Conditions: Herpes Zoster
Keywords: Shingles Herpes Zoster subunit vaccine Immunogenicity Safety Adults aged 50 years and older India
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 288
Healthy volunteers: yes

Brief summary:
The purpose of this study was to evaluate the humoral immunogenicity and safety of 2 doses of GSK Biologicals' Herpes Zoster subunit vaccine (HZ/su) administered for the prevention of Herpes Zoster (HZ) in adults aged 50 years of age (YOA) or older from India.

Detailed description:

Arms:
arm 1: Participants randomized to the HZ/su group received two doses of HZ/su vaccine, administered at Day 1 and Month 2. arm 2: Participants randomized to the Placebo group received two doses of Placebo, administered at Day 1 and Month 2.

Interventions: intervention 1: HZ/su intervention 2: Placebo
Intervention descriptions: intervention 1: Two doses of the HZ/su vaccine administered intramuscularly, one each at Day 1 and Month 2. intervention 2: Two doses of Placebo (lyophilised sucrose reconstituted with saline \[NaCl\] solution) administered intramuscularly, one each at Day 1 and Month 2.

Protocol document:
Prot_000.pdf: 
Protocol
Study ID: 214461
Official Title of Study: A Phase 3, Randomised, Observer-blind, Placebo-controlled, 
Multi-centre Study to Evaluate the Immune Response and Safety of the Herpes Zoster 
Subunit Vaccine When Administered Intramuscularly on a 2-dose Schedule in Adults 
Aged 50 Years and Older in India
NCT ID: NCT05219253
Date of Document: 25 May 2022


CONFIDENTIAL 
214461 (ZOSTER-081) 
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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Rue de l’Institut 89, 1330 Rixensart 
Tel: +32 2 656 81 11 
Primary study intervention(s) 
and number(s) 
GlaxoSmithKline Biologicals SA (GSK) lyophilised 
formulation of the Herpes Zoster subunit vaccine 
(HZ/su) (GSK1437173A) 
Other study intervention(s) 
Placebo (lyophilised sucrose reconstituted with 
saline [NaCl] solution) 
eTrack study number and 
abbreviated title 
214461 (ZOSTER-081) 
Date of protocol 
Final: 8 June 2021 
Date of protocol amendment 
Amendment 1 Final: 25 May 2022  
Title 
A phase 3, randomised, observer-blind, 
placebo- controlled, multi-centre study to evaluate 
the immune response and safety of the Herpes Zoster 
subunit vaccine when administered intramuscularly 
on a 2-dose schedule in adults aged 50 years and 
older in India. 
Brief title 
A study on the immune response and safety of a 
vaccine against Herpes Zoster in adults aged 50 
years and older in India. 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.1 
©2021 GSK group of companies or its licensor. 


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Protocol Amendment 1 Sponsor Signatory Approval 
eTrack study number and 
abbreviated title 
214461 (ZOSTER-081) 
Date of protocol 
Final: 8 June 2021 
Date of protocol amendment 
Amendment 1 Final: 25 May 2022 
Title  
A phase 3, randomised, observer-blind, 
placebo- controlled, multi-centre study to evaluate 
the immune response and safety of the Herpes 
Zoster subunit vaccine when administered 
intramuscularly on a 2-dose schedule in adults aged 
50 years and older in India. 
Sponsor signatory 
Agnes Mwakingwe-Omari,  
Clinical and Epidemiology Project Leader, 
Zoster Program, Research and Development Centre 
- United States, GlaxoSmithKline Biologicals SA. 
Signature 
 
 
 
Date 
 
Note: Not applicable if an alternative signature process (e.g. electronic signature or 
email approval) is used to get the sponsor approval. 
 


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Protocol Amendment 1 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 intervention 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 participant. 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s).  
• 
To co-operate with representative(s) 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 intervention(s), 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 
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 all other documents 
required by regulatory agencies for this study. 


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eTrack study number and 
abbreviated title 
214461 (ZOSTER-081) 
Date of protocol 
Final: 8 June 2021 
Date of protocol amendment 
Amendment 1 Final: 25 May 2022 
Title 
A phase 3, randomised, observer-blind, 
placebo- controlled, multi-centre study to evaluate 
the immune response and safety of the Herpes 
Zoster subunit vaccine when administered 
intramuscularly on a 2-dose schedule in adults aged 
50 years and older in India. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 


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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA (GSK)  
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 Events 
GSK central back up study contact for reporting SAEs: refer to the protocol Section 
8.3.3.1.  
Study contact for reporting SAEs: refer to the local study contact information 
document. 
5. GSK Helpdesk for emergency unblinding  
Refer to the protocol section 6.3.4.1. 
 


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PROTOCOL AMENDMENT 1 SUMMARY OF CHANGES TABLE 
Amendment 1 (25 May 2022) 
Overall rationale for the current Amendment  
The protocol was amended to update regarding the licensure of HZ/su in India for adults 
≥50 years of age, and for inclusion of an early supportive safety report to fulfil the post-
approval commitment to the Indian regulatory authority.  
List of main changes in the protocol and their rationale: 
All changes are tracked in Section 10.8, deleted text is in strikethrough and newly added 
text is in bold italics. 
Section # and 
title 
Description of change 
Brief rationale 
Section 1.1 - 
Synopsis 
The sections were revised to specify the 
recent update regarding the licensure of 
HZ/su in India for adults ≥50 YOA, and to 
describe the regulatory requirement of the 
early supportive safety data.  
The protocol amendment 1 was made to provide 
an update regarding the recent licensure of HZ/su 
in India for adults ≥50 YOA, and for inclusion of 
an early supportive safety report to fulfil the post-
approval commitment to the Indian regulatory 
authority. 
Section 2.1 - 
Study rationale 
Section 9.5 - 
Interim Analysis 
To fulfil the post-approval commitment to 
the Indian regulatory authority, a blinded 
early safety assessment report after 
completion of 30 days safety follow-up 
post HZ/su dose 2 (i.e., Visit 3, Month 3) 
for the initial 200 randomised participants 
will be provided 
Section 6.8 -
Concomitant 
Therapy  
All concomitant medications ongoing once 
randomized at Visit 1 (Day 1). 
The sentence was included to further clarify the 
requirement for recording concomitant 
medications ongoing at Visit 1 (Day 1), which 
remains indicated as such on Table 1- Schedule 
of Activities. 
Section 8.3.3.1 - 
Contact 
information for 
reporting SAEs, 
pIMDs and 
pregnancies  
Change in email ID to report SAEs, pIMDs 
and pregnancies 
The email ID to report SAEs, pIMDs and 
pregnancies was updated by GSK since the 
previous protocol version. Thus, the email ID has 
been replaced.  
Table 5 - Study 
intervention(s) 
administered 
Presentation of placebo was updated 
As the reconstituted Sucrose and Sodium 
Chloride (NaCl) pharmaceutical product is a 
solution for injection, the dose form of the NaCl 
solution was revised as “solution for solution for 
injection”. 
Table 17 - List of 
potential 
immune-
mediated 
diseases 
(pIMDs) 
The list of pIMDs was updated 
The list of pIMDs was updated by GSK since the 
previous protocol version. Thus, the table was 
replaced to further assist investigators. 


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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 5 
PROTOCOL AMENDMENT 1 SUMMARY OF CHANGES TABLE .................................. 6 
List of main changes in the protocol and their rationale: ........................................... 6 
1. 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1. 
Synopsis (Amended, 25 May 2022) ............................................................ 13 
1.2. 
Schema ...................................................................................................... 13 
1.3. 
Schedule of activities (SoA) ........................................................................ 15 
2. 
INTRODUCTION .................................................................................................... 17 
2.1. 
Study rationale (Amended 25 May 2022) .................................................... 17 
2.2. 
Background ................................................................................................ 17 
2.3. 
Benefit/Risk assessment ............................................................................. 18 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 21 
4. 
STUDY DESIGN .................................................................................................... 22 
4.1. 
Overall design ............................................................................................. 22 
4.2. 
Scientific rationale for study design ............................................................. 23 
4.3. 
Justification for dose ................................................................................... 23 
4.4. 
End of Study definition ................................................................................ 23 
5. 
STUDY POPULATION ........................................................................................... 24 
5.1. 
Inclusion criteria .......................................................................................... 24 
5.2. 
Exclusion criteria ......................................................................................... 24 
5.2.1. 
Medical conditions ....................................................................... 25 
5.2.2. 
Prior/Concomitant therapy (Amended 25 May 2022) ................... 25 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 26 
5.2.4. 
Other exclusions .......................................................................... 26 
5.3. 
Lifestyle considerations ............................................................................... 26 
5.4. 
Screen failures ............................................................................................ 26 
5.5. 
Criteria for temporarily delaying randomisation/study intervention 
administration ............................................................................................. 26 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 27 
6.1. 
Study intervention(s) administered .............................................................. 27 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 27 
6.3. 
Measures to minimise bias: randomisation and blinding ............................. 28 
6.3.1. 
Participant identification ............................................................... 28 
6.3.2. 
Randomisation to study intervention ............................................ 28 
6.3.3. 
Intervention allocation to the participant ....................................... 28 
6.3.4. 
Blinding and unblinding ................................................................ 29 
6.3.4.1. 
Emergency unblinding ................................................ 29 
6.3.4.2. 
Unblinding prior to regulatory reporting of SAEs ......... 29 
6.4. 
Study intervention compliance .................................................................... 30 
6.5. 
Dose modification ....................................................................................... 30 
6.6. 
Continued access to study intervention after the end of the study ............... 30 
6.7. 
Treatment of overdose ................................................................................ 30 


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6.8. 
Concomitant therapy (Amended 25 May 2022). .......................................... 30 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 31 
7.1. 
Discontinuation of study intervention ........................................................... 31 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration .............................................................................. 31 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 32 
7.3. 
Lost to follow-up .......................................................................................... 33 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 33 
8.1. 
Immunogenicity assessments ..................................................................... 33 
8.1.1. 
Biological samples ....................................................................... 34 
8.1.2. 
Laboratory assays ....................................................................... 34 
8.1.3. 
Immunological read-outs .............................................................. 34 
8.1.4. 
Immunological correlates of protection ......................................... 34 
8.2. 
Safety assessments .................................................................................... 35 
8.2.1. 
Pre-study intervention procedures ............................................... 35 
8.2.1.1. 
Informed consent ........................................................ 35 
8.2.1.2. 
Collection of demographic data .................................. 35 
8.2.1.3. 
Medical/vaccination history ......................................... 35 
8.2.1.4. 
History-directed physical examination......................... 35 
8.2.1.5. 
Pregnancy test ........................................................... 35 
8.2.1.6. 
Warnings and precautions to administration of 
study intervention ....................................................... 36 
8.2.1.7. 
Pre-study intervention administration body 
temperature ................................................................ 36 
8.2.2. 
Post-study intervention administration procedures ....................... 36 
8.3. 
Adverse Events, Serious Adverse Events and other safety reporting .......... 37 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information ............................................................... 37 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and 
other events ................................................................................. 38 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies 
and other events .......................................................................... 38 
8.3.3.1. 
Contact information for reporting SAEs, pIMDs 
and pregnancies ......................................................... 39 
8.3.4. 
Treatment of adverse events ....................................................... 39 
8.3.5. 
Participant card ............................................................................ 39 
8.4. 
Pharmacokinetics ....................................................................................... 39 
8.5. 
Genetics ..................................................................................................... 40 
8.6. 
Biomarkers ................................................................................................. 40 
8.7. 
Immunogenicity ........................................................................................... 40 
8.8. 
Health outcomes ......................................................................................... 40 
8.9. 
Study procedures to be followed during special circumstances ................... 40 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 41 
9.1. 
Statistical hypotheses ................................................................................. 41 
9.2. 
Sample size determination .......................................................................... 42 
9.3. 
Analysis sets ............................................................................................... 43 
9.3.1. 
Criteria for elimination from analysis ............................................ 43 
9.4. 
Statistical analyses ..................................................................................... 43 


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9.4.1. 
Primary endpoint .......................................................................... 43 
9.4.2. 
Secondary endpoints ................................................................... 44 
9.4.2.1. 
Secondary immunogenicity endpoints ........................ 44 
9.4.2.2. 
Secondary Safety endpoints ....................................... 44 
9.5. 
Interim analyses (Amended 25 May 2022) .................................................. 45 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 46 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 46 
10.1.1. 
Regulatory and ethical considerations ......................................... 46 
10.1.2. 
Financial disclosure ..................................................................... 46 
10.1.3. 
Informed consent process ............................................................ 47 
10.1.4. 
Data protection ............................................................................ 47 
10.1.5. 
Committees structure ................................................................... 48 
10.1.6. 
Dissemination of clinical study data ............................................. 48 
10.1.7. 
Data quality assurance ................................................................ 48 
10.1.8. 
Source documents ....................................................................... 49 
10.1.9. 
Study and site start and closure ................................................... 50 
10.1.10. Publication policy ......................................................................... 50 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 50 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of AE .................. 51 
10.3.1. 
Definition of an adverse event ...................................................... 51 
10.3.1.1. Events Meeting the AE Definition ............................... 51 
10.3.1.2. Events NOT Meeting the AE Definition ....................... 52 
10.3.2. 
Definition of an SAE ..................................................................... 52 
10.3.3. 
Solicited events ............................................................................ 53 
10.3.4. 
Unsolicited adverse events .......................................................... 54 
10.3.5. 
Adverse events of special interest ................................................ 54 
10.3.5.1. Potential immune-mediated diseases ......................... 54 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 60 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs ..................... 61 
10.3.7.1. Pregnancy .................................................................. 61 
10.3.8. 
Recording and follow-up of AEs, SAEs, pIMDs and 
pregnancies ................................................................................. 61 
10.3.8.1. Time period for collecting and recording AEs, 
SAEs, pIMDs and pregnancies ................................... 62 
10.3.8.2. Follow-up of AEs, SAEs, pIMDs, IMCs and 
pregnancies ................................................................ 63 
10.3.8.2.1. Follow-up during the study ...................... 63 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study....................... 63 
10.3.8.2.3. Follow-up of pregnancies ........................ 63 
10.3.8.3. Updating of SAE, pIMD and pregnancy 
information after removal of write access to the 
participant’s eCRF ...................................................... 64 
10.3.9. 
Assessment of intensity and toxicity ............................................. 65 
10.3.9.1. Assessment of intensity .............................................. 65 
10.3.9.2. Assessment of causality ............................................. 66 
10.3.9.3. Medically-attended visits............................................. 67 
10.3.9.4. Assessment of outcomes ............................................ 67 


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10.3.10. Reporting of SAEs, pIMDs, pregnancies and other events ........... 68 
10.3.10.1. Events requiring expedited reporting to GSK .............. 68 
10.3.10.2. Back up system in case the electronic reporting 
system does not work ................................................. 68 
10.3.10.3. Completion and transmission of pregnancy 
reports to GSK ............................................................ 68 
10.3.10.4. Reporting of pIMD to GSK .......................................... 69 
10.4. 
Appendix 4: Contraceptive guidance and collection of pregnancy 
information .................................................................................................. 69 
10.4.1. 
Definitions .................................................................................... 69 
10.4.1.1. Woman of childbearing potential (WOCBP) ................ 69 
10.4.1.1.1. Women not considered as women 
of childbearing potential .......................... 69 
10.4.2. 
Contraception guidance ............................................................... 70 
10.4.3. 
Collection of pregnancy information ............................................. 71 
10.4.3.1. Female participants who become pregnant ................ 71 
10.5. 
Appendix 5: Genetics .................................................................................. 72 
10.6. 
Appendix 6: Country-specific requirements ................................................. 72 
10.7. 
Appendix 7: Abbreviations and glossary of terms ........................................ 72 
10.7.1. 
List of abbreviations ..................................................................... 72 
10.7.2. 
Glossary of terms ......................................................................... 75 
10.8. 
Appendix 8: Protocol Amendment history ................................................... 79 
11. REFERENCES ....................................................................................................... 90 
 


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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities ............................................................................. 15 
Table 2 
Intervals between study visits ................................................................. 17 
Table 3 
Study objectives and endpoints (Amended 25 May 2022) ...................... 21 
Table 4 
Study groups, intervention and blinding .................................................. 23 
Table 5 
Study intervention(s) administered (Amended 25 May 2022) ................. 27 
Table 6 
Contact information for emergency unblinding ....................................... 29 
Table 7 
Biological samples ................................................................................. 34 
Table 8 
Laboratory assays .................................................................................. 34 
Table 9 
Immunological read-outs ........................................................................ 34 
Table 10 
Timeframes for collecting and reporting of AE, SAE and other 
safety information ................................................................................... 37 
Table 11 
Timeframes for submitting SAE, pregnancy and other events 
reports to GSK ....................................................................................... 39 
Table 12 
Contact information for reporting SAEs, pIMDs and pregnancies ........... 39 
Table 13 
Intervals between study visits during special circumstances................... 41 
Table 14 
Analysis sets .......................................................................................... 43 
Table 15 
Solicited administration site events (Amended 25 May 2022) ................. 53 
Table 16 
Solicited systemic events ....................................................................... 53 
Table 17 
List of potential immune-mediated diseases (pIMDs) (Amended, 
25 May 2022) ......................................................................................... 55 
Table 18 
Intensity scales for solicited events (Amended 25 May 2022) ................. 65 
Table 19 
Highly effective contraceptive methods .................................................. 71 
Table 17 
List of potential immune-mediated diseases (pIMDs) (Amended, 
25 May 2022) ......................................................................................... 84 
 


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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 22 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis (Amended, 25 May 2022) 
Rationale: 
GlaxoSmithKline Biologicals SA’s (GSK’s) Herpes Zoster subunit vaccine (HZ/su) is an 
adjuvanted recombinant envelope glycoprotein E (gE) subunit vaccine. The HZ/su was 
first licensed for use in October 2017 and is currently approved around the world under 
the tradename Shingrix, including in Canada, the United States (US), the European 
Economic Area (EEA) countries, Japan, Australia, New Zealand and China for the 
prevention of Herpes Zoster (HZ) in adults ≥50 years of age (YOA). In addition, in the 
EEA and Australia, Shingrix is also indicated for the prevention of HZ related 
complications, such as post-herpetic neuralgia (PHN) in adults ≥50 YOA. In the EEA, 
Shingrix is also indicated for the prevention of HZ and PHN in adults ≥18 YOA, who are 
at increased risk of HZ. 
When this ZOSTER-081 study began, HZ/su was not approved for use in India. While 
the study was ongoing, HZ/su was licensed for use in India for adults ≥50 YOA on 
21 April 2022. Despite this licensure, HZ/su is not currently available in the Indian 
market; however, when it does become available, the study participants will be notified 
by the investigators. To meet the post-approval requirements of the Indian regulatory 
authority, this study will continue as originally planned to demonstrate the 
immunogenicity and safety of HZ/su in the Indian population. This study is designed to 
evaluate the humoral immunogenicity and safety of 2 doses of HZ/su, for the prevention 
of HZ in adults ≥50 YOA. In addition, as also required by the Indian regulatory 
authority, a safety report describing the early supportive safety data will be provided 
once these data (up to Visit 3, Month 3) on the initial 200 study participants 
randomized are available.  
Objectives and endpoints: 
Refer to Table 3 for study objectives and endpoints. 
1.2. 
Schema 
This is a phase 3, observer-blind, randomised, placebo-controlled, multi-centre study to 
assess the immunogenicity and safety of HZ/su when administered intramuscularly (IM) 
on a 2-dose schedule (Day 1 and Month 2), in adults aged 50 years and older in India. 
Approximately, 288 eligible participants will be randomised 1:1 to the HZ/su or Placebo 
group (144 participants per study group) and followed in an observer-blind design. Use of 
the placebo control, observer-blind and randomised study design aims to minimise the 
potential biases in study results. 
Blood samples for humoral immunogenicity will be collected from all participants at 
Visit 1 (pre-study intervention at Day 1) and Visit 3 (Month 3). The primary 
immunogenicity analysis will be based on the Per Protocol Set (PPS) for 
immunogenicity. A second analysis of immunogenicity based on the Exposed Set (ES) 
may be performed to complement the per protocol analysis (see Section 9.4 for details).  


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All participants who receive the study intervention will be followed for safety-solicited 
administration site adverse events (AEs) and solicited systemic AEs within 7 days of each 
study intervention , unsolicited AEs within 30 days of each intervention, serious adverse 
events (SAEs), potential immune- mediated diseases (pIMDs), intercurrent medical 
conditions (IMC) and suspected HZ cases throughout the study period.  
Section 4 provides an overview of the study design. 


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1.3. 
Schedule of activities (SoA) 
Table 1 
Schedule of Activities 
Type of contact 
Visit 1 
Visit 2  
Visit 3  
Phone Contact† 
Notes 
Timepoints 
Day 1 
Month 2 
Month 3 
Month 8/Study 
Conclusion 
 
Informed consent 
● 
 
 
 
Refer to Section 10.1.3 
Check inclusion/exclusion criteria 
● 
 
 
 
Refer to Sections 5.1 and 5.2  
Collect demographic data 
● 
 
 
 
Refer to Section 8.2.1.2 
Collect medical and vaccination history 
● 
 
 
 
Refer to Section 8.2.1.3 
History directed physical examination 
O 
O 
 
 
Refer to Section 8.2.1.4 
Urine Pregnancy test (if applicable) 
● 
● 
 
 
Refer to Section 8.2.1.5 
Randomisation  
O 
 
 
 
Refer to Section 6.3 
Check contraindications to vaccination 
O 
O 
 
 
Refer to Sections 7.1.1 and 8.2.1.6 
Check criteria for temporary delay for randomisation and/or study intervention 
administration  
O 
O 
 
 
Refer to Section 5.5 
Body temperature before study intervention administration 
● 
● 
 
 
Fever is defined a temperature 
≥38C. The preferred route for 
temperature measurement is oral. 
Refer to Section 8.2.1.7  
Study intervention 
 
 
 
 
 
Study group and study intervention number allocation 
O 
 
 
 
Refer to Sections 6.3.2 and 6.3.3 
Blood sampling for antibody determination (approximately 5 mL from all 
participants) 
● 
 
● 
 
Refer to Section 8.1.1 
Administration of study intervention 
● 
● 
 
 
Refer to Section 6.1 
Record administered study intervention number 
● 
● 
 
 
Refer to Section 6.3.2 
Post- study intervention administration observation (minimum 30 mins) 
O 
O 
 
 
Refer to Section 6.1 
Study intervention number allocation for subsequent dose 
 
O 
 
 
Refer to Sections 6.3.2 and 6.3.3 
Safety assessments 
 
 
 
 
 
Distribution and training on use of diary card 
O 
O 
 
 
 
Inform participants on signs/symptoms of HZ 
O 
O 
O 
 
Refer to Section 10.3 
Recording solicited AEs (Days 1–7) post-study intervention administration by 
participants on diary cards 
O 
O 
 
 
Refer to Section 10.3.8 


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Type of contact 
Visit 1 
Visit 2  
Visit 3  
Phone Contact† 
Notes 
Timepoints 
Day 1 
Month 2 
Month 3 
Month 8/Study 
Conclusion 
 
Recording non-serious unsolicited AEs (Days 1-30) post- study intervention 
administration by participants on diary cards 
O 
O 
 
 
Refer to Section 10.3.8 
Record medically-attended visits (Days 1-30)  
● 
● 
 
 
Refer to Section 10.3.9.3 
Return of diary cards 
 
O 
O 
 
Refer to Section 10.3.8 
Diary card transcription 
 
● 
● 
 
Refer to Section 10.3.8 
Record suspected HZ cases  
● 
● 
● 
● 
Refer to Section 10.3 
Record any concomitant medications/vaccinations 
● 
● 
● 
● 
Refer to Section 6.8  
Record IMC 
● 
● 
● 
● 
Refer to Section 9.3.1 
Record SAEs, pregnancies and pIMDs 
● 
● 
● 
● 
Refer to Section 10.3.8 
Record SAEs related to study participation, or to a concurrent GSK 
medication/vaccine#  
● 
● 
● 
● 
Refer to Section 10.3.8 
Record AE/SAEs leading to withdrawal 
● 
● 
● 
● 
Refer to Section 7.2 
Study Conclusion 
 
 
 
● 
Refer to Section 4.4  
AE=Adverse Event; HZ=Herpes Zoster; IMC=Intercurrent Medical Conditions; 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.  
Zones of the table where the activity is not performed are greyed.  
#SAEs related to study participation or GSK concomitant medication/vaccine are to be recorded from the time the participant consents to participate in the study. All other SAEs are to 
be reported after administration of the first dose of study intervention.  
 


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Table 2 
Intervals between study visits 
Interval 
Planned visit interval  
Allowed interval range 
Visit 1→Visit 2 
60 days/2 Months 
49 days-83 days# 
Visit 2→Visit 3 
30 days/1 Month 
28 days-48 days# 
Visit 2→Phone contact 
180 days/6 Months 
160-210 days 
#subjects may not be eligible for inclusion in the PPS, if study visits occur outside the allowed interval.  
See Section 8.9 for allowed interval during special circumstances. 
2. 
INTRODUCTION 
2.1. 
Study rationale (Amended 25 May 2022) 
GSK’s HZ/su is an Adjuvant System 01B (AS01B) adjuvanted recombinant subunit 
vaccine consisting of Varicella Zoster Virus (VZV) gE as antigen.  
The vaccine has been evaluated in several studies in older 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 clinically acceptable [Bastidas, 2019; 
Berkowitz, 2015; Chlibek, 2013; Chlibek, 2014; Cunningham, 2016; Dagnew, 2019; 
Leroux-Roels, 2012; Lal, 2015; Lecrenier, 2018; López-Fauqued, 2019; 
Stadtmauer, 2014; Vink, 2019; Vink, 2020].  
When this ZOSTER-081 study began, HZ/su was not approved for use in India. While 
the study was ongoing, HZ/su was licensed for use in India for adults ≥50 YOA on 
21 April 2022. Despite this licensure, HZ/su is not currently available in the Indian 
market; however, when it does become available, the study participants will be notified 
by the investigators. To meet the post-approval requirements of the Indian regulatory 
authority, this study to demonstrate the immunogenicity and safety of HZ/su in the 
Indian population is to continue as originally planned. This study is designed to 
evaluate the humoral immunogenicity and safety of 2 doses of HZ/su, for the 
prevention of HZ in adults ≥50 YOA. In addition, as also required by the Indian 
regulatory authority, a safety report describing the early supportive safety data will be 
provided once these data (up to Visit 3, Month 3) on the initial 200 study participants 
randomized are available. 
2.2. 
Background 
VZV causes 2 distinct diseases. Varicella (chickenpox) occurs shortly after primary VZV 
infection and is characterised by systemic illness and a widely disseminated rash. HZ, 
commonly called shingles, occurs when VZV reactivates from latency and typically 
manifests as a localised 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. 
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, 


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throbbing, intermittent sharp or electric shock-like pain, or allodynia [Dworkin, 2007]. 
Sensory symptoms can also include numbness, dysesthesias, pruritus, and allodynia in the 
affected dermatome. Other complications of HZ include ophthalmologic, neurological, 
cutaneous and visceral disease, which can result in severe disability. 
The incidence of HZ increases with age due to immune-senescence and waning of VZV 
immunity over time following primary varicella infection. 
Please refer to the current Investigator’s Brochure (IB) for information regarding 
pre- clinical and clinical studies of GSK’s HZ/su. 
2.3. 
Benefit/Risk assessment 
Detailed information about the known and expected benefits and risks and expected AEs 
of HZ/su can be found in the IB. The important potential risks identified, and the 
mitigation strategy associated with study interventions/ procedures are listed below. 
 


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Important Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
Study vaccine: HZ/su 
Risk of potential immune-mediated diseases 
(pIMDs) following the HZ/su 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 AEs that include 
autoimmune diseases and other inflammatory and/or 
neurological disorders of interest which may or may not have 
an autoimmune aetiology. To date, there is no evidence of an 
increased risk of pIMDs following vaccination with HZ/su in 
evaluated adults 50 YOA or older [López-Fauqued, 2019] 
Close monitoring of pIMDs will be conducted per study 
protocol and analysis of safety data generated through clinical 
trials and other sources. The potential risk of events of 
possible autoimmune aetiology to occur is mentioned in the 
Informed Consent Form (ICF). In addition, the ICF advises 
participants to contact the study doctor or study staff 
immediately, should any symptoms be considered serious. 
pIMDs will be collected up to study end (Month 8/6 months 
post last intervention).  
Guillain-Barré Syndrome (GBS) 
New available information on GBS emerged from a post-
marketing observational study where the risk of GBS 
following vaccination with HZ/su was assessed in adults aged 
≥65 YOA enrolled in the Medicare health insurance in the US. 
An increased risk of GBS during the 42 days following 
vaccination was estimated as an excess of 3.13 cases per 
million doses administered. Based on the review of the 
accumulated body of the information that is currently 
available, GSK considers that the strength of the collective 
evidence is insufficient to determine a causal relationship 
between HZ/su vaccination and GBS, owing to substantial 
limitations and confounding variables.  
Close monitoring of GBS will be conducted per study protocol 
and analysis of safety data generated through clinical trials 
and other sources as part of pIMDs (including GBS). The 
potential risk of events of possible autoimmune aetiology to 
occur is mentioned in the ICF. In addition, the ICF advises 
participants to contact the study doctor or study staff 
immediately, should any symptoms be considered serious. 
pIMDs (including GBS) will be collected up to study end 
(Month 8/6 months post last intervention). 
Hypersensitivity reactions (including anaphylaxis) 
Hypersensitivity reactions may occur following exposure to 
allergens from a variety of sources including food, 
aeroallergens, venom, drugs and immunisations. Vaccines 
are a mixture of compounds and allergic sensitisation 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 intervention is to be preceded by a 
review of the participant’s 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 study 
intervention. The onset of serious vaccine-related allergic 
symptoms is typically immediate. In order to assess and 


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Important Potential/Identified Risk 
Data/Rationale for Risk 
Mitigation Strategy 
adequately treat participants who may have an allergic 
reaction to the study intervention, all participants will need to 
remain under observation (i.e. visibly followed; no specific 
procedure required) at the study clinic site for at least 
30 minutes after each study intervention dose is administered. 
Study Procedures 
Risk from blood sampling 
Blood sampling associated risk of discomfort, syncope, 
dizziness, infection at the site after or during venipuncture. 
Blood samples will be obtained in seated or supine position by 
a trained professional and medical assistance will be 
available. 
The potential risk of feeling faint, or experiencing mild local 
pain, bruising, irritation or redness at the site where blood was 
taken, is mentioned in the ICF. The amount of blood to be 
taken for sampling will not be harmful to the participant’s 
health. 
Benefits include: 
• 
Participants receiving HZ/su during the study are very likely to have a reduced risk of HZ since HZ/su is shown to be efficacious in 
many other populations. 
• 
Medical evaluation/assessments associated with study procedures (e.g. physical examination).  
Overall, taking into account the measures to minimise risk to the participants, the potential or identified risks in association with HZ/su 
vaccine and study procedures are offset by the anticipated benefits to participants receiving HZ/su. 
The benefit-risk profile of HZ/su for the prevention of HZ in adults ≥50 YOA continues to be favourable. 
 


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3. 
OBJECTIVES AND ENDPOINTS 
Table 3 
Study objectives and endpoints (Amended 25 May 2022) 
Objectives 
Endpoints 
Primary 
To determine the vaccine response rate (VRR) for 
anti-gE humoral immune response at 1-month post-
dose 2 (Month 3) of administration of HZ/su*. 
Percentage of participants showing a vaccine response for 
anti-gE antibody concentrations,) at 1-month post-dose 2 
(Month 3). 
Secondary 
To evaluate the anti-gE humoral response at 1-
month post-dose 2 (Month 3) in recipients of HZ/su 
compared to Placebo**. 
Anti-gE antibody concentration expressed as group 
geometric mean concentration (GMC) ratio at 1-month post-
dose 2 (Month 3). 
To evaluate safety and reactogenicity following 
administration of HZ/su or placebo from first dose 
up to 30 days post last dose. 
Solicited AEs: Number and percentage of participants 
reporting each solicited administration site (injection site 
redness, pain, swelling and pruritus) and solicited systemic 
AEs (fever, myalgia, fatigue, gastrointestinal [GI] symptoms, 
headache and shivering) within 7 days (Day 1 to Day 7) after 
each dose and overall. 
Unsolicited AEs: Number and percentage of participants 
reporting unsolicited AEs within 30 days (Day 1 to Day 30) 
after any dose. 
SAEs: Number and percentage of participants reporting 
SAEs from Dose 1 (Day 1) up to 30 days post last dose. 
pIMDs: Number and percentage of participants reporting 
pIMDs from Dose 1 (Day 1) up to 30 days post last dose. 
To evaluate safety following administration of HZ/su 
or placebo during the entire study period. 
SAE- Number and percentage of participants reporting 
SAEs from Dose 1 (Day 1) up to study end (phone contact 
Month 8). 
pIMDs- The number and percentage of participants 
reporting pIMDs from Dose 1 (Day 1) up to study end 
(phone contact Month 8). 
To characterise anti-gE humoral immunogenicity 
response prior to the first study intervention 
administration (Day 1) and at 1-month post-second 
study intervention administration (Month 3) in both 
groups. 
Anti-gE antibody geometric mean concentrations (GMC) and 
seropositivity rate at pre-study intervention administration 
(Day 1) and 1-month post-dose 2 (Month 3). 
Mean geometric increase (MGI) at 1-month post- dose 2 
(Month 3) compared to pre-study intervention administration 
(Day 1). 
* The success criteria for the primary objective and VRR definition are presented in Section 9.4.1. 
** The success criteria for the secondary objective are presented in Section 9.4.2.2 


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4. 
STUDY DESIGN 
4.1. 
Overall design 
Figure 1 
Study design overview  
 
 
*BS=Blood Sampling; Int=study intervention, N=number of participants planned to be randomised;  
‡ Each participant will be followed up for 6 months post last dose/Month 8.  
• 
Type of study: Self-contained. 
• 
Experimental design: Phase 3, randomised, observer-blind, placebo-controlled, 
multi-centric, single country study with 2 parallel groups (see Figure 1). 
• 
Duration of the study: Approximately 8 months for each participant. 
• 
Control: Placebo-controlled.  
• 
Blinding: Observer-blind. 
• 
Study intervention schedule: 0 and 2 months (Day 1 and Month 2). 
• 
Biological samples: Blood samples will be collected at Day 1 and Month 3 (1-month 
post-dose 2). 
• 
Follow-up contact: Phone contact at Month 8 (6 months post last study intervention 
administration). 
• 
Primary completion date (PCD): Month 3 (1-month post-dose 2). Refer to glossary 
of terms for the definition of PCD. 
• 
Data collection: Standardised electronic Case Report Form (eCRF). Solicited AEs 
and unsolicited AEs will be collected using a Participant Diary card (paper diary 
card). 
• 
Study groups: Refer to Table 4 for an overview of the study groups. 


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Table 4 
Study groups, intervention and blinding 
Study Groups 
Number of 
participants 
Age 
Study intervention 
Blinding 
Visit 1→Phone contact 
(Observer-blind) 
HZ/su  
144 
≥50 years  
VZV gE  
X 
AS01B  
Placebo  
144 
≥50 years  
Lyophilised sucrose  
X 
Saline (NaCl) solution for 
reconstitution 
4.2. 
Scientific rationale for study design 
ZOSTER-081 study will be conducted to evaluate immunogenicity and safety of HZ/su in 
participants ≥50 YOA in India. The study will enrol approximately 288 participants who 
will be randomised 1:1 to the HZ/su or Placebo group of equal size to receive 2 doses of 
study interventions administered intramuscularly 2 months apart.  
The randomisation algorithm will use a minimisation procedure accounting for age 
(50- 69 YOA, ≥70 YOA). Minimisation factors will have equal weight in the 
minimisation algorithm. 
A lyophilised sucrose cake reconstituted with saline (NaCl) solution is included as a 
control (placebo) in this study evaluating the humoral immunogenicity and safety of 
HZ/su in this population. The inclusion of placebo control and the use of observer-blind, 
randomised study design aims to minimise the potential biases in study results. 
4.3. 
Justification for dose 
The approved dose regimen for HZ/su (2-dose vaccination) with an interval of 2 months 
between doses, will be followed in this study. Refer to Section 8.9 for interval between 
doses during special circumstances. 
4.4. 
End of Study definition 
A participant is considered to have completed the study if he/she is available for the last 
scheduled contact as described in the protocol. 
End of Study (EoS): Last subject* last visit (LSLV=Phone contact at Month 8) or Date of 
the last testing/reading released of the Human Biological Samples or imaging data, 
related to primary and secondary endpoints (whichever is later). EoS must be achieved no 
later than 8 months after LSLV. Refer to glossary of terms for the definition of EoS. 
*subject=participant 


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5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardise the scientific 
integrity, regulatory acceptability of the study or safety of the participant. 
5.1. 
Inclusion criteria 
All participants must satisfy ALL the following criteria at study entry: 
• 
Participants and/or participant’s legally acceptable representative(s) (LAR) 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 participant 
and/or participant’s LAR(s) after the study has been explained according to local 
regulatory requirements and prior to performance of any study-specific procedure.  
• 
A male or female aged 50 YOA or older at the time of the first study intervention. 
• 
Healthy participants or medically stable patients as established by medical history 
and clinical examination before entering into the study.  
• 
Female participants of non-childbearing potential may be enrolled in the study. 
Please refer to Section 10.4.1.1.1 for definitions of women of non-childbearing 
potential. 
• 
Female participants of childbearing potential may be enrolled in the study, if the 
participant:  
− 
has practiced adequate contraception for 1 month prior to study intervention 
administration, and 
− 
has a negative pregnancy test on the day of study intervention administration, 
and 
− 
has agreed to continue adequate contraception during the entire treatment period 
and for 2 months after completion of the study intervention administration 
series. 
Refer to Section 10.4.1 for definitions of woman of childbearing potential and adequate 
contraception.  
5.2. 
Exclusion criteria 
The following criteria should be checked at the time of study entry. The potential 
participant MAY NOT be included in the study if ANY exclusion criterion applies: 


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5.2.1. 
Medical conditions 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study.  
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study intervention(s) or study materials or equipment. 
• 
Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal 
functional abnormality, as determined by medical history, physical examination or 
laboratory screening tests.  
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required).  
• 
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). 
5.2.2. 
Prior/Concomitant therapy (Amended 25 May 2022) 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 30 days before first dose and ending 30 days after the 
last dose of study intervention administration with the exception of licensed 
pneumococcal vaccines and non-replicating vaccines (i.e. inactivated and subunit 
vaccines, including inactivated and subunit influenza vaccines, with or without 
adjuvant for seasonal or pandemic flu) may be administered up until 8 days prior to 
Dose 1 and/or Dose 2 and/or at least 14 days after any dose of study intervention. 
[In case an emergency mass vaccination for an unforeseen public health threat (e.g. a 
pandemic) is recommended and/or organised by the public health authorities, outside 
the routine immunisation programme, the time period described above can be 
reduced if necessary for that vaccine provided it is used according to local 
governmental recommendations and that the Sponsor is notified accordingly].  
• 
Planned administration of long-acting immune-modifying drugs at any time during 
the study period (e.g. infliximab).  
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the first dose of study intervention up to 
1-month post-dose 2 (Month 3) or planned administration during the study period.  
• 
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 study intervention dose. For corticosteroids, this will mean 
prednisone equivalent ≥20 mg/day or equivalent is not allowed. Inhaled, 
intra- articular and topical steroids are allowed. 
• 
Previous vaccination against varicella or HZ. 


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5.2.3. 
Prior/Concurrent clinical study experience 
Concurrently participating in another clinical study, at any time during the study period, 
in which the participant has been or will be exposed to an investigational or a 
non- investigational intervention (drug/invasive medical device). 
5.2.4. 
Other exclusions 
• 
Pregnant or lactating female. 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions within 2 months of last study intervention administration. 
• 
Indications of drug abuse or excess alcohol use as deemed by investigator to 
potentially confound safety assessments or render participant unable or unlikely to 
adhere to protocol requirements. 
5.3. 
Lifestyle considerations 
Not applicable. 
5.4. 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are determined ineligible and subsequently not enrolled (i.e. not randomised, have not 
undergone any invasive procedure and not administered a study intervention). 
Limited data for screening failures (for example any SAEs that occurred at the visit) will 
be collected and reported in the eCRF. 
5.5. 
Criteria for temporarily delaying randomisation/study 
intervention administration 
Study intervention administration may be postponed until transient conditions cited 
below are resolved:  
• 
Acute disease and/or fever at the time of study intervention administration. Refer to 
the SoA for definition of fever and preferred location for measuring temperature in 
this study.  
• 
Participants with symptoms suggestive of active Coronavirus Disease 2019 (COVID-
19) (e.g. fever, cough, etc.) at the time of study intervention administration.  
• 
Participants with known COVID-19 diagnosed contacts may be administered study 
intervention at least 14 days after the exposure, provided that the participant remains 
symptom-free, and at the discretion of the investigator. 


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6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY  
Refer to the Glossary of terms for the definition of study intervention. 
6.1. 
Study intervention(s) administered  
Table 5 
Study intervention(s) administered (Amended 25 May 2022) 
Study Intervention Name: 
HZ/su 
Placebo 
Study Intervention /Product 
name 
VZV gE  
AS01B  
Lyophilised 
sucrose 
Saline (NaCl) 
solution 
Study Intervention 
formulation: 
VZV gE 
(50 µg) 
AS01B: QS-21 
(50 µg), MPL 
(50 µg), liposomes; 
Water for injections  
Sucrose (20 mg) 
Sodium chloride 
(NaCl) (0.9%); 
Water for injections  
Presentation: 
Powder for 
suspension 
for injection  
Suspension for 
suspension for 
injection  
Powder for 
solution for 
injection  
Solution for 
solution for 
injection  
Container 
Vial 
Vial 
Vial 
Syringe 
Type: 
Biologic 
Not applicable 
Administration site:  
Intramuscular use 
Intramuscular use 
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, Labelling and TM: 
Refer to SPM 
Manufacturer: 
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=Quantum satis  
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. 
If the investigator or delegate determines that the participant’s health on the day of 
administration temporarily precludes study intervention administration, the visit will be 
rescheduled.  
Study participants must be observed closely for at least 30 minutes after the 
administration of the study intervention. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis, syncope. 
6.2. 
Preparation/Handling/Storage/Accountability 
The study intervention must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s).  


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Only authorised study personnel should be allowed access to the study intervention. 
Storage conditions will be assessed by a sponsor study contact during pre-study activities. 
Refer to the Study Procedures Manual (SPM) for more details on storage and handling of 
the study intervention. 
6.3. 
Measures to minimise bias: randomisation and blinding  
6.3.1. 
Participant identification 
Participant identification numbers will be assigned sequentially to the individuals who 
have consented to participate in the study. Each study centre will be allocated a range of 
participant identification numbers.  
6.3.2. 
Randomisation to study intervention 
Approximately 288 eligible participants will be randomly assigned (1:1) to the study 
groups (144 participants per study group). 
The randomisation 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, United States [US]) 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 thus to reduce the overall study recruitment period, an over-randomisation of 
supplies will be prepared. 
6.3.3. 
Intervention allocation to the participant 
An automated internet-based system, Source data Base for Internet Randomisation 
(SBIR) will be used for randomisation and for identification of intervention material. 
The randomisation algorithm will use a minimisation procedure accounting for age 
(50- 69 YOA, ≥70 YOA). Minimisation factors will have equal weight in the 
minimisation algorithm. 
Once a participant identification number is allocated, the randomisation system will 
determine study group and will provide the study intervention number to be used for the 
first dose. The study intervention number to be used for subsequent dosing will be 
provided by the same automated internet-based system, SBIR. 
When SBIR is not available, please refer to the SBIR user guide or SPM for specific 
instructions. 
Refer to the SPM for additional information about the study intervention number 
allocation. 


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6.3.4. 
Blinding and unblinding 
Data will be collected in an observer-blind manner. To do so, study intervention will be 
prepared and administered by qualified unblinded study personnel who will not 
participate in data collection, evaluation, review or the entry of any study endpoint (e.g. 
reactogenicity, safety). 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no visible link between the study intervention and the identity of the participant. 
6.3.4.1. 
Emergency unblinding 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention via SBIR. 
The investigator may contact a GSK Helpdesk (refer to the Table 6) if he/she needs help 
to perform the unblinding process (i.e. if the investigator is unable to access the SBIR). 
A physician other than the investigator (e.g. an emergency room physician) or 
participant/care giver/family member may also request emergency unblinding either via 
the investigator (preferred option) or via the GSK Helpdesk (back up option). The 
participant card provides contact information for the investigator, his/her back up and 
GSK Helpdesk. 
Table 6 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Toll-free phone number: 000800 919 0928 
Fax: +32.2.401.25.75 
Email: rix.ugrdehelpdesk@gsk.com  
6.3.4.2. 
Unblinding prior to regulatory reporting of SAEs 
GSK policy requires unblinding of any unexpected SAE which is attributable/suspected 
to be attributable to the study intervention, prior to regulatory reporting. Vaccines 
Clinical Safety and Pharmacovigilance (VCSP) is responsible for unblinding the study 
intervention assignment within the timeframes defined for expedited reporting of SAEs 
(refer to the Section 10.3.10.1).  


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In addition, GSK VCSP staff may unblind the intervention assignment for any participant 
with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or SAE that is fatal or 
life-threatening. For SAEs requiring expedited reporting to 1 or more regulatory 
agencies, a copy of the report containing participant’s intervention assignment may be 
sent to investigators in accordance with local regulations and/or GSK policy. 
6.4. 
Study intervention compliance 
Participants will receive the study intervention directly from the investigator or designee, 
under medical supervision. The date of administration of each study intervention dose in 
the study clinic site will be recorded in the eCRF.  
6.5. 
Dose modification 
Not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study 
No study intervention is planned after the end of this study. However, participants in the 
placebo group may be offered HZ/su, after the study is completed, depending on the 
study results, local standards and regulations. 
6.7. 
Treatment of overdose 
Not applicable. 
6.8. 
Concomitant therapy (Amended 25 May 2022). 
At each study contact, the investigator or his/her delegate should question the participant 
and/or participant’s LAR(s) about all medications/products taken, and vaccinations 
received by the participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medications ongoing once randomized at Visit 1 (Day 1). 
• 
All concomitant medication associated with an AE, including vaccines/products, 
except vitamins and dietary supplements, administered after the first dose of study 
intervention. 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines (refer to the sections 5.2.2 
and 9.3.1 for further details). 
• 
All concomitant medication which may explain/cause/be used to treat an SAE/pIMD 
including vaccines/products, as defined in Sections 8.3.1 and 10.3.8.2. These must 
also be recorded in the Expedited Adverse Event Report. 


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• 
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.  
• 
Any medication used during the assessment or treatment of suspected HZ or its 
complications during the study. 
The Local Medical Lead (LML) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
‘Discontinuation’ of study intervention refers to any participant who has not received all 
planned doses of study intervention. A participant who discontinued study intervention 
may continue other study procedures (e.g. safety or immunogenicity), planned in the 
study protocol at the discretion of the investigator.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• 
AE requiring expedited reporting to GSK 
• 
Unsolicited non-serious AE  
• 
Solicited AE 
• 
Not willing to be vaccinated 
• 
Other (specify). 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration 
The eligibility for subsequent study intervention administration must be confirmed before 
administering any additional dose.  
Participants who meet any of the criteria listed below or criteria listed in Sections 5.2.1 
and 5.2.2 should not receive additional doses of study intervention. Such participants 
should be encouraged to continue other study procedures, at the investigators’ discretion 
(Section 10.3.8.2). All relevant criteria for discontinuation of study intervention 
administration must be recorded in the eCRF.  
• 
Participants who experience any SAE judged to be possibly or probably related to 
study intervention or non-study concomitant vaccine/product, including 
hypersensitivity reactions. 
• 
Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participant if he/she continues to 
participate in the study. 


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• 
Anaphylaxis following the administration of study intervention. 
• 
Any condition that in the judgement of the investigator would make intramuscular 
injection unsafe. 
• 
Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the 
opinion of the investigator, expose the participant 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 study intervention. Refer to 
Section 10.3.5.1 for the definition of pIMDs. 
• 
Occurrence of a suspected HZ between the first and second study intervention dose. 
• 
Receipt of vaccine against HZ or VZV outside of the study. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for him/her since the date 
of withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who was not 
available for the concluding contact planned in the protocol.  
Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. 
The primary reason for study withdrawal will be documented in the eCRF, based on the 
list below: 
• 
AE requiring expedited reporting to GSK 
• 
Unsolicited non-serious AE 
• 
Solicited AE 
• 
Withdrawal by participant, not due to an AE* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
*If a participant is withdrawn from the study because he/she/participant’s LAR(s) has 
withdrawn consent and the reason for withdrawal was provided, the investigator must 
document this reason in the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.8.2). 


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7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if he/she fails to return for scheduled 
visits and cannot be contacted by the study site.  
Please refer to the SPM for a description of actions to be taken before considering the 
participant lost to follow-up. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant.  
Immediate safety concerns should be discussed with the sponsor as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarised in the SoA (Section 1.3).  
All screening evaluations must be completed, and the results reviewed before confirming 
that potential participants meet all eligibility criteria.  
The investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for screening failure will be mentioned in 
this screening log. 
Procedures conducted as part of routine clinical management (e.g. haematologic profiles), 
and obtained before the participant and/or participant’s LAR(s) signed the Informed 
Consent Form (ICF), may be used for screening and/or for establishing a clinical baseline 
(provided the procedure met protocol specified criteria and was performed within the 
time frame defined in the SoA (Section 1.3). 
The SPM provides the investigator and site personnel with detailed administrative and 
technical information that does not impact participant safety. 
8.1. 
Immunogenicity assessments 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol.  
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
IEC/IRB approval, if required by local legislation. 
Information on further research and its rationale can be obtained from GSK.  


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Sample testing will be done in accordance with the recorded consent of the individual 
participant.  
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit/contact. This timeline 
can be adapted based on local laws, regulations or guidelines requiring different 
timeframes or procedures. In all cases, the storage period should be aligned with 
participant’s consent. These additional requirements must be formally communicated to, 
discussed and agreed with GSK. 
8.1.1. 
Biological samples 
Table 7 
Biological samples 
Sample type 
Quantity 
Unit 
Timepoint 
Subset name 
Blood for antibody determination 
~ 5 
mL 
Day 1 and Month 3 
All participants 
8.1.2. 
Laboratory assays 
Table 8 
Laboratory assays  
Assay type 
System 
Component 
Method 
Laboratory* 
Humoral Immunity (Antibody determination) 
Serum 
VZV Glycoprotein E Ab.IgG 
ELISA 
GSK ** 
*Refer to the list of clinical laboratories for details. 
** GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium; Marburg, 
Germany. CLS may delegate testing to GSK Research laboratories in Rixensart, Belgium; Rockville, USA; Sienna, 
Italy. 
Please refer to the Section 10.2 for a brief description of the assay performed in the study. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 
GSK clinical laboratories have established a Quality System supported by procedures. 
The activities of GSK clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. 
8.1.3. 
Immunological read-outs  
Table 9 
Immunological read-outs 
Blood sampling timepoint 
Subset name 
No. participants 
Component 
Type of contact and timepoint 
Visit 1 (Day 1) 
All participants 
288 
Antibody gE ELISA 
Visit 3 (Month 3) 
All participants 
288 
Antibody gE ELISA 
8.1.4. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen(s) used in the study intervention. 


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8.2. 
Safety assessments 
The investigator and his/her designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and designees 
are responsible for following up AEs that are serious, considered related to the study 
intervention or the study, or that caused the participant’s withdrawal from the study 
intervention or study. 
8.2.1. 
Pre-study intervention procedures 
8.2.1.1. 
Informed consent 
Before performing any study procedure, the signed informed consent of the participant 
and/or participant’s LAR(s) needs to be obtained in accordance to local regulatory 
requirement. Refer to Section 10.1.3 for the requirements on how to obtain informed 
consent. 
8.2.1.2. 
Collection of demographic data 
Record demographic data such as year of birth, sex, race and ethnicity in the participant’s 
eCRF. 
8.2.1.3. 
Medical/vaccination history 
Obtain the participant’s medical/vaccination history by interviewing the participant 
and/or participant’s LAR(s) and/or review of the participant’s medical records. Record 
any pre-existing conditions, signs and/or symptoms present prior to the first dose of study 
intervention in the eCRF. 
8.2.1.4. 
History-directed physical examination 
Perform a history-directed physical examination. If the investigator determines that the 
participant’s health on the day of study intervention administration temporarily precludes 
dosing, the visit will be rescheduled. Refer to the Section 5.5 for the list of criteria for 
temporary delay of study intervention administration. 
Treatment of any pre-existing or new onset condition 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. 
8.2.1.5. 
Pregnancy test 
Female participants of childbearing potential must perform a urine pregnancy test before 
the administration of any dose of study intervention. Pregnancy testing must be done 
even if the participant is menstruating at the time of the study visit. The study 
intervention may only be administered if the pregnancy test is negative.  
Refer to the Section 10.4.3.1 for the information on study continuation for participants 
who become pregnant during the study. 


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8.2.1.6. 
Warnings and precautions to administration of study intervention 
Warnings and precautions to administration of study intervention must be checked at 
each visit with planned administration of study intervention. 
8.2.1.7. 
Pre-study intervention administration body temperature 
The body temperature of each participant needs to be measured prior to any study 
intervention administration and recorded in the eCRF. The preferred route for measuring 
temperature is oral. If the participant has fever (fever is defined as temperature 
≥38.0°C/100.4°F regardless the location of measurement) on the day of study 
intervention administration, the study intervention administration visit will be 
rescheduled. 
8.2.2. 
Post-study intervention administration procedures 
All participants post-intervention will be followed up for AE/SAE/pIMD/IMC/pregnancy 
or any other event of interest and instructed to contact the investigator immediately 
should they manifest any symptoms/signs they perceive as a concern. Refer to Section 
1.3 and Section 10.3 for details. 


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8.3. 
Adverse Events, Serious Adverse Events and other safety 
reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE and other 
safety information 
Table 10 
Timeframes for collecting and reporting of AE, SAE and other safety 
information 
Event 
Dose 1 
 
 
 Dose2 
 
 
 
6 Months after last dose 
Study Conclusion 
Timing of reporting 
D1 
D7 
D31 
D1 
D7 
D31 
Administration site and 
systemic solicited events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to the study 
intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent 
GlaxoSmithKline medication/ 
vaccine a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suspected HZ episodes, IMC, 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D: Day, M: Month; HZ=Herpes Zoster, IMC=Intercurrent Medical Conditions 
Note: For each solicited and unsolicited AEs the participant experiences, the participant will be asked if he/she 
received medical attention defined as hospitalisation, 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. 
a SAEs related to study participation or GSK concomitant medication/vaccine are to be recorded from the time the 
participant consents to participate in the study. All other SAEs are to be reported after administration of the first dose of 
study intervention. 
This applies only to pregnancy cases with exposure to study intervention at any age of gestation. The timing of 
exposure to study intervention during pregnancy is estimated in relation to the first day of the last menstrual period, 
ultrasound or known date of fertilisation (e.g. assisted reproductive technology). 


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The investigator or designee will record and immediately report all SAEs to the sponsor 
or designee via the Expedited AE Reporting Form. Reporting should, under no 
circumstances, occur later than 24 hours after the investigator becomes aware of an SAE, 
as indicated in Section 10.3.10. 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 outside of the AE/SAE 
reporting periods defined in Table 10. Investigators are not obligated to actively seek AEs 
or SAEs from former study participants. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
he/she considers the event to be reasonably related to the study intervention, the 
investigator will promptly notify the study contact for reporting SAEs mentioned in the 
Table 12. 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and other 
events 
Detection and recording of AE/SAE/pIMDs/pregnancies are detailed in Section 10.3.8.  
Assessment of AE/SAE intensity, causality and outcome are described in Section 10.3.9.  
Open-ended and non-leading verbal questioning of participants and/or participant’s 
LAR(s) is the preferred method of acquiring information related to an 
AE/SAE/pIMD/pregnancy. 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies and 
other events 
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/pIMDs/pregnancy, it must be reported to GSK using the required 
documentation and within the timeframes mentioned in Table 11. This is essential for 
meeting GSK legal obligations and ethical responsibilities for participant safety and the 
safety of a study intervention under clinical investigation. 
For SAEs/pIMDs, the investigator must always provide an assessment of causality at the 
time of the initial report, as defined in the Section 10.3.9.2. 
Local regulatory requirements and sponsor policy for preparation of an investigator 
safety report of SUSAR must be followed. These reports will be forwarded to 
investigators as necessary. 
The sponsor has the legal responsibility to notify local authorities/regulatory agencies 
about the safety of an investigational study intervention. The sponsor will comply with 
country-specific regulatory requirements related to safety reporting to the regulatory 
authority, IRB/IEC and investigators. 
Please refer to the Section 10.3.10 for further details regarding the reporting of 
SAEs/pIMDs/pregnancies. 


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Table 11 
Timeframes for submitting SAE, pregnancy and other events reports 
to GSK 
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  
24 hours 
electronic pregnancy report  24 hours 
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 by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of an pIMD. 
‡ Paper Expedited Adverse Events Report will be dated and signed by the investigator (or designee) 
‡‡ 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. 
8.3.3.1. 
Contact information for reporting SAEs, pIMDs and pregnancies  
Table 12 
Contact information for reporting SAEs, pIMDs and pregnancies 
Study contact for questions regarding SAEs, pIMDs, pregnancies 
Refer to the local study contact information document 
Back up study contact for reporting SAEs, pIMDs, pregnancies  
Available 24/24 hours and 7/7 days: 
GSK Clinical Safety & Pharmacovigilance 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: ogm28723@gsk.com 
8.3.4. 
Treatment of adverse events 
Any medication administered for the treatment of an SAE/pIMD should be recorded in 
the Expedited Adverse Event Report of the participant’s eCRF screen (refer to the 
Section 10.3.10.1). 
8.3.5. 
Participant card 
The investigator (or designee) must provide the participant and/or participant’s LAR(s) 
with a “participant card” containing information about the clinical study. The participant 
and/or participant’s LAR(s) must be instructed to always keep the participant card in 
his/her/their possession for the duration of the study. In an emergency, this card serves to 
inform the responsible attending physician/LAR/caregiver/family member that the 
participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator or his/her back up. 
8.4. 
Pharmacokinetics 
Not applicable in this study. 


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8.5. 
Genetics 
Not being evaluated in the current study.  
8.6. 
Biomarkers 
Not applicable in this study. 
8.7. 
Immunogenicity 
Immunogenicity is described in Section 8.1. 
8.8. 
Health outcomes 
Not being evaluated in the current study. 
8.9. 
Study procedures to be followed during special 
circumstances 
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 participants:  
• 
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 participant’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 International Conference on 
Harmonisation-Good Clinical Practice (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 local requirements. 
• 
If despite best efforts, it is not possible to collect the biological samples within the 
interval pre-defined in the protocol (see Table 2), then the interval may be extended 
as outlined in Table 13. 
• 
If despite best efforts, it is not possible to administer the second dose of study 
intervention as defined in the protocol (see Table 2), then the interval may be 
extended as outlined in Table 13. 


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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 13 
Intervals between study visits during special circumstances  
Interval 
Planned visit 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–60 days 
Visit 2→Phone contact 
180 days (6 months) 
160-210 days 
160–210 days 
Note: Investigator should prioritise conducting the visit as close to the planned visit interval as possible. 
Impact on the PPS for immunogenicity 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 8.3. 
COVID-19 cases should be reported in the eCRF according to the World Health 
Organisation (WHO) Case Definition [WHO, 2020]. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
The study has one primary and one secondary immunogenicity confirmatory objective 
and will be assessed in hierarchical manner. The null hypothesis related to primary 
objective under consideration is VRR for anti-gE antibody concentration after second 
HZ/su dose is <60%. 
The primary objective will be met if the lower limit (LL) of the 95% Confidence Interval 
(CI) of the VRR for anti-gE antibody concentration after second HZ/su dose is ≥60%.  
The null hypothesis related to secondary confirmatory objective under consideration is 
adjusted GMC ratio between HZ/su and Placebo group for anti-gE antibody 
concentration after second study intervention dose is <3. 
The secondary confirmatory objective will be met if the LL of the 95% CI of the adjusted 
GMC ratio between HZ/su and Placebo group for anti-gE antibody concentration after 
second study intervention dose is ≥3.  
All the safety analyses under secondary objective are descriptive. 


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9.2. 
Sample size determination 
Approximately 288 (144 participants per study group) eligible participants will be 
randomised to achieve 200 (100 participants per study group) evaluable participants for 
the evaluation of the primary objective assuming that approximately 30% of the enrolled 
participants will not be evaluable. Participants who withdraw from the study will not be 
replaced. 
Considering a 95% VRR in the HZ/su group, the study has at least 99% power to meet 
the primary objective. 
Null hypothesis: The VRR for anti-gE ELISA at 1 month after second HZ/su dose in 
participants from India is less than 60%. 
Alternative hypothesis: The VRR for anti-gE ELISA at 1 month after second HZ/su dose 
in participants from India is at least 60%. 
Power to show the LL of the 95% CI for VRR at one month after second HZ/su dose. 
Endpoint 
NI criteria 
N1:N2 (evaluable) 
Reference** 
Power* 
Vaccine response rate 
– anti-gE ELISA 
LL of 95% CI for VRR ≥60% 
100:100 
95% 
≥99% 
*Power computed using PASS 2019 software, Non-Inferiority Test for one proportion, 1-sided alpha=2.5%; 
**References used for the sample size calculation: ZOSTER-006 study. 
Considering the adjusted GMC ratio of 44.31 between HZ/su and Placebo group and SD 
of 0.30 and 0.46 for HZ/su and Placebo group, respectively, the study has at least 99% 
power to meet the secondary confirmatory objective. 
Null hypothesis: The adjusted GMC ratio for anti-gE ELISA at 1 month after second 
study intervention dose in participants from India is less than 3. 
Alternative hypothesis: The adjusted GMC ratio for anti-gE ELISA at 1 month after 
second study intervention dose in participants from India is greater than or equal to 3. 
Power to show the LL of the 95% CI for adjusted GMC ratio at one month after second 
dose. 
Endpoint 
Criteria for evaluation 
N1:N2 (evaluable) 
Reference** 
Power* 
Adjusted GMC ratio  
LL of 95% CI for adjusted 
GMC ratio ≥3 
100:100 
Adjusted GMC ratio – 44.31 
SD for HZ/su group – 0.30 
SD for Placebo group – 0.46 
≥ 99% 
*Power computed using PASS 2019 software, Two-Sample T-Tests for Superiority by a Margin Allowing Unequal 
Variance  
, 1-sided alpha=2.5%; 
**References used for the sample size calculation: ZOSTER-006 study. 


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9.3. 
Analysis sets 
Table 14 
Analysis sets 
Analysis Set 
Description 
Enrolled Set 
Eligible participants who have signed an informed consent and were randomised 
or undergone an invasive procedure. 
Exposed Set 
All participants who received at least 1 dose of the study intervention. Analysis per 
group using the enrolled set is based on the administered intervention. 
Per Protocol Set 
All eligible participants who received all doses as per protocol, had 
immunogenicity results pre and post-dose 2, complied with allowed dosing/blood 
draw intervals (Table 2), without intercurrent conditions that may interfere with 
immunogenicity and without prohibited concomitant medication/vaccination. The 
analysis will be done according to the study intervention that participants received 
at dose 1. 
9.3.1. 
Criteria for elimination from analysis 
If the participant meets one of the criteria mentioned below or ones listed in the 
Section 7.1.1 (contraindication to subsequent vaccination) or Section 5.2.1 (medical 
conditions) or Section 5.2.2 (concomitant therapy), he/she may be eliminated from per 
protocol analysis. 
Participants may be eliminated from the PPS for immunogenicity if, during the study up 
to blood sampling timepoint post-dose 2, they incur a condition that has the capability of 
altering their immune response (IMC) or are confirmed to have an alteration of their 
initial immune status. Refer to Glossary of terms for the definition of IMC. 
9.4. 
Statistical analyses 
The statistical analysis plan (SAP) will be finalised prior to the first subject* first visit 
(FSFV) and it will include a more technical and detailed description of the statistical 
analyses including the supportive analyses and demography summaries. This section is a 
summary of the planned statistical analyses of the most important endpoints including 
primary and secondary endpoints.  
Unless otherwise mentioned, for all the planned analyses with CI, a 95% CI will be 
computed. 
*subject= participant 
9.4.1. 
Primary endpoint 
The primary immunogenicity analysis will be performed on PPS and if more than 5% 
participants are eliminated from PPS then complementary analysis will be performed on 
ES. 
The VRR and 95% CI for anti-gE antibody concentration as assessed by ELISA will be 
calculated in all participants at 1-month post-dose 2 (Month 3). 


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Success criterion: The objective is met if the LL of the 95% CI of the VRR for anti-gE 
antibody concentration after second HZ/su dose is at least 60%. 
The VRR is defined as the percentage of subjects who has at least: 
• 
a 4-fold increase in the post last vaccination anti-gE Ab concentration as compared 
to the pre-vaccination anti-gE Ab concentration for participants who are seropositive 
at baseline. 
OR 
• 
a 4-fold increase in the post last vaccination anti-gE Ab concentration as compared 
to the anti-gE Ab cut-off value for seropositivity for participants who are 
seronegative at baseline.  
Two-sided 95% CIs for VRR will be computed by Clopper-Pearson method [Clopper, 
1934]. 
9.4.2. 
Secondary endpoints 
Descriptive analyses of demography and more detailed safety analysis will be presented 
in the SAP. 
9.4.2.1. 
Secondary immunogenicity endpoints 
The analysis will be performed on PPS and if more than 5% participants are eliminated 
from PPS then complementary analysis will be performed on ES. 
For the secondary confirmatory group comparison, the GMC ratio with nominal 95% CI 
will also be provided. This will be obtained using an analysis of variance (ANOVA) 
model on log-transformed concentrations adjusted for age-strata (50-69 YOA and 
≥ 70 YOA) and baseline titres as continuous covariate and will use Satterthwaite method 
for adjusting the degree of freedom for unequal variance. 
Descriptive immune response with respect to anti-gE assessed by ELISA at each 
timepoint and by study group will be presented:  
• 
Number and percentage of participants with anti-gE assessed by ELISA above 
seropositivity cut-off will be tabulated with 95% CI. 
• 
GMCs will be tabulated with 95% CI. 
• 
Geometric mean of ratios of antibody concentrations at 1- month post-dose 2 
timepoint over pre-study intervention administration will be tabulated with 95% CI. 
9.4.2.2. 
Secondary Safety endpoints 
The analyses for safety will be descriptive and based on the ES. The analysis will be 
performed by group.  


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The results for the analysis of safety and reactogenicity will be tabulated as follows: 
• 
Solicited administration site AEs and solicited systemic AEs 
− 
Number and percentage of participants reporting each solicited administration 
site AE (any grade, grade 3, resulting in a medically-attended visit) during the 
7-day follow-up period after each dose and overall will be tabulated with exact 
95% CIs. 
− 
Number and percentage of participants reporting each solicited systemic AE 
(any grade, grade 3, resulting in a medically-attended visit) during the 7-day 
follow-up period after each dose and overall will be tabulated with exact 95% 
CIs. 
• 
Unsolicited AEs: Number and percentage of participants reporting unsolicited AE 
(any grade, grade 3, any related, grade 3 related, resulting in a medically-attended 
visit) within 30 days after any dose coded by the Medical Dictionary for Regulatory 
Activities (MedDRA) by primary system organ class (SOC) and preferred term (PT) 
with exact 95% CIs will be tabulated. 
• 
SAEs and pIMDs: Number and percentage of participants reporting SAEs (any and 
related), fatal SAEs (any and related) and pIMDs (any and related) from Dose 1 
(Day 1) up to 30 days post last dose and from Dose 1 (Day 1) up to study end coded 
by the MedDRA primary SOC and PT with exact 95% CIs will be tabulated. 
9.5. 
Interim analyses (Amended 25 May 2022) 
No interim analysis is planned for this study. An EoS analysis with all data including the 
safety data obtained until study end (6 months post-dose 2) will be performed. A Clinical 
Study Report (CSR) containing all available data will be written and made available to 
the investigators. Individual listings will only be provided at this stage. 
To fulfil the post-approval commitment to the Indian regulatory authority, a blinded 
early safety assessment report after completion of 30 days safety follow-up post HZ/su 
dose 2 (i.e., Visit 3, Month 3) for the initial 200 randomised participants will be 
provided.  


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight 
considerations  
10.1.1. 
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-GCP Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, 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 protocol amendments 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 participants.  
• 
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. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators must provide the sponsor with full and accurate 
financial disclosure, as requested, to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators must provide their financial interest information before initiation of the 
study centre and again at the end of the study. Investigators are responsible for providing 
a financial disclosure update if their financial interests change at any point during study 
participation and for 1 year after completion of the study. 


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10.1.3. 
Informed consent process 
The investigator or his/her representative must fully explain the nature of the study to the 
participant and/or his/her LAR(s) and answer all questions regarding the study.  
Participants and/or participant’s LAR(s) must be informed that their participation is 
voluntary.  
Freely given and written/witnessed/thumb printed informed consent must be obtained 
from each participant and/or participant’s LAR(s) prior to participation in the study.  
The content of the ICF 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 or witnessed/ thumb printed 
informed consent was obtained before the participant was enrolled in the study and the 
date the consent was obtained. The authorised person obtaining the informed consent 
must also sign the ICF.  
Participants must be re-consented to the most current version of the ICF(s) or an ICF 
addendum during their participation in the study.  
A copy of the ICF(s) must be provided to the participants and/or participant’s LAR(s).  
Participants who are rescreened are required to sign a new ICF. 
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets transferred to the sponsor will contain only the identifier. Name and any other 
information which would identify the participant will not be transferred.  
The participants and/or participant’s LAR(s) must be informed that: 
• 
His/her personal study-related data will be used by the sponsor in accordance with 
local data protection law.  
• 
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 ensure protection of the personal data of the investigator and site staff which is 
collected within the framework of and for the purpose of the study, in accordance with 
the Data Privacy Notice that will be sent to the site staff.  
The participants and/or participant’s LAR(s) must be notified about their rights regarding 
the use of their personal data in accordance with the data privacy section of the ICF. 


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10.1.5. 
Committees structure 
GSK will obtain necessary approvals for conduct of the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study. This includes IRBs/IECs for review and approval of the protocol and 
subsequent amendments, ICF and any other documentation.  
An internal GSK Safety Review Team (SRT) will oversee the safety of the study. All 
safety data, i.e. AEs, SAEs, fatal SAEs and pIMDs 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. 
10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines.  
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical trial registers. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, and 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 participants, as appropriate. 
GSK will provide the investigator with the randomisation codes for their site only after 
completion of the full statistical analysis. 
GSK intends to make anonymised participant-level data from this trial available to 
external researchers for scientific analyses or to conduct further research that can help 
advance medical science or improve patient care. This helps ensure the data provided by 
trial participants are used to maximum effect in the creation of knowledge and 
understanding. 
10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents. The document 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 trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, CRF), the copy should fulfil the 
requirements for certified copies.  


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All participant data related to the study will be recorded on printed or electronic CRF 
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. 
The investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial participants that supports 
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 for such review and inspection.  
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 
in the eCRF by authorised site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g. via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH-GCP, and all 
applicable regulatory requirements.  
Quality tolerance limits (QTLs) will be pre-defined in the Study Management Plan to 
identify systematic issues that can impact participant safety and/or the reliability of study 
results. These pre-defined parameters will be monitored during the study. Important 
deviations from the QTLs and remedial actions taken will be summarised in the CSR. 
Trial records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the investigator for 25 years from issuance of the final 
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.  
10.1.8. 
Source documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The investigator should maintain a record of 
the location(s) of their source documents.  
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any 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. 
Definitions of what constitutes source data and documents can be found in the Glossary 
of terms. 


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10.1.9. 
Study and site start and closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at its sole discretion, provided there is sufficient notice given to 
account for all participants safe exit from study.  
Regular closure of study sites will occur 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.  
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice 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 participants by the investigator 
• 
Discontinuation of further study intervention development. 
10.1.10. 
Publication policy 
GSK aims to submit the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the LSLV for interventional studies and 
follows the guidance from the International Committee of Medical Journal Editors 
(ICMJE). 
10.2. 
Appendix 2: Clinical laboratory tests 
Anti-gE ELISA: Anti-gE Ab concentrations will be measured using an anti-gE ELISA. 
Diluted blood serum samples of study participants will be added to microtitre wells 
precoated with gE antigen. Secondary peroxidase-conjugated anti-human IgG Abs will be 
added, which bind to the primary human anti-gE Abs. After incubation of the micro titre 
wells with a chromogen substrate solution, the enzymatic reaction will be stopped. 
Optical densities will be recorded and anti-gE Ab concentrations are calculated from a 
standard curve. The assay cut-off is 97 mIU/mL. 


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10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of 
AE 
10.3.1. 
Definition of an adverse event  
An AE is any untoward medical occurrence (an unfavourable/unintended sign – including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical 
study participant that is temporally associated with the study intervention. The AE may or 
may not be considered related to the study intervention. 
10.3.1.1. 
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 administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 
• 
Signs, symptoms that require medical attention (e.g. hospital stays, physician visits 
and emergency room visits). 
• 
Significant failure of an expected pharmacologic or biological action. 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated 
procedures (i.e. invasive procedures, modification of participant’s previous 
therapeutic regimen). Note the exception made here for pre-intervention events to 
the AE definition. 
• 
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. 
• 
AEs to be recorded as solicited AEs are described in the Section 10.3.3. All other 
AEs will be recorded as UNSOLICITED AEs. 


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10.3.1.2. 
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 participant before 
the first dose of study intervention. These events will be recorded in the medical 
history section of the eCRF.  
• 
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
10.3.2. 
Definition of an SAE 
An 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 participant 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 hospitalisation or prolongation of existing hospitalisation 
Note: In general, hospitalisation signifies that the participant 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 hospitalisation are also considered AEs. The 
event will also be considered serious if a complication prolongs hospitalisation or 
fulfils any other serious criteria. When in doubt as to whether ‘hospitalisation’ 
occurred or was necessary, the AE should be considered serious. 
• 
Results in disability/incapacity  
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 participant. 


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• 
Abnormal pregnancy outcomes (e.g. spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, ectopic pregnancy). 
• 
Other situations 
− 
Medical or scientific judgement must be exercised in deciding whether 
reporting is appropriate in other situations. Important medical events that may 
not be immediately life-threatening or result in death or hospitalisation but 
may jeopardise the participant or require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition should 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; and convulsions that do not result in 
hospitalisation. 
10.3.3. 
Solicited events 
• 
Solicited administration site events 
The following administration site events will be solicited: 
Table 15 
Solicited administration site events (Amended 25 May 2022) 
Pain at injection site  
Redness at injection site  
Swelling at injection site  
Pruritus at injection site 
• 
Solicited systemic events 
The following systemic events will be solicited as per GSK’s routine practice for HZ/su 
in older adults: 
Table 16 
Solicited systemic events 
Fatigue 
Fever 
GI symptoms† 
Headache 
Myalgia 
Shivering 
†Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain. 
Note: participant’s and/or participant’s LAR(s) will be instructed to measure and record 
the oral temperature in the evening. If additional temperature measurements are taken at 
other times of the day, participants and/or participant’s LAR(s) will be instructed to 
record the highest temperature in the diary card. 


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10.3.4. 
Unsolicited adverse events 
An unsolicited AE is an AE that was not included in a list of solicited events using a 
Participant Diary. Unsolicited events must have been spontaneously communicated by a 
participant and/or participant’s LAR(s) who has signed the informed consent. Unsolicited 
AEs include both serious and non-serious AEs. 
Potential unsolicited AEs may be medically-attended (i.e., symptoms or illnesses 
requiring a hospitalisation, or an emergency room visit, or visit to/by a health care 
provider). The participants and/or participant’s LAR(s) will be instructed to contact the 
site as soon as possible to report medically-attended event(s), as well as any events that, 
though not medically-attended, are of participant and/or participant’s LAR(s) concern. 
Detailed information about reported unsolicited AEs will be collected by qualified site 
personnel and documented in the participant’s records. 
Unsolicited AEs that are not medically-attended or perceived as a concern by the 
participant and/or participant’s LAR(s) will be collected during an interview with the 
participants and by review of available medical records at the next visit. 
10.3.5. 
Adverse events of special interest 
pIMDs are the only AESI collected during this study. 
10.3.5.1. 
Potential immune-mediated diseases 
Potential immune-mediated diseases (pIMDs) are a subset of AESIs that 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 17 (Please refer to the Section 
10.3.8.1 for reporting details). 
The investigator must exercise his/her medical/scientific judgement to determine 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 17 
List of potential immune-mediated diseases (pIMDs) (Amended, 25 
May 2022) 
Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid syndrome 
 
Autoimmune aplastic anemia 
 
Autoimmune hemolytic anemia 
• 
Includes warm antibody hemolytic anemia and cold antibody 
hemolytic anemia 
Autoimmune lymphoproliferative 
syndrome (ALPS) 
 
Autoimmune neutropenia  
 
Autoimmune pancytopenia 
 
Autoimmune thrombocytopenia 
• 
Frequently used related terms include: “autoimmune 
thrombocytopenic purpura”, “idiopathic thrombocytopenic 
purpura (ITP)”, “idiopathic immune thrombocytopenia”, “primary 
immune thrombocytopenia”. 
Evans syndrome 
 
Pernicious anemia 
 
Thrombosis with 
thrombocytopenia syndrome 
(TTS) 
 
Thrombotic thrombocytopenic 
purpura 
• 
Also known as “Moschcowitz-syndrome” or “microangiopathic 
hemolytic anemia” 
Cardio-pulmonary inflammatory disorders 
Idiopathic 
Myocarditis/Pericarditis 
Including but not limited to: 
• 
Autoimmune / Immune-mediated myocarditis 
• 
Autoimmune / Immune-mediated pericarditis 
• 
Giant cell myocarditis 
Idiopathic pulmonary fibrosis 
Including but not limited to: 
• 
Idiopathic interstitial pneumonia (frequently used related terms 
include “Interstitial lung disease”, “Pulmonary fibrosis”, “Immune-
mediated pneumonitis”) 
• 
Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar proteinosis 
(PAP) 
• 
Frequently used related terms include: “pulmonary alveolar 
lipoproteinosis”, “phospholipidosis” 
Endocrine disorders 
Addison’s disease 
 
Autoimmune / Immune-mediated 
thyroiditis  
Including but not limited to: 
• 
Hashimoto thyroiditis (autoimmune hypothyroidism, lymphocytic 
thyroiditis) 
• 
Atrophic thyroiditis  
• 
Silent thyroiditis  
• 
Thyrotoxicosis 


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Medical Concept 
Additional Notes 
Autoimmune diseases of the 
testis and ovary 
• 
Includes autoimmune oophoritis, autoimmune ovarian failure and 
autoimmune orchitis 
Autoimmune hyperlipidemia 
 
Autoimmune hypophysitis 
 
Diabetes mellitus type I 
 
Grave's or Basedow’s disease 
• 
Includes Marine Lenhart syndrome and Graves' ophthalmopathy, 
also known as thyroid eye disease (TED) or endocrine 
ophthalmopathy 
Insulin autoimmune syndrome 
 
Polyglandular autoimmune 
syndrome 
• 
Includes Polyglandular autoimmune syndrome type I, II and III 
Eye disorders 
Ocular Autoimmune / Immune-
mediated disorders 
Including but not limited to: 
• 
Acute macular neuroretinopathy (also known as acute macular 
outer retinopathy) 
• 
Autoimmune / Immune-mediated retinopathy  
• 
Autoimmune / Immune-mediated uveitis, including idiopathic 
uveitis and sympathetic ophthalmia  
• 
Cogan's syndrome: an oculo-audiovestibular disease 
• 
Ocular pemphigoid 
• 
Ulcerative keratitis 
• 
Vogt-Koyanagi-Harada disease 
Gastrointestinal disorders 
Autoimmune / Immune-mediated 
pancreatitis 
 
Celiac disease 
 
Inflammatory Bowel disease  
Including but not limited to:  
• 
Crohn’s disease  
• 
Microscopic colitis  
• 
Terminal ileitis 
• 
Ulcerative colitis  
• 
Ulcerative proctitis 
Hepatobiliary disorders 
Autoimmune cholangitis 
 
Autoimmune hepatitis 
 
Primary biliary cirrhosis 
 
Primary sclerosing cholangitis 
 
Musculoskeletal and connective tissue disorders  
Gout 
• 
Includes gouty arthritis 


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Medical Concept 
Additional Notes 
Idiopathic inflammatory 
myopathies 
Including but not limited to: 
• 
Dermatomyositis 
• 
Inclusion body myositis 
• 
Immune-mediated necrotizing myopathy 
• 
Polymyositis 
Mixed connective tissue disorder 
 
Polymyalgia rheumatica (PMR) 
 
Psoriatic arthritis (PsA) 
 
Relapsing polychondritis 
 
Rheumatoid arthritis  
Including but not limited to: 
• 
Rheumatoid arthritis associated conditions 
• 
Juvenile idiopathic arthritis 
• 
Palindromic rheumatism 
• 
Still's disease 
• 
Felty’s syndrome 
Sjögren’s syndrome 
 
Spondyloarthritis 
Including but not limited to:  
• 
Ankylosing spondylitis 
• 
Juvenile spondyloarthritis 
• 
Keratoderma blenorrhagica 
• 
Psoriatic spondylitis  
• 
Reactive Arthritis (Reiter's Syndrome) 
• 
Undifferentiated spondyloarthritis 
Systemic Lupus Erythematosus  
• 
Includes Lupus associated conditions (e.g. Cutaneous lupus 
erythematosus, Lupus nephritis, etc.) or complications such as 
shrinking lung syndrome (SLS) 
Systemic Scleroderma (Systemic 
Sclerosis) 
• 
Includes Reynolds syndrome (RS), systemic sclerosis with diffuse 
scleroderma and systemic sclerosis with limited scleroderma (also 
known as CREST syndrome) 
Neuroinflammatory/neuromuscular disorders 
Acute disseminated 
encephalomyelitis (ADEM) and 
other inflammatory 
demyelinating variants  
Includes the following: 
• 
Acute necrotising myelitis 
• 
Bickerstaff's brainstem encephalitis  
• 
Disseminated necrotizing leukoencephalopathy (also known as 
Weston-Hurst syndrome, acute hemorrhagic leuko-encephalitis, or 
acute necrotizing hemorrhagic encephalomyelitis)  
• 
Myelin oligodendrocyte glycoprotein antibody-associated disease 
• 
Neuromyelitis optica (also known as Devic’s disease) 
• 
Noninfective encephalitis / encephalomyelitis / myelitis 
• 
Postimmunization encephalomyelitis  


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Medical Concept 
Additional Notes 
Guillain-Barré syndrome (GBS) 
• 
Includes variants such as Miller Fisher syndrome and the acute 
motor and sensory axonal neuropathy (AMSAN) 
Idiopathic cranial nerve 
palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• 
Cranial nerve neuritis (e.g. Optic neuritis) 
• 
Idiopathic nerve palsies/paresis (e.g. Bell’s palsy) 
• 
Melkersson-Rosenthal syndrome 
• 
Multiple cranial nerve palsies/paresis  
Multiple Sclerosis (MS) 
Includes the following: 
• 
Clinically isolated syndrome (CIS)  
• 
Malignant MS (the Marburg type of MS)  
• 
Primary-progressive MS (PPMS) 
• 
Radiologically isolated syndrome (RIS) 
• 
Relapsing-remitting MS (RRMS) 
• 
Secondary-progressive MS (SPMS) 
• 
Uhthoff's phenomenon  
Myasthenia gravis 
• 
Includes ocular myasthenia and Lambert-Eaton myasthenic 
syndrome 
Narcolepsy 
• 
Includes narcolepsy with or without presence of unambiguous 
cataplexy 
Peripheral inflammatory 
demyelinating neuropathies and 
plexopathies 
Including but not limited to: 
• 
Acute Brachial Radiculitis (also known as Parsonage-Turner 
Syndrome or neuralgic amyotrophy) 
• 
Antibody-mediated demyelinating neuropathy 
• 
Chronic idiopathic axonal polyneuropathy (CIAP) 
• 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 
(CIDP), including atypical CIDP variants (e.g. multifocal acquired 
demyelinating sensory and motor neuropathy also known as 
Lewis-Sumner syndrome) 
• 
Multifocal motor neuropathy (MMN)  
Transverse myelitis (TM) 
• 
Includes acute partial transverse myelitis (APTM) and acute 
complete transverse myelitis (ACTM) 
Renal disorders 
Autoimmune / Immune-mediated 
glomerulonephritis  
Including but not limited to: 
• 
IgA nephropathy 
• 
IgM nephropathy 
• 
C1q nephropathy 
• 
Fibrillary glomerulonephritis 
• 
Glomerulonephritis rapidly progressive 
• 
Membranoproliferative glomerulonephritis 
• 
Membranous glomerulonephritis 


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Medical Concept 
Additional Notes 
• 
Mesangioproliferative glomerulonephritis 
• 
Tubulointerstitial nephritis and uveitis syndrome 
Skin and subcutaneous tissue disorders 
Alopecia areata 
 
Autoimmune / Immune-mediated 
blistering dermatoses  
Including but not limited to:  
• 
Bullous Dermatitis 
• 
Bullous Pemphigoid  
• 
Dermatitis herpetiformis  
• 
Epidermolysis bullosa acquisita (EBA)  
• 
Linear IgA-mediated bullous dermatosis (LABD), also known as 
Linear IgA disease 
• 
Pemphigus  
Erythema multiforme 
 
Erythema nodosum 
 
Reactive granulomatous 
dermatitis  
Including but not limited to 
• 
Interstitial granulomatous dermatitis 
• 
Palisaded neutrophilic granulomatous dermatitis 
Lichen planus 
• 
Includes liquen planopilaris 
Localised Scleroderma 
(Morphoea) 
• 
Includes Eosinophilic fasciitis (also called Shulman syndrome) 
Psoriasis 
 
Pyoderma gangrenosum 
 
Stevens-Johnson Syndrome 
(SJS) 
Including but not limited to:  
• 
Toxic Epidermal Necrolysis (TEN)  
• 
SJS-TEN overlap 
Sweet’s syndrome 
• 
Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• 
Arteritic anterior ischemic optic neuropathy (AAION or arteritic 
AION) 
• 
Giant cell arteritis (also called temporal arteritis)  
• 
Takayasu's arteritis  
Medium sized and/or small 
vessels vasculitis  
Including but not limited to: 
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis 
(type unspecified)  
• 
Behcet's syndrome  
• 
Buerger’s disease (thromboangiitis obliterans) 
• 
Churg–Strauss syndrome (allergic granulomatous angiitis)  


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Medical Concept 
Additional Notes 
• 
Erythema induratum (also known as nodular vasculitis) 
• 
Henoch-Schonlein purpura (also known as IgA vasculitis) 
• 
Microscopic polyangiitis 
• 
Necrotizing vasculitis 
• 
Polyarteritis nodosa 
• 
Single organ cutaneous vasculitis, including leukocytoclastic 
vasculitis, hypersensitivity vasculitis and acute hemorrhagic 
edema of infancy (AHEI) 
• 
Wegener's granulomatosis  
Other (including multisystemic) 
Anti-synthetase syndrome 
 
Capillary leak syndrome 
• 
Frequently used related terms include : “systemic capillary leak 
syndrome (SCLS)” or “Clarkson's Syndrome” 
Goodpasture syndrome 
• 
Frequently used related terms include : “pulmonary renal 
syndrome” and “anti-Glomerular Basement Membrane disease 
(anti-GBM disease)” 
Immune-mediated enhancement 
of disease 
• 
Includes vaccine associated enhanced disease (VAED and 
VAERD). Frequently used related terms include “vaccine-mediated 
enhanced disease (VMED)”, “enhanced respiratory disease 
(ERD)”, “vaccine-induced enhancement of infection”, “disease 
enhancement”, “immune enhancement”, and “antibody-dependent 
enhancement (ADE) 
Immunoglobulin G4 related 
disease 
 
Langerhans' cell histiocytosis 
 
Multisystem inflammatory 
syndromes 
Including but not limited to: 
• 
Kawasaki’s disease 
• 
Multisystem inflammatory syndrome in adults (MIS-A) 
• 
Multisystem inflammatory syndrome in children (MIS-C)  
Overlap syndrome 
 
Raynaud’s phenomenon 
 
Sarcoidosis 
• 
Includes Loefgren syndrome 
Susac's syndrome 
 
10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs  
In the absence of a diagnosis, abnormal laboratory findings assessments (e.g. clinical 
chemistry, haematology, urinalysis) or other abnormal assessments or other abnormal 
results (e.g. physical examination) the investigator considers clinically significant will be 
recorded as an AE or SAE, if they meet the definition of an AE or SAE (refer to the 
Sections 10.3.1 and 10.3.2).  


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The investigator must exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs  
10.3.7.1. 
Pregnancy 
Female participants who become pregnant after the first study intervention dose must not 
receive subsequent doses of the study intervention but may continue other study 
procedures at the discretion of the investigator. 
While pregnancy itself is not considered an AE or SAE, any abnormal pregnancy 
outcome or complication or elective termination of a pregnancy for medical reasons will 
be recorded and reported as an SAE. Please refer to the Section 10.3.2 for definition of 
SAE.  
10.3.8. 
Recording and follow-up of AEs, SAEs, pIMDs and pregnancies 
The participants and/or participant’s LAR(s) will be instructed to contact the investigator 
immediately should they experience any signs or symptoms they perceive as serious.  
When an AE/SAE occurs, it is the investigator’s responsibility to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) related to 
the event. The investigator will then record all relevant information regarding an AE/SAE 
on the eCRF. The investigator may not send photocopies of the participant’s medical 
records to GSK instead of appropriately completing the eCRF.  
There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers will be blinded on 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 instead of individual signs/symptoms. 
A Paper Diary (pDiary), hereafter referred to as Participant Diary, will be used in this 
study to capture details of solicited administration site or systemic events (i.e. on the day 
of study intervention administration and during the next 6 days) or any unsolicited AEs 
(i.e. on the day of study intervention administration and during the next 29 days) 
occurring after dosing. For solicited events continuing after 7 days, the participant and/or 
participant’s LAR(s) will be instructed to record events until resolution. The participant 
and/or participant’s LAR(s) will be instructed to return the completed diary card to the 
investigator at the next study visit. The participant should be trained on how and when to 
complete the Participant Diary. 


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Anyone who measures administration site or systemic events and who will record the 
event in the Participant Diary should be trained on using the diary. This training must be 
documented in the participant’s source record. If any individual other than the participant 
is making entries in the Participant Diary, their identity must be documented in the 
Participant Diary/participant’s source record. 
The investigator or delegate will transcribe the required information into the eCRF in 
English.  
10.3.8.1. 
Time period for collecting and recording AEs, SAEs, pIMDs and 
pregnancies 
All AEs that occur during 30 days following administration of each dose of study 
intervention (Day 1 to Day 30) must be recorded into the appropriate section of the 
eCRF, irrespective of their intensity or whether or not they are considered related to the 
study intervention. 
The time period for collecting and recording all SAEs will begin at the first receipt of 
study vaccine and will end 6 months following administration of the last dose of study 
vaccine for each participant. See Section 10.3.10 for instructions on reporting of SAEs. 
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 participant 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 participant 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 8.3 for instructions on reporting of 
pregnancies. This applies to pregnancy cases with exposure to the study intervention at 
any age of gestation. The timing of exposure to the study intervention during pregnancy 
is estimated in relation to the first day of the last menstrual period, ultrasound or known 
date of fertilisation (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 6 months following administration of the last dose of study 
vaccine. See Section 8.3 for instructions on reporting of pIMDs.  


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10.3.8.2. 
Follow-up of AEs, SAEs, pIMDs, IMCs and pregnancies 
After the initial AE/SAE/pIMD/IMCs/pregnancy or any other event of interest, the 
investigator is required to proactively follow each participant at subsequent 
visits/contacts. All SAEs, pIMDs (serious and non-serious), IMCs and pregnancies will 
be followed until the event is resolved, stabilised, otherwise explained, or the participant 
is lost to follow-up. 
Other non-serious AEs must be followed until 30 days following administration of last 
dose or until the participant is lost to follow-up. 
10.3.8.2.1. Follow-up during the study 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant and provide additional relevant information on the participant’s condition to 
GSK (within 24 hours for SAEs).  
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 participant. 
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.  
If a participant dies during their participation in the study or during a recognised 
follow- up period, GSK will be provided with any available post-mortem findings, 
including histopathology. 
10.3.8.2.2. Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information to GSK on a 
previously reported SAE/pIMD using a paper/electronic Expedited Adverse Events 
Report and/or pregnancy report as applicable. The investigator is obliged to perform or 
arrange for the conduct of supplemental clinical examinations/tests and/or evaluations to 
elucidate the nature and/or causality of the SAE/pIMD as fully as possible. 
10.3.8.2.3. Follow-up of pregnancies 
Pregnant participants 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 does not 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 


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Furthermore, if the investigator becomes aware of any SAE occurring as a result of a 
post-study pregnancy AND it is considered by the investigator to be reasonably related to 
the study intervention, he/she must report this information to GSK as described in the 
Section 10.3.10. 
10.3.8.3. 
Updating of SAE, pIMD and pregnancy information after removal of 
write access to the participant’s eCRF 
When additional SAE, pIMD or pregnancy information is received after write access to 
the participant’s eCRF is removed, 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 
Section 8.3.3.1 or to GSK VCSP department within the defined reporting time frames 
specified in the Table 11. 


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10.3.9. 
Assessment of intensity and toxicity 
10.3.9.1. 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 18 
Intensity scales for solicited events (Amended 25 May 2022) 
Adults (≥50 years) 
Event 
Intensity grade 
Parameter 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing normal 
everyday activities. 
 
2 
Moderate: Painful when limb is moved and interferes with everyday 
activities. 
 
3 
Severe: Significant pain at rest. Prevents normal everyday 
activities. 
Redness at administration site 
Greatest surface diameter in mm 
Swelling at administration site 
Greatest surface diameter in mm  
Pruritus at administration site 
0 
None 
 
1 
Mild: Itchy sensation that neither interferes with nor preventing 
normal everyday activities. 
 
2 
Moderate: Itchy sensation that interferes with normal everyday 
activities. 
 
3 
Severe: Itchy sensation that prevents normal everyday activities. 
Temperature* 
 
Temperature in °C/°F (with 1 decimal) 
Headache 
0 
None 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
None  
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Gastrointestinal symptoms 
0 
None 
 
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 
Shivering 
0 
None 
 
1 
Shivering that is easily tolerated 
 
2 
Shivering that interferes with normal activity 
 
3 
Shivering that prevents normal activity 
* Refer to the SoA (Section 1.3) for the definition of fever and the preferred location for temperature measurement. 


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The maximum intensity of injection administration site redness/swelling and fever will be 
scored at GSK as follows: 
 
Redness/swelling 
Fever 
0: 
≤20 mm 
<38.0°C (100.4°F) 
1: 
>20-≤50 mm 
≥38.0°C (100.4°F)- ≤38.5°C (101.3°F) 
2: 
>50-≤100 mm 
>38.5°C (101.3°F)- ≤39.0°C (102.2°F) 
3: 
>100 mm 
>39.0°C (102.2°F) 
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. 
The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the participant, 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 likely necessitate the administration of corrective therapy. 
An AE that is assessed as grade 3 (severe) should not be confused with an 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 the Section 10.3.2. 
10.3.9.2. 
Assessment of causality 
All solicited administration site and systemic events occurring within 7 days of study 
intervention administration will be considered causally related to the study intervention.  
The investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgement.  
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The investigator will also consult 
the IB and/or Prescribing Information for marketed products to assist in making his/her 
assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study intervention? 
YES 
: 
There is a reasonable possibility that the study intervention contributed to 
the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study intervention. There are other, more likely 
causes and administration of the study intervention is not suspected to 
have contributed to the AE. 


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If an event meets the criteria to be determined ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the investigator 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 study intervention, if applicable. 
• 
An error in study intervention administration. 
• 
Other cause (specify).  
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Expedited 
Adverse Events Report to GSK.  
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. The investigator may change his/her opinion of causality after 
receiving additional information and update the SAE information accordingly.  
10.3.9.3. 
Medically-attended visits 
For each solicited and unsolicited AE the participant experiences, the participant will be 
asked if the participant received medical attention (defined as hospitalisation, 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.  
10.3.9.4. 
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). 


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10.3.10. 
Reporting of SAEs, pIMDs, pregnancies and other events 
10.3.10.1. Events requiring expedited reporting to GSK 
Once an investigator becomes aware that an SAE has occurred, the investigator (or 
designee) must complete the information in the electronic Expedited Adverse Events 
Report WITHIN 24 HOURS, even if the investigator does not have complete information 
on the SAE. It must be completed as thoroughly as possible, with all available details of 
the event. The report must be dated and signed by the investigator (or designee).  
The SAE report must be updated WITHIN 24 HOURS of the receipt of updated 
information on the SAE. The investigator will always provide an assessment of causality 
at the time of the initial report. 
Refer to the Table 11 for the details on timeframes for reporting of 
SAEs/pIMDs/pregnancies.  
The investigator will be required to confirm the review of SAE causality by ticking the 
‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 hours of 
submission of the SAE. 
Refer to the Section 10.3.10.2 for information on back up systems in case the electronic 
reporting system does not work. 
10.3.10.2. Back up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designee) must fax 
or email a completed, dated and signed paper Expedited Adverse Events Report to the 
study contact for reporting SAEs (refer to the Sponsor Information) or to GSK VCSP 
department within 24 hours of becoming aware of the SAE.  
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
within 24 hours after the electronic reporting system is working again. The information 
reported through the electronic SAE reporting system will be considered valid for 
regulatory reporting purposes. 
10.3.10.3. Completion and transmission of pregnancy reports to GSK  
Once the investigator becomes aware that a participant is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 24 HOURS. 
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. 


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10.3.10.4. Reporting of pIMD to GSK 
Once a pIMD is diagnosed (serious or non-serious) in a study participant, 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. 
Refer to Section 10.3.10.2 for back up system in case the electronic reporting system 
does not work. 
10.4. 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
10.4.1. 
Definitions 
10.4.1.1. 
Woman of childbearing potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
10.4.1.1.1. Women not considered as women of childbearing potential 
• 
Premenarchal 
Menarche is the first onset of menses in a young female. Menarche is normally 
preceded by several changes associated with puberty including breast development 
and pubic hair growth.  
Additional evaluation should be considered if a participant’s fertility status is unclear 
(e.g. amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention. 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
− 
Current bilateral tubal ligation or occlusion 


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Note: Documentation can come from the site personnel’s: review of participant’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 a 
non-hormonal, highly effective contraception method if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrolment. 
10.4.2. 
Contraception guidance 
• 
Female participants of childbearing potential are eligible to participate if they agree 
to use a highly effective contraceptive method consistently and correctly according 
to the methods listed in GSK’s list of highly effective contraceptive methods (Table 
19).  


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Table 19 
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 ovulation 
• 
Oral 
• 
Intravaginal  
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
injectable  
Highly Effective Methods That Are User Independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomised partner  
(A vasectomised 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 sterilisation prior to the female participant’s entry into the study, and this male is the 
sole partner for that participant, 
(The information on the male sterility can come from the site personnel’s review of the 
participant’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 participant.)  
10.4.3. 
Collection of pregnancy information 
10.4.3.1. 
Female participants who become pregnant 
Refer to the Sections 8.3.1, 8.3.2, 10.3.8.1 and 10.3.8.3 for further information on 
detection, recording, reporting and follow-up of pregnancies. 
Any female participant who becomes pregnant during the study will be discontinued from 
the study treatment. 


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10.5. 
Appendix 5: Genetics 
Not Applicable 
10.6. 
Appendix 6: Country-specific requirements 
Investigators should comply with all requirements of the National Ethical guidelines for 
Biomedical and Health research involving human participants 2017 guidelines by Indian 
Council of Medical Research, New Drugs Clinical Trial Rules 2019 of India, ICH-GCP 
Guideline E6 (R2), IRB/IEC standard operating procedures, local regulations, provide 
written status to the IRB/IEC annually or more frequent in accordance with procedures 
and policies established by the IRB/IEC and regulatory authority.  
10.7. 
Appendix 7: Abbreviations and glossary of terms 
10.7.1. 
List of abbreviations  
Ab: 
Antibody 
AE: 
Adverse Event 
AESI: 
Adverse Event of Specific Interest 
AS01B: 
Adjuvant System 01B -MPL, QS21, liposome based Adjuvant 
System (50 µg MPL and 50 µg QS21) 
CI: 
Confidence Interval 
CIOMS: 
Council for International Organisations of Medical Sciences 
CLS:  
Clinical Laboratory Sciences 
CoP: 
Correlate of Protection 
COVID-19: 
Coronavirus Disease 2019 
CSR: 
Clinical Study Report 
eCRF: 
electronic Case Report Form 
EDD: 
Estimated Date of Delivery 
EEA: 
European Economic Area 
EGA: 
Estimated Gestational Age 
ELISA: 
Enzyme-linked Immunosorbent Assay 
EoS: 
End of Study 
ES: 
Exposed Set 
FSH: 
Follicle Stimulating Hormone 
GCP: 
Good Clinical Practice 
gE: 
VZV Glycoprotein E 


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GI: 
Gastrointestinal 
GMC: 
Geometric Mean Concentration 
GSK: 
GlaxoSmithKline Biologicals SA 
HIPAA: 
Health Insurance Portability and Accountability Act 
HRT: 
Hormonal Replacement Therapy 
HZ/su: 
Herpes Zoster subunit vaccine 
HZ: 
Herpes Zoster 
IB: 
Investigator Brochure 
IC: 
Immunocompromised 
ICF: 
Informed Consent Form 
ICH: 
International Conference on Harmonisation 
ICMJE: 
International Committee of Medical Journal Editors 
IEC: 
Independent Ethics Committee 
IgG: 
Immunoglobulin G 
IM: 
Intramuscular/Intramuscularly 
IMC 
Intercurrent Medical Conditions  
IRB: 
Institutional Review Board 
IUD: 
Intrauterine device 
IUS: 
Intrauterine hormone-releasing system 
LAR: 
Legally Acceptable Representative 
LL: 
Lower Limit 
LML: 
Local Medical Lead 
LMP: 
Last Menstrual Period 
LSLV: 
Last Subject* Last Visit (*Subject=Participant) 
MedDRA: 
Medical Dictionary for Regulatory Activities 
MGI: 
Mean Geometric Increase 
MPL: 
3-O-desacyl-4’-monophosphoryl lipid A 
NaCl: 
Saline solution 
PCD: 
Primary Completion Date 
pDairy: 
Paper Dairy 
PHN: 
Post-Herpetic Neuralgia 
pIMD: 
Potential Immune-Mediated Disease 
PPS: 
Per Protocol Set 


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PT: 
Preferred Term 
QS21: 
Quillaja saponaria Molina, fraction 21 (purified saponin extract 
from the South American tree) 
QTL: 
Quality Tolerance Limit 
SAE: 
Serious Adverse Event 
SAP: 
Statistical Analysis Plan 
SAS: 
Statistical Analysis System 
SBIR: 
Source data Base for Internet Randomisation  
SDV: 
Source Document Verification 
SmPC: 
Summary of Product Characteristics 
SoA: 
Schedule of Activities 
SOC: 
System Organ Class 
SPM: 
Study Procedures Manual 
SRT: 
Safety Review Team 
SUSAR: 
Suspected Unexpected Serious Adverse Reactions 
US 
United States 
VCSP: 
Vaccine Clinical Safety and Pharmacovigilance 
VRR: 
Vaccine Response Rate 
VZV: 
Varicella Zoster Virus 
WHO: 
World Health Organisation 
WOCBP: 
Woman of Childbearing Potential 
YOA: 
Years of Age 


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10.7.2. 
Glossary of terms 
Adverse event 
Any untoward medical occurrence in a patient or clinical 
investigation participant, 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 intervention 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 SAE.  
In an observer-blind study, the participant, the site and 
sponsor personnel involved in the clinical evaluation of 
the participants are blinded while other study personnel 
may be aware of the treatment assignment.  
Caregiver 
A ‘caregiver’ is someone who  
− 
lives in the close surroundings of a participant 
and has a continuous caring role or 
− 
has substantial periods of contact with a 
participant and is engaged in his/her daily 
health care (e.g. a relative of the participant, a 
nurse who helps with daily activities in case of 
residence in a nursing home).  
In the context of a clinical study, a caregiver could 
include an individual appointed to oversee and support 
the participant's compliance with protocol specified 
procedures. 
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
End of Study  
(Synonym of End of Trial) 
For studies with collection of Human Biologicals 
Samples or imaging data, EoS is defined as the date of 
the last testing/reading released of the Human Biological 


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Samples or imaging data, related to primary and 
secondary endpoints/outcomes. EoS must be achieved 
no later than 8 months after Last Subject* Last Visit 
(*Subject=Participant). 
Enrolled participant 
‘Enrolled’ means a participant’s and/or participant’s 
LAR(s) agreement to participate in a clinical study 
following completion of the informed consent process. 
Potential participants who are screened for determining 
eligibility for the study, but do not participate in the 
study, are not considered enrolled, unless otherwise 
specified by the protocol.  
Refer to the Section 9.3 of the protocol for the definition 
of ‘enrolled set’ applicable to the study.  
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. 
Immunological correlate 
of protection 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intercurrent medical 
condition 
A condition that has the capability of altering the 
immune response to the study intervention or is 
confirmed to have an alteration of the participant’s 
initial immune status. 
Intervention 
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 participant. 
Intervention number 
A number identifying an intervention to a participant, 
according to intervention allocation. 
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 
and functions. 


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Participant 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject 
Participant number 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Primary completion date 
The date that the final participant 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. 
Protocol amendment 
The International Council on Harmonisation (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK further details this to include a change to an 
approved protocol that affects the safety of participants, 
scope of the investigation, study design, or scientific 
integrity of the study. 
Protocol administrative 
change 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  
Randomisation 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Self-contained study 
Study with objectives not linked to the data of another 
study. 
Site Monitor 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Solicited event 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified follow-up period following study 
intervention administration. 
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 legible documents, data, and records (e.g. 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participant’s 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, participant files, and records 
kept at the pharmacy, laboratories and at 
medico- technical departments involved in the clinical 
trial). 
Study intervention 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Unsolicited adverse event 
Any AE (non-serious and serious) 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 AE. 


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10.8. 
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 1 
25 May 2022 
Protocol  
8 June 2021 
Detailed description of the current Protocol amendment: 
All changes made from the previous protocol version are detailed in this section. Deleted 
text is in strikethrough and newly added text is in bold italics. 
Section 1.1 Synopsis 
The section was updated to specify regarding the licensure of HZ/su in India for adults 
≥50 YOA, and for inclusion of an early supportive safety report to fulfil the 
post-approval commitment to the Indian regulatory authority. The edits are as below. 
Currently When this ZOSTER-081 study began, HZ/su was is not approved for use in 
India. While the study was ongoing, HZ/su was licensed for use in India for adults ≥50 
YOA on the 21 April 2022. Despite this licensure, HZ/su is not currently available in 
the Indian market; however, when it does become available, the study participants will 
be notified by the investigators. To meet the post-approval requirements of the Indian 
regulatory authoritiesy for licensure and this study will continue as originally planned to 
demonstrate the immunogenicity and safety of of HZ/su in the Indian population, 
ZOSTER-081 study is planned. This study will is designed to evaluate the humoral 
immunogenicity and safety of 2 doses of HZ/su, for the prevention of HZ in adults ≥50 
YOA. In addition, as also required by the Indian regulatory authority, a safety report 
describing the early supportive safety data will be provided once these data (up to Visit 
3, Month 3) on the initial 200 study participants randomized are available.  
Section 2.1 Study Rationale: 
The section was updated to specify regarding the licensure of HZ/su in India for adults 
≥50 YOA, and for inclusion of an early supportive safety report to fulfil the 
post-approval commitment to the Indian regulatory authority. The edits are as below. 
When this ZOSTER-081 study began, HZ/su was not approved for use in India. While 
the study was ongoing, HZ/su was licensed for use in India for adults ≥50 YOA on 
21 April 2022. Despite this licensure, HZ/su is not currently available in the Indian 
market; however, when it does become available, the study participants will be notified 
by the investigators. To meet the post-approval requirements of the Indian regulatory 
authority, this study to demonstrate the immunogenicity and safety of HZ/su in the 
Indian population is to continue as originally planned. This study is designed to 
evaluate the humoral immunogenicity and safety of 2 doses of HZ/su, for the 
prevention of HZ in adults ≥50 YOA. In addition, as also required by the Indian 
regulatory authority, a safety report describing the early supportive safety data will be 


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provided once these data (up to Visit 3, Month 3) on the initial 200 study participants 
randomized are available. 
Currently, HZ/su is not approved for use in India. To meet the requirements of Indian 
regulatory authorities for licensure and to demonstrate the immunogenicity and safety of 
HZ/su in the Indian population, ZOSTER-081 study is planned. This study will evaluate 
the humoral immunogenicity and safety of 2 doses of GSK’s HZ/su for the prevention of 
HZ in Indian adults ≥50 YOA.  
Section 5.2.2: Prior/Concomitant therapy 
The below paragraph was presented as a separate bullet point, wherein the text was an 
explanation to the bullet point above it, thus the bullet was removed and text was placed 
in between brackets.  
[In case an emergency mass vaccination for an unforeseen public health threat (e.g. a 
pandemic) is recommended and/or organised by the public health authorities, outside 
the routine immunisation programme, the time period described above can be 
reduced if necessary for that vaccine provided it is used according to local 
governmental recommendations and that the Sponsor is notified accordingly].  
Table 5: Study Intervention administered 
As the reconstituted Sucrose and Sodium Chloride (NaCl) pharmaceutical product is a 
solution for injection, the dose form of the NaCl solution was revised as “solution for 
solution for injection”. Changes to the table from the previous version of the protocol are 
shown in the below table, deleted text is in strikethrough and newly added text is in bold 
italics. 
Study Intervention Name: 
HZ/su 
Placebo 
Study Intervention /Product 
name 
VZV gE  
AS01B  
Lyophilised 
sucrose 
Saline (NaCl) 
solution 
Study Intervention 
formulation: 
VZV gE 
(50 µg) 
AS01B: QS-21 
(50 µg), MPL 
(50 µg), liposomes; 
Water for injections  
q.s.0.5 ml 
Sucrose (20 mg) 
Sodium chloride 
(NaCl) (0.9%); 
Water for injections  
q.s.0.5 ml 
Presentation: 
Powder for 
suspension 
for injection  
Suspension for 
suspension for 
injection  
Powder for 
solution for 
injection  
Solution for 
suspension 
solution for 
injection  
Container 
Vial 
Vial 
Vial 
Syringe 
Type: 
Biologic 
Not applicable 
Administration site:  
Intramuscular use 
Intramuscular use 
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, Labelling and TM: 
Refer to SPM 
Manufacturer: 
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=Quantum satis  


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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. 
Section 6.8: Concomitant therapy. 
The below sentence was included to further clarify the requirement for recording 
concomitant medications ongoing at Visit 1 (Day 1), which remains indicated as such on 
Table 1-Schedule of Activities. 
• 
All concomitant medications ongoing once randomized at Visit 1 (Day 1). 
Section 8.3.3.1: Contact information for reporting SAEs, pIMDs and pregnancies 
The email ID to report SAEs, pIMDs and pregnancies was updated by GSK since the 
previous protocol version. The changes are as below. 
Email address: Rix.CT-safety-vac@gsk.com ogm28723@gsk.com 
Section 9.5: Interim Analysis 
The below addition was made to describe the early safety assessment report requirement. 
To fulfil the post-approval commitment to the Indian regulatory authority, a blinded 
early safety assessment report after completion of 30 days safety follow-up post HZ/su 
dose 2 (i.e., Visit 3, Month 3) for the initial 200 randomised participants will be 
provided. 
Table 3, Table 15 and Table 18: 
Typographical error pruritis was corrected to pruritus. 
 


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Table 17 List of Potential Immune-Mediated Diseases (pIMDs) 
The list of pIMDs was updated by GSK since the previous protocol version. Thus, the table was replaced to further assist investigators. 
The deleted table is presented in strikethrough and the updated table is presented in bold italics below. 
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: 
o 
Chronic inflammatory demyelinating 
polyneuropathy,  
o 
Multifocal motor neuropathy,  
o 
Polyneuropathies associated with 
monoclonal gammopathy. 
• 
Narcolepsy. 
• 
Systemic lupus erythematosus and 
associated conditions 
• 
Systemic scleroderma (Systemic 
sclerosis), including: 
o 
Diffuse Scleroderma 
o 
CREST syndrome 
• 
Idiopathic inflammatory myopathies, 
including: 
o 
Dermatomyositis  
o 
Polymyositis  
• 
Anti-synthetase syndrome. 
• 
Rheumatoid Arthritis and associated 
conditions including:  
o 
Juvenile Idiopathic Arthritis 
o 
Still’s disease. 
• 
Polymyalgia rheumatica. 
• 
Spondyloarthropathies, including:  
o 
Ankylosing Spondylitis,  
o 
Reactive Arthritis (Reiter’s 
Syndrome), 
o 
Undifferentiated Spondyloarthritis, 
o 
Psoriatic Arthritis, 
o 
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). 
Vasculitis 
Blood disorders 
Others 
• 
Large vessels vasculitis including:  
o 
Giant Cell Arteritis (Temporal Arteritis), 
o 
Takayasu’s Arteritis.  
• 
Autoimmune haemolytic anaemia. 
• 
Autoimmune thrombocytopenia. 
• 
Antiphospholipid syndrome. 
• 
Autoimmune glomerulonephritis including: 
o 
IgA nephropathy,  
o 
Glomerulonephritis rapidly progressive,  


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• 
Medium sized and/or small vessels vasculitis 
including:  
o 
Polyarteritis nodosa, 
o 
Kawasaki’s disease,  
o 
Microscopic Polyangiitis,  
o 
Wegener’s Granulomatosis (granulomatosis 
with polyangiitis),  
o 
Churg–Strauss syndrome (allergic 
granulomatous angiitis or eosinophilic 
granulomatosis with polyangiitis),  
o 
Buerger’s disease (thromboangiitis 
obliterans),  
o 
Necrotising vasculitis (cutaneous or 
systemic),  
o 
Anti-neutrophil cytoplasmic antibody (ANCA) 
positive vasculitis (type unspecified), 
o 
Henoch-Schonlein purpura (IgA vasculitis),  
o 
Behcet’s syndrome, 
o 
Leukocytoclastic vasculitis. 
• 
Pernicious anaemia. 
• 
Autoimmune aplastic anaemia. 
• 
Autoimmune neutropenia. 
• 
Autoimmune pancytopenia. 
o 
Membranous glomerulonephritis,  
o 
Membranoproliferative 
glomerulonephritis,  
o 
Mesangioproliferative 
glomerulonephritis.  
o 
Tubulointerstitial nephritis and uveitis 
syndrome. 
• 
Ocular autoimmune diseases including: 
o 
Autoimmune uveitis  
o 
Autoimmune retinitis. 
• 
Autoimmune myocarditis. 
• 
Sarcoidosis. 
• 
Stevens-Johnson syndrome. 
• 
Sjögren’s syndrome. 
• 
Alopecia areata. 
• 
Idiopathic pulmonary fibrosis. 
• 
Goodpasture syndrome. 
• 
Raynaud’s phenomenon. 
Liver disorders 
Gastrointestinal disorders 
Endocrine disorders 
• 
Autoimmune hepatitis. 
• 
Primary biliary cirrhosis. 
• 
Primary sclerosing cholangitis. 
• 
Autoimmune cholangitis. 
• 
Inflammatory Bowel disease, including: 
o 
Crohn’s disease,  
o 
Ulcerative colitis,  
o 
Microscopic colitis,  
o 
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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Table 17 
List of potential immune-mediated diseases (pIMDs) (Amended, 25 
May 2022) 
Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid syndrome 
 
Autoimmune aplastic anemia 
 
Autoimmune hemolytic anemia 
• 
Includes warm antibody hemolytic anemia and cold antibody 
hemolytic anemia 
Autoimmune lymphoproliferative 
syndrome (ALPS) 
 
Autoimmune neutropenia  
 
Autoimmune pancytopenia 
 
Autoimmune thrombocytopenia 
• 
Frequently used related terms include: “autoimmune 
thrombocytopenic purpura”, “idiopathic thrombocytopenic 
purpura (ITP)”, “idiopathic immune thrombocytopenia”, “primary 
immune thrombocytopenia”. 
Evans syndrome 
 
Pernicious anemia 
 
Thrombosis with 
thrombocytopenia syndrome 
(TTS) 
 
Thrombotic thrombocytopenic 
purpura 
• 
Also known as “Moschcowitz-syndrome” or “microangiopathic 
hemolytic anemia” 
Cardio-pulmonary inflammatory disorders 
Idiopathic 
Myocarditis/Pericarditis 
Including but not limited to: 
• 
Autoimmune / Immune-mediated myocarditis 
• 
Autoimmune / Immune-mediated pericarditis 
• 
Giant cell myocarditis 
Idiopathic pulmonary fibrosis 
Including but not limited to: 
• 
Idiopathic interstitial pneumonia (frequently used related terms 
include “Interstitial lung disease”, “Pulmonary fibrosis”, “Immune-
mediated pneumonitis”) 
• 
Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar proteinosis 
(PAP) 
• 
Frequently used related terms include: “pulmonary alveolar 
lipoproteinosis”, “phospholipidosis” 
Endocrine disorders 
Addison’s disease 
 
Autoimmune / Immune-mediated 
thyroiditis  
Including but not limited to: 
• 
Hashimoto thyroiditis (autoimmune hypothyroidism, lymphocytic 
thyroiditis) 
• 
Atrophic thyroiditis  
• 
Silent thyroiditis  
• 
Thyrotoxicosis 


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Medical Concept 
Additional Notes 
Autoimmune diseases of the 
testis and ovary 
• 
Includes autoimmune oophoritis, autoimmune ovarian failure and 
autoimmune orchitis 
Autoimmune hyperlipidemia 
 
Autoimmune hypophysitis 
 
Diabetes mellitus type I 
 
Grave's or Basedow’s disease 
• 
Includes Marine Lenhart syndrome and Graves' ophthalmopathy, 
also known as thyroid eye disease (TED) or endocrine 
ophthalmopathy 
Insulin autoimmune syndrome 
 
Polyglandular autoimmune 
syndrome 
• 
Includes Polyglandular autoimmune syndrome type I, II and III 
Eye disorders 
Ocular Autoimmune / Immune-
mediated disorders 
Including but not limited to: 
• 
Acute macular neuroretinopathy (also known as acute macular 
outer retinopathy) 
• 
Autoimmune / Immune-mediated retinopathy  
• 
Autoimmune / Immune-mediated uveitis, including idiopathic 
uveitis and sympathetic ophthalmia  
• 
Cogan's syndrome: an oculo-audiovestibular disease 
• 
Ocular pemphigoid 
• 
Ulcerative keratitis 
• 
Vogt-Koyanagi-Harada disease 
Gastrointestinal disorders 
Autoimmune / Immune-mediated 
pancreatitis 
 
Celiac disease 
 
Inflammatory Bowel disease  
Including but not limited to:  
• 
Crohn’s disease  
• 
Microscopic colitis  
• 
Terminal ileitis 
• 
Ulcerative colitis  
• 
Ulcerative proctitis 
Hepatobiliary disorders 
Autoimmune cholangitis 
 
Autoimmune hepatitis 
 
Primary biliary cirrhosis 
 
Primary sclerosing cholangitis 
 
Musculoskeletal and connective tissue disorders  
Gout 
• 
Includes gouty arthritis 


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Medical Concept 
Additional Notes 
Idiopathic inflammatory 
myopathies 
Including but not limited to: 
• 
Dermatomyositis 
• 
Inclusion body myositis 
• 
Immune-mediated necrotizing myopathy 
• 
Polymyositis 
Mixed connective tissue disorder 
 
Polymyalgia rheumatica (PMR) 
 
Psoriatic arthritis (PsA) 
 
Relapsing polychondritis 
 
Rheumatoid arthritis  
Including but not limited to: 
• 
Rheumatoid arthritis associated conditions 
• 
Juvenile idiopathic arthritis 
• 
Palindromic rheumatism 
• 
Still's disease 
• 
Felty’s syndrome 
Sjögren’s syndrome 
 
Spondyloarthritis 
Including but not limited to:  
• 
Ankylosing spondylitis 
• 
Juvenile spondyloarthritis 
• 
Keratoderma blenorrhagica 
• 
Psoriatic spondylitis  
• 
Reactive Arthritis (Reiter's Syndrome) 
• 
Undifferentiated spondyloarthritis 
Systemic Lupus Erythematosus  
• 
Includes Lupus associated conditions (e.g. Cutaneous lupus 
erythematosus, Lupus nephritis, etc.) or complications such as 
shrinking lung syndrome (SLS) 
Systemic Scleroderma (Systemic 
Sclerosis) 
• 
Includes Reynolds syndrome (RS), systemic sclerosis with diffuse 
scleroderma and systemic sclerosis with limited scleroderma (also 
known as CREST syndrome) 
Neuroinflammatory/neuromuscular disorders 
Acute disseminated 
encephalomyelitis (ADEM) and 
other inflammatory 
demyelinating variants  
Includes the following: 
• 
Acute necrotising myelitis 
• 
Bickerstaff's brainstem encephalitis  
• 
Disseminated necrotizing leukoencephalopathy (also known as 
Weston-Hurst syndrome, acute hemorrhagic leuko-encephalitis, or 
acute necrotizing hemorrhagic encephalomyelitis)  
• 
Myelin oligodendrocyte glycoprotein antibody-associated disease 
• 
Neuromyelitis optica (also known as Devic’s disease) 
• 
Noninfective encephalitis / encephalomyelitis / myelitis 
• 
Postimmunization encephalomyelitis  


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Medical Concept 
Additional Notes 
Guillain-Barré syndrome (GBS) 
• 
Includes variants such as Miller Fisher syndrome and the acute 
motor and sensory axonal neuropathy (AMSAN) 
Idiopathic cranial nerve 
palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• 
Cranial nerve neuritis (e.g. Optic neuritis) 
• 
Idiopathic nerve palsies/paresis (e.g. Bell’s palsy) 
• 
Melkersson-Rosenthal syndrome 
• 
Multiple cranial nerve palsies/paresis  
Multiple Sclerosis (MS) 
Includes the following: 
• 
Clinically isolated syndrome (CIS)  
• 
Malignant MS (the Marburg type of MS)  
• 
Primary-progressive MS (PPMS) 
• 
Radiologically isolated syndrome (RIS) 
• 
Relapsing-remitting MS (RRMS) 
• 
Secondary-progressive MS (SPMS) 
• 
Uhthoff's phenomenon  
Myasthenia gravis 
• 
Includes ocular myasthenia and Lambert-Eaton myasthenic 
syndrome 
Narcolepsy 
• 
Includes narcolepsy with or without presence of unambiguous 
cataplexy 
Peripheral inflammatory 
demyelinating neuropathies and 
plexopathies 
Including but not limited to: 
• 
Acute Brachial Radiculitis (also known as Parsonage-Turner 
Syndrome or neuralgic amyotrophy) 
• 
Antibody-mediated demyelinating neuropathy 
• 
Chronic idiopathic axonal polyneuropathy (CIAP) 
• 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 
(CIDP), including atypical CIDP variants (e.g. multifocal acquired 
demyelinating sensory and motor neuropathy also known as 
Lewis-Sumner syndrome) 
• 
Multifocal motor neuropathy (MMN)  
Transverse myelitis (TM) 
• 
Includes acute partial transverse myelitis (APTM) and acute 
complete transverse myelitis (ACTM) 
Renal disorders 
Autoimmune / Immune-mediated 
glomerulonephritis  
Including but not limited to: 
• 
IgA nephropathy 
• 
IgM nephropathy 
• 
C1q nephropathy 
• 
Fibrillary glomerulonephritis 
• 
Glomerulonephritis rapidly progressive 
• 
Membranoproliferative glomerulonephritis 
• 
Membranous glomerulonephritis 


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Medical Concept 
Additional Notes 
• 
Mesangioproliferative glomerulonephritis 
• 
Tubulointerstitial nephritis and uveitis syndrome 
Skin and subcutaneous tissue disorders 
Alopecia areata 
 
Autoimmune / Immune-mediated 
blistering dermatoses  
Including but not limited to:  
• 
Bullous Dermatitis 
• 
Bullous Pemphigoid  
• 
Dermatitis herpetiformis  
• 
Epidermolysis bullosa acquisita (EBA)  
• 
Linear IgA-mediated bullous dermatosis (LABD), also known as 
Linear IgA disease 
• 
Pemphigus  
Erythema multiforme 
 
Erythema nodosum 
 
Reactive granulomatous 
dermatitis  
Including but not limited to 
• 
Interstitial granulomatous dermatitis 
• 
Palisaded neutrophilic granulomatous dermatitis 
Lichen planus 
• 
Includes liquen planopilaris 
Localised Scleroderma 
(Morphoea) 
• 
Includes Eosinophilic fasciitis (also called Shulman syndrome) 
Psoriasis 
 
Pyoderma gangrenosum 
 
Stevens-Johnson Syndrome 
(SJS) 
Including but not limited to:  
• 
Toxic Epidermal Necrolysis (TEN)  
• 
SJS-TEN overlap 
Sweet’s syndrome 
• 
Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• 
Arteritic anterior ischemic optic neuropathy (AAION or arteritic 
AION) 
• 
Giant cell arteritis (also called temporal arteritis)  
• 
Takayasu's arteritis  
Medium sized and/or small 
vessels vasculitis  
Including but not limited to: 
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis 
(type unspecified)  
• 
Behcet's syndrome  
• 
Buerger’s disease (thromboangiitis obliterans) 
• 
Churg–Strauss syndrome (allergic granulomatous angiitis)  


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• 
Erythema induratum (also known as nodular vasculitis) 
• 
Henoch-Schonlein purpura (also known as IgA vasculitis) 
• 
Microscopic polyangiitis 
• 
Necrotizing vasculitis 
• 
Polyarteritis nodosa 
• 
Single organ cutaneous vasculitis, including leukocytoclastic 
vasculitis, hypersensitivity vasculitis and acute hemorrhagic 
edema of infancy (AHEI) 
• 
Wegener's granulomatosis  
Other (including multisystemic) 
Anti-synthetase syndrome 
 
Capillary leak syndrome 
• 
Frequently used related terms include : “systemic capillary leak 
syndrome (SCLS)” or “Clarkson's Syndrome” 
Goodpasture syndrome 
• 
Frequently used related terms include : “pulmonary renal 
syndrome” and “anti-Glomerular Basement Membrane disease 
(anti-GBM disease)” 
Immune-mediated enhancement 
of disease 
• 
Includes vaccine associated enhanced disease (VAED and 
VAERD). Frequently used related terms include “vaccine-mediated 
enhanced disease (VMED)”, “enhanced respiratory disease 
(ERD)”, “vaccine-induced enhancement of infection”, “disease 
enhancement”, “immune enhancement”, and “antibody-dependent 
enhancement (ADE) 
Immunoglobulin G4 related 
disease 
 
Langerhans' cell histiocytosis 
 
Multisystem inflammatory 
syndromes 
Including but not limited to: 
• 
Kawasaki’s disease 
• 
Multisystem inflammatory syndrome in adults (MIS-A) 
• 
Multisystem inflammatory syndrome in children (MIS-C)  
Overlap syndrome 
 
Raynaud’s phenomenon 
 
Sarcoidosis 
• 
Includes Loefgren syndrome 
Susac's syndrome 
 
 


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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. 
Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of 
binomial. Biometrika. 1934;26:04-13. 
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;19(9):988-1000. 
Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of 
herpes zoster. Clin Infect Dis. 2007;44 Suppl 1:S1–26 
Lal H, Cunningham AL, Godeaux O et al. Efficacy of an Adjuvanted Herpes Zoster 
Subunit Vaccine in Older Adults. N Engl J Med. 2015:372;2087-96. 
Lecrenier et al. Development of adjuvanted recombinant zoster vaccine and its 
implications for shingles prevention. Expert Rev Vaccines. 2018;17(7):619-34. 
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. 
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):2482-93. 
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. 


CONFIDENTIAL 
214461 (ZOSTER-081) 
Protocol Amendment 1 Final 
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91 
Stadtmauer EA et al. A phase ½ study of an adjuvanted varicella-zoster virus subunit 
vaccine in autologous hematopoietic cell transplant recipients. Blood. 2014;124:2921-29. 
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;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. 2020;70(2):181-90. 
World Health Organization (WHO). Global surveillance for COVID-19 caused by 
human,infection with COVID-19 virus. Interim guidance. 20 March 2020.  

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  214461
Official Title of Study: A Phase 3, Randomised, Observer-blind, Placebo-controlled, 
Multi-centre Study to Evaluate the Immune Response and Safety of the Herpes Zoster 
Subunit Vaccine When Administered Intramuscularly on a 2-dose Schedule in Adults 
Aged 50 Years and Older in India
NCT ID: NCT05219253
Date of Document: 11 November 2022


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
214461 
XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021  
Page 1 of 31 
Information Type: 
Statistical Analysis Plan (SAP) 
TITLE PAGE 
Protocol Title: 
A phase 3, randomised, observer-blind, placebo-controlled, 
multi-centre study to evaluate the immune response and 
safety of the Herpes Zoster subunit vaccine when 
administered intramuscularly on a 2-dose schedule in adults 
aged 50 years and older in India. 
Study Number: 
214461 
Compound Number: 
GSK1437173A 
Abbreviated Title: 
ZOSTER-081 
Sponsor Name: GlaxoSmithKline Biologicals SA (GSK)  
Regulatory Agency Identifier Number(s) Not Applicable 
Registry 
ID 
Clintrials.gov 
Not Applicable 
Copyright 2022 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 


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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
LIST OF ABBREVIATIONS ............................................................................................. 6 
VERSION HISTORY ....................................................................................................... 8 
1. 
INTRODUCTION .................................................................................................... 10 
1.1. 
Objectives and Endpoints ........................................................................... 10 
1.2. 
Study Design .............................................................................................. 11 
2. 
STATISTICAL HYPOTHESES ............................................................................... 12 
2.1. 
Multiplicity Adjustment ................................................................................ 13 
3. 
ANALYSIS SETS ................................................................................................... 13 
3.1. 
Intervals between study visits ..................................................................... 13 
3.2. 
Criteria for eliminating data from Analysis Sets ........................................... 13 
3.2.1. 
Elimination from Enrolled Set ....................................................... 14 
3.2.2. 
Elimination from Exposed Set (ES) .............................................. 14 
3.2.3. 
Elimination from Per-protocol analysis Set (PPS) ........................ 14 
3.2.3.1. 
Excluded participants ................................................. 14 
4. 
STATISTICAL ANALYSES ..................................................................................... 16 
4.1. 
General Considerations .............................................................................. 16 
4.1.1. 
General Methodology .................................................................. 16 
4.1.2. 
Baseline Definition ....................................................................... 16 
4.2. 
Primary Endpoints Analyses ....................................................................... 16 
4.2.1. 
Definition of endpoints ................................................................. 16 
4.2.2. 
Main analytical approach ............................................................. 17 
4.3. 
Secondary Endpoints Analyses .................................................................. 17 
4.3.1. 
Key/Confirmatory secondary endpoints ....................................... 17 
4.3.1.1. 
Confirmatory secondary immunogenicity 
endpoints .................................................................... 17 
4.3.1.2. 
Definition of endpoints ................................................ 17 
4.3.1.3. 
Main analytical approach ............................................ 17 
4.3.2. 
Key secondary immunogenicity endpoint ..................................... 18 
4.3.3. 
Key secondary safety endpoints .................................................. 18 
4.3.4. 
Supportive secondary endpoints .................................................. 19 
4.4. 
Tertiary/Exploratory Endpoints Analyses..................................................... 19 
4.5. 
Other Safety Analyses ................................................................................ 19 
4.5.1. 
COVID-19 Assessment and COVID-19 AEs ................................ 19 
4.6. 
Other Analyses ........................................................................................... 20 
4.7. 
Interim Analyses ......................................................................................... 20 
4.7.1. 
Blinded Early Safety Report ......................................................... 20 
4.8. 
Changes to Protocol Defined Analyses ....................................................... 21 
5. 
SAMPLE SIZE DETERMINATION ......................................................................... 21 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 22 


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6.1. 
Appendix 1 Study Population Analyses ....................................................... 22 
6.1.1. 
Participant Disposition ................................................................. 22 
6.1.2. 
Demographic and Baseline Characteristics .................................. 22 
6.1.3. 
Protocol Deviations ...................................................................... 23 
6.1.4. 
Prior and Concomitant Medications ............................................. 23 
6.1.5. 
Prior and Concomitant Vaccinations ............................................ 23 
6.1.6. 
Study Intervention Compliance .................................................... 23 
6.1.7. 
Additional Analyses Due to the COVID-19 Pandemic .................. 23 
6.2. 
Appendix 2 Data Derivations Rule .............................................................. 24 
6.2.1. 
Attributing events to vaccine doses .............................................. 24 
6.2.2. 
Handling of missing data .............................................................. 24 
6.2.2.1. 
Dates .......................................................................... 24 
6.2.2.2. 
Laboratory data .......................................................... 25 
6.2.2.3. 
Daily recording of solicited events .............................. 25 
6.2.2.3.1. 
Studies with paper diaries ....................... 25 
6.2.3. 
Data derivation ............................................................................ 26 
6.2.3.1. 
Age at first dose in years ............................................ 26 
6.2.3.2. 
Temperature ............................................................... 26 
6.2.3.3. 
Numerical serology results ......................................... 26 
6.2.3.4. 
Geometric mean concentrations (GMCs) .................... 27 
6.2.3.5. 
Onset day ................................................................... 27 
6.2.3.6. 
Duration of events ...................................................... 27 
6.2.3.7. 
Counting rules for combining solicited and 
unsolicited adverse events ......................................... 27 
6.2.3.8. 
Counting rules for occurrences of solicited 
events......................................................................... 28 
6.2.3.9. 
Counting rules for occurrence of unsolicited 
adverse events ........................................................... 29 
6.2.4. 
Display of decimals ...................................................................... 29 
6.2.4.1. 
Percentages ............................................................... 29 
6.2.4.2. 
Demographic/baseline characteristics statistics .......... 29 
6.2.4.3. 
Serological summary statistics ................................... 30 
7. 
REFERENCES ....................................................................................................... 31 
 


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LIST OF TABLES 
PAGE 
Table 1 
Study groups, intervention and blinding .................................................. 12 
Table 2 
Intervals between study visits ................................................................. 13 
Table 3 
Intensity scales for solicited events ........................................................ 28 
 


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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 11 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse event 
CI 
Confidence Interval 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
DCGI 
Drug Controller General of India 
eCRF 
Electronic Case Report Form 
ELISA 
Enzyme Linked Immunosorbent Assay 
EoS 
End of Study 
ES 
Exposed Set 
gE 
VZV glycoprotein E 
GMC 
Geometric Mean Concentration 
GSK 
GlaxoSmithKline Biologicals SA 
HZ 
Herpes Zoster 
ICF 
Inform Consent Form 
IMC 
Intercurrent Medical Condition 
LL 
Lower Limit of the confidence interval 
LSLV 
Last Subject Last Visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
MGI 
Mean Geometric Increase 
PCD 
Primary Completion Date 
PII 
Personal Identifiable Information 
pIMD 
Potential Immune-Mediated Disease 
PPS 
Per Protocol Set 
PT 
Preferred Term 


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SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SMQ 
Standardized MedDRA Query 
SOC 
System Organ Class 
VRR 
Vaccine Response Rate 
YOA 
Years of Age 


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Version history 
SAP 
Version 
Approval 
Date 
Protocol 
Version 
(Date) on 
which SAP 
is Based 
Change 
Rationale 
SAP 
25 Jan 2022 
8 June 2021 
Not Applicable 
Original 
version 
SAP 
Amendment 
1 
29 Apr 2022 8 June 2021 
• 
New blinded early 
safety analyses are 
added into Section 
4.6 Other analyses 
• 
Changes to 
Introduction section 
and Section 4.8 
SAP amended 
to 
accommodate 
Drug 
Controller 
General of 
India (DCGI) 
requirement 
for early 
safety data 
SAP 
Amendment 
2 
16 Sep 2022 25 May 2022 • 
Analysis to be 
performed for 
Blinded early safety 
report has been 
moved from section 
4.6 to section 4.7 as 
it is now included in 
the protocol 
amendment 1 and 
two new tables have 
been added to the 
report 
• 
Section 6.2.2.1 a 
point added for date 
imputation 
• 
Changes to section 
6.2.2.3.1 to count 
denominator 
correctly for fever 
solicited adverse 
event  
• 
Changes to section 
6.2.3.1 for 
calculation of age 
Based on 
protocol 
amendment 1 


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SAP 
Version 
Approval 
Date 
Protocol 
Version 
(Date) on 
which SAP 
is Based 
Change 
Rationale 
SAP 
Amendment 
3 
11 Nov 2022 
25 May 2022 • 
Changes to section 
4.7.1 – item 5 to 
remove related and 
grade 3 related 
from solicited 
systemic events 
output 
As per 
protocol, all 
solicited 
administratio
n site and 
systemic 
events 
occurring 
within 7 days 
of study 
intervention 
administratio
n will be 
considered 
causally 
related to the 
study 
intervention 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the CSR 
and in the analysis planned for the Blinded Early Safety Report for Study ZOSTER-081 
(214461).  
1.1. 
Objectives and Endpoints 
Objectives 
Estimands/Endpoints 
Primary 
To determine the vaccine response rate (VRR) for 
anti-gE humoral immune response at 1-month post-
dose 2 (Month 3) of administration of HZ/su*. 
Percentage of participants showing a vaccine response for 
anti-gE antibody concentrations at 1-month post-dose 2 
(Month 3). 
Secondary 
To evaluate the anti-gE humoral response at 1-month 
post-dose 2 (Month 3) in recipients of HZ/su 
compared to Placebo**. 
Anti-gE antibody concentration expressed as group 
geometric mean concentration (GMC) ratio at 1-month 
post-dose 2 (Month 3). 
To evaluate safety and reactogenicity following 
administration of HZ/su or placebo from first dose up 
to 30 days post last dose. 
Solicited AEs: Number and percentage of participants 
reporting each solicited administration site AE (injection 
site redness, pain, swelling and pruritus) and solicited 
systemic AEs (fever, myalgia, fatigue, gastrointestinal [GI] 
symptoms, headache and shivering) within 7 days (Day 1 
to Day 7) after each dose and overall. 
Unsolicited AEs: Number and percentage of participants 
reporting unsolicited AEs within 30 days (Day 1 to Day 30) 
after any dose. 
SAEs: Number and percentage of participants reporting 
SAEs from Dose 1 (Day 1) up to 30 days post last dose. 
pIMDs: Number and percentage of participants reporting 
pIMDs from Dose 1 (Day 1) up to 30 days post last dose. 
To evaluate safety following administration of HZ/su 
or placebo during the entire study period. 
SAE- Number and percentage of participants reporting 
SAEs from Dose 1 (Day 1) up to study end (phone contact 
Month 8). 
pIMDs- The number and percentage of participants 
reporting pIMDs from Dose 1 (Day 1) up to study end 
(phone contact Month 8). 
To characterise anti-gE humoral immunogenicity 
response prior to the first study intervention 
administration (Day 1) and at 1-month post-second 
study intervention administration (Month 3) in both 
groups. 
Anti-gE antibody geometric mean concentrations (GMC) 
and seropositivity rate at pre-study intervention 
administration (Day 1) and 1-month post-dose 2 (Month 3). 
Mean geometric increase (MGI) at 1-month post- dose 2 
(Month 3) compared to pre-study intervention 
administration (Day 1). 


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*The success criteria for the primary objective and VRR definition are presented in Sections 4.2.2 and 4.2.1 
respectively 
**The success criteria for the secondary objective are presented in Section 4.3.3 
Primary Estimand 
The primary clinical question of interest is to show that the immunogenicity for anti-gE 
antibody is comparable in the Indian population with respect to the vaccine response rate 
(VRR) 1 month post Dose 2 of Shingrix vaccination in eligible participants who complied 
with the study intervention (refer to section 3 for the definition of the per protocol set 
used for the primary analysis and to section 4.2.2 for the statistical method). 
1.2. 
Study Design 
The overview of the study design is presented in Figure 1 below. 
Figure 1 
Study design overview  
 
 
*BS=Blood Sampling; Int=study intervention, N=number of participants planned to be randomised;  
‡ Each participant will be followed up for 6 months post last dose/Month 8.  
• 
Type of study: Self-contained. 
• 
Experimental design: Phase 3, randomised, observer-blind, placebo-controlled, 
multi-centric, single country study with 2 parallel groups (see Figure 1). 
• 
Duration of the study: Approximately 8 months for each participant. 
• 
Control: Placebo-controlled  
• 
Blinding: Observer-blind 
• 
Study intervention schedule: 0 and 2 months (Day 1 and Month 2) 
• 
Biological samples: Blood samples will be collected at Day 1 and Month 3 (1-month 
post-dose 2). 


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• 
Follow-up contact: Phone contact at Month 8 (6 months post last study intervention 
administration). 
• 
Primary completion date (PCD): Month 3 (1-month post-dose 2).  
• 
Data collection: Standardised electronic Case Report Form (eCRF). Solicited AEs 
and unsolicited AEs will be collected using a Participant Diary card (paper diary 
card). 
• 
Study groups: Refer to Table 1 for an overview of the study groups. 
Table 1 
Study groups, intervention and blinding 
Study Groups 
Number of 
participants 
Age 
Study intervention 
Blinding 
Visit 1→Phone 
contact 
(Observer-blind) 
HZ/su  
144 
50 years  
VZV gE  
X 
AS01B  
Placebo  
144 
50 years  
Lyophilised sucrose  
X 
Saline (NaCl) solution for 
reconstitution 
• 
Study intervention assignment: The study will enrol approximately 288 
participants who will be randomised 1:1 to the HZ/su or Placebo group of equal size 
to receive 2 doses of study interventions administered intramuscularly 2 months 
apart. 
The randomisation algorithm will use a minimisation procedure accounting for age 
(50- 69 YOA, ≥70 YOA). Minimisation factors will have equal weight in the 
minimisation algorithm. 
• 
End of Study (EoS): End of Study (EoS) is achieved after Last subject* last visit 
(LSLV=Phone contact at Month 8) or Date of the last testing/reading released of the 
Human Biological Samples or imaging data, related to primary and secondary 
endpoints (whichever is later).  
*subject=participant. 
2. 
STATISTICAL HYPOTHESES  
The study has one primary and one secondary immunogenicity confirmatory objective 
which will be assessed in a hierarchical manner. The null hypothesis related to the 
primary objective under consideration is that the VRR for anti-gE antibody concentration 
1 month after the second HZ/su dose is <60%. 
The primary objective will be met if the lower limit (LL) of the 95% Confidence Interval 
(CI) of the VRR for anti-gE antibody concentration 1 month after the second HZ/su dose 
is ≥60%.  
The null hypothesis related to the secondary confirmatory objective under consideration 
is that the adjusted GMC ratio between the HZ/su and the Placebo group for anti-gE 
antibody concentration 1 month after the second study intervention dose is <3. 


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The secondary confirmatory objective will be met if the LL of the 95% CI of the adjusted 
GMC ratio between the HZ/su and the Placebo group for anti-gE antibody concentration 
1 month after the second study intervention dose is ≥3.  
All the safety analyses and humoral immunogenicity response under the secondary 
objective are descriptive. 
2.1. 
Multiplicity Adjustment 
The hypotheses are tested hierarchically, so no multiplicity adjustment is required. 
3. 
ANALYSIS SETS 
Analysis Set 
Definition/Criteria 
Enrolled Set 
Eligible participants who have signed an informed consent and were randomised or 
undergone an invasive procedure. 
Exposed Set (ES) 
All participants who received at least 1 dose of the study intervention. Analysis per 
group using the enrolled set is based on the administered intervention. 
Per Protocol Set (PPS) 
All eligible participants who received all doses as per protocol, had immunogenicity 
results pre- and post-dose 2, complied with allowed dosing/blood draw intervals 
(Table 2), without intercurrent conditions that may interfere with immunogenicity 
and without prohibited concomitant medication/vaccination. The analysis will be 
done according to the study intervention that participants received at dose 1. 
3.1. 
Intervals between study visits 
The intervals allowed for the inclusion of the PPS is the ‘allowed interval per protocol’ as 
defined in Table 2 below: 
Table 2 
Intervals between study visits 
Interval 
Planned visit interval 
Allowed interval range 
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–60 days 
Visit 2→Phone contact 
180 days/6 Months 
160-210 days 
160–210 days 
#Participants may not be eligible for inclusion in the PPS, if study visits occur outside the allowed interval. 
3.2. 
Criteria for eliminating data from Analysis Sets 
Elimination codes are used to identify participants to be eliminated from analysis. Details 
are provided below for each analysis set.  


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3.2.1. 
Elimination from Enrolled Set  
Code 800 (fraudulent data), 900 (invalid ICF) and 1010 (treatment number not allocated) 
will be used for identifying participants eliminated from Enrolled Set. 
3.2.2. 
Elimination from Exposed Set (ES) 
Code 1030 (Study treatment not administered at all), 800 (fraudulent data), code 900 
(invalid informed consent) and code 1010 (treatment number not allocated) will be used 
for identifying participants eliminated from ES.  
3.2.3. 
Elimination from Per-protocol analysis Set (PPS) 
3.2.3.1. 
Excluded participants 
A participant 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 intervention 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) 
Visit 1 to Visit 3 
1050 
Randomisation failure 
All 
1060 
Randomisation code was broken 
Visit 1 to Visit 3 
1070** 
Study intervention not according to protocol: - 
• 
Participants got vaccinated with the correct 
study intervention 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 study intervention is wrong 
or unknown 
Visit 1, Visit 2 


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Code 
Condition under which the code is used 
Visit (timepoints) 
where the code is 
applicable 
• 
Wrong replacement or study intervention 
administered (not compatible with the vaccine 
regimen associated to the treatment number) 
1080 
Temperature deviated study intervention 
administered 
Visit 1, Visit 2 
1090 
Expired study intervention 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 5.2.1 and 5.2.2 of the 
protocol) in the period from the first dose of study 
intervention and ending at Visit 3 (Day 1 to Month 
3)  
Visit 1 to Visit 3 
2050* 
Underlying medical condition forbidden by the 
protocol  
Any intercurrent medical condition (IMC) (refer to 
section 9.3.1 of the protocol) which can affect the 
immune response to the study intervention during 
the study up to 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 
2080 
Participant did not comply with study intervention 
schedule 
DOSE 1 – DOSE 2 = 49-83 days 
Visit 2 
2090 
Participant did not comply with blood sample 
schedule 
DOSE2-blood sample (BS)2 = 28-48 days 
Visit 3 
2100 
Serological results not available post-vaccination 
Check for humoral result for PPS 
Visit 3 
2120 
Obvious incoherence or abnormality or error in 
data 
Check for humoral result for PPS 
Visit 3 
2500 
Participant who didn’t receive two doses   
Visit 2 
*Attribution of these elimination codes to participants need CRDL review of individual listing 
**Attribution of these elimination codes will be evaluated on case-by-case basis and requires CRDL confirmation 


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4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
4.1.1. 
General Methodology 
95% confidence levels will be used unless otherwise specified.  
The exact confidence intervals around within-group proportions are derived using the 
method of Clopper and Pearson [Clopper, 1934]. 
Unless otherwise specified, continuous data will be summarized using descriptive 
statistics: n, mean, standard deviation (SD), median, minimum and maximum. 
Categorical data will be summarized as the number and percentage of participants in each 
category. 
4.1.2. 
Baseline Definition 
For all endpoints the baseline value will be the latest pre-dose assessment with a non-
missing value. 
Unless otherwise stated, if baseline data is missing, no derivation will be performed, and 
baseline will be set to missing. 
4.2. 
Primary Endpoints Analyses 
The primary immunogenicity analysis will be performed on the PPS and if more than 5% 
participants are eliminated from the PPS then a complementary analysis will be 
performed on ES. 
4.2.1. 
Definition of endpoints 
The VRR is defined as the percentage of participants who has at least: 
• 
a 4-fold increase in the post last vaccination anti-gE antibody concentration as 
compared to the pre-vaccination anti-gE antibody concentration for participants who 
are seropositive at baseline. 
OR 
• 
a 4-fold increase in the post last vaccination anti-gE antibody concentration as 
compared to the anti-gE antibody cut-off value (97 mIU/ml) for seropositivity for 
participants who are seronegative at baseline.  
Two-sided 95% CIs for VRR will be computed by Clopper-Pearson method [Clopper, 
1934]. 


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4.2.2. 
Main analytical approach 
The point estimate and the 95% CI for VRR on anti-gE antibody concentration as 
assessed by ELISA will be calculated in all participants at 1-month post-dose 2 (Month 
3). 
As stated in Section 2 the objective is met if the LL of the 95% CI of the VRR for anti-gE 
antibody concentration 1 month after the second HZ/su dose is at least 60%. 
4.3. 
Secondary Endpoints Analyses 
4.3.1. 
Key/Confirmatory secondary endpoints 
4.3.1.1. 
Confirmatory secondary immunogenicity endpoints  
The secondary confirmatory immunogenicity analysis will be performed on the PPS and 
if more than 5% participants are eliminated from the PPS then a complementary analysis 
will be performed on ES. 
4.3.1.2. 
Definition of endpoints 
The geometric mean concentration (GMC) calculations are performed by taking the anti-
log of the mean of the log base 10 concentration transformations. For descriptive 
statistics only, antibody concentrations below the cut-off of the assay will be imputed 
with a value equal to half the cut-off for the purpose of GMC calculation. 
4.3.1.3. 
Main analytical approach 
For the secondary confirmatory group comparison, the GMC ratio with nominal 95% CI 
will also be provided. This will be obtained using an analysis of variance (ANOVA) 
model on log-transformed concentrations adjusted for age-strata (50-69 YOA and 
 70 YOA) and baseline titres as continuous covariate and will use Satterthwaite method 
for adjusting the degree of freedom for unequal variance. 
For this analysis, the following SAS code using the proc mixed procedure will be used to 
do the model fitting: 
PROC MIXED DATA=sero; 
CLASS grp_labl agecat;/*age-minimization factor*/ 
MODEL log_val=grp_labl agecat base/DDFM=satterth; 
REPEATES/GROUP=grp_labl; 
LSMEANS grp_labl /AT MEANS CL DIFF ALPHA=0.05 COV; 
ODS OUTPUT LSMEANS=m_lsml; 
ODS OUTPUT DIFFS=m_difl; 
RUN; 
The group GMC ratio will be based on a back transformation of group contrast in an 
ANCOVA model applied to the logarithm-transformed concentrations. 


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4.3.2. 
Key secondary immunogenicity endpoint  
Descriptive statistics of immune response with respect to anti-gE assessed by ELISA at 
each timepoint and by study group will be presented:  
• 
Number and percentage of participants with anti-gE assessed by ELISA above 
seropositivity cut-off will be tabulated with 95% CI. 
• 
GMCs will be tabulated with 95% CI. 
• 
Geometric mean of ratios of antibody concentrations at 1- month post-dose 2 
timepoint over pre-study intervention administration (MGI) will be tabulated with 
95% CI. 
4.3.3. 
Key secondary safety endpoints 
The analyses for safety will be descriptive and based on the ES. The analyses will be 
performed by study group.  
The results for the analysis of safety and reactogenicity will be tabulated as follows: 
• 
Solicited administration site AEs and solicited systemic AEs 
− 
Number and percentage of participants reporting each solicited administration 
site AE (any grade, grade 3, resulting in a medically-attended visit) during the 7-
day follow-up period after each dose and overall per participant and per dose 
will be tabulated with exact 95% CIs. 
− 
Number and percentage of participants reporting each solicited systemic AE 
(any grade, grade 3, resulting in a medically-attended visit) during the 7-day 
follow-up period after each dose and overall per participant and per dose will be 
tabulated with exact 95% CIs. 
• 
Unsolicited AEs: Number and percentage of participants reporting unsolicited AE 
(any grade, grade 3, any related, grade 3 related, resulting in a medically-attended 
visit) within 30 days after any dose coded by the Medical Dictionary for Regulatory 
Activities (MedDRA) by primary system organ class (SOC) and preferred term (PT) 
with exact 95% CIs will be tabulated. 
• 
SAEs and pIMDs: Number and percentage of participants reporting SAEs (any and 
related), fatal SAEs (any and related) and pIMDs (any and related) from Dose 1 
(Day 1) up to 30 days post last dose and from Dose 1 (Day 1) up to study end coded 
by the MedDRA primary SOC and PT with exact 95% CIs will be tabulated. 
• 
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 from 
first study intervention up to study end.  
• 
Listing of pregnancy during the entire study period will be generated.  


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4.3.4. 
Supportive secondary endpoints 
Not applicable 
4.4. 
Tertiary/Exploratory Endpoints Analyses 
Not Applicable. 
4.5. 
Other Safety Analyses 
Below are the other safety analyses planned for the final analysis and based on the ES. 
These analyses will be performed by study group. 
• 
The percentage of participants with at least 1 administrative site adverse event 
(solicited only), with at least one systemic AE (solicited only) and with any AE 
(solicited only), all with onset during the solicited 7-day follow-up period, will be 
tabulated with exact 95% CI after each vaccine dose and overall. The same 
tabulations will be done for grade 3 solicited AEs. 
• 
In the solicited systemic adverse event table, fever will be reported per 0.5°C 
cumulative increments. 
• 
Duration of each solicited administrative site and systemic AE during the solicited 
follow-up period will be presented. Total duration of each individual solicited 
administrative site and systemic AE will be tabulated. 
• 
Duration of each grade 3 solicited administrative site and systemic AE during the 
solicited follow-up period will be presented. Total duration of each individual 
solicited grade 3 administrative site and systemic AE will be tabulated. 
4.5.1. 
COVID-19 Assessment and COVID-19 AEs 
A standardized MedDRA Query (SMQ) will be used to identify all COVID-19 AEs. 
The overall incidence of AEs and SAEs of COVID-19, COVID-19 AEs leading to study 
intervention discontinuation, COVID-19 AEs leading to study withdrawal, and severe 
COVID-19 AEs will be summarized. The incidence of these events at individual PT level 
can be obtained from the standard AE/SAE summaries. 
COVID-19 assessments (confirmed, probable and suspected diagnosis) for participants 
with COVID-19 AEs will be summarized. 
The number and percentages of participants with concomitant vaccination (COVID-19) 
before and during the study will be tabulated with exact 95% CI. 
Summaries of the number of participants who had a COVID-19 diagnosis test performed 
and the number of participants with positive, negative, or indeterminate results will be 
presented. 
Additional tables may be planned as required. 


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4.6. 
Other Analyses 
Not applicable. 
4.7. 
Interim Analyses 
No interim analysis is planned for this study. An EoS analysis with all data including the 
safety data obtained until study end (6 months post-dose 2) will be performed. A Clinical 
Study Report (CSR) containing all available data will be written and made available to 
the investigators. Individual listings will only be provided at this stage. 
4.7.1. 
Blinded Early Safety Report 
To fulfil the post-approval commitment to the Indian regulatory authority, a blinded early 
safety assessment report after completion of 30 days safety follow-up post HZ/su dose 2 
(i.e., Visit 3, Month 3) for the initial 200 randomised participants will be provided and 
the following analyses will be performed. The analyses performed will be descriptive in 
nature. 
1. Table on summary of participants withdrawn up to the snapshot date with reasons for 
withdrawal on the Exposed Set 
2. Summary of demography and baseline characteristics on the Exposed Set 
3. Table showing the exposure to study intervention on the Enrolled Set 
4. Number and percentage of participants with any, grade 3, or medically attended 
solicited administration site events, per dose, in the Exposed Set.  
5. Number and percentage of participants with any, grade 3, or medically attended 
solicited systemic events, per dose, in the Exposed Set 
6. Number and percentage of participants with any, grade 3, related, or grade 3 related 
unsolicited adverse events with onset within 30 days following any dose in the 
Exposed Set 
7. Number and percentage of participants with serious adverse events from first dose up 
to 30 days post last dose in the Exposed Set 
8. Number and percentage of participants with serious adverse events from first dose up 
to snapshot day in the Exposed Set 
9. Number and percentage of participants with pIMDs from first dose up to 30 days 
post last dose in the Exposed Set 
10. Number and percentage of participants with pIMDs from first dose up to snapshot 
day in the Exposed Set 
11. Listing of SAEs from first dose up to snapshot day. 
12. Listing of pIMDs from first dose up to snapshot day. 
All the data derivation rules for demography and safety analyses of Appendix 2 will be 
applicable for the above demography and safety analyses. 


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4.8. 
Changes to Protocol Defined Analyses 
Not applicable.  
5. 
SAMPLE SIZE DETERMINATION 
Approximately 288 (144 participants per study group) eligible participants will be 
randomised to achieve 200 (100 participants per study group) evaluable participants for 
the evaluation of the primary objective assuming that approximately 30% of the enrolled 
participants will not be evaluable. Participants who withdraw from the study will not be 
replaced. 
Considering a 95% VRR in the HZ/su group, the study has at least 99% power to meet 
the primary objective under the hypothesis given below:- 
• 
Null hypothesis: The VRR for anti-gE ELISA at 1 month after second HZ/su dose in 
participants from India is less than 60%. 
• 
Alternative hypothesis: The VRR for anti-gE ELISA at 1 month after second HZ/su 
dose in participants from India is at least 60%. 
Power to show the LL of the 95% CI for VRR at one month after second HZ/su dose. 
Endpoint 
NI criteria 
N1:N2 (evaluable) 
Reference** 
Power* 
Vaccine response rate 
– anti-gE ELISA 
LL of 95% CI for VRR ≥60% 
100:100 
95% 
≥99% 
*Power computed using PASS 2019 software, Non-Inferiority Test for one proportion, 1-sided alpha=2.5%; 
**References used for the sample size calculation: ZOSTER-006 study. 
Considering the adjusted GMC ratio of 44.31 between HZ/su and Placebo group and SD 
of 0.30 and 0.46 for HZ/su and Placebo group, respectively, the study has at least 99% 
power to meet the secondary confirmatory objective under below hypothesis. 
• 
Null hypothesis: The adjusted GMC ratio for anti-gE ELISA at 1 month after second 
study intervention dose in participants from India is less than 3. 
• 
Alternative hypothesis: The adjusted GMC ratio for anti-gE ELISA at 1 month after 
second study intervention dose in participants from India is greater than or equal to 
3. 
Power to show the LL of the 95% CI for adjusted GMC ratio at one month after second 
dose. 


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Endpoint 
Criteria for evaluation 
N1:N2 
(evaluable) 
Reference** 
Power* 
Adjusted GMC ratio  
LL of 95% CI for adjusted 
GMC ratio ≥3 
100:100 
Adjusted GMC ratio – 44.31 
SD for HZ/su group – 0.30 
SD for Placebo group – 0.46 
≥ 99% 
*Power computed using PASS 2019 software, Two-Sample T-Tests for Superiority by a Margin Allowing Unequal 
Variance, 
1-sided alpha=2.5%; 
**References used for the sample size calculation: ZOSTER-006 study. 
6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Study Population Analyses 
6.1.1. 
Participant Disposition 
A summary of the number and percentage of participants who completed the study as 
well as those who withdrew from the study will be provided. Reasons for study 
withdrawal will be summarized. For those who neither completed nor withdrawn, they 
will be categorized as on study intervention or in follow up. This analysis will be based 
on the ES. 
The number of participants enrolled into the study as well as the number of participants 
excluded from the PPS analyses will be presented through 2 consort tables: 
• 
Consort table 1: Showing the participants disposition from participants with ICF 
signed to Enrolled Set and from Enrolled Set to ES. 
• 
Consort table 2: Showing the participants disposition for ES to PPS. 
6.1.2. 
Demographic and Baseline Characteristics 
Demographic and other baseline characteristics will be described for the ES and the PPS 
Demographic characteristics (age at first vaccination with study intervention in years, age 
category [50-69, ≥70 YOA], sex, race and ethnicity) will be summarized 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. 
Number of participants by center will be presented on ES. Percentage of Enrolled 
participants by age categories (18-64,65-84, ≥85) YOA will be tabulated by group for the 
purpose of web disclosure. 


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6.1.3. 
Protocol Deviations 
The number of participants enrolled into the study as well as the number of participants 
excluded from the per protocol set (PPS) analyses will be tabulated for the total 
population. 
The number of participants enrolled into the study as well as the number of participants 
excluded from the ES will be tabulated for the total population. This will be based on all 
enrolled participants. 
Important protocol deviations will be summarized. Protocol deviations which result in 
exclusion from an analysis set will also be summarized. Data will be reviewed prior to 
unblinding and freezing the database to ensure all deviations leading to analysis 
population exclusions are captured and categorised in the protocol deviations ADaM 
dataset. 
6.1.4. 
Prior and Concomitant Medications 
No table is planned for the prior medications taken by participants. 
The proportion of participants with concomitant medications (any medication, any 
antipyretic and any antipyretic taken prophylactically, respectively) will be tabulated, 
within 30 days post each vaccination (i.e., on the day of vaccination and 29 subsequent 
days) with study intervention and overall, with exact 95% CI. 
6.1.5. 
Prior and Concomitant Vaccinations 
No table is planned for the prior vaccinations taken by participants. 
The proportion of participants with concomitant vaccinations will be tabulated, within 30 
days post each vaccination (i.e., on the day of vaccination and 29 subsequent days) with 
study intervention and overall, with exact 95% CI. 
6.1.6. 
Study Intervention Compliance 
The number of doses administered will be tabulated. 
The number and percentage of participants who returned the diary cards and those who 
returned the diary cards with documentation of the presence or absence of AEs will be 
tabulated on the Exposed Set. 
Summary of time interval between Visit 1 or 2 and Visit 2 and Visit 3 will be tabulated 
for the Exposed Set. 
6.1.7. 
Additional Analyses Due to the COVID-19 Pandemic 
Depending on how the COVID-19 pandemic evolves, the SAP may be amended to reflect 
the additional analyses corresponding to COVID-19. 


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6.2. 
Appendix 2 Data Derivations Rule 
This section contains standard rules for data display and derivation for clinical and 
epidemiological studies.  
6.2.1. 
Attributing events to vaccine doses 
The dose relative to an event is the most recent study intervention dose given to a 
participant 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 case report form (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. 
6.2.2. 
Handling of missing data 
6.2.2.1. 
Dates 
When partially completed dates (i.e. dates missing a day and/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. 
The following exceptions apply: 
When partially completed dates (i.e. with missing day or month) are used in calculations, 
the following rules will be applied: 
• 
Adverse event start dates with missing day: 
− 
If the month is not the same as the study intervention dose, then the imputed 
start date will be the 1st of the month 
− 
If the event starts in the same month as at least one of the study interventions, 
the flag indicating if the event occurred before or after study intervention 
(AE.AESTRTPT) will be used to complete the date. If ‘after vaccination’ is 
selected, the imputed start date will match the study intervention dose given 
during that month. If ‘before vaccination’ is selected, the imputed date will be 
one day before the study intervention dose given during that month. 
− 
If we cannot impute the missing parts of the date using the rule under above 
categories, then we need to apply Version 15 rule - 15 for the missing day and 
30JUN for missing month and day. 


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• 
Adverse event start dates with missing day and month: 
− 
If the year is not the same as the vaccine dose, then the imputed start date will be 
the 1st of January. 
− 
If the event starts in the same year as the vaccine dose, the flag indicating if the 
event occurred before or after vaccination (AE.AESTRTPT) will be used to 
complete the date. If ‘after vaccination’ is selected, the imputed start date will 
match the first study intervention dose given during that year. If ‘before 
vaccination’ is selected, the imputed date will be one day before the first study 
intervention dose given during that year. 
− 
If we cannot impute the missing parts of the date using the rule under above 
categories, then we need to apply Version 15 rule - 15 for the missing day and 
30JUN for missing month and day. 
• 
Adverse event end dates with missing day: the imputed end date will be the last day 
of the month (30 or 31) or the study conclusion date whichever comes first. 
• 
Adverse event end dates with missing day and month: the imputed end date will be 
the last day of the year (31st of December) or the study conclusion date whichever 
comes first. 
All incomplete concomitant medication/vaccination start/end date will follow the rules 
above. 
6.2.2.2. 
Laboratory data 
Missing laboratory results (immunological data) will not be replaced.   
6.2.2.3. 
Daily recording of solicited events 
6.2.2.3.1. Studies with paper diaries 
For studies using paper diaries which have questions in the eCRF 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 to one occurrence of the specific administration site (or systemic) events. If 
there is 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. 
• 
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, then that participant would not be considered for ‘Any’ rows of the 
solicited event summary tables. 


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• 
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 event over the Day X to Day Y post-dose period: 
Solicited 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, grade 2, or 
grade 3 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 
At least grade 1 
All participants with at least one occurrence of the adverse event at grade 1, grade 2, or 
grade 3 between Day X and Day Y 
At least grade 2 
All participants with at least one occurrence of the adverse event at grade 2 or grade 3 
between Day X and Day Y 
At least grade 3 
All participants with at least one occurrence of the adverse event at grade 3 between 
Day X and Day Y 
6.2.3. 
Data derivation 
6.2.3.1. 
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 
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 June 
30th of the year. 
6.2.3.2. 
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 
6.2.3.3. 
Numerical serology results 
Numerical serology results will be derived from the content of IS.ISORRES in the SDTM 
dataset. For assays with a specific cut-off, the following derivation rules apply: 


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IS.ISORRES 
Derived value 
“value” and value is < cut-off 
cut-off/2 
“value” and value is >= cut-off 
Value 
6.2.3.4. 
Geometric mean concentrations (GMCs) 
Geometric Mean Concentration (GMC) calculations are performed by taking the inverse 
logarithm of the mean of the log concentration transformations. Non quantifiable 
antibody concentrations will be converted as described in section 6.2.3.3 for the purpose 
of GMC calculation. Cut-off values are defined by the laboratory before the analysis. 
6.2.3.5. 
Onset day 
The onset day for an event (e.g. AE, concomitant 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 study dose). 
6.2.3.6. 
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 3 March 2018 and ends on 12 
March 2018 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. 
6.2.3.7. 
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. 
Solicited events will be coded by MedDRA as per the following codes: 
Solicited event 
Lower level term code 
Corresponding Lower 
level term decode  
Pain 
10022086 
Injection site pain 
Erythema 
10015150 
Injection site erythema 
Swelling 
10053425 
Injection site swelling 
Pruritus 
10022093 
Injection site pruritus 
Fever 
10016558 
Pyrexia 


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Solicited event 
Lower level term code 
Corresponding Lower 
level term decode  
Headache 
10019211 
Headache 
Fatigue 
10016256 
Fatigue 
Myalgia 
10028411 
Myalgia 
Shivering 
10040558 
Shivering 
GI symptom 
10017944 
Gastrointestinal disorder 
The latest available MedDRA version will be used for coding 
6.2.3.8. 
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.  
Table 3 
Intensity scales for solicited events 
Adults (50 years) 
Event 
Intensity grade 
Parameter 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing normal 
everyday activities. 
 
2 
Moderate: Painful when limb is moved and interferes with everyday 
activities. 
 
3 
Severe: Significant pain at rest. Prevents normal everyday activities. 
Redness at administration site 
Greatest surface diameter in mm 
Swelling at administration site 
Greatest surface diameter in mm  
Pruritis at administration site 0 
None 
 
1 
Mild: Itchy sensation that neither interferes with nor preventing 
normal everyday activities. 
 
2 
Moderate: Itchy sensation that interferes with normal everyday 
activities. 
 
3 
Severe: Itchy sensation that prevents normal everyday activities. 
Temperature* 
 
Temperature in °C/°F (with 1 decimal) 
Headache 
0 
None 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
None  
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Gastrointestinal symptoms 
0 
None 
 
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 


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Adults (50 years) 
Event 
Intensity grade 
Parameter 
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 
Shivering 
0 
None 
 
1 
Shivering that is easily tolerated 
 
2 
Shivering that interferes with normal activity 
 
3 
Shivering that prevents normal activity 
* Fever is defined as temperature ≥38.0°C/100.4°F regardless of the location of measurement. The preferred route for 
measuring temperature is oral. 
The maximum intensity of injection administration site redness/swelling and fever will be 
scored at GSK as follows: 
Intensity 
grade 
Redness/swelling 
Fever 
0: 
20 mm 
<38.0°C (100.4°F) 
1: 
>20-50 mm 
≥38.0°C (100.4°F)- 38.5°C (101.3°F) 
2: 
>50-100 mm 
>38.5°C (101.3°F)- 39.0°C (102.2°F) 
3: 
>100 mm 
>39.0°C (102.2°F) 
6.2.3.9. 
Counting rules for occurrence of unsolicited adverse events 
Unsolicited adverse event summaries are including serious adverse events unless 
specified otherwise.  
As per CDISC Vaccines Therapeutic Area guide, the solicited events which continue 
beyond the observation period are stored in the Adverse Events (AE) domain, but they do 
not contribute to the summaries of unsolicited adverse events. 
Missing severity, 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. 
6.2.4. 
Display of decimals 
6.2.4.1. 
Percentages 
Percentages and their corresponding confidence limits will be displayed with one decimal 
except for 100% in which case no decimal will be displayed.  
6.2.4.2. 
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. 


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6.2.4.3. 
Serological summary statistics 
For anti-gE ELISA, geometric mean concentrations (GMC) and their confidence limits 
will be presented with one decimal, as well as GMC fold increase from pre-dose. 
GMC group ratios and their confidence limits will be displayed with 2 decimals 
regardless of the actual values. 


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7. 
REFERENCES 
Clopper CJ, Pearson E. The Use of Confidence or Fiducial Limits Illustrated in the case 
of the Binomial. Biometrika. 1934;26:404-13.