclusion criteria or the criteria listed below, they 
should not receive additional vaccinations. However, the subjects should be encouraged 
to continue other study procedures at the discretion of the investigator (Section 8.5.5). 
• 
Anaphylaxis following the administration of vaccine. 
• 
Subjects who experience any SAE judged to be possibly or probably related to study 
vaccine or non-study vaccines, including hypersensitivity reactions. 
• 
Subjects who develop any new condition which, in the opinion of the investigator, 
may pose additional risk to the subject if he/she continues to participate in the study. 
• 
Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the 
opinion of the investigator, exposes the subject to unacceptable risk from subsequent 
vaccination. In such cases, the investigator should use his/her clinical judgement 
prior to administering the next dose of the vaccine. Refer to Section 12.5.5.1 for the 
definition of pIMDs. 
• 
Occurrence of suspected or confirmed HZ between the first and second vaccine dose. 
• 
Receipt of vaccine against VZV outside of the study. 
7.8. 
Warnings and precautions 
Warnings and precautions to vaccination must be checked at the beginning of each 
vaccination visit.  
Refer to the approved product label/package insert. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 2).  
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns.  
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the subject(s) should discontinue study 
treatment. 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 


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All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable.  
8.1. 
General study aspects 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects. 
8.1.1. 
Data Collection 
Diary cards will be distributed to subject or subject’s LAR/caregiver by the investigator 
or his/her delegate. The study staff/investigator will provide instructions to the subject or 
subject’s LAR/caregiver for completing the diary cards and explain the importance of 
timely completion and returning the diary cards to the site. Any supplied diary cards 
should be completed by the subject themselves or a site trained assistant (such as LAR, a 
family member or a caregiver). 
If assistance is needed, a site trained and designated assistant should aid with reading the 
questions (verbatim) and/or transcribing the subject’s responses on the questionnaires 
and/or diary cards. This assistance should be provided at the time the subject is required 
to complete the questionnaire or diary card (i.e. in “real time”, not retrospectively). 
Training of the assistant is to be given by the study staff (see Table 3). Study staff will 
ask the subject (at the time of return or at subsequent contact) if he/she received any 
assistance in completing diary cards or questionnaires. If the subject had assistance 
completing the diary card, it should be noted in the eCRF.  
All subjects will receive: 
• 
Diary cards: To be completed by the subject or subject’s LAR/caregiver after each 
vaccination for recording of solicited AEs (from day of vaccination to subsequent 6 
days), unsolicited AEs including medically attended visits (from day of vaccination 
to subsequent 29 days), and all concomitant medications/vaccinations taken from day 
of vaccination to subsequent 29 days or to next study visit. 
• 
HZ-specific diary card: At Visit 1, all subjects/subject’s LAR/caregiver will receive 
a HZ-specific diary card. This is to be completed by the subjects/subject’s 
LAR/caregiver beginning immediately (and only) upon development of any 
signs/symptoms suggestive of HZ (to record the date of onset of rash and/or pain) 
and prior to visiting the study site for evaluation of suspected HZ. 


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8.1.2. 
Monthly contacts 
After Visit 3 (Month 3), monthly contacts between the subjects/ subject’s LAR/caregiver 
and the investigator/delegate will take place to collect information on any event of 
interest that may have occurred. Also, subjects with suspected HZ will be contacted as 
outlined in Table 4. The contacts will take place using the most convenient method suited 
for the sites (e.g., telephone calls by site staff or designee). A guidance document 
outlining the information that needs to be collected at each contact will be provided to 
serve as a guidance to develop the local script (Refer to the SPM). The logistic details on 
the set-up of the contacts will be documented by each site. At each contact, the 
subject/subject’s LAR/caregiver will respond to a standard set of questions in a language 
that is understandable to them. The investigator or delegate will transcribe the relevant 
information on any event of interest in the appropriate language of the subject’s eCRF to 
English. 
8.2. 
Pre-vaccination procedures 
8.2.1. 
Informed Consent 
Before performing any study procedure, the signed informed consent of the subject needs 
to be obtained. Refer to section 12.4.3 for the requirements on how to obtain informed 
consent. 
8.2.2. 
Collection of demographic data 
Record demographic data such as year of birth, sex, race and ethnicity in the subject’s 
eCRF. 
8.2.3. 
Medical and vaccination history 
Obtain the subject’s medical and vaccination history by interview and/or review of the 
subject’s medical records and record pre-existing conditions or signs and/or symptoms 
present in a subject prior to the first study vaccination in the eCRF. 
8.2.4. 
History directed physical examination 
Perform a history directed physical examination. If the investigator determines that the 
subject’s health on the day of vaccination temporarily precludes vaccination, the visit will 
be rescheduled. 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. 


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8.2.5. 
Pregnancy test 
Female subjects of childbearing potential are to have a urine pregnancy test prior to any 
study vaccine administration. The study vaccine may only be administered if the 
pregnancy test is negative.  
Note: Pregnancy test must be performed even if the subject is menstruating at the time of 
the study visit. 
8.2.6. 
Check contraindications, warnings and precautions to 
vaccination  
Contraindications to vaccination must be checked at the beginning of each vaccination 
visit. Refer to Sections 7.7 and 7.8 for more details. 
8.2.7. 
Pre-vaccination body temperature 
The subjects’ body temperature (axillary route is the preferred route of measurement) 
needs to be measured prior to any study vaccine administration. If the subject has fever 
(for this study, fever is defined as temperature 37.3°C as per guidelines from the 
Chinese authorities for axillary measurement) on the day of vaccination, the vaccination 
visit will be rescheduled within the allowed interval for this visit (see Section 6.3). 
In rare situations when there is no other alternative, the temperature may be recorded by 
other route. If the temperature is taken by another route (oral, rectal or tympanic), the 
route should be documented. 
8.2.8. 
Record any concomitant medications/vaccinations and any 
intercurrent medical conditions 
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 7.5. IMCs must be checked and recorded in the eCRF as described 
in Section 7.6. 
8.3. 
Efficacy assessments 
8.3.1. 
Case Definitions 
8.3.1.1. 
Suspected Herpes Zoster 
A suspected case of HZ is defined as a new unilateral rash accompanied by pain (broadly 
defined to include allodynia, pruritus or other sensations) and no alternative diagnosis. If 
a case is not clinically diagnosed as suspected HZ, the investigator should not progress 
further with evaluation of the case.  


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The HZ onset date is the earlier of the following 2 events:  
1. the HZ rash start date; or  
2. the date on which pain at the site of a subsequent HZ rash is first noted. 
The end date of a HZ episode is defined as the first time at which a subject had no rash 
(papules, vesicles, ulcers or crusts) present. This end date will be recorded in the eCRF. 
The investigator is to record in the eCRF if HZ associated symptoms is ongoing at the 
end-date of HZ rash. 
The occurrence of HZ will be recorded in HZ-specific eCRF screens. The reporting 
period for cases of HZ will be from Day 1 to study end. Refer to Section 8.3.2 for more 
details on the evaluation and follow-up of suspected HZ cases. 
8.3.1.2. 
Confirmed HZ 
A suspected case of HZ can be confirmed by GSK in 2 ways: 
• 
By PCR: 
Rash lesion samples will be collected from subjects clinically diagnosed as having a 
suspected case of HZ. The samples will be transferred to a validated laboratory 
designated by GSK and analyzed using standardized and validated procedures for 
laboratory diagnosis of HZ by PCR. Refer to Section 12.2 for details of PCR assay to 
be performed on HZ lesion samples and for details of the PCR testing algorithm to 
classify suspected cases of HZ. 
• 
By the HZ Ascertainment Committee (HZAC): 
All suspected HZ cases will be referred to the HZAC. The HZAC will classify all 
referred cases as either “HZ” or “not HZ” or “not able to decide”. The HZAC 
classification will serve as the final case definition only when the case cannot be 
confirmed or excluded by PCR, e.g., when all samples from a given subject are 
inadequate (as when both VZV and β-actin PCR results are negative), or when no 
samples are available for a given subject. Therefore, definitive PCR results, when 
available, will determine the final HZ case assignment. In such cases, the HZAC 
classification will not contribute to HZ case determination decision. 
The HZAC will consist of 3 to 5 physicians with HZ expertise. HZAC members will 
be blinded to group assignments. For every case, each reviewing HZAC member will 
be asked to make a clinical determination of whether the case is HZ based on review 
of the available clinical information (e.g., summary of the rash and pain evaluations, 
digital photographs of the subject's rash, and clinical progress notes). A suspected 
case of HZ will be considered as “HZ” if the HZAC members concur unanimously; 
otherwise, it will be classified as “not HZ”. A case of “not able to decide” will be 
classified as “not HZ”. As described above, the HZAC case assignment will only be 
considered as the final case assignment if definitive PCR results are not available. 
Further details will be provided in the HZAC charter. 


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8.3.2. 
Evaluation of suspected HZ cases 
All subjects and/or subjects’ LAR/caregiver will be educated with regards to the signs 
and symptoms of HZ with the characteristic HZ rash. Subjects and/or subject’s 
LAR/caregiver will be instructed to contact the investigator immediately and visit the 
study site (within 48 hours, if possible) if they develop signs/symptoms suggestive of HZ. 
The investigator or delegate will perform a targeted clinical examination when the subject 
visits the study site for the first evaluation of the suspected case of HZ [Visit HZ-1 at Day 
HZ-1]. If the case is not compatible with the diagnosis of HZ, further evaluation of this 
event should not progress for the purpose of this study. However, the case should be 
handled as AE/SAE, if applicable. 
The schedule of visits/contacts that will take place for follow-up of clinically diagnosed 
suspected HZ cases is presented in Table 4. 
For clinically diagnosed suspected HZ cases, the following will take place at Visit HZ-1: 
• 
The investigator or delegate will verify the completed HZ-specific diary card 
returned by the subject (or the subject’s LAR/caregiver, if applicable). The 
information from the diary card will be transcribed into the eCRF. The investigator 
or their delegate will record relevant information regarding the HZ episode in the 
eCRF (such as date of onset of pain and/or rash, date of clinical diagnosis of HZ, 
location and nature of HZ lesions, HZ-related complications if any); 
• 
The rash will be documented by digital photography. Please refer to the SPM for 
specific instructions; 
• 
The study staff/investigator will record concomitant medication/vaccination, 
including concomitant medication for HZ treatment. Concomitant medication the 
subject has already received and/or will receive for HZ treatment will be recorded in 
the eCRF. The study staff/investigator will check if the subject received any medical 
attention [hospitalization, emergency room visit, or a visit to or from medical 
personnel (medical doctor)] for HZ or any HZ-related complication; 
• 
Rash lesion samples (3 replicate samples on the same day) will be collected from 
subjects clinically diagnosed as having a suspected case of HZ; 
• 
After Visit HZ-1 until Visit HZ-5, visits/contacts will take place for follow-up of the 
HZ episode according to the schedule presented in Table 4. When a case initially 
clinically diagnosed as suspected HZ is subsequently no longer considered by the 
investigator as suspected HZ, this will be noted in the eCRF. However, study 
procedures to be performed during the follow-up period for a suspected HZ case 
should be continued. 
• 
HZ related complications will be followed as AE/SAE, as appropriate. Please refer to 
Section 8.5.4. 


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The following will take place at each visit or contact that occurs for each episode: 
• 
The study staff/investigator will: 1) record relevant information regarding the 
suspected HZ case (such as the location and nature of HZ lesions, the end date of the 
rash, HZ-related complications, if any); 2) record concomitant 
medications/vaccinations, including concomitant medication the subject has already 
received and/or will receive for HZ treatment or treatment of any HZ-related 
complications; and 3) check if the subject received any medical attention 
[hospitalization, emergency room visit, or a visit to or from medical personnel 
(medical doctor)] for HZ or any HZ-related complication. 
• 
Additional photographs of HZ lesions may be taken after the first visit for the HZ 
episode to help note the progression of the rash. 
• 
If the investigator determines that adequate rash samples are not present at the first 
visit (that is < 3 lesions present or only papules present), the investigator has the 
option of collecting three additional samples prior to or at the second Visit HZ-2. 
8.3.3. 
Follow up of suspected HZ cases (Amended, 23 November 2020) 
Data will be collected on all suspected HZ cases that occur from Visit 1 (Day 1) until the 
study conclusion. For each suspected case of HZ that the investigator concludes is 
clinically consistent with HZ, data will be collected weekly until Day HZ-29 and weekly 
from Day HZ-30 until the HZ rash resolves. If the rash hasn't resolved the subject will be 
seen weekly until the rash resolves. The end date of the pain associated with this HZ 
episode should be recorded. At the time of LSLV, if a subject has an ongoing HZ case, 
he/she will be followed up till Day HZ-29. 
The investigator will note in the subject’s eCRF the end date of HZ rash and if any HZ-
associated symptoms are still ongoing. Complications of the HZ episode (for example, 
PHN, disseminated HZ, ophthalmic disease) should be recorded as AE/SAE, as 
appropriate. (Amended, 23 November 2020) 
If pain reappears in the same area after a 4-week pain-free period and is not accompanied 
by a new HZ rash, it will be assigned to the previous HZ-episode. 
The presence of a new rash will be considered a new episode. Visits/contacts will start 
from Day HZ-1 defined as the first visit following appearance of the new rash.  
8.3.4. 
Use of specified study materials 
When materials are provided by GSK, it is MANDATORY that all clinical samples be 
collected and stored exclusively using those materials in the appropriate manner. The use 
of other materials could result in the exclusion of the subject from the per-protocol 
analysis (See Section 10.2 for the definition of populations for analyses). The investigator 
must ensure that his/her personnel and the laboratory(ies) under his/her supervision 
comply with this requirement. However, when GSK does not provide material for 
collecting and storing clinical samples, appropriate materials from the investigator’s site 
must be used. Refer to the Module on Clinical Trial Supplies in the SPM. 


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8.3.5. 
Biological samples (Amended, 23 November 2020) 
Refer to the central lab manual for detailed instructions for the collection, handling and 
processing of the samples. 
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the identification number for the subject (subject number). 
Collected samples will be used for protocol mandated research and purposes related to 
the improvement, development and quality assurance of the laboratory tests described in 
this protocol. This may include the management of the quality of these tests, the 
maintenance or improvement of these tests, the development of new test methods, as well 
as making sure that new tests are comparable to previous methods and work reliably. 
It is also possible that future findings may make it desirable to use the samples acquired 
in this study for future research, not described in this protocol. Therefore, all subjects will 
be asked to give a specific consent to allow GSK or a contracted partner to use the 
samples for future research. Future research will be subject to the laws and regulations in 
China and will only be performed once an Independent Ethics Committee (IEC) or 
Institutional Review Board (IRB) has approved this research. 
Information on further investigations and their rationale can be obtained from GSK. 
Any sample testing will be done in line with the consent of the individual  
subject(s)/subject’s /LAR. 
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s).  
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit/contact), unless local rules, regulations or 
guidelines require different timeframes or different procedures, which will then be in line 
with the subject consent. These extra requirements need to be communicated formally to 
and discussed and agreed with GSK. (Amended, 23 November 2020) 
The biological samples collected in the study, the quantity needed, the unit and the time 
points are described in Table 14. 
Table 14 
Biological samples 
Sample type 
Quantity 
Unit 
Timepoint 
Sub-set name 
HZ lesion sample 
preferably 
3 samples 
- 
unscheduled 
All subjects with suspected HZ episodes 
during the study 
Approx= Approximately; 
; HZ= Herpes Zoster; mL= milliliter 
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8.3.6. 
Laboratory assays  
Please refer to Section 12.2 for a detailed description of the assays performed in the 
study. Please refer to Section 12.3 for the address of the clinical laboratories used for 
sample analysis. 
Laboratory assays which will be used in this study are summarized in 
 
and Table 16 (Molecular Biology), respectively.  
8.3.6.1. 
Herpes Zoster lesion samples (Amended, 23 November 2020) 
Clinical specimens of HZ lesions will be collected from subjects clinically diagnosed as 
having a suspected case of HZ (see Section 8.3.2). Samples for HZ cases assessment 
should be kept at –20°C or –70/80°C until shipment. 
Refer to the central lab manual for more details on sample storage conditions. 
Please refer to Section 12.2 for a detailed description of the assays performed in the 
study. Please refer to Section 12.3 for the address of the clinical laboratories used for 
sample analysis.  
Table 16 
Molecular Biology 
System 
Component 
Method 
Unit 
Laboratory 
HZ lesion sample 
Varicella Zoster Virus DNA 
PCR 
No unit 
To be identified 
HZ lesion sample 
Actin Gene DNA 
PCR 
No unit 
To be identified 
HZ= Herpes Zoster; DNA= Deoxyribose nucleic acid; PCR= Polymerase Chain Reaction 
The contract research organization’s (CRO’s) clinical laboratories have established a 
Quality System supported by procedures. Clinical laboratories contracted by GSK 
conform to Good Clinical Laboratory Practice guidelines and operate in compliance with 
regulatory standards. (Amended, 23 November 2020) 
Additional testing on the vaccine and/or on the disease under study may be performed 
within the framework of the study if deemed necessary for accurate interpretation of the 
data or should such assay(s) become available at GSK. These assays may not be 
represented in the objectives/endpoints of the study protocol. 
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8.3.7. 
Biological Sample Evaluation 
8.3.8. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen used in the study vaccine. 
8.4. 
Study procedures during special circumstances (Amended, 
23 November 2020) 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, the 
following measures may be implemented for enrolled subjects:   
The impact of special circumstances to the study conduct will be documented in the 
clinical study report.  
• 
Safety follow-up may be made by a telephone call, other means of virtual contact or 
home visit, if appropriate. 
• 
Diary cards may be transmitted from and to the site by electronic means and/or 
conventional mail.  
• 
Biological samples may be collected at a different location* other than the study site 
or at subject’s home. Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use. 
* It is the investigator’s responsibility to identify an alternate location. The investigator 
should ensure that this alternate location meets ICH GCP requirements, such as adequate 
facilities to perform study procedures, appropriate training of the staff and documented 
delegation of responsibilities in this location and to refer to the requirements of China 
authority and the ethical committees. 
• 
If despite best efforts it is not possible to collect the biological samples within the 
interval predefined in the protocol (see Table 5), then the interval may be extended 
as outlined in Table 18. 
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• 
If despite best efforts it is not possible to administer the second dose of study 
intervention as defined in the protocol (see Table 5), a maximum dose interval of 180 
days may be used (see Table 18). 
− 
In case the investigator needs to conduct visits 2 and 3 during the allowed 
extended interval due to the special circumstances, then the best efforts should 
be made to conduct a safety follow-up by telephone contact at the time when  
visits 2 and 3 were initially planned (as close to the optimal window as possible) 
and approximately monthly thereafter until visits 2 and 3 procedures can be 
conducted. 
Table 18 
Intervals between study visits during special circumstances 
(Amended, 23 November 2020) 
Interval 
Optimal length of interval 
Allowed interval per 
Protocol 
Allowed interval during 
special circumstances 
Visit 1 →Visit 2  
60 days (2 months) 
49 days - 83 days 
49 days – 180 days 
Visit 2→Visit 3  
30 days (1 month) 
28 days- 48 days 
28 days- 90 days 
Between Monthly 
Contacts*  
30 days (1 month) 
20 – 40 days 
20 – 40 days 
Visit 2→Month 14 Contact 
(for the last enrolled subject 
only)   
365 days (12 months) 
344-395 days 
344 - 395 days 
Note: Investigator should prioritize conducting the visit as close to the optimal window as possible. 
• 
Visits for suspected HZ may take place in a different location* other than the study 
site or at subject’s home. If this is not feasible, then the medical evaluation of 
suspected HZ may take place virtually with documentation of all the signs and 
symptoms as outlined in Table 4 and Table 6. 
− 
If the subject is not able to contact the study staff/investigator to evaluate/ 
clinically diagnose the suspected HZ case, the subject should be encouraged to 
document all the signs and symptoms and record the progression of the rash and 
share it with the investigator when possible. 
− 
Digital photographs can be taken by the study staff/investigator at a different 
location* other than the study site or at subject’s home. If this is not feasible, 
subjects might be asked to take photographs of their Hz lesions themselves. The 
photographs will be transferred to the investigator. 
Impact on the modified exposed set for vaccine efficacy analysis and per protocol set for 
 will be determined on a case by case basis. 
COVID-19 cases identified during the study (as per standard of care) will be captured 
and reported using standard AE, medically-attended AE or SAE criteria, as outlined in 
Section 8.5. 
COVID-19 cases should be reported in the eCRF according to the WHO Case 
Definition [WHO, 2020]. (Amended, 23 November 2020) 
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8.5. 
Safety Assessments 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and any 
designees remain responsible for following up AEs that are serious, considered related to 
the study treatment or the study, or that caused the subject to discontinue the study 
treatment or study. 
8.5.1. 
Safety definitions 
Please refer to Section 12.5 for safety definitions. 


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8.5.2. 
Time period and frequency for collecting AE and serious adverse 
event (SAE) information 
An overview of the protocol-required reporting periods for safety outcomes is given in 
Table 19. Refer to the Section 12.5.8.1 for details on the time period for recording safety 
information. 
Table 19 
Reporting periods for collecting safety information (Amended, 23 
November 2020) 
Events 
Dose 
1 
(Visit 
1) 
7 days 
Post 
first 
Dose 
30 
days 
Post 
first 
Dose 
 
Dose 2 
(Visit 2) 
7 days 
Post 
last 
vaccinat
ion 
30 days 
Post last 
vaccination 
(Visit 3) 
One year 
Post last 
vaccination 
Monthly 
contact 
until study 
end* 
Day 1 
 
 
 
Month 2 
 
Month 3 
Month 14 
 
Timing of 
reporting 
Day 1 Day 7 Day 30 
 
Day 61 
Day 67 
Day 91 
 
 
Solicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
(including cellulitis) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medically attended 
visits  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading 
to withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to the 
study vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
study participation 
or concurrent 
GlaxoSmithKline 
medication/ 
vaccine a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs b 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HZ episodes  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE= Adverse event; HZ= Herpes Zoster; pIMDs= potential immune mediated diseases; SAE= serious adverse event 
Note: For each solicited and unsolicited AEs the subject experiences, the subject will be asked if he/she received 
medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical 
doctor) for any reason and this information will be recorded in the eCRF. 


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a SAEs related to study participation or GlaxoSmithKline concomitant medication/vaccine are to be recorded from the 
time the subject consents to participate in the study. All other SAEs are to be reported after administration of the first 
dose of vaccine. 
b All pIMDs are to be reported up to 12 months post last vaccination. Beyond this time period, only related 
SAEs (including related serious pIMDs as per investigator assessment) are to be reported. 
 This applies to pregnancy cases with exposure to the study treatment at any age of gestation. The timing of 
exposure to the study treatment during pregnancy is estimated in relation to the first day of the last menstrual period, 
ultrasound or known date of fertilization (e.g., assisted reproductive technology). 
* Study conclusion will be scheduled based on the projected date of the last contact of the last enrolled subject, that is 
14 months (approximately 430 days) from the enrolment date. 
All SAEs will be recorded and reported via Expedited AE Reporting Form to the sponsor 
or designee immediately and under no circumstance should this exceed 24 hours after the 
investigator became aware of it, as indicated in Section 12.5. The investigator will submit 
any updated SAE data to the sponsor within 24 hours of it being available. 
A post-study AE/SAE is defined as any event that occurs beyond the study conclusion 
contact for the subject. Investigators are not obligated to actively seek AEs or SAEs in 
former study subjects. However, if the investigator learns of any SAE, including a death, 
at any time after a subject has been discharged from the study, and he/she considers the 
event to be reasonably related to the study vaccine, the investigator will promptly notify 
the Study Contact for Reporting SAEs. 
8.5.3. 
Method of detecting AEs and SAEs 
The method of recording, evaluating, and assessing intensity, causality and outcome of 
AEs and SAEs and the procedures for completing and transmitting SAE reports are 
provided in Section 12.5.8. 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the subjects/subject’s LAR(s) is the preferred method 
to inquire about AE occurrence.  
8.5.4. 
Reporting of serious adverse events, pregnancies, and other 
events 
Table 20 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK (Amended, 23 November 2020) 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
Pregnancies 
2 weeks* 
electronic pregnancy report  
2 weeks* 
electronic pregnancy report  
pIMDs  
24 hours** ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
* Timeframe allowed after receipt or awareness of the information. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD 
‡ The investigator will be required to confirm review of the SAE/pIMD causality by ticking the ‘reviewed’ box in the 
electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/pIMD. 
 This applies to pregnancy cases with exposure to the study treatment at any age of gestation. The timing of 
exposure to the study treatment during pregnancy is estimated in relation to the first day of the last menstrual period, 
ultrasound or known date of fertilization (e.g., assisted reproductive technology). 


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8.5.4.1. 
Contact information for reporting of SAEs, pIMDs and pregnancies  
Table 21 
Contact information for reporting of serious adverse events (SAEs), 
pIMDs and pregnancies (Amended, 23 November 2020) 
Study contact for questions regarding SAEs, pIMDs and pregnancies 
Refer to the local study contact information document 
Back-up Study Contact for Reporting SAEs, pIMDs and pregnancies  
24/24 hour and 7/7 day availability: 
GSK Clinical Safety & Pharmacovigilance 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: Rix.CT-safety-vac@gsk.com 
Refer to Section 12.5.9.3 for details. 
 This applies to pregnancy cases with exposure to the study treatment at any age of gestation. The 
timing of exposure to the study treatment during pregnancy is estimated in relation to the first day of the 
last menstrual period, ultrasound or known date of fertilization (e.g., assisted reproductive technology). 
8.5.4.2. 
Regulatory reporting requirements for SAEs 
Prompt notification of an SAE by the investigator to the sponsor is essential for meeting 
legal obligations and ethical responsibilities for the safety of subjects and the safety of a 
study treatment under clinical investigation.  
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB/IEC and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g. summary or listing of SAE) from the sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 
8.5.5. 
Follow-up of AEs, SAEs, pIMDs and pregnancies 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts. All SAEs and pIMDs, will be followed until the 
event is resolved, stabilized, otherwise explained, or the subject is lost to follow-up. 
Further information on follow-up procedures is given in Section 12.5.11. 


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8.5.6. 
Treatment of adverse events 
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of a SAE/pIMDs 
should be recorded in Expedited Adverse Event Report of the subject’s eCRF (refer to 
Section 7.5). 
8.5.7. 
Subject card 
Study subjects/subject’s LAR(s) must be provided with the address and telephone 
number of the main contact for information about the clinical study. 
The investigator (or designate) must therefore provide a “subject card” to each 
subject/subject’s LAR(s). In an emergency situation, this card serves to inform the 
responsible attending physician that the subject is in a clinical study and that relevant 
information may be obtained by contacting the investigator. 
Subjects/subject’s LAR(s) must be instructed to keep subject cards in their possession at 
all times during the study duration. 
8.6. 
Genetic Research (Pharmacogenetics) 
Human genetics are not evaluated in this study. 
9. 
DISCONTINUATION CRITERIA 
9.1. 
Discontinuation from the study 
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who is 
not available for the concluding contact foreseen in the protocol.  
All data and samples collected until the date of withdrawal/last contact of the subject will 
be used for the analysis. 
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact. 
Investigators will make an attempt to contact those subjects who do not return for 
scheduled visits or follow-up (Refer to Section 9.3). 
Primary reason for study withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself, by subject’s LAR(s) or by the investigator, as well as which 
of the following possible reasons was responsible for withdrawal: 
• 
AEs requiring expedited reporting 
• 
Unsolicited non-serious AE 


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• 
Solicited AE 
• 
Protocol deviation  
• 
Withdrawal by subject, not due to an AE* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
*In case a subject is withdrawn from the study because he/she/subject’s LAR(s) has 
withdrawn consent, the investigator will document the reason for withdrawal of consent, 
if specified by the subject/subject’s LAR(s), in the eCRF. 
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 12.5.11). 
9.2. 
Discontinuation of study vaccine 
A ‘withdrawal’ from the study vaccine refers to any subject who does not receive the 
complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A subject withdrawn from the study vaccine may continue further study 
procedures (safety or immunogenicity) if planned in the study protocol, as deemed 
appropriate by the investigator. 
Primary reason relative to premature discontinuation of the study vaccine will be 
documented on the Vaccine Administration screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination/treatment was made by 
the subject himself/herself, by subject’s LAR (s) or by the investigator, as well as which 
of the following possible reasons was responsible for withdrawal: 
• 
AE requiring expedited reporting 
• 
Non-serious adverse event (specify) 
• 
Unsolicited non-serious AE 
• 
Solicited AE 
• 
Not willing to be vaccinated 
• 
HZ episode 
• 
Vaccination against VZV outside of the study 
• 
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9.3. 
Lost to follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study. 
• 
Before a subject is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• 
Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Sample size determination 
This study is planned to enroll approximately 6138 subjects equally randomized 
(approximately 3069 subjects) to the RZV and Placebo groups.  
The sample size of the study has been determined to have at least 90% power for the 
confirmatory VE primary objective of ≥ 25% (LL of the 2-sided 95% CI of VE). 
Based on the assumption of a true conservative VE of 85% (reference ZOSTER-006 
study) for prevention of confirmed HZ cases during the 12 months of follow-up post 
second dose, a total number of 27 cases of HZ will be needed to demonstrate with at least 
90% power that the lower limit (LL) of the 2-sided 95% confidence interval (CI) for the 
VE is above 25% (By Pass 2012, One Proportion Power Analysis, one-sided test, one-
sided alpha=2.5%). In case the number of confirmed HZ cases required for VE evaluation 
are not met, the follow-up duration will be extended. 
10.1.1. 
Hypotheses related to primary and secondary objectives 
The efficacy of RZV against HZ in this population for primary objective will be 
demonstrated if the LL of the 2-sided 95% CI of VE is above 25%. 
Of note, analyses under secondary objective are descriptive. 


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10.1.2. 
Sample size calculation 
Table 22 shows the power achieved with the target sample size (2762 evaluable subjects 
per group) with a randomization ratio of 1:1 to demonstrate the primary objective of VE 
under the alternative hypothesis that with true VE at 85%, lower limit of 2-sided 95% CI 
of VE observed will be 25% (Pass 2012, One Proportion Power Analysis, one-sided 
test, one-sided alpha=2.5%.). 
An attack rate of HZ of 0.85% per year in the Placebo group, a drop-out rate of 5% and 
an incidence of 5% for non-compliance to vaccine schedule were assumed for sample 
size calculations. 
Table 22 
Sample size and expected number of cases in ZOSTER-076 
Endpoints 
Vaccine efficacy 
Expected Number of 
HZ confirmed cases 
 
Sample Size 
Power 
 
VE -
assumed 
VE - LL of 
95% CI 
Placebo 
All 
Attack rate 
in control  
Evaluable  Enrolled* 
 
HZ 
confirmed 
85% 
25% 
23 
27 
0.85% 
5524 
6138 
At 
least 
90% 
*By PASS 12, One Proportion Power Analysis, one-sided test, one-sided alpha=2.5%. *Assuming 10% drop out or 
non-evaluable subjects 
The following conditions are planned prior to the final HZ VE analyses of the study. The 
number of HZ cases mentioned refers to the cases in the primary cohort for efficacy (i.e. 
the mES). 
1. At least 27 confirmed HZ cases for the overall HZ VE analysis.  
2. All subjects will be followed up till the last enrolled subject completes 12 months 
follow-up post last vaccination. In case the 27 cases needed for VE analysis are not 
accrued during this period, the follow-up will be extended. 
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10.2. 
Populations for analyses (Amended, 23 November 2020) 
For purposes of analysis, the following analysis sets are defined: 
Analysis Set (Amended, 23 
November 2020) 
Description (Amended, 23 November 2020) 
Enrolled  
Eligible subjects who have signed an informed consent and were 
randomized or undergone an invasive procedure 
Exposed  
All subjects who receive at least 1 dose of the study treatment. The allocation 
in a group is done in function of the administered treatment. 
The ES for the analysis of solicited AEs will include all participants who 
received at least 1 dose of the study treatment who have documented solicited 
AEs (i.e. diary card for solicited AEs completed and returned). 
The ES for the analysis of any other AEs other than solicited AEs will include 
all participants who received at least 1 dose of the study treatment.  
The ES for the analysis of cellular immunogenicity will include all subjects 
vaccinated for whom data concerning at least one cellular immunogenicity 
endpoint measure is available.  
Modified Exposed 
The modified exposed set excludes subjects from the exposed set who were 
not administered 2 doses of the study vaccine per protocol, or who developed 
a confirmed case of HZ prior to 30 days after the second vaccination.  
10.3. 
Statistical analyses 
10.3.1. 
Subjects disposition (Amended, 23 November 2020) 
Number of enrolled and vaccinated (at least 1 vaccination) subjects, included in each 
group or in total for a given age category or for all age categories will be described.  
10.3.2. 
Demography and baseline characteristics analyses 
Demographic and other baseline characteristics will be described by assigned group and 
for the total for Exposed Set (ES) and modified Exposed Set (mES) and the 
 
Demographic characteristics (age at first study vaccination in years, gender, race and 
ethnicity) will be summarized by overall and vaccine groups using descriptive statistics: 
• 
Frequency tables will be generated for categorical variables such as center. 
• 
Mean, standard deviation, median, minimum and maximum will be provided for 
continuous data such as age. 
• 
Cohort description and withdrawal status will be summarized by group and overall. 
All the important protocol deviation will be presented. 
All the above analysis will be performed by age strata (50-69 YOA and > 70 YOA) on 
ES and mES. 
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10.3.3. 
Efficacy analyses 
The primary analysis of efficacy will be based on the mES. A secondary analysis based 
on the ES will performed to complement the mES analysis. 
10.3.3.1. 
Case accountability (Amended, 23 November 2020) 
Rules for HZ cases for efficacy analysis: 
• 
An “event” in the efficacy analysis is defined as an endpoint of interest, i.e., 
confirmed case of HZ. 
• 
The incidence rate of an “event” is determined with reference to the first “event” 
observed in the subject, should several “events” occur in the same subject.  
• 
The HZ-free period for a subject is calculated from HZ onset to time zero relative to 
the cohort considered: first vaccination for ES and beyond the HZ-case exclusion 
period following the second injection for mES.  
The follow-up time for each subject will start: 
• 
at the day after first vaccination (Day 1) if analyses were done on the ES for efficacy, 
or 
• 
at 30 days after second vaccination if analyses were done on the mES. (Amended, 23 
November 2020) 
The follow-up time for each subject will end on the: 
• 
Date of the last visit/contact for subjects who did not have an event; 
• 
Last contact date for subjects dropped out if not preceded by an event;  
• 
Date of the event  
• 
Date of vaccination against VZV outside the study. 
The follow-up time at risk is computed using the following formula: 
• 
stop – start +1. 
The time at risk is expressed in Person-Year and derived from the follow up time (follow 
up time in days/365.25). 
The number of Person-Years at risk over an interval of time is defined as the sum of the 
confirmed HZ-free episodes over all subjects at risk during that interval, either up to the 
cut-off date for the analysis, the censoring date or the occurrence of the first HZ case for 
a subject. 


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Endpoint 
Statistical Analysis Methods 
Primary 
Confirmed HZ cases for efficacy 
The primary analysis of efficacy on the mES will be based on the occurrence of the primary 
endpoint anytime from 30 days after the administration of the second dose of the study vaccine 
up to study end. All subjects from the mES will contribute to the comparison. 
It will consider the exact inference on the relative risk adjusted for age strata conditionally to the 
total number of HZ cases observed and time at risk. This method computes an exact CI around 
the rate ratio (ratio of the event rates in the vaccinated versus control group) and takes into 
account the sum of the time at risk of the subjects within each group.  
Incidence rate and VE with 95% CI will be calculated. The VE will be defined as 1 minus the 
relative risk (RR). RR is defined as the ratio of the incidence rates of the vaccine group over the 
placebo group 
VE= (1 – relative risk) x 100 
The VE of RZV against HZ will be demonstrated if the LL of the two-sided 95% CI of VE is 
above 25%. All p-values reported will be related to the null hypothesis test VE = 0. 
The CI for VE will be derived from the exact CI from RR [Miettinen, 1985]. 
Secondary 
Confirmed HZ cases during the study in each age category (Descriptive) 
The number of confirmed HZ cases, follow-up days, associated rate, VE with 95% CI will be 
presented by each age category, descriptively, as for the primary endpoint. 
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Endpoint 
Statistical Analysis Methods 
Exploratory 
10.3.5. 
Safety analyses (Amended, 23 November 2020) 
The primary analysis of safety will be performed on the Exposed Set.  
All analyses will also be performed by age strata (50-69 YOA and 70 YOA). 
Endpoint 
Statistical Analysis Methods 
Secondary 
The percentage of subjects with at least 1 local AE (solicited and unsolicited), with at least 1 
general AE (solicited and unsolicited) and with any AE during the solicited follow-up period will 
be tabulated with exact 95% CI after each vaccine dose and overall. The percentage of doses 
followed by at least 1 local AE (solicited and unsolicited), by at least 1 general AE (solicited 
and unsolicited) and by any AE will be tabulated, with exact 95% CI. The percentage of 
subjects with at least 1 local AE (solicited only), with at least one general AE (solicited only) 
and with any AE (solicited only) during the solicited 7-day follow-up period will be tabulated with 
exact 95% CI after each vaccine dose and overall. The same calculations will be performed for 
AEs rated as grade 3.  
The percentage of subjects reporting each individual solicited local and general AE during the 
solicited follow-up period will be tabulated with exact 95% CI. The percentage of doses 
followed by each individual solicited local and general AE will be tabulated, with exact 95% CI. 
Fever will be reported per 0.5°C cumulative increments and the same tabulation will be 
performed for fever with causal relationship to the study vaccine. For all other solicited AE, the 
same tabulation will be performed for grade 1, grade 2 and grade 3 AEs and for any and grade 
3 general AEs with relationship to the study vaccine. 
The proportion of solicited AEs resulting in a medically attended visit will be tabulated. 
Duration of each individual solicited local and general AE during the solicited follow-up period 
will be presented. Total duration of each individual solicited local and general AE will be 
tabulated. 
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Endpoint 
Statistical Analysis Methods 
The percentage of subjects with at least 1 report of unsolicited AE (including cellulitis) classified 
by MedDRA and reported within 30 days (Days 1-30) post-vaccination period will be tabulated 
with exact 95% CI. The same tabulation will be performed for grade 3 unsolicited AEs, for 
unsolicited AEs with a relationship to vaccination, grade 3 unsolicited AEs with a relationship to 
vaccination. 
Number and percentage of any, grade 3, related, grade 3 related and medically-attended 
adverse events reported within 30 days (Days 1-30) post-vaccination period according to 
MedDRA primary preferred terms. 
Number and percentage of SAEs from first vaccination up to 12 months post last vaccination 
will be presented with 95% CI. The same tabulation will also be done for the interval starting 
from first vaccination up to 30 days post last vaccination. 
Number and percentage of SAEs causally related to vaccination for the interval starting from 
first vaccination up to 30 days post last vaccination and from first vaccination up to 12 months 
post last vaccination and from study start up to study end will be presented with 95% CI.  
Number and percentage of subjects experiencing fatal SAEs, classified by MedDRA Primary 
System Organ Class and Preferred Term will be tabulated using date of onset of SAE for the 
time periods–from first vaccination up to 30 days post last vaccination and first vaccination up 
to 12 months post last vaccination and from study start up to study end will be presented with 
95% CI. Fatal SAEs will also be tabulated using the date of death within the same time periods. 
Number and percentage of fatal SAEs causally related to vaccination for the interval- starting 
from first vaccination up to 30 days post last vaccination and from first vaccination up to 12 
months post last vaccination and from study start up to study end will be presented with 95% 
CI. 
Number and percentage of pIMDs from first vaccination up to 12 months post last vaccination 
will be presented with 95% CI. The same tabulation will also be done for the interval, starting 
from first vaccination up to 30 days post last vaccination.  
Number and percentage of pIMDs causally related to vaccination from first vaccination up to 12 
months post last vaccination will be presented with 95% CI. The same tabulation will also be 
done for the interval starting from first vaccination up to 30 days post last vaccination and, for 
serious pIMDs causally related to vaccination, after 12 months post last vaccination up 
to study end. (Amended, 23 November 2020) 
The proportion of subjects with concomitant medication will be tabulated, within 30 days post 
vaccination and overall, with exact 95% CI. 
Listing of fatal SAEs, SAEs, pIMDs and withdrawals (from the study or from vaccination) due to 
AEs, SAEs, solicited and unsolicited AEs will be generated for corresponding follow-up period. 
Listing of pregnancy during the entire study period will be generated. Listing for all the 
suspected HZ episodes will be generated. 
10.3.6. 
Interim analyses (Amended, 23 November 2020) 
No interim analyses will be performed. 
10.4. 
Sequence of analyses (Amended, 23 November 2020) 
The final analysis covering all primary and secondary endpoints will be performed when 
all data up to study conclusion are available. A clinical study report will be written at this 
stage and individual listings will be included. If the data for exploratory endpoints 
become available at a later stage, (an) additional analysis/ analyses will be performed. 
These analyses will be documented in annex(es) to the study report.  


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11. 
REFERENCES 
Bastidas A et al. Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster 
After Autologous Stem Cell Transplantation A Randomized Clinical Trial. JAMA. 
2019;322(2):123-133 
Berkowitz EM et al. Safety and immunogenicity of an adjuvanted herpes zoster subunit 
candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled 
study. J Infect Dis 2015;211:1279-87. 
Chlibek R et al. Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus 
subunit candidate vaccine against herpes zoster in adults > 50 YOA. J Infect Dis 2013; 
208:1953-61. 
Chlibek R et al. Safety and immunogenicity of three different formulations of an 
adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, 
randomized, controlled study. Vaccine 2014; 32:1745-53. 
Cunningham AL, Lal H, Kovac M, et al., Efficacy of the Herpes Zoster Subunit Vaccine 
in Adults 70 Years of Age or Older. N Engl J Med. 2016; 375(11): 1019-32. 
Dagnew AF, Ilhan O, Lee WS, et al Immunogenicity and safety of the adjuvanted 
recombinant zoster vaccine in adults with haematological malignancies: a phase 3, 
randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019;  
Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of 
herpes zoster. Clin Infect Dis. 2007;44 Suppl 1:S1–26. 
EMA Guideline on the exposure to medicinal products during pregnancy: need for 
post-authorisation data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community 
level in May 2006); 
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_g
uideline/2009/11/WC500011303.pdf 
FDA, U.S. Department of Health and Human Services, Center for Biologics Evaluation 
and Research. Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Version of 
September 2007. 
Lal H, Cunningham AL, Godeaux O et al. Efficacy of an Adjuvanted Herpes Zoster 
Subunit Vaccine in Older Adults. N Engl J Med. 2015: DOI: 10.1056/NEJMoa1501184. 
Lecrenier et al. Development of adjuvanted recombinant zoster vaccine and its 
implications for shingles prevention. Expert Rev Vaccines 2018 Jul;17(7):619-634. 
Leroux-Roels I et al. A phase ½ clinical trial evaluating safety and immunogenicity of a 
varicella zoster glycoprotein E subunit vaccine candidate in young and older adults. J 
Infect Dis 2012 ; 206 :1280-90. 


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Li Y, An Z, Yin D, Liu Y, et al. Disease burden of herpes zoster among population aged 
> 50 years old in China: a community based retrospective survey. PloS One. 2016; 
11(4):e0152660. 
López-Fauqued M, Campora L, Delannois F, et al. Safety profile of the adjuvanted 
recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials. 
Vaccine. 2019;37(18):2482-2493. 
Lu L, Yang YK, Xie XM, et al. A retrospective survey on herpes zoster disease burden 
and characteristics in Beijing, China. Hum Vacc Immunother. 2018:1-4. 
Miettinen OS, Nurminen M. Comparative analysis of two rates. Statistics in Medicine. 
1985; 4:213–226.  
Oxman MN, Levin MJ, Johnson GR, et al. Shingles Prevention Study Group. A vaccine 
to prevent herpes zoster and post-herpetic neuralgia in older adults. N Engl J Med. 2005; 
352: 2271-84. 
Ruggerberg JU, Gold MS, Bayas JM, et al. Anaphylaxis: case definition and guidelines 
for data collection, analysis, and presentation of immunization safety data. Vaccine 
2007:25(31):5675-84. 
Stadtmauer EA et al. A phase ½ study of an adjuvanted varicella-zoster virus subunit 
vaccine in autologous hematopoietic cell transplant recipients. Blood 2014; 124:2921-9 
Vink P, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in 
patients with solid tumors, vaccinated before or during chemotherapy: A randomized 
trial. Cancer. 2019(a);125(8):1301-12. 
Vink, P, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine 
in chronically immunosuppressed adults following renal transplant: a phase III, 
randomized clinical trial. Clin Infect Dis. 2019(b); Mar 7. 
World Health Organization (WHO). Global surveillance for COVID-19 caused by 
human infection with COVID-19 virus. Interim guidance. 20 March 2020. (Amended, 
23 November 2020) 
Zhu Q, Zheng H, Qu H, Deng H, et al. Epidemiology of herpes zoster among adults aged 
50 and above in Guangdong, China. Hum Vacc Immunother 2015; 11(8):2113-8. 


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12. 
APPENDICES 
12.1. 
Appendix 1: Abbreviations, glossary of terms and 
trademarks 
12.1.1. 
List of abbreviations  
AE: 
Adverse event 
AESI 
Adverse Event of Specific Interest 
AS01B: 
MPL, QS21, liposome based Adjuvant System (50 μg 
MPL and 50 μg QS21) 
CI: 
Confidence Interval 
CLS: 
Clinical Laboratory Sciences 
CMV 
Cytomegalovirus 
CRO: 
Contract Research Organization 
CSR 
Clinical Study Report 
DNA: 
Deoxyribonucleic acid 
EBV 
Epstein Barr virus  
eCRF: 
electronic Case Report Form  
EGA 
Estimated Gestational Age 
EoS: 
End of Study 
ES: 
Exposed Set 
(e)TDF: 
Electronic Temperature excursion Decision Form 
FSH 
Follicle Stimulating Hormone 
GCP: 
Good Clinical Practice 
gE: 
VZV glycoprotein E 
GSK: 
GlaxoSmithKline Biologicals SA 
HIV: 
Human Immunodeficiency Virus 
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HRT 
Hormonal Replacement Therapy 
HZ: 
Herpes Zoster 
HZAC: 
Herpes Zoster Ascertainment Committee  
IB: 
Investigator Brochure 
IC: 
Immunocompromised 
ICF: 
Informed Consent Form 
IEC 
Independent Ethics Committee 
IM: 
Intramuscular/Intramuscularly 
IMC 
Intercurrent Medical Condition 
IRB 
Institutional Review Board 
LAR 
Legally Acceptable Representative 
LL: 
Lower Limit 
LMP: 
Last Menstrual Period 
LOD 
Limit of Detection 
M 
Month 
MedDRA: 
Medical Dictionary for Regulatory Activities 
mES 
modified Exposed Set 
mL: 
Milliliter 
MPL: 
3-O-desacyl-4’-Monophosphoryl Lipid A 
NA: 
Not Applicable 
NaCl: 
Sodium Chloride (saline) 
PBMC 
Peripheral Blood Mononuclear Cells 
PCD: 
Primary Completion Date 
PCR: 
Polymerase Chain Reaction 
pDiary 
Paper Diary Card 


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PHN: 
Postherpetic Neuralgia 
pIMD: 
Potential Immune-Mediated Disease 
PPS 
Per Protocol Set 
QS-21: 
Quillaja 68aponaria Molina, fraction 21 (Licensed by 
GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation) 
RR 
Relative Risk 
RZV 
Recombinant Zoster Vaccine 
SAE: 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS: 
Statistical Analysis System 
SBIR: 
Source data Base for Internet Randomization 
SD 
Standard Deviation 
SoA 
Schedule of Activities 
SPM: 
Study Procedures Manual 
SRT 
Safety Review Team 
su: 
Subunit 
TBC 
To Be Confirmed 
VE: 
Vaccine Efficacy 
VZV: 
Varicella Zoster Virus 
YOA: 
Years of Age 


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12.1.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered 
related to the medicinal product.  
An adverse event (AE) can therefore be any 
unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new 
or exacerbated) temporally associated with the use of a 
medicinal product. For marketed medicinal products, 
this also includes failure to produce expected benefits 
(i.e. lack of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
trial, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a serious adverse 
event.  
In an observer-blind study, the subject and the site and 
sponsor personnel involved in the clinical evaluation of 
the subjects are blinded while other study personnel may 
be aware of the treatment assignment (see Section 7.3 
for details on observer-blinded studies). 
Caregiver: 
Someone who lives in the close surroundings of a 
subject having a continuous caring role or may be 
someone having substantial periods of contact with a 
subject and is engaged in his/her daily health care (e.g. a 
relative of the subject, a nurse who helps with daily 
activities in case of residence in a nursing home). In a 
context of a clinical study, a caregiver could include an 
individual appointed to oversee and support the subject's 
compliance with protocol specified procedures. 
Certified copy: 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e. by a dated 
signature or by generation through a validated process) 
to have the same information, including data that 
describe the context, content, and structure, as the 
original. 
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 


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End of Study (EoS)  
(Synonym of End of Trial) 
For studies with collection of human biological samples 
and/or imaging data, the EoS is defined as Last testing 
results released of samples collected at Visit Month 13* 
* In this case EoS must be achieved no later than 8 
months after LSLV. 
Epoch: 
Interval of time in the planned conduct of a study. An 
epoch is associated with a purpose (e.g. screening, 
randomization, treatment, follow-up), which applies 
across all arms of a study. NOTE: Epoch is intended as a 
standardized term to replace: period, cycle, phase, stage.  
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis (see Section 10.2 
for details on criteria for evaluability). 
Immunological correlate 
of protection: 
The defined immune response above which there is a 
high likelihood of protection in the absence of any host 
factors that might increase susceptibility to the 
infectious agent. 
Investigational vaccine: 
(Synonym of 
Investigational Medicinal 
Product) 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorisation when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use.  
Investigator 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
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Legally acceptable 
representative (LAR): 
(The terms legal 
representative or legally 
authorized representative 
are used in some settings.) 
An individual or juridical or other body authorized under 
applicable law to consent, on behalf of a prospective 
subject, to the subject's participation in the clinical trial. 
Potential Immune-
Mediated Disease: 
Potential immune-mediated diseases (pIMDs) are a 
subset of AEs that include autoimmune diseases and 
other inflammatory and/or neurologic disorders of 
interest which may or may not have an autoimmune 
aetiology. 
Primary completion date: 
The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for all primary outcomes, whether the clinical trial was 
concluded according to the pre-specified protocol or was 
terminated. 
Randomization: 
Process of random attribution of treatment to subjects in 
order to reduce bias of selection. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Site Monitor: 
An individual assigned by the sponsor who is 
responsible for assuring proper conduct of clinical 
studies at 1 or more investigational sites. 
Solicited adverse event: 
AEs to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the subject or an observer during 
a specified post-vaccination follow-up period. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data 
are contained in source documents (original records or 
certified copies). 


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Source documents: 
Original documents, data, and records (e.g. hospital 
records, clinical and office charts, laboratory notes, 
memoranda, subjects' diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified 
after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-
rays, subject files, and records kept at the pharmacy, at 
the laboratories and at medico-technical departments 
involved in the clinical trial). 
Study vaccine: 
Any investigational vaccine/product being tested and/or 
any authorised use of a vaccine/product/placebo as a 
reference or administered concomitantly, in a clinical 
trial that evaluates the use of an investigational 
vaccine/product. 
Subject: 
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient 
of the vaccine or as a control. 
Subject number: 
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study. 
Study procedures manual 
(SPM): 
Manual that provides the investigator and the site 
personnel with administrative and detailed technical 
information that does not impact the safety of the 
patients. 
Treatment: 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject. 
Treatment number: 
A number identifying a treatment to a subject, according 
to treatment allocation. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event. 


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12.1.3. 
Trademarks 
Trademark Information 
Trademarks of the GSK group of 
companies 
 
Generic description 
Shingrix 
 
Zoster vaccine recombinant, Adjuvanted 
12.2. 
Appendix 2: Clinical laboratory tests 
The tests detailed in Section 8.3.5 will be performed by the laboratory designated by the 
sponsor. 
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 6 of the protocol. 
The investigator is not allowed to do extra testing on samples outside of what has been 
agreed upon by the ethic committees. 
• 
PCR assay for confirmation of suspected case of HZ  
HZ cases will be confirmed by a PCR based algorithm that assesses the presence of VZV 
Deoxyribonucleic Acid (DNA) in samples, and the adequacy of the samples (by assessing 
the presence of β-actin DNA).  
VZV and β-actin DNA in HZ clinical specimens will be assessed using real-time PCR 
detection by the 5’ nuclease assay based on the Taqman probe technology. β-actin PCR 
will be performed on VZV negative samples only, to confirm the adequacy of the 
sampling procedure by demonstrating the presence of human material in the collected 
CCI


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sample and rule out false VZV negative results. Samples found negative by both VZV 
and β-actin–PCRs negative, will be deemed inadequate. 
In the Taqman-based PCR experiments, the amplification of a PCR product is monitored 
in real-time by means of fluorogenic probes that bind specifically to the amplified 
product. The reporter fluorophore is at the 5’ end of the Taqman probe and the quencher 
is at the 3’ end. As long as the probe is intact, no fluorescence is produced by the 
fluorophore. During the PCR polymerization step, the 5’ nuclease activity of the DNA 
polymerase separates the fluorophore from the quencher, and a measurable fluorescent 
signal proportional to the DNA copy number is produced. 
As mentioned above, the 5' nuclease-based PCR assay allows the determination of the 
DNA copy number within samples, but in the present study the VZV and β-actin DNA 
PCR data on samples from suspected HZ lesions (swabs of vesicles, papules and crusts, 
and crusts themselves) will be used qualitatively only according to the above mentioned 
approach. 
• 
Ascertainment of VZV illness including the GSK PCR testing algorithm to 
classify suspected cases 
To classify the suspected case of VZV illness, the samples from the rash lesions (if 
available) will be collected for central laboratory testing by PCR (3 samples, collected on 
the same day, per subject). If during clinical evaluation, the investigator determines that 
adequate rash lesion samples cannot be collected (that is, less than 3 lesions present, or if 
only papules are present), the investigator has the option of collecting 3 additional 
samples preferably within 7 days, if there is rash progression (that is, appearance of 
new/additional lesions if originally less than 3 lesions present, or appearance of vesicles 
if originally only papules present). When the subject returns for repeat sample collection, 
if possible, 3 samples from separate lesions should be collected. Refer to the SPM for 
further details on sample collection. 
Each rash lesion will be tested using standardized and validated molecular assays 
according to the PCR testing algorithm described below. 
A hierarchical case definition algorithm used in GSK’s Phase III efficacy trials, similar to 
the algorithm used by Merck in their Shingles Prevention Study (Zostavax efficacy study) 
[Oxman, 2005] will be used to classify each suspected case of VZV illness as a 
confirmed case or not. 
• 
If at least 1 sample coming from a given subject is “VZV positive” by PCR (as 
defined below), the PCR algorithm will classify the “suspected VZV illness” as a 
“confirmed case”. 
• 
If all the samples coming from a given subject are “VZV negative” (as defined 
below), then β-actin PCR will be performed. If one or more “VZV negative” samples 
are “β-actin positive”, this means that the sampling procedure is valid and that the 
“suspected VZV illness” will be classified as “not a case of VZV illness”. 


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• 
If PCR results for a particular subject do not confirm or exclude a “suspected VZV 
illness case” (that is, samples coming from a given subject are considered as 
“inadequate” as both VZV and β-actin PCR results are negative, or no samples are 
available for the subject), only then will the classification by the HZAC be used to 
confirm or exclude the suspected case of VZV illness. 
This algorithm includes the following steps (see Figure 2): 
1. DNA extraction from the rash lesion. 
2. VZV real-time PCR assay targeting the ORF62 gene is performed to detect VZV in 
the rash lesion: 
a. 
If the VZV PCR signal is ≥ the cut-off level, that is, the technical limit of 
detection (LOD) of the assay, the sample will be considered as “VZV positive”. 
b. If the VZV PCR signal is above 0 copy/PCR but below the cut-off level of the 
assay, it will be considered as “VZV borderline” and will be re-tested twice in 
order to obtain 3 results per sample. The sample will be considered as “VZV 
positive” if at least 2 results out of the 3 obtained are ≥ the cut-off level of the 
assay and it will be considered “VZV negative” if fewer than 2 samples are ≥ the 
cut-off level of the assay. 
c. 
If the VZV PCR signal is equal to 0 copies/PCR, the sample will be considered 
as “VZV negative”. If every sample is VZV negative, then extracted DNA from 
the samples will be assessed for the presence of β-actin DNA to confirm the 
validity of the rash lesion sampling procedure (see step 3). 
3. As described above, if all the samples are VZV negative for a given subject, then β-
actin PCR will be performed on “VZV negative” samples to confirm the validity of 
the sampling procedure. 
a. 
If the β-actin PCR signal is below the cut-off level of the assay (β-actin 
Negative), the sample will be considered as “inadequate” as no β-actin DNA 
from human cells is detected within the rash lesion sample. If all samples are β-
actin Negative, then the classification by the HZAC will be used to confirm or 
exclude the VZV illness. 
b. If the β-actin PCR signal is ≥ the cut-off level of the assay (β-actin Positive), the 
sample will be considered as “valid” but without any VZV DNA. If at least one 
sample is β-actin Positive, then the HZAC classification of a suspected case, will 
not be part of the decision-making process for case confirmation. 
Note: The cut-off level of the VZV PCR and β-actin PCR assays is defined as the 
technical limit of detection of these assays (LOD; that is, lowest concentration that can be 
detected by PCR in at least 95% of the tests). 


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Figure 2 
Algorithm for HZ case definition by GSK PCR 
 
VZV: Varicella Zoster Virus; PCR: real-time Polymerase Chain Reaction; DNA: Deoxyribonucleic Acid; ORF: Open 
Reading Frame; HZAC: Herpes Zoster Ascertainment Committee 
* If the VZV PCR signal is above 0 copy/PCR but below the cut-off level of the assay, it will be considered as “VZV 
borderline” and will be re-tested twice in order to obtain 3 results per sample. The sample will be considered as “VZV 
positive” if at least 2 results out of the three obtained are ≥ the cut-off level of the assay and it will be considered “VZV 
negative” if fewer than 2 results are ≥ the cut-off level of the assay. See then below ‘All samples are VZV Negative’. 
Note: The cut-off level of the VZV PCR assay was defined as the technical limit of detection of the assay (LOD; that is, 
lowest concentration that can be detected by PCR in at least 95% of the tests) 
12.3. 
Appendix 3: Clinical laboratories 
Laboratory for human biological samples management, PCR testing and 
 testing is 
listed below: 
Laboratory 
Address 
Covance Pharmaceutical 
Research and Development 
Shanghai 
Building N°338, Jialilue Road, 
Zhangjiang Hi-Tech Park  
Shanghai 201203 China 
 
CCI


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12.4. 
Appendix 4: Study governance considerations 
12.4.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, Informed Consent Form (ICF), Investigator 
Brochure, and other relevant documents (e.g. advertisements) must be submitted, to 
an IRB/IEC by the investigator for review and approval. These documents will be 
signed and dated by the investigator before the study is initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study subjects.  
• 
GSK will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
12.4.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interest prior 
initiation of the centre and at the end of the study. Investigators are responsible for 
providing an update of Financial Disclosure if their financial interest changes at any point 
during their participation in a study and for 1 year after completion of the study.  


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12.4.3. 
Informed consent process 
The investigator or his/her representative will explain the nature of the study to the 
subject or his/her legally authorized representative and answer all questions regarding the 
study.  
Subjects/subject’s LAR(s) must be informed that their participation is voluntary.  
Freely given and written or witnessed/thumb printed informed consent must be obtained 
from each subject and/or subject’s LAR(s), as appropriate, prior to participation in the 
study.  
The content of informed consent form must meet the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study centre. 
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
A copy of the ICF(s) must be provided to the subject or the subject’s LAR(s).  
Subjects who are rescreened are required to sign a new ICF. 
12.4.4. 
Data protection 
Subject will be assigned a unique identifier by the sponsor. Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject’s 
names or any information which would make the subject identifiable will not be 
transferred.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  
The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorised personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
GSK will also ensure the protection of personal data of investigator and the site staff 
which will be collected within the frame and for the purpose of the study.  
12.4.5. 
Publication policy 
GSK aims to publish the results of this study in searchable, peer reviewed scientific 
literature. GSK will target to submit within 18 months from LSLV for interventional 
studies and from the completion of the analysis for non-interventional studies and follows 
the guidance from the International Committee of Medical Journal Editors. 


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12.4.6. 
Dissemination of clinical study data 
The key design elements of this protocol will be posted on the GSK Clinical Study 
Register and on publicly accessible registers including ClinicalTrials.gov. Where 
required, protocol summaries will also be posted on national or regional clinical trial 
registers or databases in compliance with the applicable regulations. 
GSK also assures that results will be submitted to ClinicalTrials.gov within the required 
time-frame, in compliance with the current regulations mentioned in the table below.  
At the time of study results posting, the full study protocol and statistical analysis plan 
will also be posted on ClinicalTrials.gov.  
 
Clinicaltrial.gov 
Protocol summary 
Before enrolment of subjects 
Results summary 
Within 12 months of PCD (Primary and safety 
endpoint results)/Within 12 months of LSLV* (for 
secondary endpoint results) 
* As defined in the study protocol. 
Under the framework of the SHARE initiative, anonymized patient-level data from GSK 
sponsored interventional studies that evaluate products will be made available within 6 
months of this publication to independent researchers whose research proposals have 
been approved by an independent panel. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, provided reasonable access to statistical 
tables, figures, and relevant reports. GSK will also provide the investigator with the full 
summary of the study results. The investigator is encouraged to share the summary 
results with the study subjects, as appropriate. 
12.4.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents including source documents. The storage system used during the trial and for 
archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential documents for the trial may be added or reduced where justified (in advance of 
trial initiation) based on the importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, eCRF), the copy should fulfil the 
requirements for certified copies.  
All subject data relating to the study will be recorded on printed or eCRF unless 
transmitted to the sponsor or designee electronically (e.g. laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF.  


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The investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial subjects that supports the 
information entered in the eCRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data.  
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data should be traceable, should not 
obscure the original entry, and should be explained if necessary (e.g. via an audit trail). 
Safety and rights of subjects must be protected and study be conducted in accordance 
with the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Trial records and source documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/equivalent summary unless local regulations or institutional 
policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor.  
12.4.8. 
Source documents 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Investigator should maintain a record of the location(s) of 
their source documents.  
Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available. 
Definition of what constitutes source data and source documents can be found in the 
glossary of terms. 
12.4.9. 
Study and site closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure will 
be upon study completion. A study site is considered closed when all required 
data/documents and study supplies have been collected and a study-site closure visit has 
been performed. 


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The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of subjects by the investigator 
• 
Discontinuation of further study treatment development 
The investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the Study Conclusion screen eCRF. 
After study conclusion, placebo recipients may be offered RZV, if supported by 
study results. 
12.5. 
Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting 
12.5.1. 
Definition of AE 
12.5.1.1. 
AE Definition 
An AE is any untoward medical occurrence in a clinical study subject, temporally 
associated with the use of a study treatment, whether or not considered related to the 
study treatment. 
NOTE: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment. 
12.5.1.2. 
Events Meeting the AE Definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study vaccine administration even 
though they may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 


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• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
vaccine or a concurrent medication (overdose per se should not be reported as an 
AE/SAE). 
• 
Signs, symptoms temporally associated with study vaccine administration. 
• 
Significant failure of expected pharmacological or biological action.  
• 
Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen). 
• 
Medically attended visits related to adverse events (e.g. Hospital stays, physician 
visits and emergency room visits). 
AEs to be recorded as endpoints (solicited AEs) are described in Section 12.5.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
 “Lack of efficacy" or "vaccination failure of expected pharmacological action" per se 
will not be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from lack 
of efficacy will be reported as AE or SAE if they fulfil the definition of an AE or SAE.  
12.5.1.3. 
Events NOT Meeting the AE Definition  
• 
Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.  
• 
Pre-existing conditions or signs and/or symptoms present in a subject prior to the 
first study vaccination. These events will be recorded in the medical history section 
of the eCRF. 
12.5.2. 
Definition of SAE 
A SAE is any untoward medical occurrence that: 
• 
Results in death, 
• 
Is life-threatening, 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe. 
• 
Requires hospitalization or prolongation of existing hospitalization, 
Note: In general, hospitalization signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or in an out-patient setting. Complications 
that occur during hospitalization are also considered AEs. If a complication prolongs 
hospitalization or fulfils any other serious criteria, the event will also be considered 


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serious. When in doubt as to whether ‘hospitalisation’ occurred, or was necessary, 
the AE should be considered serious. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline is 
NOT considered an AE. 
• 
Results in disability/incapacity, OR 
Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhoea, influenza like illness, and accidental trauma (e.g. sprained 
ankle) which may interfere or prevent everyday life functions but do not constitute a 
substantial disruption. 
• 
Is a congenital anomaly/birth defect in the offspring of a study subject 
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization. 
Any HZ complications listed below will be recorded by the investigator/the study staff in 
the HZ-specific eCRF screens and on the AE/SAE reporting screens, as applicable. 
The reporting period for HZ complications will be from Day 1 to study end. Recorded 
complications not ultimately associated with a confirmed HZ case will not be considered 
as complication of HZ. 
Post-herpetic 
neuralgia 
PHN is defined by the presence of HZ-associated severe 
pain persisting or appearing more than 90 days after onset of 
the HZ rash. 
Disseminated disease 
Defined as ≥ 6 HZ lesions clearly outside the primary 
dermatome as per the investigator’s judgment. 
Ophthalmic disease 
Defined as HZ affecting any eye structure as per the 
investigator’s judgment. 
Neurologic disease 
Defined as cranial or peripheral nerve palsies, myelitis, 
meningoencephalitis, stroke, etc. that is temporally 
associated with an episode of HZ and, in the opinion of the 
investigator, is caused directly by VZV infection arising 
from the HZ episode. 


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Visceral disease 
Defined as an abnormality of one or more internal organs 
(e.g., hepatitis, pneumonitis, gastroenteritis, etc.) that is 
temporally associated with an episode of HZ and, in the 
opinion of the investigator, is caused directly by VZV 
infection arising from the HZ episode. 
HZ vasculitis 
Vasculopathy or vasculitis (based on clinical, laboratory or 
radiologic findings) that is temporally associated with an 
episode of HZ and, in the opinion of the investigator, is 
caused directly by the VZV infection arising from the HZ 
episode. 
Stroke 
A diagnosis of stroke requires that criteria 1, 2 and 3 are 
fulfilled or criteria 1 and 4 and in the opinion of the 
investigator is temporally associated with an episode of HZ 
Criterion 1: Rapid onset of localizing neurological deficit 
and/or change in level of consciousness;  
Criterion 2: Localizing neurological deficit or change in 
level of consciousness that lasts greater than 24 hours; 
Criterion 3: No other cerebral process, peripheral lesion, or 
other disorder is the cause of the localizing neurological 
deficit or change in level of consciousness; 
Criterion 4: Computerized Tomography (CT) scan or 
Magnetic Resonance Imaging (MRI) scan evidence of an 
acute thrombotic or hemorrhagic lesion. 
12.5.3. 
Solicited adverse events 
a. Solicited local (injection-site) adverse events 
The following local (injection-site) AEs will be solicited: 
Table 23 
Solicited local adverse events 
All age groups 
Pain at injection site 
Redness at injection site 
Swelling at injection site 


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b. Solicited general adverse events 
The following general AEs will be solicited:  
Table 24 
Solicited general adverse events 
Fatigue 
Fever 
Nausea 
Vomiting 
Diarrhoea 
Abdominal pain* 
Headache 
Myalgia 
Shivering* 
*Abdominal pain and shivering are not listed in the solicited general AEs as per the 
grading criteria for AEs in clinical trials of preventive vaccines in China. However, they 
are solicited as per GSK routine practice for RZV in older adults.  
For analysis purpose, the symptoms of nausea, vomiting and diarrohea will be presented 
separately as per guidelines in China. In addition, nausea, vomiting, diarrhoea and/or 
abdominal pain will be collectively presented as “Gastrointestinal symptoms “as per GSK 
standard method of reporting solicited general AEs 
Note: Subjects/subject’s LAR(s) will be instructed to measure and record the axillary 
temperature in the evening. Should additional temperature measurements be performed at 
other times of day, subjects/subject’s LAR(s) will be instructed to record the highest 
temperature in the diary card. 
12.5.4. 
Unsolicited adverse events 
An unsolicited AE is an AE that is not a specific symptom solicited using a Subject Diary 
and that is spontaneously recorded by a subject/subject’s LAR(s) who has signed the 
informed consent. 
Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses 
requiring hospitalization, or emergency room visit, or visit to/by a health care provider) 
or were of concern to the subjects/subject’s LAR(s). In case of such events, 
subjects/subject’s LAR(s) will be instructed to contact the site as soon as possible to 
report the event(s). The detailed information about the reported unsolicited AEs will be 
collected by the qualified site personnel during the interview and will be documented in 
the subject’s records. 
Unsolicited AEs that are not medically attended nor perceived as a concern by 
subjects/subject’ LAR(s) will be collected during interview with the subjects/subject’s 
LAR(s) and by review of available medical records at the next visit. 


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12.5.5. 
Adverse events of special interest (AESIs) 
12.5.5.1. 
Potential immune-mediated diseases 
Potential immune-mediated diseases (pIMDs) include autoimmune diseases and other 
inflammatory and/or neurologic disorders of interest which may or may not have an 
autoimmune aetiology. AEs that need to be recorded and reported as pIMDs include 
those listed in the Table 25. 
However, the investigator will exercise his/her medical and scientific judgement in 
deciding whether other diseases have an autoimmune origin (i.e. pathophysiology 
involving systemic or organ-specific pathogenic autoantibodies) and should also be 
recorded as a pIMD. 


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Table 25 
List of potential immune-mediated diseases (pIMDs) 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• 
Cranial nerve neuropathy, including paralysis and 
paresis (e.g. Bell’s palsy). 
• 
Optic neuritis. 
• 
Multiple sclerosis. 
• 
Transverse myelitis. 
• 
Guillain-Barré syndrome, including Miller Fisher 
syndrome and other variants. 
• 
Acute disseminated encephalomyelitis, including site 
specific variants e.g.: non-infectious encephalitis, 
encephalomyelitis, myelitis, myeloradiculoneuritis. 
• 
Myasthenia gravis, including Lambert-Eaton 
myasthenic syndrome. 
• 
Demyelinating peripheral neuropathies including: 
• 
Chronic inflammatory demyelinating polyneuropathy,  
• 
Multifocal motor neuropathy  
• 
Polyneuropathies associated with monoclonal 
gammopathy. 
• 
Narcolepsy. 
• 
Systemic lupus erythematosus and associated 
conditions 
• 
Systemic scleroderma (Systemic sclerosis), including: 
• 
Diffuse Scleroderma 
• 
CREST syndrome 
• 
Idiopathic inflammatory myopathies, including: 
• 
Dermatomyositis  
• 
Polymyositis  
• 
Anti-synthetase syndrome. 
• 
Rheumatoid Arthritis and associated conditions 
including:  
• 
Juvenile Idiopathic Arthritis 
• 
Still’s disease. 
• 
Polymyalgia rheumatica. 
• 
Spondyloarthropathies, including:  
• 
Ankylosing Spondylitis,  
• 
Reactive Arthritis (Reiter's Syndrome), 
• 
Undifferentiated Spondyloarthritis, 
• 
Psoriatic Arthritis, 
• 
Enteropathic arthritis. 
• 
Relapsing Polychondritis. 
• 
Mixed Connective Tissue disorder. 
• 
Gout. 
• 
Psoriasis. 
• 
Vitiligo. 
• 
Erythema nodosum. 
• 
Autoimmune bullous skin diseases (including 
pemphigus, pemphigoid and dermatitis 
herpetiformis). 
• 
Lichen planus. 
• 
Sweet’s syndrome. 
• 
Localised Scleroderma (Morphoea). 


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Vasculitis 
Blood disorders 
Others 
• 
Large vessels vasculitis including:  
• 
Giant Cell Arteritis (Temporal Arteritis), 
• 
Takayasu's Arteritis.  
• 
Medium sized and/or small vessels vasculitis 
including:  
• 
Polyarteritis nodosa, 
• 
Kawasaki's disease,  
• 
Microscopic Polyangiitis,  
• 
Wegener's Granulomatosis (granulomatosis with 
polyangiitis),  
• 
Churg–Strauss syndrome (allergic granulomatous 
angiitis or eosinophilic granulomatosis with 
polyangiitis),  
• 
Buerger’s disease (thromboangiitis obliterans),  
• 
Necrotising vasculitis (cutaneous or systemic),  
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive 
vasculitis (type unspecified), 
• 
Henoch-Schonlein purpura (IgA vasculitis),  
• 
Behcet's syndrome, 
• 
Leukocytoclastic vasculitis. 
• 
Autoimmune haemolytic anemia. 
• 
Autoimmune thrombocytopenia. 
• 
Antiphospholipid syndrome. 
• 
Pernicious anemia. 
• 
Autoimmune aplastic anemia. 
• 
Autoimmune neutropenia. 
• 
Autoimmune pancytopenia. 
• 
Autoimmune glomerulonephritis including: 
• 
IgA nephropathy,  
• 
Glomerulonephritis rapidly progressive,  
• 
Membranous glomerulonephritis,  
• 
Membranoproliferative glomerulonephritis,  
• 
Mesangioproliferative glomerulonephritis.  
• 
Tubulointerstitial nephritis and uveitis 
syndrome. 
• 
Ocular autoimmune diseases including: 
• 
Autoimmune uveitis  
• 
Autoimmune retinitis. 
• 
Autoimmune myocarditis. 
• 
Sarcoidosis. 
• 
Stevens-Johnson syndrome. 
• 
Sjögren’s syndrome. 
• 
Alopecia areata. 
• 
Idiopathic pulmonary fibrosis. 
• 
Goodpasture syndrome. 
• 
Raynaud’s phenomenon. 


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Liver disorders 
Gastrointestinal disorders 
Endocrine disorders 
• 
Autoimmune hepatitis. 
• 
Primary biliary cirrhosis. 
• 
Primary sclerosing cholangitis. 
• 
Autoimmune cholangitis. 
• 
Inflammatory Bowel disease, including: 
• 
Crohn’s disease,  
• 
Ulcerative colitis,  
• 
Microscopic colitis,  
• 
Ulcerative proctitis. 
• 
Celiac disease. 
• 
Autoimmune pancreatitis. 
• 
Autoimmune thyroiditis (Hashimoto thyroiditis). 
• 
Grave's or Basedow’s disease. 
• 
Diabetes mellitus type I. 
• 
Addison’s disease. 
• 
Polyglandular autoimmune syndrome. 
• 
Autoimmune hypophysitis. 
 


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12.5.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events  
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
haematology, urinalysis) or other abnormal assessments (e.g. physical examination) that 
are judged by the investigator to be clinically significant will be recorded as AE or SAE 
if they meet the definition of an AE or SAE (refer to Sections 12.5.1 and 12.5.2). 
Clinically significant abnormal laboratory findings or other abnormal assessments that 
are present at baseline and significantly worsen following the start of the study will also 
be reported as AEs or SAEs. However, clinically significant abnormal laboratory findings 
or other abnormal assessments that are associated with the disease being studied, unless 
judged by the investigator as more severe than expected for the subject’s condition, or 
that are present or detected at the start of the study and do not worsen, will not be 
reported as AEs or SAEs. 
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant. 
12.5.7. 
Events or outcomes not qualifying as adverse events or serious 
adverse events 
12.5.7.1. 
Pregnancy 
Female subjects who are pregnant or lactating at the time of vaccination must not receive 
additional doses of study vaccine but may continue other study procedures at the 
discretion of the investigator. 
While pregnancy is not considered an AE or SAE, any adverse pregnancy outcome or 
complication or elective termination of a pregnancy for medical reasons will be recorded 
and reported as an AE or a SAE. 
Note: The pregnancy should always be recorded on an electronic pregnancy report. 
The following should always be considered as SAE and will be reported as described in 
Sections 12.5.9.1 and 12.5.9.4: 
• 
Spontaneous pregnancy loss, including: 
− 
spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation) 
− 
ectopic and molar pregnancy 
− 
stillbirth (intrauterine death of foetus after 22 weeks of gestation). 
Note: the 22 weeks’ cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure [EMA, 2006]. It is recognized that national 
regulations might be different. 


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• 
Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life).  
• 
Any congenital anomaly or birth defect identified in the offspring of a study subject 
(either during pregnancy, at birth or later) regardless of whether the foetus is 
delivered dead or alive. This includes anomalies identified by prenatal ultrasound, 
amniocentesis or examination of the products of conception after elective or 
spontaneous abortion. 
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the investigator to be reasonably related to the study vaccine will be reported to GSK 
as described in Section 12.5.9. While the investigator is not obligated to actively seek this 
information from former subjects, he/she may learn of a pregnancy through spontaneous 
reporting. 
12.5.8. 
Detecting and recording adverse events, serious adverse events 
and pregnancies 
A Paper Diary (pDiary) hereafter referred to as Subject Diary will be used in this study to 
capture solicited AEs and unsolicited AEs. The subject should be trained on how and 
when to complete each field of the Subject Diary. 
The subjects/subject’s LAR (s) will be instructed to contact the investigator immediately 
should the subjects manifest any signs or symptoms they perceive as serious.  
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
Diary. If a person other than the subject/subject’s/LAR(s) enters information into the 
Subject Diary, this person’s identity must be documented in the Subject Diary. Any 
individual that makes entries into the Subject Diary must receive training on completion 
of the Subject Diary at the time of the visit when Subject Diary is dispensed. This 
training must be documented in the subject’s source record. 
At each vaccination visit, diary cards will be provided to the subject. The subject will be 
instructed to measure and record the axillary body temperature, any solicited 
local/general AEs (i.e. on the day of vaccination and during the next 6 days) or any 
unsolicited AEs (i.e. on the day of vaccination and during the next 30 days occurring 
after vaccination. The subject will be instructed to return the completed diary card to the 
investigator at the next study visit. 
• 
Collect and verify completed diary cards during discussion with the subject on Visit 
2 (Month 1) and Visit 3 (Month 3). 
• 
Any unreturned diary cards will be sought from the subject through telephone call(s) 
or any other convenient procedure.  
The investigator will transcribe the collected information into the eCRF in English. 


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12.5.8.1. 
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies (Amended, 23 November 2020) 
All AEs during 30 days following administration of each dose of study vaccine (Day 1 to 
Day 30) must be recorded into the appropriate section of the eCRF, irrespective of 
intensity or whether or not they are considered vaccination-related. 
The time period for collecting and recording all SAEs will begin at the first receipt of 
study vaccine and will end 12 months following administration of the last dose of study 
vaccine for each subject. See Section 12.5.9 for instructions on reporting of SAEs. 
However, any SAEs assessed as related to study participation (e.g. study treatment, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or related to 
a GlaxoSmithKline product will be recorded from the time a subject consent to 
participate in the study. 
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the first receipt of study vaccine. 
SAEs that are related to the study vaccine will be collected and recorded from the time 
of the first receipt of study vaccine until the subject is discharged from the study. 
In addition to the above-mentioned reporting requirements and in order to fulfil 
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) or are 
related to a concurrent GlaxoSmithKline medication/vaccine will be collected and 
recorded from the time the subject consents to participate in the study until she/he is 
discharged from the study. 
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccine until study end. See section 12.5.9 for instructions on reporting of 
pregnancies. This applies to pregnancy cases with exposure to the study treatment at any 
age of gestation. The timing of exposure to the study treatment during pregnancy is 
estimated in relation to the first day of the last menstrual period, ultrasound or known 
date of fertilization (e.g., assisted reproductive technology). 
The time period for collecting and recording of pIMDs will begin at the first receipt of 
study vaccine and will end 12 months following administration of the last dose of study 
vaccine. Beyond this time period, only serious pIMDs that are related to the study 
vaccine are to be reported. See section 12.5.9.5 for instructions on reporting of pIMDs. 
(Amended, 23 November 2020) 


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12.5.8.2. 
Evaluation of adverse events and serious adverse events 
12.5.8.2.1. Active questioning to detect adverse events and serious adverse 
events 
As a consistent method of collecting AEs, the subject/subject’s LAR(s) should be asked a 
non-leading question such as: 
‘Have you felt different in any way since receiving the vaccine or since the previous 
visit?’ 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers will be blinded on the copies of 
the medical records prior to submission to GSK. 
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms. 
12.5.8.2.2. Assessment of adverse events 
Assessment of intensity 
Solicited local and general AEs are listed in Section 12.5.3. The intensity scales described 
below are based on guidelines in China where possible, and as per GSK standard grading 
for events which do not have an intensity scale in China e.g. abdominal pain 
(gastrointestinal symptoms) and shivering.  
From an analysis perspective, the intensity of nausea, vomiting and diarrhoea will be 
presented separately as per the guidelines of Chinese authorities. In addition, as per GSK 
standard grading, the solicited general AEs of nausea, vomiting, diarrhoea and/or 
abdominal pain will be presented collectively as “gastrointestinal symptoms”. For 
analysis as per GSK standard grading, the maximum intensity of any one of these 
solicited general AEs (i.e. nausea, vomiting and diarrhoea) reported by a subject will be 
attributed as maximum intensity of “gastrointestinal symptoms” for that subject. 


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The intensity of the following solicited AEs will be assessed as described below: 
Table 26 
Intensity scales for solicited symptoms in adults 
Adults 
Adverse Event 
Intensity grade 
Parameter 
Pain at injection site 
0 
None 
1 
Mild: Do not influence or do slightly influence limb activities. 
2 
Moderate Influence limb activities. 
3 
Severe: Influence daily life. 
4 
Lose the basic selfcare ability, or hospitalization 
Redness at injection site 
 
Record greatest surface diameter in mm 
Swelling at injection site 
 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C (with 1 decimal) 
Headache 
0 
Normal 
1 
Mild: Headache that is easily tolerated 
2 
Moderate: Headache that interferes with normal activity 
3 
Severe: Headache that prevents normal activity 
4 
Refractory; require emergency presentation or hospitalization 
Fatigue 
0 
Normal 
1 
Mild: Fatigue that is easily tolerated 
2 
Moderate: Fatigue that interferes with normal activity 
3 
Severe: Fatigue that prevents normal activity 
4 
Emergency presentation or hospitalization 
Gastrointestinal symptom 
(Diarrhea) 
0 
Normal 
1 
Slight or transient, 3-4 times/day, stool with abnormal properties, or 
slight diarrhea persisting for not more than 1 week 
2 
Moderate or persistent, 5-7 times/days, stool with abnormal properties, 
or diarrhea >1 week 
3 
>7 times/day, stool with abnormal properties, or bloody diarrhea, 
orthostatic hypotension, electrolyte imbalance, and requiring 
intravenous fluid >2 L 
4 
Hypotensive shock, requiring 
hospitalization for treatment 
Gastrointestinal symptom 
(Nausea) 
0 
Normal 
1 
Transient (<24 h) or intermittent, while food intake basically normal 
2 
Persistent nausea, leading to decreased food intake (24-48 h) 
3 
Persistent nausea, leading to little food intake (>48 h) or require 
intravenous fluid infusion 
4 
Life-threatening (such as hypotensive shock) 
Gastrointestinal symptom 
(Vomiting) 
0 
Normal 
1 
1-2 times/24 h and do not influence activities 
2 
3-5 times/24 h or activities restricted 
3 
>6 times within 24 h or require intravenous fluid infusion 
4 
Due to hypotension, require hospitalization or nutrition by other routes 
Gastrointestinal symptom 
0 
Normal 
(Abdominal pain) 
1 
Mild: Gastrointestinal symptoms that are easily tolerated 
2 
Moderate: Gastrointestinal symptoms that interfere with normal activity 
3 
Severe: Gastrointestinal symptoms that prevent normal activity 
Myalgia 
0 
None  
1 
Mild: Myalgia that is easily tolerated 
2 
Moderate: Myalgia that interferes with normal activity 
3 
Severe: Myalgia that prevents normal activity 
4 
Emergency presentation or hospitalization 


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Adults 
Adverse Event 
Intensity grade 
Parameter 
Shivering 
0 
None 
1 
Shivering that is easily tolerated 
2 
Shivering that interferes with normal activity 
3 
Shivering that prevents normal activity 
* For this study, fever is defined as temperature  37.3°C as per guidelines from the Chinese authorities for axillary 
measurement. The preferred location for measuring temperature in this study will be the axilla. 
The maximum intensity of local injection site redness/swelling will be scored at GSK 
using GSK’s standard grading scale (based on the US Food and Drug Administration 
(FDA) guidelines [FDA, 2007]) and the guidelines of grading standards for AEs set by 
the Chinese authorities as follows. 
 
 
GSK standard grading scale 
Grading scale defined by Chinese 
authorities 
0 
: 
< 20 mm diameter 
Absent 
1 
: 
 20 mm to 50 mm diameter 
25 mm to <50 mm 
2 
: 
> 50 mm to 100 mm diameter 
50 mm to <100 mm  
3 
: 
> 100 mm diameter 
>100 mm  
4 
 
Not defined 
Abscess, exfoliative dermatitis, and 
dermis or deep tissue necrosis 
Fever will be graded as:  
 
 
GSK standard grading scale 
Grading scale defined by Chinese 
authorities (for axillary 
measurement) 
0 
: 
<38.0°C 
<37.3°C 
1 
: 
38.0°C – 38.5°C 
37.3°C – <38°C 
2 
: 
>38.5°C – 39.0°C  
38.0°C -<38.5°C 
3 
: 
>39.0°C 
38.5°C - <39.5°C 
 
4 
 
Not defined 
≥ 39.5°C 
The preferred location for measuring temperature in this study will be the axilla. If 
temperature is measured by other routes (such as oral or rectal), fever grading as per GSK 
scale will remain the same irrespective of route of measurement. For the grading scale as 
per Chinese authorities, the following conversion will be used: 
• 
Axillary temperature = Oral temperature minus 0.2℃; 
• 
Axillary temperature = Rectal temperature minus 0.5℃.  
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement. 


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The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities  
In adults, such an AE would, for example, prevent attendance at 
work and would necessitate the administration of corrective 
therapy. 
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE.  
Grade 3 is a category used for rating the intensity of an event; and both AEs and SAEs 
can be assessed as Grade 3. An event is defined as ‘serious’ when it meets 1 of the pre-
defined outcomes as described in Section 12.5.2. 
Assessment of causality 
The investigator is obligated to assess the relationship between study vaccine and the 
occurrence of each AE/SAE using clinical judgement. In case of concomitant 
administration of multiple vaccines/products, if possible, the investigator should specify 
if the AE could be causally related to a specific vaccine/product administered (i.e. 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine cannot be determined, the investigator should indicate the AE to be 
related to all products. 
Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study vaccine will be considered and investigated. The investigator will also consult the 
IB and/or Prescribing Information for marketed products to determine his/her assessment. 
There may be situations when a SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important that the 
investigator always makes an assessment of causality for every event prior to submission 
of the Expedited Adverse Events Report to GSK. The investigator may change his/her 
opinion of causality in light of follow-up information and update the SAE information 
accordingly. The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question: 
Is there a reasonable possibility that the AE may have been caused by the study vaccine? 


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YES 
: 
There is a reasonable possibility that the study vaccine contributed to 
the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study vaccine. There are other, more likely causes 
and administration of the study vaccine is not suspected to have 
contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 12.5.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the vaccine, if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify). 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
12.5.8.2.3. Medically attended visits 
For each solicited and unsolicited symptom the subject experiences, the subject/subject’s 
LAR(s) will be asked if he/she/the subject received medical attention defined as 
hospitalization, or an otherwise unscheduled visit to or from medical personnel for any 
reason, including emergency room visits. This information will be recorded in the eCRF. 


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12.5.9. 
Reporting of serious adverse events, pregnancies, and other 
events 
12.5.9.1. 
Prompt reporting of serious adverse events, pregnancies, and other 
events to GSK 
SAEs that occur in the time period defined in Section 12.5.8 will be reported promptly to 
GSK within the timeframes described in Table 20, once the investigator determines that 
the event meets the protocol definition of a SAE. 
Pregnancies that occur in the time period defined in Section 12.5.8 will be reported 
promptly to GSK within the timeframes described in Table 20, once the investigator 
becomes aware of the pregnancy.  
pIMDs that occur in the time period defined in Section 12.5.8 will be reported promptly 
to GSK within the timeframes described in Table 20, once the investigator determines 
that the event meets the protocol definition of a pIMDs. 
12.5.9.2. 
SAEs requiring expedited reporting to GSK 
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event. Even if the investigator does 
not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated 
WITHIN 24 HOURS. 
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE. 
12.5.9.3. 
Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the Sponsor Information) or to GSK Clinical 
Safety and Pharmacovigilance department within 24 hours.  
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system.  


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12.5.9.4. 
Completion and transmission of pregnancy reports to GSK  
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 2 WEEKS. 
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the pregnancy 
report. 
12.5.9.5. 
Reporting of pIMD to GSK (Amended, 23 November 2020) 
Once a pIMD is diagnosed (serious or non-serious) in a study subject, the investigator (or 
designate) must complete the information in the electronic Expedited Adverse Events 
Report WITHIN 24 HOURS after he/she becomes aware of the diagnosis. The report 
allows specify that the event is a pIMD and whether it is serious or non-serious. The 
report will always be completed as thoroughly as possible with all available details of the 
event, in accordance with the pIMD standard questionnaire provided. Even if the 
investigator does not have all information regarding a pIMD, the report should still be 
completed within 24 hours. Once additional relevant information is received, the report 
should be updated WITHIN 24 HOURS. 
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the pIMD causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the pIMD. 
The seriousness assessment of the pIMDs will use the same criteria as apply for SAEs 
(see Section 12.5.2). (Amended, 23 November 2020) 
Refer to Section 12.5.9.3 for back-up system in case the electronic reporting system does 
not work. 
12.5.10. 
Updating of SAE, pregnancy, and pIMD information after removal 
of write access to the subject’s eCRF 
When additional SAE, pregnancy, or pIMD information is received after removal of the 
write access to the subject’s eCRF, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
Sponsor Information) or to GSK Clinical Safety and Pharmacovigilance department 
within the designated reporting time frames specified in Table 20. 


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12.5.11. 
Follow-up of adverse events, serious adverse events, pIMDs and 
pregnancies 
12.5.11.1. Follow-up during the study 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide additional relevant information on the subject’s condition to GSK 
(within 24 hours for SAEs; refer to Table 20). 
All SAEs and pIMDs (serious or non-serious) documented at a previous visit/contact and 
designated as not recovered/not resolved or recovering/resolving will be reviewed at 
subsequent visits/contacts until the last visit of the subject. 
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until 30 
days after the last vaccination. 
12.5.11.2. Follow-up after the subject is discharged from the study 
The investigator will follow subjects: 
• 
with SAEs, pIMDs (serious or non-serious), or subjects withdrawn from the study as 
a result of an AE, until the event has resolved, subsided, stabilized, disappeared, or 
until the event is otherwise explained, or the subject is lost to follow-up or until 30 
days after last vaccination.  
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK using a paper/electronic Expedited Adverse 
Events Report and/or pregnancy report as applicable. 
GSK may request that the investigator performs or arranges the conduct of additional 
clinical examinations/tests and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obliged to assist. If a subject dies 
during participation in the study or during a recognized follow-up period, GSK will be 
provided with any available post-mortem findings, including histopathology. 
12.5.11.3. Follow-up of pregnancies 
Pregnant subjects will be followed to determine the outcome of the pregnancy. At the end 
of the pregnancy, whether full-term or premature, information on the status of the mother 
and child will be forwarded to GSK using the electronic pregnancy report and the 
Expedited Adverse Events Report if applicable. Generally, the follow-up period doesn’t 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE. 


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12.6. 
Appendix 6: Contraceptive guidance and collection of 
pregnancy information 
12.6.1. 
Definitions 
12.6.1.1. 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below) 
12.6.1.1.1. Women in the following categories are not considered WOCBP 
• 
Premenarchal 
Menarche is the onset of menses for the first time in a young female and is preceded 
by several changes associated with puberty including breast development and pubic 
hair growth. Menarche usually occurs within 1-2 years of breast development, 
thelarche. However, a young female can become pregnant before her first menses. 
Thus, a conservative definition of non-childbearing potential in a pre-menarcheal 
female is a young female who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue). 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s: review of subject’s medical 
records, medical examination, or medical history interview. 
• 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.  
• 
Females on HRT and whose menopausal status is in doubt will be required to use 1 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrolment. 
12.6.2. 
Contraception guidance 
• 
Female subjects of childbearing potential are eligible to participate if they agree to 
use an adequate contraception consistently and correctly according to the methods 
listed in GSK list of highly effective contraceptive methods provided in Table 27.  


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Table 27 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Combined (oestrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationb  
• 
oral 
• 
intravaginal  
• 
transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulationb  
• 
injectable  
Highly Effective Methods That Are User Independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulationb 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.)  
Male partner sterilization prior to the female subject’s entry into the study, and this male is the sole 
partner for that subject, 
(The information on the male sterility can come from the site personnel’s review of the 
subject’s medical records; medical examination and/or semen analysis, or medical history 
interview provided by her or her partner). 
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the subject.)  
NOTES:  
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects in clinical studies.  
b. 
Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of 
the contraceptive method. In this case 2 highly effective methods of contraception should be utilized during the 
treatment period and for at least 30 days before vaccination and 2 months after the last dose of study treatment  


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12.6.3. 
Collection of pregnancy information 
12.6.3.1. 
Female Subjects who become pregnant 
• 
Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 2 
weeks of learning of a subject's pregnancy.  
• 
Subject will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on subject and neonate, which will be 
forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.  
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in 12.5.9. While the investigator is not obligated to actively seek this 
information in former study subjects, he or she may learn of an SAE through 
spontaneous reporting.  
Any female subject who becomes pregnant while participating will be discontinued from 
study treatment. 
12.7. 
Appendix 7: Country-specific requirements 
Not Applicable. 


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12.8. 
Appendix 8: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment 
is located directly before the Table of Contents (TOC). 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 2 
23-NOV-2020 
Amendment 1 
23-APR-2020 
Final Protocol 
26-FEB-2020 
Overall Rationale for Amendment 1: 
eTrack study number 
and Abbreviated Title 
212884 (ZOSTER-076) 
Amendment number: 
Amendment 1 
Amendment date: 
23 April 2020 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
In this protocol amendment, Section 8.4 has been added as a precautionary 
measure in case of a public health crisis/special circumstances (e.g., COVID-19 
pandemic). 
Section 8.4 outlines the measures which include allowing flexibility in schedule 
and procedures to optimize site staff safety, patient safety and to preserve study 
integrity. As much as possible all study specified visits and procedures should be 
completed according to the protocol, taking into account clinical judgment and 
local public health guidance to protect the safety of staff and subjects. 
Other minor changes include: 
• 
In section 8.3.3, for each suspected case of HZ that the investigator concludes is 
clinically consistent with HZ, data will be collected ‘weekly’ instead of ‘daily’to 
align with the eCRF. 
• 
In Table 6, the term ‘group’ has been added to RZV and Placebo to denote the 
study groups. 
In section 5.1 and 7.2.2.2.1, the ‘>’80 YOA has been changed to ‘≥’80 YOA to avoid a 
gap in the age. 
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Detailed description of Protocol Amendment 2: 
Note: Two additional tables, Table 1 (Document history) and Table 2 (List of main 
changes in the protocol and their rationale), were included. The table numbering was 
updated accordingly.  
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections: 
Title page 
Co-ordinating author  
 and 
 
(4Clinics for GSK), Scientific Writers 
Contributing authors  
• 
 
• 
 and 
, Clinical 
Safety Representatives Safety Evaluation & Risk 
Management (SERM) Safety physicians 
• 
, deputy Qualified Person 
for Pharmacovigilance (dQPPV) and 
, 
Belgium 
• 
 
 
• 
 and 
, Global Regulatory 
Affairs  
• 
 and 
 
Clinical Trial Supply Managers 
• 
 and 
, Global Patents 
• 
 /and 
, Clinical 
Laboratory Science Readout Team Leaders 
• 
 
• 
 and 
, Clinical and 
Epidemiology Project Lead (CEPL) for ZOSTER, 
Clinical R&D. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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Section 1 Synopsis 
Overall Design 
New diagram: 
Original diagram: 
Section 2: Schedule of Activities (SoA) 
Table 3 Schedule of Activities  
Epoch 
Type of contact 
Timepoints 
Sampling Timepoints 
Record SAEs, pIMDs and 
pregnancies 
Record SAEs related to study 
participation, or to a concurrent 
GlaxoSmithKline GSK 
medication/vaccine 
 This applies only to pregnancy cases with exposure to the study treatment Shingrix at any age of gestation. The 
timing of exposure to the study treatment Shingrix during pregnancy is estimated in relation to the first day of the last 
menstrual period, ultrasound or known date of fertilization (e.g., assisted reproductive technology). 
RZV Group (N=3069)
Randomization (1:1)
Visit 1
Day 1
Vacc 1
BS
Visit 2
Month 2
Vacc 2
Visit 3
Month 3
BS
Monthly Contact Until 
Study End ‡
Epoch 001 (Vaccination phase)
Epoch 002 (Follow-up phase)
Placebo Group (N=3069)


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Table 5 Intervals between study visits 
Interval 
Optimal length of interval 
Allowed interval 
Visit 1 → Visit 2 
49 days - 83 days# 
Visit 2 → Visit 3
28 days- 48 days# 
# Subjects may not be eligible for inclusion in the modified Exposed Set (mES) and/or per protocol set (PPS) for 
 if study visits occur outside the allowed interval. 
Section 3.2 Background 
VZV causes 2 distinct diseases. Varicella (chickenpox) occurs shortly after primary VZV 
infection and is characterized by systemic illness and a widely disseminated rash. HZ, 
commonly called shingles, occurs when VZV reactivates from latency and typically 
manifests as a localized, pain and dermatomal rash. 
The typical HZ rash usually lasts 2 to 4 weeks and is typically accompanied by acute 
neuritis presented as pain that is often described as burning, shooting, or stabbing. In 
some patients, even touching the affected area lightly may cause pain, a phenomenon 
known as allodynia. This HZ-associated pain may be severe, and pruritus, which can also 
be severe, may be as common as pain. 
The most common complication of HZ is PHN, which . PHN is defined as pain that 
persists after the resolution of the HZ rash. 
Section 3.3.1 Risk assessment 
Important Potential/Identified 
Risk 
Data/Rationale for Risk 
Mitigation Strategy 
Study vaccine: RZV 
Risk of potential immune mediated 
diseases (pIMDs) following the 
RZV vaccination 
Based on the theoretical concern 
that vaccination with an adjuvanted 
vaccine containing potent 
immunostimulants may interfere 
with immunological self-tolerance, 
pIMDs are adverse events of 
special interest (AESI) undergoing 
special safety monitoring for all 
GSK vaccines containing Adjuvant 
Systems. pIMDs are a subset of 
adverse events (AEs) that include 
autoimmune diseases and other 
inflammatory and/or neurological 
disorders of interest which may or 
may not have an autoimmune 
etiology. Up to date, there is no 
evidence of an increased risk of 
pIMDs following vaccination with 
RZV in the populations evaluated 
adults 50 YOA or older [López-
Fauqued, 2019] 
Close monitoring of pIMDs as per 
study protocol and analysis of safety 
data generated through clinical trials 
and other sources. The potential risk of 
events of possible autoimmune 
etiology to occur is mentioned in the 
Informed Consent Form (ICF). In 
addition, the ICF advises subjects to 
contact the study doctor or the study 
staff immediately, should they get any 
symptoms that they feel may be 
serious. pIMDs will be collected up to 
12 months after administration of the 
last dose of study vaccine, and pIMDs 
considered serious and related to 
study vaccine will be collected from 
12 months after administration of 
the last dose of study vaccine until 
study end. The occurrence of pIMD 
cases will be described in the clinical 
study report (CSR). 
CCI


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Section 4 
Objectives and endpoints 
Table 7 Study objectives and endpoints 
Objectives 
Endpoints 
 
Secondary 
 
 
To evaluate vaccine reactogenicity and safety 
Solicited local and general adverse events (AEs) 
− 
Occurrence, intensity, and resulting in medically 
attended visit and duration of each solicited local 
AE within 7 days (Days 1 - 7) after each 
vaccination  
− 
Occurrence, intensity, resulting in medically 
attended visit and duration and relationship to 
vaccination of each solicited general AE within 7 
days (Days 1 - 7) after each vaccination.  
 
Serious Adverse Events (SAEs)  
− 
 
− 
Occurrence of SAEs related to study participation 
or to GlaxoSmithKline GSK concomitant 
medication/vaccine during the entire study 
period.  
 
pIMDs 
 
− 
Occurrence and relationship to vaccination of 
related serious pIMDs after 12 months post 
last vaccination up from Day 1 to study end.  
Section 5.2 Overall design 
Figure 1 Study design overview 
New diagram: 
 
RZV Group (N=3069)
Randomization (1:1)
Visit 1
Day 1
Vacc 1
BS
Visit 2
Month 2
Vacc 2
Visit 3
Month 3
BS
Monthly Contact Until 
Study End ‡
Epoch 001 (Vaccination phase)
Epoch 002 (Follow-up phase)
Placebo Group (N=3069)


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Original diagram 
−
Epoch 001 (Vaccination phase): 
−
Epoch 002 (Follow-up phase): Starting with the first monthly contact after Visit
3 (Month 3) and ending at the monthly contact that occurs within 30 days of the
projected study conclusion date of the last enrolled subject, that is, 14 months
(approximately 430 days) from the enrolment date of the last enrolled subject.
•
Safety monitoring: An internal GSK Safety Review Team (SRT) will oversee the
safety of the ZOSTER-076 study. All safety data, i.e. suspected HZ cases, AEs,
SAEs, fatal SAEs, pIMDs and cellulitis will be reviewed in a blinded manner by the
SRT at regular intervals together with data from other ongoing ZOSTER vaccine
studies.
Section 5.3 Number of subjects 
Approximately 100 subjects (50 subjects in each of HZ/su RZV and Placebo group) will 
be part of the 
 
Section 6.2.2 Prior/Concomitant therapy 
•
Planned or chronic administration (defined as more than 14 days in total) of
immunosuppressants or other immune-modifying drugs during the period starting 3
months prior to the first vaccine. For corticosteroids, this will mean prednisone
205 mg/day, or equivalent, is not allowed. Inhaled, intra-articular and topical
steroids are allowed.
Section 7.2.3 Allocation of subjects to assay subsets 
Around 100 subjects (50 in each of HZ/su RZV and Placebo group) enrolled at the 
designated site(s) will be included in the 
.  
CCI
CCI
CCI


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Section 7.5.2 Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from analyses 
•
Planned orCchronic administration (i.e. more than 14 days in total) of
immunosuppressants or other immune-modifying drugs during the study period. For
corticosteroids, this will mean prednisone 205 mg/day or equivalent is not allowed.
Inhaled, intra-articular and topical steroids are allowed.
Section 8.3.3 Follow up of suspected HZ cases 
The investigator will note in the subject’s eCRF the end date of HZ rash and if any HZ-
associated symptoms are still ongoing. Complications of the HZ episode (for example, 
PHN, disseminated HZ, ophthalmic disease) HZ should be recorded as AE/SAE, as 
appropriate. 
Section 8.3.5 Biological samples 
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit/contact), unless local rules, regulations or 
guidelines require different timeframes or different procedures, which will then be in line 
with the subject consent. These extra requirements need to be communicated formally to 
and discussed and agreed with GSK 
Section 8.3.6.1 Herpes Zoster lesion samples 
The contract research organization’s (CRO’s) clinical laboratories have established a 
Quality System supported by procedures. Clinical laboratories contracted by GSK 
conform to Good Clinical Laboratory Practice guidelines and operate in compliance with 
regulatory standards.  
Section 8.4 Study procedures during special circumstances 
Table 18 Intervals between study visits during special circumstances 
Interval 
Optimal length of interval 
Visit 2→Month 14 Contact 
(for the last enrolled subject 
only)  
365 days (1224 months) 
COVID-19 cases identified during the study (as per standard of care) will be captured 
and reported using standard AE, medically-attended AE or SAE criteria, as outlined in 
Section 8.5. 
COVID-19 cases should be reported in the eCRF according to the WHO Case 
Definition [WHO, 2020].  


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Section 8.5.2 Time period and frequency for collecting AE and serious adverse event 
(SAE) information 
Table 19 Reporting periods for collecting safety information 
Events 
Timing of 
reporting 
 
SAEs related to 
study participation 
or concurrent 
GlaxoSmithKline 
GSK medication/ 
vaccine a 
pIMDs b 
Pregnancies 
a SAEs related to study participation or GSK GlaxoSmithKline concomitant medication/vaccine are to be recorded 
from the time the subject consents to participate in the study. All other SAEs are to be reported after administration of 
the first dose of vaccine. 
b All pIMDs are to be reported up to 12 months post last vaccination. Beyond this time period, only related 
SAEs (including related serious pIMDs as per investigator assessment) are to be reported. 
 This applies only to pregnancy cases with exposure to the study treatment Shingrix at any age of gestation. The 
timing of exposure to the study treatment Shingrix during pregnancy is estimated in relation to the first day of the last 
menstrual period, ultrasound or known date of fertilization (e.g., assisted reproductive technology). 
Section 8.5.4 Reporting of serious adverse events, pregnancies, and other events 
Table 20 Timeframes for submitting serious adverse event, pregnancy and other 
events reports to GSK 
Type of Event 
 
Pregnancies 
 
 This applies only to pregnancy cases with exposure to the study treatment Shingrix at any age of gestation. The 
timing of exposure to the study treatment Shingrix during pregnancy is estimated in relation to the first day of the last 
menstrual period, ultrasound or known date of fertilization (e.g., assisted reproductive technology). 


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Section 8.5.4.1 Contact information for reporting of SAEs, pIMDs and pregnancies 
Table 21 Contact information for reporting of serious adverse events (SAEs), 
pIMDs and pregnancies  
Study contact for questions regarding SAEs, pIMDs and pregnancies 
Back-up Study Contact for Reporting SAEs, pIMDs and pregnancies 
 This applies only to pregnancy cases with exposure to the study treatment Shingrix at any age of 
gestation. The timing of exposure to the study treatment Shingrix during pregnancy is estimated in 
relation to the first day of the last menstrual period, ultrasound or known date of fertilization (e.g., 
assisted reproductive technology). 
Section 10.2 Populations for analyses 
Analysis Set 
Description 
Enrolled 
All subjects who sign informed consent. 
Eligible subjects who have signed an informed consent and were 
randomized or undergone an invasive procedure 
Randomized 
All subjects for whom valid signed informed consent form is available and 
treatment is allocated. 
Section 10.3.1 Subject disposition 
Number of enrolled, randomized, and vaccinated (at least 1 vaccination) subjects, included in each group or in total for 
a given age category or for all age categories will be described.  
Section 10.3.3.1 Case accountability 
The follow-up time for each subject will start: 
•
at 30 days after second vaccination (Month 3) if analyses were done on the mES.
Section 10.3.5 Safety analyses 
Endpoint 
Statistical Analysis Methods 
Secondary 
Number and percentage of pIMDs causally related to vaccination from first vaccination up to 12 
months post last vaccination will be presented with 95% CI. The same tabulation will also be 
done for the interval starting from first vaccination up to 30 days post last vaccination and, for 
serious pIMDs causally related to vaccination, after 12 months post last vaccination up 
from first vaccination to study end. 
Section 10.3.6 Interim analyses 
Interim report of demography and safety will be produced for license renewal 
requirements; no statistical adjustment will be performed. The cut-off date for the interim 
report will be based on the regulatory requirement for license renewal. To ensure the 
study team remains blinded, any analysis will be performed by an unblinded statistician 
outside GSK. This will be done on data as clean as possible. 
No formal interim analyses of efficacy will be performed. 


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Individual data will not be available.No interim analyses will be performed. 
Section 10.4 Sequence of analyses 
For the license renewal requirement in China, an interim report on data as clean as 
possible on safety/reactogenicity data will be performed as mentioned in Section 10.3.6. 
Section 11 References 
World Health Organization (WHO). Global surveillance for COVID-19 caused by 
human infection with COVID-19 virus. Interim guidance. 20 March 2020.  
Section 12.5.8.1 Time period for detecting and recording adverse events, serious 
adverse events and pregnancies 
The time period for collecting and recording all SAEs will begin at the first receipt of 
study vaccine and will end 12 months following administration of the last dose of study 
vaccine for each subject. See Section 12.5.9 for instructions on reporting of SAEs. 
However, any SAEs assessed as related to study participation (e.g. study treatment, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or related to 
a GSK GlaxoSmithKline product will be recorded from the time a subject consent to 
participate in the study. 
SAEs that are related to the study vaccine will be collected and recorded from the time 
of the first receipt of study vaccine until the subject is discharged from the study. 
In addition to the above-mentioned reporting requirements and in order to fulfil 
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) or are 
related to a concurrent GSK GlaxoSmithKline medication/vaccine will be collected and 
recorded from the time the subject consents to participate in the study until she/he is 
discharged from the study. 
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccine until study end. See section 12.5.9 for instructions on reporting of 
pregnancies. This applies only to pregnancy cases with exposure to the study treatment 
Shingrix at any age of gestation. The timing of exposure to the study treatment Shingrix 
during pregnancy is estimated in relation to the first day of the last menstrual period, 
ultrasound or known date of fertilization (e.g., assisted reproductive technology). 
The time period for collecting and recording of pIMDs will begin at the first receipt of 
study vaccine and will end 12 months following administration of the last dose of study 
vaccine. Beyond this time period, only serious pIMDs that are related to the study 
vaccine are to be reported. See section 12.5.9.5 for instructions on reporting of pIMDs. 


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Section 12.5.9.5 Reporting of pIMD to GSK 
The seriousness assessment of the pIMDs will use the same criteria as apply for SAEs 
(see Section 12.5.2).  
Section 12.8. Appendix 8:  Protocol Amendment History 
eTrack study number 
and Abbreviated Title 
204939 (ZOSTER-062) 212884 (ZOSTER-076) 
IND number 
BB-IND-13857 
EudraCT number 
2016-000744-34 
Amendment number: 
Amendment 1 

SAP_001.pdf: 
Statistical Analysis Plan Amendment 1
Study ID:  212884
Official Title of Study: A phase IV, randomized, observer-blind, placebo-controlled, 
multi-center study to assess the prophylactic efficacy against Herpes Zoster, 
immunogenicity and safety of Shingrix when administered intramuscularly on a 2-dose 
schedule in Chinese adults aged 50 years and older 
NCT number: NCT04869982
Date of Document: 10 May 2023


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Page 1 of 41 
Statistical Analysis Plan 
Title: 
A phase IV, randomized, observer-blind, placebo-
controlled, multi-center study to assess the 
prophylactic efficacy against Herpes Zoster, 
immunogenicity and safety of Shingrix when 
administered intramuscularly on a 2-dose schedule in 
Chinese adults aged 50 years and older 
eTrack study number and 
Abbreviated Title 
212884 (ZOSTER-076) 
Scope: 
All data pertaining to the above study. 
Date of Statistical Analysis 
Plan 
Final: 08 February 2021 
Amendment 1 Final: 10 May 2023 
APP 9000058193 Statistical Analysis Plan Template V5  (Effective date: 1July2020) 


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Page 2 of 41 
TABLE OF CONTENTS 
PAGE 
LIST OF ABBREVIATIONS ............................................................................................. 6 
1. 
DOCUMENT HISTORY ............................................................................................ 7 
2. 
OBJECTIVES/ENDPOINTS ..................................................................................... 8 
3. 
STUDY DESIGN .................................................................................................... 10 
4. 
ANALYSIS SETS ................................................................................................... 12 
4.1. 
Definition ..................................................................................................... 12 
4.1.1. 
Enrolled Set ................................................................................. 12 
4.1.2. 
Exposed Set ................................................................................ 12 
4.1.3. 
Modified Exposed Set .................................................................. 12 
4.1.4. 
Per Protocol Set ........................................................................... 13 
4.2. 
Criteria for eliminating data from Analysis Sets ........................................... 13 
4.2.1. 
Elimination from Enrolled Set ....................................................... 13 
4.2.2. 
Elimination from Exposed Set (ES) .............................................. 13 
4.2.3. 
Elimination from modified Exposed Set (mES) ............................. 14 
4.2.3.1. 
Excluded subjects....................................................... 14 
4.2.4. 
Elimination from Per-protocol analysis Set (PPS) ........................ 15 
4.2.4.1. 
Excluded subjects....................................................... 15 
4.2.5. 
Elimination from unsolicited and solicited safety set ..................... 16 
5. 
STATISTICAL ANALYSES ..................................................................................... 16 
5.1. 
General Considerations .............................................................................. 16 
5.2. 
Subjects Disposition.................................................................................... 17 
5.3. 
Demography ............................................................................................... 17 
5.3.1. 
Analysis of demographics/baseline characteristics planned 
in the protocol .............................................................................. 17 
5.3.2. 
Additional considerations ............................................................. 17 
5.4. 
Exposure .................................................................................................... 18 
5.4.1. 
Analysis of exposure planned in the protocol ............................... 18 
5.4.2. 
Additional considerations ............................................................. 18 
5.5. 
Efficacy/Effectiveness ................................................................................. 18 
5.5.1. 
Analysis of efficacy planned in the protocol .................................. 18 
5.5.1.1. 
Primary Objective ....................................................... 18 
5.5.1.2. 
Secondary Objective .................................................. 18 
5.5.2. 
Additional considerations ............................................................. 19 
5.6. 
Immunogenicity ........................................................................................... 20 
5.6.1. 
Analysis of immunogenicity planned in the protocol ..................... 20 
5.6.2. 
Additional considerations ............................................................. 20 
5.7. 
Analysis of safety and reactogenicity .......................................................... 21 
5.7.1. 
Analysis of safety and reactogenicity planned in the 
protocol ........................................................................................ 21 
5.7.2. 
Additional considerations ............................................................. 22 
6. 
ANALYSIS INTERPRETATION .............................................................................. 23 
7. 
INTERIM ANALYSES ............................................................................................. 24 


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7.1. 
Sequence of analyses ................................................................................. 24 
7.2. 
Statistical considerations for interim analyses ............................................. 24 
8. 
CHANGES TO THE PROTOCOL DEFINED STATISTICAL ANALYSIS ................. 25 
9. 
NON-STANDARD DATA DERIVATION RULES AND STATISTICAL 
METHODS ............................................................................................................. 25 
9.1. 
Data derivation............................................................................................ 25 
9.1.1. 
Demography ................................................................................ 25 
9.2. 
Statistical Method ....................................................................................... 26 
9.2.1. 
HZ incidence ................................................................................ 26 
9.2.3. 
Safety .......................................................................................... 28 
10. ANNEXES .............................................................................................................. 37 
10.1. 
Business rules for standard data derivations and statistical methods .......... 37 
10.1.1. 
Attributing events to vaccine doses .............................................. 37 
10.1.2. 
Handling of missing data .............................................................. 37 
10.1.2.1. Dates .......................................................................... 37 
10.1.2.2. Laboratory data .......................................................... 38 
10.1.2.3. Daily recording of solicited adverse events ................. 38 
10.1.2.3.1. Studies with electronic diaries ................. 38 
10.1.2.3.2. Studies with paper diaries ....................... 38 
10.1.2.4. Unsolicited adverse events ......................................... 39 
10.1.3. 
Data derivation............................................................................. 40 
10.1.3.1. Age at first dose in years ............................................ 40 
10.1.3.2. Temperature ............................................................... 40 
10.1.3.3. Onset day ................................................................... 40 
10.1.3.4. Duration of events ...................................................... 40 
10.1.3.5. Counting rules for combining solicited and 
unsolicited adverse events ......................................... 40 
10.1.3.6. Counting rules for occurrences of solicited 
events ......................................................................... 41 
10.1.4. 
Display of decimals ...................................................................... 41 
10.1.4.1. Percentages ............................................................... 41 
10.1.4.2. Demographic/baseline characteristics statistics .......... 41 
10.1.5. 
Statistical methodology ................................................................ 41 
10.1.5.1. Exact confidence intervals around proportions ........... 41 
10.2. 
TFL TOC ..................................................................................................... 41 
11. REFERENCES ....................................................................................................... 41 
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LIST OF TABLES 
PAGE 
Table 1 
Number of subjects required for enrolment ............................................. 11 
Table 2 
Intervals between study visits applicable for PPS ................................... 13 
Table 3 
Intensity scales for solicited symptoms in adults ..................................... 28 


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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 10 


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List of abbreviations 
AE 
Adverse event 
AAC 
All Analyses Complete 
CI 
Confidence Interval 
CRF 
Case Report Form 
CTRS 
Clinical Trial Registry Summary 
EoS 
End of Study 
ES 
Exposed Set 
gE 
VZV glycoprotein E 
GM 
Geometric Mean 
GSK 
GlaxoSmithKline Biologicals SA 
HZ 
Herpes Zoster 
HZAC 
HZ Ascertainment Committee 
ICF 
Inform Consent Form 
ICS 
Intracellular staining 
LL 
Lower Limit of the confidence interval 
MedDRA 
Medical Dictionary for Regulatory Activities 
mES 
Modified Exposed Set 
PBMC 
Peripheral Blood Mononuclear Cells 
PCR 
Polymerase Chain Reaction 
pIMD 
Potential Immune-Mediated Disease 
PPS 
Per Protocol Set 
RAPIDO DV 
Reporting & Analysis Plan Improving Design and Delivery of 
Outputs Data Viewer 
RR 
Relative Risk 
RZV 
Recombinant Zoster Vaccine 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBIR 
GSK Biological’s Internet Randomisation System 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SR 
Study Report 
TFL 
Tables Figures and Listings  
TOC 
Table of Content 
VE 
Vaccine Efficacy 
YOA 
Years of Age 
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1. 
DOCUMENT HISTORY 
Date 
Description 
Protocol Version 
08 FEB 2021 
Initial Version  
Amendment 2 Final:  
23 NOV 2020 
10 May 2023 
Amendment 1: Following are the changes from 
SAP from 08 FEB 2021:- 
• Added RAPIDO DV 
• Added analysis of deviation from protocol-
defined age and visit interval on ES. 
• Updated model of vaccine efficacy: added by 
agecat statement and removed agecat from 
model. 
• Substituted kaplan meier curves by cumulative 
incidence curves. 
• Calculation and derivation rule for some 
solicited adverse event grade 4 and duration 
has been added  
• Related grade 1 and related grade 2 have been 
added to GSK and Chinese scale analyses. 
• Substituted ‘grade 3’ by at ‘least grade 3’ in 
solicited local and solicited general summaries 
based on GSK scale. Also, added the categories 
that will be displayed for fever in solicited 
general summaries 
• Update of grade 3 definition for redness and 
swelling based on Chinese scale 
• Update of the Preferred Terms used to 
determine grade 4 for Redness and Swelling. 
• Update in handling of missing data in section 
10.1.2.3.2 
• Analysis for secondary safety endpoint related 
to ‘SAE due to study participation and GSK 
concomitant medication/vaccination’ has been 
added.  
• Analysis of concomitant medication related to 
confirmed HZ episode has been added 
• Covid-19 related analyses have been added 
• Minor edits in text for clarification. 
• Added site specific Covid-19 pandemic measure 
periods 
 
Amendment 2 Final:  
23 NOV 2020 


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2. 
OBJECTIVES/ENDPOINTS 
Below are the study objectives and endpoints:-  
Objectives 
Endpoints 
Primary 
To evaluate vaccine efficacy (VE) in the 
prevention of HZ compared to placebo in 
Chinese adults  50 YOA, as measured by 
the reduction in herpes zoster (HZ) risk. 
Criterion: The objective is met if the lower 
limit (LL) of the 2-sided 95% confidence 
interval (CI) of VE is above 25%. 
Confirmed HZ cases in the modified Exposed Set 
(mES). 
Secondary 
To evaluate VE in the prevention of HZ 
compared to placebo in subjects within 
each of the following age ranges: 50-69 
years of age (YOA) and ³ 70 YOA, as 
measured by the reduction in HZ risk 
Confirmed HZ cases within each of the following 
age ranges: 50-69 YOA and ³ 70 YOA in the 
mES. 
To evaluate vaccine reactogenicity and 
safety 
Solicited local and general adverse events (AEs) 
• Occurrence, intensity and resulting in 
medically attended visit of each solicited 
local AE within 7 days (Days 1 − 7) after 
each vaccination 
• Occurrence, intensity and resulting in 
medically attended visit and relationship to 
vaccination of each solicited general AE 
within 7 days (Days 1 − 7) after each 
vaccination. 
Unsolicited AEs 
• Occurrence, intensity, resulting in a 
medically-attended visit, and relationship 
to vaccination of unsolicited AEs 
(including cellulitis) within 30 days (Days 
1 − 30) post-vaccination period, 
according to the Medical Dictionary for 
Regulatory Activities (MedDRA) 
classification. 
Serious Adverse Events (SAEs) 
• Occurrence and relationship to 
vaccination of SAEs from Day 1 up to 30 
days post last vaccination. 


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Objectives 
Endpoints 
• Occurrence and relationship to 
vaccination of SAEs from Day 1 up to 12 
months post last vaccination. 
• Occurrence of SAEs related to study 
vaccine, from Day 1 up to end of study. 
• Occurrence of SAEs related to study 
participation or to GlaxoSmithKline 
concomitant medication/vaccine, from 
Day 1 up to end of study.  
• Occurrence and relationship to 
vaccination of fatal SAEs from Day 1 up 
to 30 days post last vaccination. 
•  Occurrence and relationship to 
vaccination of fatal SAEs from Day 1 up 
to 12 months post last vaccination.  
• Occurrence of related-fatal SAEs from 
Day 1 up to end of study. 
potential Immune-Mediated Diseases (pIMDs) 
• 
Occurrence and relationship to 
vaccination of pIMDs from Day 1 up to 30 
days post last vaccination. 
• 
Occurrence and relationship to 
vaccination of pIMDs from Day 1 up to 12 
months post last vaccination. 
• 
Occurrence of related serious pIMDs 
after 12 months post last vaccination up 
to study end. 
Exploratory 
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3. 
STUDY DESIGN 
Figure 1 
Study design overview 
 
; N= number of subjects planned to be enrolled; Vacc= Vaccination 
RZV= Recombinant Zoster Vaccine 
 
‡ All subjects will be followed-up until last enrolled subject has completed 1 year of follow-up post last vaccination. In 
case criteria for vaccine efficacy analyses are not met during this period, the follow-up will be extended. 
• 
Experimental design: Phase IV, randomized, observer-blind, placebo-controlled, 
multi-centric, single-country study with 2 parallel groups. 
• 
Duration of the study: The duration of the study will vary for each subject. The 
duration of the study will be up to the study conclusion contact that occurs within 
30 days of the projected study conclusion date of the last enrolled subject, that is, 
14 months (approximately 430 days) from the enrolment date. Therefore, subjects 
enrolled early in the trial will be followed for longer duration than the subjects who 
enrol later in the trial. In case criteria for VE analyses are not met during this period, 
the follow-up will be extended. 
The study conclusion visit/ contact for subjects with an ongoing episode of HZ at the 
time of last subject last contact will occur at Visit HZ-5 (Day HZ-29).  
− 
Epoch 001 (Vaccination phase): Starting at Visit 1 (Day 1) until Visit 3 (Month 
3) at one month post last vaccination. 
− 
Epoch 002 (Follow-up phase): Starting with the first monthly contact after 
Visit 3 (Month 3) and ending at the monthly contact that occurs within 30 days 
of the projected study conclusion date of the last enrolled subject, that is, 14 
months (approximately 430 days) from the enrolment date of the last enrolled 
subject. 
• 
Primary completion Date (PCD): The primary completion date will be when the 
last subject completes his/her study conclusion contact (within 30 days of the 
projected study conclusion date of the last enrolled subject, that is, 14 months 
(approximately 430 days) from the enrolment date. In case criteria for VE analyses 
are not met during this period, the follow-up will be extended. 
RZV Group (N=3069)
Randomization (1:1)
Visit 1
Day 1
Vacc 1
BS
Visit 2
Month 2
Vacc 2
Visit 3
Month 3
BS
Monthly Contact Until 
Study End ‡
Epoch 001 (Vaccination phase)
Epoch 002 (Follow-up phase)
Placebo Group (N=3069)
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• 
End of Study (EoS): 1) After all the subjects complete their study conclusion 
contact, occurring within 30 days of the projected study conclusion date of the last 
enrolled subject, that is, 14 months (approximately 430 days) from the enrolment 
date of the last subject; In case criteria for VE analyses are not met during this 
period, the follow-up will be extended and 2) the release of all polymerase chain 
reaction (PCR) test results for the HZ rash lesion samples. Refer to section 7.1 for 
more detail.  
• 
Control: placebo controlled  
• 
Vaccination schedule: 0 and 2 months 
• 
Treatment allocation: Eligible subjects will be randomized (1:1) to RZV group or 
Placebo group. The randomization algorithm will use a stratification procedure 
accounting for age (50-69 YOA and 70 YOA). 
• 
Sampling schedule: 
• 
 
 
 
• 
Clinical specimens of HZ lesions will be collected from all subjects who are 
clinically diagnosed with a suspected case of HZ (Section 8.3.2 of the protocol). 
• 
A urine specimen will be collected from all female subjects of child-bearing 
potential (see glossary of terms in the protocol definition of woman of child 
bearing potential) at Visit 1 (Day 1) and Visit 2 (Month 2). 
• 
Study group and treatment number allocation: The target will be to enrol 
approximately 6138 eligible subjects who will be randomly assigned to 2 study 
groups in a (1:1) ratio (approximately 3069 subjects in each group). 
The enrolment will be performed to ensure distribution of the population across the 2 age 
strata (50-69 YOA and >70 YOA). Approximately 75-80% and 20-25% subject should be 
enrolled in 50-69 YOA and >70 YOA, respectively. The expected distribution of subjects 
within these 2 age strata is as shown in Table 1. 
To ensure that the collection of date of birth will not jeopardize the privacy of Personally 
Identifiable Information (PII), only year of birth (YYYY) will be collected. 
Table 1 
Number of subjects required for enrolment 
Age Stratum 
Vaccine 
Targeted number (%) of subjects 
50-69 YOA 
RZV 
4604-4910 (75-80%) 
Placebo 
≥ 70 YOA 
RZV 
1228-1534 (20-25%) 
Placebo 
Allocation of the subject to a study group at the investigator site will be performed using 
a randomization system on internet (SBIR). Within each age stratum, the randomization 
algorithm will use a minimization procedure accounting for center, gender, age (50-59, 
60-69, 70-79 and ≥80 YOA) and a combined minimization factor to reflect the presence 
of any of the following conditions: type 2 diabetes mellitus, asthma, chronic obstructive 
pulmonary disease, chronic kidney disease and depression. Minimization factors will 
have equal weight in the minimization algorithm. 
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• 
Allocation of subjects to assay subsets - 
 
 
 
 
 
  
4. 
ANALYSIS SETS 
4.1. 
Definition 
4.1.1. 
Enrolled Set 
The enrolled set will include all eligible subjects who have signed an informed consent 
and were randomized or undergone an invasive procedure. 
4.1.2. 
Exposed Set 
Exposed Set (ES) will include all subjects who receive at least 1 dose of the study 
treatment. The allocation in a group is done in function of the administered treatment. 
The ES for the analysis of solicited AEs will include all participants who received at least 
1 dose of the study treatment and who have documented solicited AEs (i.e. diary card for 
solicited AEs completed and returned). 
The ES for the analysis of any other AEs other than solicited AEs will include all 
participants who received at least 1 dose of the study treatment.  
 
 
4.1.3. 
Modified Exposed Set 
The modified Exposed Set (mES) excludes subjects from the ES who were not 
administered 2 doses of the study treatment per protocol, or who developed a confirmed 
case of HZ prior to 30 days after the second vaccination (Refer to section 4.2.3 for more 
detail on the criteria). 
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4.1.4. 
Per Protocol Set  
All subjects who received at least 1 dose of the study treatment to which they are 
randomised and have post-vaccination data minus subjects with protocol deviations that 
lead to exclusion. The Per Protocol Set (PPS) (in vaccinated subjects) will include all 
evaluable vaccinated subjects: 
• 
; 
• 
who have received 2 doses of study vaccine; 
• 
for whom the study vaccine has been administered as per protocol; 
• 
who have not received medication/vaccine forbidden in the protocol (refer to Section 
4.2.4 for details on the criteria); 
• 
who meet all eligibility criteria (refer to Sections 6.1 and 6.2 of the protocol); 
• 
who comply with the procedures and intervals defined in the protocol; 
• 
who do not meet any of the criteria for elimination during the study (refer to Section 
4.2.4 for details on the criteria); 
• 
for whom data concerning immunogenicity endpoint measures are available. 
The intervals allowed for the inclusion in the PPS is the ‘allowed interval per protocol’ as 
defined in following table: 
Table 2 
Intervals between study visits applicable for PPS  
Interval 
Optimal length of interval 
Allowed interval per protocol 
Visit 1→Visit 2 
60 days (2 months) 
49 days - 83 days 
Visit 2→Visit 3 
30 days (1 month) 
28 days - 48 days 
4.2. 
Criteria for eliminating data from Analysis Sets 
Elimination codes are used to identify subjects to be eliminated from analysis. Detail is 
provided below for each set.  
4.2.1. 
Elimination from Enrolled Set  
Code 800 (fraudulent data), 900 (invalid ICF) and 1010 (treatment number not allocated) 
will be used for identifying subjects eliminated from Enrolled Set. 
4.2.2. 
Elimination from Exposed Set (ES) 
Code 1030 (Study treatment not administered at all), 800 (fraudulent data), 900 (invalid 
ICF) and 1010 (treatment number not allocated) will be used for identifying subjects 
eliminated from ES.  
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4.2.3. 
Elimination from modified Exposed Set (mES) 
Code 1030 (Study treatment not administered at all), 800 (fraudulent data), 900 (invalid 
ICF), 1010 (treatment number not allocated), 1070 (treatment not administered according 
to protocol), 2500 (Subject who didn’t receive two doses) and 3500 (Subject having 
confirmed HZ episode prior to 30 days after the dose 2) will be used for identifying 
subjects eliminated from mES.  
Please note that impact of COVID-19 on the modified Exposed Set for vaccine efficacy 
analysis will be determined on a case-by-case basis. 
4.2.3.1. 
Excluded subjects 
A subject will be excluded from the mES analysis under the following conditions. Please 
note that impact of COVID 19 on the mES will be determined on a case-by-case basis. 
Code 
Condition under which the code is used 
Visit (timepoints) where the 
code is applicable 
800 
Fraudulent data 
All 
900 
Invalid ICF 
Visit 1 
1010 
Treatment number not allocated 
Visit 1 
1030 
Study vaccine not administered at all 
Visit 1 
1070** 
Vaccination not according to protocol: 
• 
Subjects got vaccinated with the 
correct vaccine but containing a lower 
volume 
• 
Administration not according to 
protocol for reason specified by 
investigator other than route, side and 
site.  
• 
Site and route of vaccination is wrong 
or unknown 
• 
Wrong replacement or study vaccine 
administered (not compatible with the 
vaccine regimen associated to the 
treatment number) 
Visit 1, Visit 2 
2500 
Subjects who didn’t receive two doses   
Visit 2 
3500 
Subjects having confirmed HZ 
episode prior to 30 days after the dose 2 
Visit 1 to Visit 3 
  ** Attribution of these elimination codes will be evaluated on case-by-case basis and requires CRDL confirmation 


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4.2.4. 
Elimination from Per-protocol analysis Set (PPS) 
4.2.4.1. 
Excluded subjects 
A subject will be excluded from the PPS analysis under the following conditions. Please 
note that impact of COVID 19 on the per protocol set will be determined on a case-by-
case basis. 
Code 
Condition under which the code is used 
Visit (timepoints) 
where the code is 
applicable 
800 
Fraudulent data 
All 
900 
Invalid ICF 
Visit 1 
1010 
Treatment number not allocated 
Visit 1 
1030 
Study vaccine not administered at all 
Visit 1 
1040* 
Administration of concomitant vaccine(s) 
forbidden in the protocol 
Any concomitant vaccination not foreseen by the 
study protocol administered in the period starting 
30 days before the first dose of the study vaccine 
and ending at Visit 3 (Day -30 to Month 3) 
- 30 days to Visit 1 
through Visit 3 
1050 
Randomisation failure 
All 
1060 
Randomisation code was broken 
Visit 1 to Visit 3 
1070** 
Vaccination not according to protocol: 
• 
Subjects got vaccinated with the correct 
vaccine but containing a lower volume 
• 
Administration not according to protocol for 
reason specified by investigator other than 
route, side and site.  
• 
Site and route of vaccination is wrong or 
unknown 
• 
Wrong replacement or study vaccine 
administered (not compatible with the vaccine 
regimen associated to the treatment number) 
Visit 1, Visit 2 
1080 
Vaccine temperature deviation 
Visit 1, Visit 2 
1090 
Expired vaccine administered 
Visit 1, Visit 2 
2010 
Protocol violation (inclusion/exclusion criteria) 
Visit 1 
2040* 
Administration of any medication forbidden by the 
protocol (refer to Section 7.5.2 of the protocol) 
administered in the period from the first dose of 
study vaccine and ending at Visit 3 (Day 1 to 
Month 3)  
Visit 1 to Visit 3 


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Code 
Condition under which the code is used 
Visit (timepoints) 
where the code is 
applicable 
2050* 
Underlying medical condition forbidden by the 
protocol  
Any intercurrent medical condition (IMC) (refer to 
section 7.6 of the protocol) which can affect the 
immune response to the study vaccine and ending 
at Visit 3 (Day 1 to Month 3) 
Visit 1 to Visit 3 
2060* 
Concomitant infection related to the vaccine which 
may influence immune response 
Visit 1 to Visit 3 
2070* 
Concomitant infection not related to the vaccine 
which may influence immune response 
Visit 1 to Visit 3 
2080 
Subjects did not comply with vaccination schedule 
DOSE 1 – DOSE 2 = 49-83 days 
Visit 2 
2090 
Subjects did not comply with blood sample 
schedule 
DOSE2 - blood sample (BS)2 = 28-48 days 
Visit 3 
2100 
Serological results not available post-vaccination 
 
Visit 3 
2120 
Obvious incoherence or abnormality or error in 
data 
 
Visit 3 
2500 
Subjects who didn’t receive two doses   
Visit 2 
3500 
Subjects having confirmed HZ 
episode prior to 30 days after the dose 2 
Visit 1 to Visit 3 
2130 
 
 
  *Attribution of these elimination codes to subject need CRDL review of individual listing 
  ** Attribution of these elimination codes will be evaluated on case-by-case basis and requires CRDL confirmation 
# 
 
 
4.2.5. 
Elimination from unsolicited and solicited safety set 
Unsolicited and solicited safety set is not applicable for the study.  
5. 
STATISTICAL ANALYSES 
The standard data derivation rules and stat methods are described in section 10.1 while 
the study specific data derivation rules and stat methods are described in section 9 of the 
SAP. 
Analysis on Covid-19 cases has been added in the analysis of safety section of the SAP. 
5.1. 
General Considerations 
Note: Subject-level data will be available interactively via RAPIDO DV after AAC. 
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5.2. 
Subjects Disposition 
Number of enrolled and vaccinated (at least 1 vaccination) subjects, included in each 
group or in total for a given age category or for all age categories will be described.  
5.3. 
Demography 
5.3.1. 
Analysis of demographics/baseline characteristics planned in the 
protocol 
Demographic and other baseline characteristics will be described by assigned group and 
for the total for ES and mES and the 
. 
Demographic characteristics (age at first study vaccination in years, gender, race and 
ethnicity) will be summarized overall and by study groups using descriptive statistics: 
• 
Frequency tables will be generated for categorical variables such as center. 
• 
Mean, standard deviation, median, minimum and maximum will be provided for 
continuous data such as age. 
Cohort description and withdrawal status will be summarized by group and overall. All 
important protocol deviations leading to elimination will be presented. 
All the above analyses will be performed by age strata (50-69 YOA and  70 YOA) on 
ES and mES. 
5.3.2. 
Additional considerations 
Following additional tables will also be generated:  
• 
Number of subjects by centers will be presented on ES. 
• 
Deviation from protocol-defined age and visit interval on ES. 
• 
The following table will be generated for web disclosure: 
- 
Percentage of enrolled subjects by age categories (18-64, 65-84, ≥85) YOA will 
be tabulated by group. 
• 
Summary of important protocol deviations leading to elimination from any analysis 
will be presented for the Enrolled Set overall and by age strata. 
• 
The number of subjects enrolled into the study as well as the number of subjects 
excluded from mES and PPS analyses will be presented through 3 consort tables, 
overall and by age strata only for Consort table 1 and 2: 
- 
Consort table 1 - Showing the subjects disposition from Enrolled Set to ES 
- 
Consort table 2 – Showing the subjects disposition from ES to mES 
- 
Consort table 3 - Showing the subjects disposition from ES to PPS 
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5.4. 
Exposure 
5.4.1. 
Analysis of exposure planned in the protocol 
None  
5.4.2. 
Additional considerations 
The number of doses administered will be tabulated. The number of doses administered 
will be tabulated by age stratum. 
5.5. 
Efficacy/Effectiveness 
The primary analysis of efficacy will be based on the mES. A secondary analysis based 
on the ES will performed to complement the mES analysis. 
5.5.1. 
Analysis of efficacy planned in the protocol 
5.5.1.1. 
Primary Objective 
The primary inferential analysis of efficacy on the mES will be based on the occurrence 
of the primary endpoint anytime from 30 days after the administration of the second dose 
of the study vaccine up to study end. All subjects from the mES will contribute to the 
comparison. 
It will consider the exact inference on the relative risk (RR) adjusted for age strata 
conditionally to the total number of HZ cases observed and time at risk. This method 
computes an exact CI around the rate ratio (ratio of the event rates in the RZV group 
versus control group) and takes into account, the sum of the time at risk of the subjects 
within each group.  
Incidence rate and VE with 95% CI will be calculated using Poisson method. The VE 
will be defined as 1 minus the RR. RR is defined as the ratio of the incidence rates of the 
RZV group over the placebo group [VE= (1 – RR) x 100] 
The VE of RZV against HZ will be demonstrated if the LL of the two-sided 95% CI of 
VE is above 25%. All p-values reported will be related to the null hypothesis test VE = 0. 
The calculation of the time at risk and other statistical method detail are provided in 
Section 9.2.1.  
5.5.1.2. 
Secondary Objective  
The number of confirmed HZ cases, follow-up days, associated rate, VE with 95% CI 
will be presented by each age category, descriptively, as for the primary endpoint. 


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5.5.2. 
Additional considerations 
Following descriptive table and figure will be generated by study groups on mES and ES: 
• 
For each study group, the number of subjects at risk, person-year, number and 
incidence of confirmed HZ will be tabulated overall. 
• 
Forest plot for vaccine efficacy against HZ by age strata and overall during the entire 
study period  
• 
Cumulative incidence curve for HZ for each study group.  
• 
Number and percentage of episodes of all confirmed HZ episodes during the entire 
study period. 
• 
Number and percentage of confirmed HZ episodes out of all the suspected cases 
reported.  
• 
Number and percentage of suspected cases for which at least one PCR sample was 
collected on ES only. 
• 
Distribution of suspected HZ cases using the HZ classification tools (PCR testing & 
HZ Ascertainment Committee (HZAC))  
• 
The vaccine efficacy will be assessed by Poisson method for primary objective and 
fitted via the PROC GENMOD procedure according to the following code 
PROC GENMOD DATA=pois_ve EXACTONLY; 
BY AGECAT; 
STRATA AGECAT; 
CLASS AGECAT/PARAM=ref;  
MODEL nb_cases = group_nb/DIST=poisson OFFSET = Log_T LINK=log; 
EXACT group_nb /ESTIMATE OUTDIST=dist ALPHA=0.05; 
ODS OUTPUT ExactParmEst=estimate ExactTests=ExactTest; 
RUN; 
 
Where, 
nb_case = number of cases 
agecat = Age strata categories (50-69 and >=70 YOA)  
group_nb = Group information of the subject (treatment received by subject) 
Log_T = Log of the follow-up time 
 
DATA VE ; 
SET ESTIMATE; 
FORMAT VE best12. ll best12. ul best12.; 
VE = ( 1 - exp (estimate)) * 100; 
ll = ( 1 - exp (UPPERCL)) * 100; 
ul = ( 1 - exp (LOWERCL)) * 100; 
RUN; 


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5.6.2. 
Additional considerations 
None  
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5.7. 
Analysis of safety and reactogenicity 
5.7.1. 
Analysis of safety and reactogenicity planned in the protocol 
The primary analysis of safety will be performed on the ES. All analyses will also be 
performed by age strata (50-69 YOA and 70 YOA). Following analysis is planned to be 
performed:  
The percentage of subjects with at least 1 local AE (solicited and unsolicited), with at 
least 1 general AE (solicited and unsolicited) and with any AE (solicited and unsolicited) 
during the solicited follow-up period will be tabulated with exact 95% CI after each 
vaccine dose and overall. The percentage of doses followed by at least 1 local AE 
(solicited and unsolicited), by at least 1 general AE (solicited and unsolicited) and by any 
AE will be tabulated, with exact 95% CI. The percentage of subjects with at least 1 local 
AE (solicited only), with at least one general AE (solicited only) and with any AE 
(solicited only) during the solicited 7-day follow-up period will be tabulated with exact 
95% CI after each vaccine dose and overall.  
The percentage of subjects reporting each solicited local and general AE during the 
solicited follow-up period will be tabulated with exact 95% CI. The percentage of doses 
followed by each individual solicited local and general AE will be tabulated, with exact 
95% CI. Fever will be reported with any (>=38.0), >=38.0 - <=38.5, >38.5 - <=39.0 and 
>39.0 in GSK scale. In Chinese scale, it will be reported with any (>=37.3), 37.3 - 
<38.0, 38.0 - <38.5, 38.5 - <39.5 and >=39.5. The same tabulation will be performed for 
fever with causal relationship to the study vaccine.  
In the table presented based on the GSK scale, for all other solicited AEs, the same table 
will have grade 1, grade 2 and at least grade 3 AEs and for any and at least grade 3 
general AEs with relationship to the study vaccine. Related grade 1 and related grade 2 
will also be displayed. 
In the table presented based on the Chinese scale, for all other solicited AEs, the same 
table will have grade 1, grade 2, grade 3 and grade 4 applicable for table with Chinese 
intensity scale) AEs and for any, grade 3 and grade 4 general AEs with relationship to 
the study vaccine. Related grade 1 and related grade 2 will also be displayed. 
The proportion of solicited AEs resulting in a medically attended visit will be tabulated.  
The percentage of subjects with at least 1 report of unsolicited AE (including cellulitis) 
classified by MedDRA primary system organ class (SOC) and preferred terms (PT) will 
be reported within 30 days (Days 1-30) post each vaccination with exact 95% CI. The 
same tabulation will be performed for grade 3 unsolicited AEs, for unsolicited AEs with a 
relationship to vaccination, grade 3 unsolicited AEs with a relationship to vaccination. 
Number and percentage of any, grade 3, related, grade 3 related and medically attended 
unsolicited AEs reported within 30 days (Days 1-30) post any vaccination according to 
MedDRA primary system organ class and preferred terms will be presented. 


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Number and percentage of SAEs from first vaccination up to 12 months post last 
vaccination will be presented with 95% CI. The same tabulation will also be done for the 
interval- starting from first vaccination up to 30 days post last vaccination. 
Number and percentage of SAEs causally related to vaccination for the interval- starting 
from first vaccination up to 30 days post last vaccination and from first vaccination up to 
12 months post last vaccination and from study start up to study end will be presented 
with 95% CI.  
Number and percentage of subjects experiencing fatal SAEs, classified by MedDRA 
Primary System Organ Class and Preferred Term will be tabulated using date of onset of 
SAE for the time periods –from first vaccination up to 30 days post last vaccination and 
first vaccination up to 12 months post last will be presented with 95% CI. 
Number and percentage of fatal SAEs causally related to vaccination for the interval- 
starting from first vaccination up to 30 days post last vaccination and from first 
vaccination up to 12 months post last vaccination and from study start up to study end 
will be presented with 95% CI. 
Number and percentage of pIMDs from first vaccination up to 12 months post last 
vaccination will be presented with 95% CI. The same tabulation will also be done for the 
interval – starting from first vaccination up to 30 days post last vaccination.  
Number and percentage of pIMDs causally related to vaccination from first vaccination 
up to 12 months post last vaccination will be presented with 95% CI. The same tabulation 
will also be done for the interval – starting from first vaccination up to 30 days post last 
vaccination. Number and percentage of serious pIMDs causally related to vaccination 
from 12 months post last vaccination up to study end and will be presented with 95% CI. 
The proportion of subjects with concomitant medication will be tabulated, within 30 days 
post each vaccination and overall only, with exact 95% CI. 
Listing of fatal SAEs, SAEs, pIMDs and withdrawals (from the study or from 
vaccination) due to AEs, SAEs, solicited and unsolicited AEs will be generated.  
Listing of pregnancy during the entire study period will be generated.  
Listing for all the suspected HZ episodes will be generated. 
5.7.2. 
Additional considerations 
The table on solicited local and general AEs will be presented separately according to 
GSK grading and grading scale provided by Chinese authorities.  
Duration of each solicited local and general AE during the solicited follow-up period will 
be presented. Total duration of each individual solicited local and general AE will be 
tabulated. 


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Duration of each grade 3 solicited local and general AE during the solicited follow-up 
period will be presented in the table by GSK grading. Duration of each grade 3 and above 
solicited local and general AE during the solicited follow-up period will be presented in 
the table by Chinese authority grading.  
Listing of complication related to confirmed HZ episode will be presented.  
Number and percentage of subjects experiencing fatal SAEs, classified by MedDRA 
Primary System Organ Class and Preferred Term will be tabulated using date of onset of 
SAE from study start up to study end will be presented with 95% CI for web disclosure. 
The table for web disclosure related to solicited adverse events endpoint will be based on 
both GSK and Chinese intensity scale.  
Summary of subjects with serious adverse events related to study participation and not 
by the study vaccines or to GlaxoSmithKline concomitant medication/vaccine during 
the entire study period based on ES. 
Following listings of concomitant medications related to confirmed HZ episode will be 
presented based on Exposed Set: 
• 
Pain rescue medication to control HZ pain 
• 
Antiviral treatment for HZ 
• 
Other therapy for HZ 
Additional analyses/considerations due to COVID-19 pandemic on ES: 
• 
Summary of COVID-19 Assessment. 
• 
Incidence of COVID-19 as an AE and SAE. A standardized MedDRA Query 
(SMQ) will be used to identify all COVID-19 cases reported as AEs. 
• 
A column to identify COVID-19 AEs/SAEs will be added to listing of (S)AEs and 
solicited adverse events leading to study or treatment discontinuation from first 
vaccination up to study end. 
6. 
ANALYSIS INTERPRETATION 
The primary objective of VE in the prevention of HZ compared to placebo in Chinese 
adults 50 YOA, as measured by the reduction in HZ risk is considered met if the LL of 
the 2-sided 95% CI of VE is above 25%. 
For all secondary objectives, analyses will be descriptive with the aim to characterize the 
differences in reactogenicity, safety and immunogenicity between groups. 


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7. 
INTERIM ANALYSES 
7.1. 
Sequence of analyses 
The analysis of all primary and secondary endpoints will be performed when all data up 
to study conclusion are available. A clinical study report (CSR) will be written at this 
stage and individual listings will be included.  
One final analysis is planned and will be triggered when the following will take place: 
• 
When at least 27 confirmed cases of HZ have accrued in the primary cohort for 
efficacy (cut-off date for primary efficacy analysis); AND 
• 
When all subjects have completed at least 12 months safety follow-up post last 
vaccination. 
Data contributing to the analysis of the primary efficacy objective (confirmed HZ cases) 
will be collected until the cut-off date. After the cut-off date, case confirmation of any 
new suspected HZ will not be performed. Once the study reaches the cut-off date, the 
conclusion contact for a subject will be planned based on the status of the safety follow-
up: 
• 
Cut-off date reached before the completion of safety follow-up – Continue the 
monthly safety follow-up after the cut-off date until all subjects have completed 12 
months of follow-up post last dose. 
• 
Cut-off date reached after the completion of safety follow-up – Continue the 
monthly contacts after the completion of the 12 months safety follow-up period until 
at least 27 confirmed HZ cases have accrued (cut-off date).  
When the trigger for primary efficacy analysis is reached, subjects with an ongoing HZ 
episode will be followed until Day HZ-29.  
The conclusion contact of the last subject will be the study end. 
If the data for exploratory endpoints become available at a later stage, (an) additional 
analysis/ analyses will be performed. These analyses will be documented in the annex 
study report. 
Description 
Disclosure Purpose 
(CTRS=public posting, SR=Study report, internal) 
Final 
Public disclosure, Study report 
7.2. 
Statistical considerations for interim analyses 
No interim analysis will be performed. 


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8. 
CHANGES TO THE PROTOCOL DEFINED STATISTICAL 
ANALYSIS 
Following is the change from protocol defined statistical analysis:-  
• 
Fatal SAEs will not be tabulated using the date of death within the same time 
periods. 
• 
 
• 
Grade 3 for redness/swelling will be defined as redness/swelling with diameter 
>=100 mm in Chinese scale 
• 
Preferred Terms to identify Grade 4 for swelling and redness have been added 
• 
The analysis on at least 1 local AE (solicited and unsolicited; solicited only) with at 
least 1 general AE (solicited and unsolicited; solicited only) and with any AE 
(solicited and unsolicited; solicited only) during the solicited follow-up period with 
causal relationship with vaccine and AE rated as at least grade 3 according to GSK 
and Chinese scale will not be performed. 
9. 
NON-STANDARD DATA DERIVATION RULES AND 
STATISTICAL METHODS 
The following sections describe additional derivation rules and statistical methods which 
are not presented in section 10.1. 
9.1. 
Data derivation 
9.1.1. 
Demography 
For computation of age, following rule need to be considered: 
• 
Age will be calculated as the number of years between the date of birth and the date 
of first vaccination. 
• 
To ensure that the collection of date of birth will not jeopardise the privacy of 
Personal Identifiable Information (PII), only a partial date of birth (YYYY) will be 
collected. As the date and month will be missing, the date will be replaced by the 
June 30th of the year. 
CCI


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9.2. 
Statistical Method 
9.2.1. 
HZ incidence 
• 
For the primary analysis of HZ incidence, first confirmed HZ episode will be 
considered.  
• 
The HZ onset date is the earlier of the following two events: 1) the HZ rash start 
date; or 2) the date on which pain/itching or abnormal sensation at the site of a 
subsequent HZ rash is first noted. 
• 
A suspected case of HZ can be confirmed by GSK in two ways: 
- 
By PCR: Rash lesion samples will be collected from subjects clinically 
diagnosed as having a suspected case of HZ. The samples will be transferred to 
GSK or a validated laboratory designated by GSK Biologicals and analyzed 
using standardized and validated procedures for laboratory diagnosis of HZ by 
PCR (see Section 12.2 of the protocol).  
- 
By the HZ Ascertainment Committee (HZAC): All suspected HZ cases will 
be referred to the HZAC. The HZAC will classify all referred cases as either 
“HZ” or “not HZ” or “not able to decide” (see Section 12.2 of the protocol). The 
HZAC classification will serve as the final case definition only when the case 
cannot be confirmed or excluded by PCR. Therefore, definitive PCR results, 
when available, will determine the final HZ case assignment. In such cases, the 
HZAC classification will not contribute to HZ case determination decision 
• 
For a given subject and for HZ episode, missing or non-evaluable measurements will 
not to be imputed for the primary analysis. The missing endpoint and censoring are 
considered to occur independently, and the pattern being either Missing Completely 
At Random (MCAR) or Missing At Random (MAR) only. 
• 
For HZ analysis, due to the algorithm used and taking into account both laboratory 
and HZAC results, no imputation and no sensitivity analysis for missing data will be 
performed. 
• 
The “follow-up time at risk” for confirmed HZ is expressed in days and is computed 
according to the following rules: 
- 
The start date of the follow-up time (start) will be computed as follows: 
• 
From the dose 1 administration date for the analysis on the ES; 
• 
From 30 days post-dose 2 date for the analysis on the mES. 
- 
The end date of the follow-up time (stop) will be computed as follows: 
• 
Date of the last visit/contact for subjects who did not have an event; 
• 
Last contact date for subjects dropped out of the study, if not preceded by an 
event; 


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• 
Date of the event 
• 
Date of HZ and/or VZV vaccination outside the study, if not preceded by an 
event 
• 
The follow-up time at risk is computed using the following formula: 
- 
stop – start +1. 
The time at risk will be expressed in Person-Year and derived from the follow up time 
(follow up time in days/365.25). 
CCI


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9.2.3. 
Safety 
• 
For the analysis of HZ related complications/unsolicited AEs/SAEs/pIMDs/ 
concomitant medication, all vaccinated subjects will be considered and subjects who 
did not report an event will be considered as subjects without an event. 
• 
AEs that need to be reported as pIMDs are listed in Table 23 of the protocol. The 
table presenting pIMDs, will also include the AEs considered as pIMDs as per 
MedDRA dictionary. 
• 
Assessment of intensity for solicited local and general AEs will be done separately as 
per GSK scale and Chinese scale. From an analysis perspective, the intensity of 
nausea, vomiting and diarrhoea will be presented separately as per the guidelines of 
Chinese authorities. In addition, as per GSK standard grading, the solicited general 
AEs of nausea, vomiting, diarrhoea and/or abdominal pain will be presented 
collectively as “gastrointestinal symptoms”.  
For analysis as per GSK standard grading, the maximum intensity of any one of 
these solicited general AEs (i.e. nausea, vomiting and diarrhoea and abdominal 
pain) reported by a subject will be attributed as maximum intensity of 
“gastrointestinal symptoms” for that subject. Maximum of grade 3 and 4 will be 
considered as grade 3 for all applicable solicited symptoms (not only 
gastrointestinal symptoms) in GSK standard grading table. 
The intensity of the following solicited AEs will be assessed as described below: 
Table 3 
Intensity scales for solicited symptoms in adults 
Adults 
Adverse Event 
Intensity 
grade 
Parameter 
Pain at injection site 
0 
None 
1 
Mild: Do not influence or do slightly influence limb activities. 
2 
Moderate Influence limb activities. 
3 
Severe: Influence daily life. 
4 
Lose the basic selfcare ability, or hospitalization 
Redness at 
injection site 
 
Record greatest surface diameter in mm 
Swelling at injection 
site 
 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C (with 1 decimal) 
Headache 
0 
Normal 
1 
Mild: Headache that is easily tolerated 
2 
Moderate: Headache that interferes with normal activity 
3 
Severe: Headache that prevents normal activity 
4 
Refractory; require emergency presentation or hospitalization 
Fatigue 
0 
Normal 
1 
Mild: Fatigue that is easily tolerated 
2 
Moderate: Fatigue that interferes with normal activity 
3 
Severe: Fatigue that prevents normal activity 
 
4 
Emergency presentation or hospitalization 
Gastrointestinal 
symptom (Diarrhea) 
0 
Normal 
1 
Slight or transient, 3-4 times/day, stool with abnormal properties, or slight 
diarrhea persisting for not more than 1 week 


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Adults 
Adverse Event 
Intensity 
grade 
Parameter 
 
2 
Moderate or persistent, 5-7 times/days, stool with abnormal properties, or 
diarrhea >1 week 
 
3 
>7 times/day, stool with abnormal properties, or bloody diarrhea, orthostatic 
hypotension, electrolyte imbalance, and requiring intravenous fluid >2 L 
 
4 
Hypotensive shock, requiring hospitalization for treatment 
Gastrointestinal 
symptom (Nausea) 
0 
Normal 
1 
Transient (<24 h) or intermittent, while food intake basically normal 
 
2 
Persistent nausea, leading to decreased food intake (24-48 h) 
 
3 
Persistent nausea, leading to little food intake (>48 h) or require intravenous 
fluid infusion 
 
4 
Life-threatening (such as hypotensive shock) 
Gastrointestinal 
symptom (Vomiting) 
0 
Normal 
1 
1-2 times/24 h and do not influence activities 
 
2 
3-5 times/24 h or activities restricted 
 
3 
>6 times within 24 h or require intravenous fluid infusion 
 
4 
Due to hypotension, require hospitalization or nutrition by other routes 
Gastrointestinal 
symptom 
(Abdominal pain) 
0 
Normal 
1 
Mild: Gastrointestinal symptoms that are easily tolerated 
2 
Moderate: Gastrointestinal symptoms that interfere with normal activity 
 
3 
Severe: Gastrointestinal symptoms that prevent normal activity 
Myalgia 
0 
None  
 
1 
Mild: Myalgia that is easily tolerated 
 
2 
Moderate: Myalgia that interferes with normal activity 
 
3 
Severe: Myalgia that prevents normal activity 
* For this study, fever is defined as temperature  37.3°C as per guidelines from the Chinese authorities for axillary 
measurement. The preferred location for measuring temperature in this study will be the axilla. 
The maximum intensity of local injection site redness/swelling will be scored at GSK 
using GSK’s standard grading scale (based on the US Food and Drug Administration 
(FDA) guidelines [FDA, 2007]) and the guidelines of grading standards for AEs set by 
the Chinese authorities as follows. 
Grade 
GSK standard grading scale 
Grading scale defined by Chinese 
authorities 
0 
< 20 mm diameter 
Absent 
1 
 20 mm to 50 mm diameter 
25 mm to <50 mm 
2 
> 50 mm to 100 mm diameter 
50 mm to <100 mm  
3 
> 100 mm diameter 
>=100 mm  
4 
Not defined 
Abscess, exfoliative dermatitis, and 
dermis or deep tissue necrosis* 
*The solicited symptom diary card doesn’t allow to choose grade 4 swelling or redness. 
Per team agreement, the grade 4 of swelling and redness will be identified when the 
below Preferred Terms (from MedDRA version 25.0) are reported as unsolicited 
adverse events within or ongoing 7 days post each dose: 
• 
Dermatitis exfoliative 
• 
Necrosis 


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• 
Skin necrosis 
• 
Soft tissue necrosis 
• 
Abscess 
• 
Abscess sterile 
• 
Abscess limb 
• 
Abscess soft tissue 
Fever will be graded as:  
Grade 
GSK standard grading scale 
Grading scale defined by Chinese 
authorities (for axillary measurement) 
0 
<38.0°C 
<37.3°C 
1 
38.0°C –38.5°C 
37.3°C – <38°C 
2 
>38.5°C –39.0°C  
38.0°C -<38.5°C 
3 
>39.0°C 
38.5°C - <39.5°C 
4 
Not defined 
≥ 39.5°C 
The preferred location for measuring temperature in this study will be the axilla. If 
temperature is measured by other routes (such as oral or rectal), fever grading as per GSK 
scale will remain the same irrespective of route of measurement. For the grading scale as 
per Chinese authorities, the following conversion will be used: 
- 
Axillary temperature = Oral temperature minus 0.2℃; 
- 
Axillary temperature = Rectal temperature minus 0.5℃.  
- 
Axillary temperature = Tympanic membrane temperature 
• 
For the duration of solicited adverse event within the solicited symptom follow-up 
or total duration, the unknown or missing end date will not be imputed. 
• 
The definition of HZ related complication is described in section 12.5.2 of the 
protocol and is presented below:- 
Post-herpetic 
neuralgia 
PHN is defined by the presence of HZ-associated severe pain 
persisting or appearing more than 90 days after onset of the HZ 
rash. 
Disseminated 
disease 
Defined as ≥ 6 HZ lesions clearly outside the primary dermatome 
as per the investigator’s judgment. 
Ophthalmic 
disease 
Defined as HZ affecting any eye structure as per the investigator’s 
judgment. 


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Neurologic 
disease 
Defined as cranial or peripheral nerve palsies, myelitis, 
meningoencephalitis, stroke, etc. that is temporally associated with 
an episode of HZ and, in the opinion of the investigator, is caused 
directly by VZV infection arising from the HZ episode. 
Visceral disease 
Defined as an abnormality of one or more internal organs (e.g., 
hepatitis, pneumonitis, gastroenteritis, etc.) that is temporally 
associated with an episode of HZ and, in the opinion of the 
investigator, is caused directly by VZV infection arising from the 
HZ episode 
HZ vasculitis 
Vasculopathy or vasculitis (based on clinical, laboratory or 
radiologic findings) that is temporally associated with an episode of 
HZ and, in the opinion of the investigator, is caused directly by the 
VZV infection arising from the HZ episode. 
Stroke 
A diagnosis of stroke requires that criteria 1, 2 and 3 are fulfilled or 
criteria 1 and 4 and in the opinion of the investigator is temporally 
associated with an episode of HZ 
Criterion 1: Rapid onset of localizing neurological deficit and/or 
change in level of consciousness;  
Criterion 2: Localizing neurological deficit or change in level of 
consciousness that lasts greater than 24 hours; 
Criterion 3: No other cerebral process, peripheral lesion, or other 
disorder is the cause of the localizing neurological deficit or change 
in level of consciousness; 
Criterion 4: Computerized Tomography (CT) scan or Magnetic 
Resonance Imaging (MRI) scan evidence of an acute thrombotic or 
hemorrhagic lesion 
• 
A specific COVID-19 eCRF page is used to collect any event related to COVID-19 
pandemic. Input from local regulatory, local medical affairs and sites was provided 
to define pandemic measures periods at each site. Start date of pandemic measure 
period will be considered first day of month and end date of pandemic measure 
period will be considered as last day of month. 


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Location 
Center 
First 
subject 
first visit 
date at 
Center 
Start date 
of 
pandemic 
measure 
period 
End date 
of 
pandemic 
measure 
period 
Reason/s for pandemic 
measure period 
Shanghai 
248981 14-May-21 
Mar21 
May21 
Strong recommendation of 
mass vaccination of 
Covid-19 vaccines to wide 
population.  
Isolated cases in country 
lack of resources that 
delay the Study start 
Mar22 
Jun22 
Covid-19 outbreak in 
Shanghai 
High business, public life 
and health impact 
Widespread disease in 
region and community 
Citywide static 
management 
lack of resources that lead 
to miss of month phone 
contact 
Oct22 
Nov22 
Province/Partial control to 
prevent Covid-19 
Isolated cases in country 
Lack of resources that 
impact data entry 
Nov22 
Jan23 
High business public life 
and health impact 
Widespread disease in 
country 
Sustained community 
spread in geographic area 
local to GSK community 
Public health service 
capacity exceeded 
lack of resources that 
impact data entry 
248302 21-Jul-21 
Mar21 
May21 
Strong recommendation of 
mass vaccination of 
Covid-19 vaccines to wide 
population.  
Isolated cases in country 
lack of resources that 
delay the Study start 


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Location 
Center 
First 
subject 
first visit 
date at 
Center 
Start date 
of 
pandemic 
measure 
period 
End date 
of 
pandemic 
measure 
period 
Reason/s for pandemic 
measure period 
Mar22 
Jun22 
Covid-19 outbreak in 
Shanghai 
High business, public life 
and health impact 
Widespread disease in 
region and community 
Citywide static 
management 
Lack of resources that 
impact data entry 
Oct22 
Nov22 
Province/Partial control to 
prevent Covid-19 
Isolated cases in country 
Lack of resources that 
impact data entry 
Nov22 
Jan23 
High business public life 
and health impact 
Widespread disease in 
country 
Sustained community 
spread in geographic area 
local to GSK community 
Public health service 
capacity exceeded 
lack of resources that 
impact data entry 
248303 15-Jul-21 
Mar21 
May21 
Strong recommendation of 
mass vaccination of 
Covid-19 vaccines to wide 
population.  
Isolated cases in country 
lack of resources that 
delay the Study start 
Mar22 
Jun22 
Covid-19 outbreak in 
Shanghai 
High business, public life 
and health impact 
Widespread disease in 
region and community 
Citywide static 
management 
Lack of resources that 
impact data entry 


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Location 
Center 
First 
subject 
first visit 
date at 
Center 
Start date 
of 
pandemic 
measure 
period 
End date 
of 
pandemic 
measure 
period 
Reason/s for pandemic 
measure period 
Oct22 
Nov22 
Province/Partial control to 
prevent Covid-19 
Isolated cases in country 
Lack of resources that 
impact data entry 
Nov22 
Jan23 
High business public life 
and health impact 
Widespread disease in 
country 
Sustained community 
spread in geographic area 
local to GSK community 
Public health service 
capacity exceeded 
lack of resources that 
impact data entry 
247421 06-Jun-21 
Mar21 
May21 
Strong recommendation of 
mass vaccination of 
Covid-19 vaccines to wide 
population.  
Isolated cases in country 
lack of resources that 
delay the Study start 
Mar22 
Jun22 
Covid-19 outbreak in 
Shanghai 
High business, public life 
and health impact 
Widespread disease in 
region and community 
Citywide static 
management 
Lack of resources that 
impact data entry 
Oct22 
Nov22 
Province/Partial control to 
prevent Covid-19 
Isolated cases in country 
Lack of resources that 
impact data entry 


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Location 
Center 
First 
subject 
first visit 
date at 
Center 
Start date 
of 
pandemic 
measure 
period 
End date 
of 
pandemic 
measure 
period 
Reason/s for pandemic 
measure period 
Nov22 
Jan23 
High business public life 
and health impact 
Widespread disease in 
country 
Sustained community 
spread in geographic area 
local to GSK community 
Public health service 
capacity exceeded 
lack of resources that 
impact data entry 
Lianshui 
247564 11-Sep-21 
Mar21 
Jul21 
Strong recommendation of 
mass vaccination of 
Covid-19 vaccines to wide 
population.  
Isolated cases in country 
lack of resources that 
delay the Study start 
Jul21 
Aug21 
Covid19 outbreak in 
Nanjing city and Jiangsu 
province 
Province/Partial control to 
prevent Covid-19 
Lack of resources that 
delay the study start 
Mar22 
Jun22 
Covid-19 outbreak in 
Shanghai 
Province/Partial control to 
prevent Covid-19 
Lack of resources that 
delay the data entry 
Oct22 
Nov22 
Province/Partial control to 
prevent Covid-19 
Isolated cases in country 
Lack of resources that 
delay the data entry 
Nov22 
Jan23 
High business public life 
and health impact 
Widespread disease in 
country 
Sustained community 
spread in geographic area 


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Location 
Center 
First 
subject 
first visit 
date at 
Center 
Start date 
of 
pandemic 
measure 
period 
End date 
of 
pandemic 
measure 
period 
Reason/s for pandemic 
measure period 
local to GSK community 
Public health service 
capacity exceeded 
lack of resources that 
impact data entry 
Ganyu 
248595 15-Sep-21 
Mar21 
Jul21 
Strong recommendation of 
mass vaccination of 
Covid-19 vaccines to wide 
population.  
Isolated cases in country 
lack of resources that 
delay the Study start 
Jul21 
Aug21 
Covid19 outbreak in 
Nanjing city and Jiangsu 
province 
Province/Partial control to 
prevent Covid-19 
Lack of resources that 
delay the study start 
Mar22 
Jun22 
Covid-19 outbreak in 
Shanghai 
Province/Partial control to 
prevent Covid-19 
Lack of resources that 
impact the data entry 
Jul22 
Aug22 
Covid-19 epidemic in 
Ganyu 
citywide static 
management  
Partial control and travel 
restrictions to prevent and 
control Covid-19 
lack of resources that 
impact the data entry 
Oct22 
Nov22 
Province/Partial control to 
prevent Covid-19 
Isolated cases in country 
Lack of resources that 
impact the data entry 


CONFIDENTIAL 
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Statistical Analysis Plan Amendment 1 
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Page 37 of 41 
Location 
Center 
First 
subject 
first visit 
date at 
Center 
Start date 
of 
pandemic 
measure 
period 
End date 
of 
pandemic 
measure 
period 
Reason/s for pandemic 
measure period 
Nov22 
Jan23 
High business public life 
and health impact 
Widespread disease in 
country 
Sustained community 
spread in geographic area 
local to GSK community 
Public health service 
capacity exceeded 
lack of resources that 
impact data entry 
10. 
ANNEXES  
10.1. 
Business rules for standard data derivations and statistical 
methods 
This section contains standard rules for data display and derivation for clinical and 
epidemiological studies. These rules will be applied along with those detailed in section 9 
(additional study-specific rules). 
10.1.1. 
Attributing events to vaccine doses 
The dose relative to an event is the most recent study dose given to a subject prior to the 
start of a given event. For example, if the start date of an adverse event is between Dose 1 
and Dose 2, the relative dose will be Dose 1. 
If an event starts on the same day as a study dose, the relative dose will be derived from 
the additional information provided in the CRF using the contents of the flag indicating if 
the event occurred before or after study dose. If ‘after study dose’ is selected, the relative 
dose for the event will be the one administered on the start day of the event. If ‘before 
study dose’ is selected, the relative dose for the event will be the dose prior to this one. 
10.1.2. 
Handling of missing data 
10.1.2.1. 
Dates 
When partially completed dates (i.e. with missing day or month) are used in calculations, 
the following standard rules will be applied: 
• 
A missing day will be replaced by 15 
• 
A missing day and month will be replaced by June 30th. 


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The following exceptions apply: 
• 
Adverse event start dates with missing day: If the event starts in the same month as at 
least one of the study doses, the contents of AE.AESTRTPT (the flag indicating if 
the event occurred before or after study dose) will be used to complete the date. If 
‘after study dose’ is selected, the imputed start date will match the first (or only) 
study dose given during that month. If ‘before study dose’ is selected, the imputed 
date will be one day before the first (or only) study dose given during that month. 
• 
Adverse event start dates with missing day and month: If the event starts in the same 
year as at least one of the study doses, the contents of AE.AESTRTPT (the flag 
indicating if the event occurred before or after vaccination) will be used to complete 
the date. If ‘after vaccination’ is selected, the imputed start date will match the first 
(or only) study dose given during that year. If ‘before vaccination’ is selected, the 
imputed date will be one day before the first (or only) study dose given during that 
year. 
• 
All other cases of incomplete AE or concomitant medication/vaccination start date 
will follow the standard rules above. 
10.1.2.2. 
Laboratory data 
Missing laboratory results (including immunological data) will not be replaced. 
10.1.2.3. 
Daily recording of solicited adverse events 
10.1.2.3.1. Studies with electronic diaries 
Not applicable for the study 
10.1.2.3.2. Studies with paper diaries 
For studies using paper diaries which have questions in the CRF indicating the presence 
or absence of solicited events, the following rules are applicable. 
• 
Denominators for the summary of administration site (or systemic) solicited events 
will be calculated using the number of participants who respond “Yes” or “No” to 
at least one occurrence of the specific administration site (or systemic) solicited 
event. If there are at least 1 non-missing value of temperature from day 1 to day 7 
post vaccination, that occurrence will be counted as well in the denominator of 
systemic solicited events. 
• 
When a specific solicited event is marked as having not occurred following a specific 
study dose (i.e. SDTM CE.CEOCCUR=N for the specified post-dose period for the 
event in question), all daily measurements will be imputed as Grade 0. 


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• 
For fever, if there are missing values and/or non-missing values of temperature 
from day 1 to day 7 post vaccination which are not qualifying fever definition per 
protocol for GSK intensity and Chinese intensity tables, then that subject would 
not be considered for ‘Any’ rows of the solicited event summary tables. 
• 
When a specific solicited event is marked as having occurred following a specific 
study dose (i.e. SDTM CE.CEOCCUR=Y for the specified post-dose period for the 
event in question), any missing daily recordings will be given imputed values to 
allow them to contribute to the ‘Any’ rows but not to specific grade rows of the 
solicited event summary tables. 
• 
The following table shows how participants contribute to each category for a specific 
solicited adverse event over the Day X to Day Y post-dose period: 
Solicited adverse 
event category 
Participants included in the calculation of the numerator 
Any 
All participants with at least one occurrence of the adverse event at grade 1, 2, or 3 for table 
by GSK intensity scale and at grade 1, 2, 3 or 4 for table by Chinese intensity scale between 
Day X and Day Y or with the adverse event marked as present and at least one missing daily 
recording between Day X and Day Y 
Grade 1 
All participants with at least one occurrence of the adverse event at grade 1 between 
Day X and Day Y 
Grade 2 
All participants with at least one occurrence of the adverse event at grade 2 between 
Day X and Day Y 
At least grade 3 
All participants with at least grade 3 or grade 4 
Grade 4* 
All participants with at least one occurrence of the adverse event at grade 4 between Day X 
and Day Y 
          *this is specific to the study as grade 4 has also been defined for some solicited adverse event collected in the    
           study as per Chinese regulation. 
10.1.2.4. 
Unsolicited adverse events 
Unsolicited adverse event summaries are including serious adverse events unless 
specified otherwise.  
Missing relationship with study vaccine, and outcome of unsolicited adverse events will 
not be replaced and will appear as ‘UNKNOWN’ when displayed in a statistical output. 
Missing severity will follow the next imputation rules: 
• 
If serious adverse event = ‘Y’ then severity = ‘Severe’ 
• 
If serious adverse event = ‘N’ and action taken with study vaccine(s) as a result of 
the event = ‘Dose not changed’ and subject did not withdraw from the study due to 
this event, then severity = ‘Mild’ 
• 
If previous two rules were not applicable, then severity = ‘Moderate’  


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10.1.3. 
Data derivation 
10.1.3.1. 
Age at first dose in years 
When age at first dose is to be displayed in years, it will be calculated as the number of 
complete calendar years between the date of birth and the date of first dose. For example: 
DOB = 10SEP1983, Date of first dose = 09SEP2018 -> Age = 34 years 
DOB = 10SEP1983, Date of first dose = 10SEP2018 -> Age = 35 years 
10.1.3.2. 
Temperature 
Temperatures will be presented in degrees Celsius (°C). Temperatures reported in degrees 
Fahrenheit (°F) will be converted as follows: 
Temperature (Celsius) = ((Temperature (Fahrenheit) - 32) x 5)/9 
10.1.3.3. 
Onset day 
The onset day for an event (e.g. AE, medication, vaccination) is the number of days 
between the last study dose and the start date of the event. This is 1 for an event occurring 
on the same day as a study dose (and reported as starting after first dose). 
10.1.3.4. 
Duration of events 
The duration of an event with a start and end date will be the difference between the start 
and end date plus one day, i.e. an event that starts on 03MAR2018 and ends on 
12MAR2018 has a duration of 10 days. 
The duration of solicited events will be calculated as the sum of the individual days with 
the adverse event reported at grade 1 or higher during the solicited event period. 
If symptom is ongoing and the end date of event is partially or fully missing, end date 
will not be imputed for the calculation of duration. 
10.1.3.5. 
Counting rules for combining solicited and unsolicited adverse events 
For output combining solicited and unsolicited adverse events, all serious adverse events 
will be considered systemic events since the administration site flag is not included in the 
expedited adverse event CRF pages. Unsolicited adverse events with missing 
administration site flag will also be considered systemic. 
Multiple events with the same preferred term which start on the same day are counted as 
only one occurrence. 


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10.1.3.6. 
Counting rules for occurrences of solicited events 
When the occurrences of solicited events are summarized, each event recorded as having 
occurred during a specific period will be counted as only one occurrence regardless of the 
number of days on which it occurs. 
10.1.4. 
Display of decimals 
10.1.4.1. 
Percentages 
Percentages and their corresponding confidence limits will be displayed with one decimal 
except for 100% in which case no decimal will be displayed.  
10.1.4.2. 
Demographic/baseline characteristics statistics 
The mean, median, and standard deviation for continuous baseline characteristics will be 
presented with one decimal. 
The maximum and minimum of transformed body temperatures will be displayed with 
one decimal. 
10.1.5. 
Statistical methodology 
10.1.5.1. 
Exact confidence intervals around proportions 
The exact confidence intervals around within-group proportions are derived using the 
method of Clopper and Pearson [Clopper, 1934]. 
10.2. 
TFL TOC 
The Table Figure Listing (TFL) Table Of Content (TOC) which itemizes the planned list 
of TFL for final analysis with their associated lay-out is developed as a separate 
document. 
11. 
REFERENCES 
Clopper CJ, Pearson E. The Use of Confidence or Fiducial Limits Illustrated in the case 
of the Binomial. Biometrika. 1934;26:404-13. 
FDA, U.S. Department of Health and Human Services, Center for Biologics Evaluation 
and Research. Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Version of 
September 2007.