Long Term Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine 1437173A and Assessment of Re-vaccination With 2 Additional Doses, in Healthy Subjects Aged 60 Years of Age and Older
Phase: PHASE3
Conditions: Herpes Zoster
Sponsor: GlaxoSmithKline

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Clinical Study Protocol
Sponsor:
GlaxoSmithKline Biologicals
Rue de l’Institut 89, 1330 Rixensart, Belgium
Primary Study vaccine

GlaxoSmithKline Biologicals’ Lyophilised 
formulation of the Herpes Zoster (HZ) vaccine 
(GSK 1437173A)
eTrack study number and 
Abbreviated Title
204926 (ZOSTER-060 EXT:003)
EudraCT number
2015-004400-30
Date of protocol
Final Version 1: 12 November 2015
Date of protocol 
amendment
Amendment 1 Final: 18 August 2017
Title
Long term immunogenicity and safety study of GSK 
Biologicals’ Herpes Zoster subunit (HZ/su) vaccine 
1437173A and assessment of re-vaccination with 2 
additional doses, in healthy subjects aged 60 years of 
age and older.
Detailed Title
A phase IIIB, open, long term extension study to 
evaluate the persistence of immune responses and the 
safety of GSK Biologicals’ Herpes Zoster subunit 
(HZ/su) vaccine 1437173A, at Months 108 and 120 
post-vaccination and the assessment of re-vaccination 
with two additional doses administered at 10 years 
after the initial vaccination in study ZOSTER-003 in 
healthy subjects aged 60 years of age and older.
Co-ordinating authors
(Amended 18 August 2017)

 Scientific Writer

 (XPE Pharma & Science 
contractor for GSK Biologicals)
Contributing authors
(Amended 18 August 2017)

 Clinical Research and 
Development Lead

 Clinical Research and 
Development Lead

 Study Delivery Lead

 Study Delivery Lead

 Lead Statistician

 Project Statistician
 
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eTrack study number and 
Abbreviated Title
204926 (ZOSTER-060 EXT:003)
EudraCT number
2015-004400-30
Detailed Title
A phase IIIB, open, long term extension study to 
evaluate the persistence of immune responses and the 
safety of GSK Biologicals’ Herpes Zoster subunit 
(HZ/su) vaccine 1437173A, at Months 108 and 120 
post-vaccination and the assessment of re-vaccination 
with two additional doses administered at 10 years 
after the initial vaccination in study ZOSTER-003 in 
healthy subjects aged 60 years of age and older.
Contributing authors
(Amended 18 August 2017)

 Project Statistician

 Study Manager

 Clinical Read-out Team Lead, 
Clinical Laboratories Science

 Study Manager, Clinical 
Laboratories Science

Vaccine Supply Coordinator

 Clinical Safety representative

Clinical Safety representative

Project Data Manager

Global Regulatory Affairs

 Global Patent

Zoster Project Level Clinical Research 
and Development Lead, Belgian RDC

 Clinical and Epidemiology 
Project Lead for Zoster, Belgian RDC
GSK Biologicals’ Protocol DS v 14.1.1
Copyright 2015-2017 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorised copying or use of this information is prohibited.
 
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Protocol Amendment 1 Sponsor Signatory Approval
eTrack study number and 
Abbreviated Title
204926 (ZOSTER-060 EXT:003)
EudraCT number
2015-004400-30
Date of protocol amendment
Amendment 1 Final: 18 August 2017
Detailed Title 
A phase IIIB, open, long term extension study to 
evaluate the persistence of immune responses and the 
safety of GSK Biologicals’ Herpes Zoster subunit 
(HZ/su) vaccine 1437173A, at Months 108 and 120 
post-vaccination and the assessment of re-vaccination 
with two additional doses administered at 10 years 
after the initial vaccination in study ZOSTER-003 in 
healthy subjects aged 60 years of age and older.
Sponsor signatory
(Amended 18 August 2017)
Lidia Oostvogels, Clinical and Epidemiology Project
Lead for Zoster, Belgian RDC
Signature
Date
 
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Protocol Amendment 1 Rationale
Amendment number:
Amendment 1
Rationale/background for changes:

This protocol amendment was developed to clarify in Section 8.2.1 that:

All SAEs will be collected and recorded from the time of the first receipt of 
study vaccine at Visit 2 until the subject is discharged from the study or until 
the end of the study;

All AEs/SAEs leading to withdrawal from the study will be collected and 
recorded from Visit 1 up to the last study visit at the end of the study;
and by aligning Table 4 and Table 15 with the text in Section 8.2.1.

Although no confirmed signals related to hypersensitivity reactions (including 
anaphylaxis) have been identified during the HZ/su clinical program, a mitigation 
strategy for the potential risk has been added to the Risk Assessment Section 1.3.1.

The list of the contributing authors was updated and minor typographic errors were 
corrected.
 
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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 (GSK) Biologicals.

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 Biologicals’ investigational vaccine and other study-related duties and 
functions as described in the protocol.

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 Biologicals and the express written informed 
consent of the subject and/or the subject’s legally acceptable representative.

To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).

To co-operate with a representative of GSK Biologicals in the monitoring process of 
the study and in resolution of queries about the data.

That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine, and more generally about his/her financial 
ties with the sponsor. GSK Biologicals will use and disclose the information solely 
for the purpose of complying with regulatory requirements.
Hence I:

Agree to supply GSK Biologicals with any necessary information regarding 
ownership interest and financial ties (including those of my spouse and dependent 
children).

Agree to promptly update this information if any relevant changes occur during the 
course of the study and for one year following completion of the study.

Agree that GSK Biologicals may disclose any information it has about such 
ownership interests and financial ties to regulatory authorities.

Agree to provide GSK Biologicals with an updated Curriculum Vitae and other 
documents required by regulatory agencies for this study.
 
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eTrack study number and 
Abbreviated Title
204926 (ZOSTER-060 EXT:003)
EudraCT number
2015-004400-30
Date of protocol amendment
Amendment 1 Final: 18 August 2017
Detailed Title
A phase IIIB, open, long term extension study to 
evaluate the persistence of immune responses and the 
safety of GSK Biologicals’ Herpes Zoster subunit 
(HZ/su) vaccine 1437173A, at Months 108 and 120 
post-vaccination and the assessment of re-vaccination 
with two additional doses administered at 10 years 
after the initial vaccination in study ZOSTER-003 in 
healthy subjects aged 60 years of age and older.
Investigator name
Signature
Date
 
ame, function and 
title
Signature
Date
 
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Sponsor Information
1.
Sponsor
GlaxoSmithKline Biologicals
Rue de l’Institut 89, 1330 Rixensart, Belgium
2.
Sponsor Medical Expert for the Study
Refer to the local study contact information document.
3.
Sponsor Study Monitor
Refer to the local study contact information document.
4.
Sponsor Study Contact for Reporting of a Serious Adverse Event
GSK Biologicals Central Back-up Study Contact for Reporting SAEs: refer to
protocol Section 8.3.2.
GSK Biologicals Central Safety Physician and Back-up Phone contact: refer to
protocol Section 8.3.2.
 
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SYNOPSIS
Detailed Title
A phase IIIB, open, long term extension study to evaluate the 
persistence of immune responses and the safety of GSK 
Biologicals’ Herpes Zoster subunit (HZ/su) vaccine 
1437173A, at Months 108 and 120 post-vaccination and the 
assessment of re-vaccination with two additional doses 
administered at 10 years after the initial vaccination in study 
ZOSTER-003 in healthy subjects aged 60 years of age and 
older.
Indication
Prevention of Herpes Zoster (HZ) and related complications 
in adults aged 50 years and older and in immunocompromised 
(IC) adults aged 18 years and older.
Rationale for the 
study and study 
design

Rationale for the study
GlaxoSmithKline (GSK) Biologicals’ candidate vaccine for 
the prevention of Herpes Zoster (HZ), HZ/su, a recombinant 
subunit (su) vaccine consisting of Varicella-Zoster virus 
(VZV) glycoprotein E (gE) as antigen and an adjuvant system 
(AS01), has been and is being evaluated in several studies in 
older adults and immunocompromised adults. In these studies 
it was shown to elicit strong cellular and humoral immune 
responses. Furthermore, the safety and reactogenicity profile 
of the candidate vaccine was acceptable. Based on phase II 
data from the antigen dose-ranging study, ZOSTER-003, and 
the adjuvant dose comparison study, ZOSTER-010, the 
formulation using gE antigen dose of 50 µg and the adjuvant 
system AS01B (HZ/su vaccine) was selected for the final 
vaccine and for use in all future studies. Henceforth, the final 
vaccine formulation will be referred to as HZ/su. The results 
of the previous studies in older adults demonstrated strong 
vaccine-induced immune responses following HZ/su 
administration at 0 and 2 months, supporting the selection of a 
2-dose vaccine schedule.
Two large pivotal Phase III trials (ZOSTER-006 enrolled 
subjects ≥ 50 YOA and ZOSTER-022 enrolled subjects ≥ 70 
YOA) are ongoing to evaluate the vaccine efficacy (VE) and 
safety of HZ/su vaccine. These trials have enrolled more than 
30,000 subjects who either received the HZ/su vaccine or 
placebo control vaccine on a 0, 2-month schedule. The final 
HZ/su vaccine efficacy results from the ZOSTER-006 Phase 
III trial demonstrated an overall vaccine efficacy against HZ 
of 97.2% [95% CI: 93.7-99.0], with no safety concerns raised.
Results received up to date from the ZOSTER-022 Phase III 
trial and from a prespecified pooled analysis over both studies 
confirmed these findings.
 
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In study ZOSTER-003, subjects were randomized into 5 
groups and were administered different formulations 
including the candidate HZ/su vaccine. These subjects were 
then followed at Month 12 (ZOSTER-011), Month 24 
(ZOSTER-012), and Month 36 (ZOSTER-013) for safety and 
immunogenicity of the different formulations. Study 
ZOSTER-024 followed all subjects who received 2 doses of 
the selected formulation (50µg gE/AS01B [HZ/su vaccine]) in 
study ZOSTER-003, at Months 48, 60 and 72. The results 
indicated that HZ/su-induced immune responses remained 
above baseline levels at Month 72. The current long-term 
follow-up (LTFU) study (ZOSTER-060) is planned to 
evaluate the persistence of immune response to the HZ 
vaccine as well as safety up to 10 years after the first dose of 
initial vaccination course. This study will also assess immune
responses after re-vaccination with 2 additional doses of the 
HZ/su administered at ten years after the initial vaccination 
course from study ZOSTER-003. If the immune responses 
wane over time, the increase in immunogenicity following 
revaccination with 2 additional doses of HZ/su vaccine could 
support the concept of administering additional doses with the 
expectation that this may translate into preserving VE.
Even though an immunologic threshold of protection has not 
been identified, these data may provide information that will 
help us evaluate the potential of HZ/su to provide long-term 
protection against HZ.

Rationale for the study design
In this LTFU study (ZOSTER-060), subjects who received 2 
doses of HZ/su in the earlier ZOSTER-003 study will be 
followed up at Month 108/Year 9 and Month 120/Year 10 
post first dose of vaccine for safety and immunogenicity.
In order to assess the effect of re-vaccination with 2 additional 
doses of HZ/su vaccine, all the subjects will receive 2 
additional doses of the HZ/su vaccine, on a 0, 2-month 
schedule at ten years after the initial vaccination course in 
study ZOSTER-003.
In alignment with the previous persistence studies, this study 
has no control group.
Blood samples for the evaluation of persistence of humoral 
and cellular immunogenicity as well immunogenicity after re-
vaccination will be taken from all subjects who participate in 
the study.
 
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Objectives
Primary

To evaluate persistence of humoral and cell mediated 
immune responses overall at Months 108 and 120 post 
first dose of initial vaccination course in study ZOSTER-
003.
Secondary
For the persistence phase Months 108 and 120 post first dose 
of initial vaccination in study ZOSTER-003:

To evaluate the persistence of humoral and cell mediated 
immune responses within each age cohort (60-69 YOA 
and ≥70 YOA at the time of the initial vaccination) at 
Months 108 and 120 post first dose of initial vaccination 
course.

To evaluate the safety of the study vaccine from Months 
108 to Months 120 post first dose of initial vaccination 
course.
For the re-vaccination phase:

To evaluate humoral and cell mediated immune responses 
to a two dose re-vaccination course at one month after 
each dose (Months 121 and 123) and 12 months after last 
dose (Month 134) when administered 10 years after the 
initial vaccination course.

To evaluate the reactogenicity and safety of the study 
vaccine after re-vaccination with two additional doses.
Study design

Experimental design: Phase IIIB, open-label, multi-
centric, single group.

Duration of the study: The intended duration of the study 
per subject is approximately 26 months.

Epoch 001: Long-term follow-up starting at Visit 1 
(Month 108, Year 9) and ending at Visit 6 (Month 
134).

Study group: Subjects vaccinated with 2 doses of HZ/su
(group 50µg gE/AS01B) in study ZOSTER-003 will be 
offered participation in this study.
Synopsis Table 1
Study groups and epochs foreseen in the study
Study Groups
Number of 
subjects
Epochs
Epoch 001
50µg gE/AS01B
~100
x
 
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Synopsis Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
HZ/su
VZV gE
50µg gE/AS01B
AS01B

Control: uncontrolled.

Vaccination schedule: Visit 2 (Month 120) and Visit 4 
(Month 122) in the re-vaccination phase.

Treatment allocation: All subjects will receive HZ/su and 
will be assigned to the two age cohorts (60-69 years of 
age [YOA] and ≥ 70 YOA at the time of vaccination) as 
defined in the ZOSTER-003 study.

Blinding: Open-label.
Synopsis Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
Open-label

Sampling schedule: Blood samples for immunogenicity 
evaluation will be collected at the following study visits:

Visit 1 (Month 108/Year 9), Visit 2 (Month 120/Year 
10), Visit 3 (Month 121/ one month after re-
vaccination dose 1), Visit 5 (Month 123/ one month 
after re-vaccination dose 2) and Visit 6 (Month 134/ 12 
months after re-vaccination dose 2).

Type of study: extension of other protocols, i.e., ZOSTER-
003.

Data collection: Electronic Case Report Form (eCRF).
Number of subjects
Subjects who were vaccinated with 2 doses of HZ/su during 
study ZOSTER-003 will be offered enrolment into this LTFU 
study.
 
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Endpoints
Primary

Antigen-specific antibody (Ab) concentrations at Months 
108 and 120 post first dose of initial vaccination course in 
study ZOSTER-003.

Anti-gE Ab concentrations as determined by ELISA at 
Months 108 and 120.

Cell-Mediated Immunity (CMI) in terms of frequencies of 
antigen-specific CD4 T-cells at Months 108 and 120 post
first dose of initial vaccination course in study ZOSTER-
003.

Frequencies of CD4+ T cells with antigen-specific 
Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) 
and/or Tumour Necrosis Factor alpha (TNF-α) and/or 
CD40 Ligand (CD40L) secretion/expression to gE as 
determined by Intracellular Cytokine Staining (ICS) at 
Months 108 and 120.
Secondary
For the follow-up of persistence phase Months 108 and 120 
post first dose of initial vaccination course in study ZOSTER-
003:

Antigen-specific antibody (Ab) concentrations within each 
age cohort (60-69 YOA and ≥70 YOA at the time of initial 
vaccination) at persistence Months 108 and 120.

Anti-gE Ab concentrations as determined by ELISA at 
Months 108 and 120.

Cell-Mediated Immunity (CMI) in terms of frequencies of 
antigen-specific CD4 T-cells within each age cohort (60-69 
YOA and ≥70 YOA at the time of initial vaccination) at 
persistence Months 108 and 120 post first dose of initial 
vaccination course.

Frequencies of CD4+ T cells with antigen-specific 
Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) 
and/or Tumour Necrosis Factor alpha (TNF-α) and/or 
CD40 Ligand (CD40L) secretion/expression to gE as 
determined by Intracellular Cytokine Staining (ICS) at 
Months 108 and 120.

Serious Adverse events:

Occurrence of all serious adverse events (SAEs) 
related to study participation or to a concurrent GSK 
medication/vaccine (including HZ/su administered 
during the ZOSTER-003 study) between Months 108 
and 120.
 
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For the re-vaccination phase:

Antigen-specific antibody (Ab) concentrations post re-
vaccination.

Anti-gE antibody concentrations as determined by 
ELISA in all subjects at one month after each vaccine 
dose (Months 121 and 123) and 12 months after last
dose (Month 134).

Cell-Mediated Immunity (CMI) in terms of frequencies of 
antigen-specific CD4 T- cells at one month after each 
vaccine dose (Months 121 and 123) and 12 months after 
last dose (Month 134).

Frequencies of CD4+ T cells with antigen-specific 
Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) 
and/or Tumour Necrosis Factor alpha (TNF-α) and/or 
CD40 Ligand (CD40L) secretion/expression to gE as 
determined by Intracellular Cytokine Staining (ICS) at 
Months 121, 123 and 134.

Solicited local and general symptoms:

Occurrence and intensity of each solicited local 
symptom within 7 days (Days 0-6) after each 
vaccination in all subjects;

Occurrence, intensity and relationship to vaccination 
of each solicited general symptom within 7 days (Days 
0-6) after each vaccination, in all subjects;

Unsolicited adverse events (AEs)

Occurrence, intensity and relationship to vaccination 
of unsolicited Aes during 30 days (Days 0-29) after 
each vaccination, according to the Medical Dictionary 
for Regulatory Activities (MedDRA) classification in 
all subjects

SAEs

Occurrence and relationship to vaccination of all SAEs 
from dose 1 of re-vaccination until study end.

Occurrence of any fatal SAEs from dose 1 of re-
vaccination until study end.

Potential immune-mediated diseases (pIMDs)

Occurrence and relationship to vaccination of any 
pIMDs from dose 1 of re-vaccination until study end in 
all subjects.
 
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TABLE OF CONTENTS
PAGE
SPONSOR INFORMATION ............................................................................................7
SYNOPSIS......................................................................................................................8
LIST OF ABBREVIATIONS...........................................................................................21
GLOSSARY OF TERMS ...............................................................................................23
TRADEMARKS .............................................................................................................26
1.
INTRODUCTION....................................................................................................27
1.1.
Background ................................................................................................27
1.2.
Rationale for the study and study design ....................................................28
1.2.1.
Rationale for the study.................................................................28
1.2.2.
Rationale for the study design......................................................29
1.3.
Benefit : Risk Assessment ..........................................................................29
1.3.1.
Risk Assessment (Amended 18 August 2017) .............................30
1.3.2.
Benefit Assessment.....................................................................31
1.3.3.
Overall Benefit: Risk Conclusion..................................................31
2.
OBJECTIVES.........................................................................................................31
2.1.
Primary objective ........................................................................................31
2.2.
Secondary objectives..................................................................................31
3.
STUDY DESIGN OVERVIEW ................................................................................32
4.
STUDY COHORT...................................................................................................34
4.1.
Number of subjects/centres ........................................................................34
4.2.
Inclusion criteria for enrolment....................................................................34
4.3.
Exclusion criteria for enrolment...................................................................35
5.
CONDUCT OF THE STUDY ..................................................................................36
5.1.
Regulatory and ethical considerations, including the informed 
consent process..........................................................................................36
5.2.
Subject identification and randomisation of treatment .................................37
5.2.1.
Treatment allocation ....................................................................37
5.3.
Method of blinding ......................................................................................37
5.4.
General study aspects ................................................................................37
5.4.1.
Data collection .............................................................................37
5.5.
Outline of study procedures ........................................................................39
5.6.
Detailed description of study procedures ....................................................40
5.6.1.
Informed consent.........................................................................40
5.6.2.
Check inclusion and exclusion criteria .........................................41
5.6.3.
Collect demographic data ............................................................41
5.6.4.
Medical history.............................................................................41
5.6.5.
History directed physical examination..........................................42
5.6.6.
Check contraindications, warnings and precautions to 
vaccination...................................................................................42
 
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5.6.7.
Assess pre-vaccination body temperature ...................................42
5.6.8.
Training on self-reporting by subjects ..........................................43
5.6.8.1.
Reminder for follow-up contacts between Visit 
5 and Visit 6 ...............................................................43
5.6.9.
Sampling......................................................................................43
5.6.9.1.
Blood sampling for safety or immune response 
assessments ..............................................................43
5.6.10.
Study Vaccine administration.......................................................44
5.6.11.
Check and record concomitant medication/vaccination and 
intercurrent medical conditions ....................................................44
5.6.12.
Recording of AEs, SAEs and pIMDs............................................44
5.6.13.
Study conclusion..........................................................................45
5.7.
Biological sample handling and analysis.....................................................45
5.7.1.
Use of specified study materials ..................................................46
5.7.2.
Biological samples.......................................................................46
5.7.3.
Laboratory assays .......................................................................46
5.7.4.
Biological samples evaluation......................................................47
5.7.4.1.
Immunological read-outs ............................................47
5.7.5.
Immunological correlates of protection.........................................47
6.
STUDY VACCINE AND ADMINISTRATION...........................................................48
6.1.
Description of study vaccine .......................................................................48
6.2.
Storage and handling of study vaccine .......................................................48
6.3.
Dosage and administration of study vaccine...............................................49
6.4.
Replacement of unusable vaccine doses....................................................49
6.5.
Contraindications to subsequent vaccination ..............................................49
6.6.
Concomitant medications/products and concomitant vaccinations..............51
6.6.1.
Recording of concomitant medications/products and 
concomitant vaccinations.............................................................51
6.6.2.
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from ATP analyses........................52
6.7.
Intercurrent medical conditions that may lead to elimination of a 
subject from ATP analyses .........................................................................52
7.
HEALTH ECONOMICS ..........................................................................................52
8.
SAFETY.................................................................................................................53
8.1.
Safety definitions ........................................................................................53
8.1.1.
Definition of an adverse event......................................................53
8.1.2.
Definition of a serious adverse event ...........................................54
8.1.3.
Solicited adverse events..............................................................55
8.1.3.1.
Solicited local (injection-site) adverse events..............55
8.1.3.2.
Solicited general adverse events................................55
8.1.4.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................55
8.1.5.
Adverse events of specific interest...............................................56
8.1.5.1.
Potential immune-mediated diseases .........................56
8.2.
Detecting and recording adverse events and serious adverse 
events.........................................................................................................58
8.2.1.
Time period for detecting and recording adverse events 
and serious adverse events (Amended 18 August 2017).............58
 
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8.2.2.
Post-Study adverse events and serious adverse events..............61
8.2.3.
Evaluation of adverse events and serious adverse events...........61
8.2.3.1.
Active questioning to detect adverse events 
and serious adverse events........................................61
8.2.3.2.
Assessment of adverse events...................................62
8.2.3.2.1.
Assessment of intensity..........................62
8.2.3.2.2.
Assessment of causality .........................63
8.2.3.3.
Assessment of outcomes............................................64
8.3.
Reporting of serious adverse events and other events................................65
8.3.1.
Prompt reporting of serious adverse events and other 
events to GSK Biologicals............................................................65
8.3.2.
Contact information for reporting serious adverse events 
and pIMDs ...................................................................................65
8.3.3.
Completion and transmission of SAE reports to GSK 
Biologicals ...................................................................................66
8.3.3.1.
Back-up system in case the electronic 
reporting system does not work..................................66
8.3.4.
Reporting of pIMDs to GSK Biologicals........................................66
8.3.5.
Updating of SAE and pIMD information after removal of 
write access to the subject’s eCRF ..............................................67
8.3.6.
Regulatory reporting requirements for serious adverse 
events..........................................................................................67
8.4.
Follow-up of adverse events and serious adverse events...........................67
8.4.1.
Follow-up of adverse events and serious adverse events............67
8.4.1.1.
Follow-up during the study..........................................67
8.4.1.2.
Follow-up after the subject is discharged from 
the study.....................................................................68
8.5.
Treatment of adverse events ......................................................................68
8.6.
Subject card................................................................................................68
9.
SUBJECT COMPLETION AND WITHDRAWAL.....................................................69
9.1.
Subject completion .....................................................................................69
9.2.
Subject withdrawal......................................................................................69
9.2.1.
Subject withdrawal from the study ...............................................69
9.2.2.
Subject withdrawal from investigational vaccine...........................70
10. STATISTICAL METHODS......................................................................................70
10.1.
Primary endpoints.......................................................................................70
10.2.
Secondary endpoints ..................................................................................70
10.3.
Determination of sample size......................................................................72
10.4.
Cohorts for Analyses ..................................................................................72
10.4.1.
Total enrolled cohort....................................................................72
10.4.2.
ATP cohort for analysis of persistence (LTFU).............................72
10.4.3.
Total Vaccinated cohort for re-vaccination phase.........................72
10.4.3.1.
According-to-protocol (ATP) cohort for analysis 
of immunogenicity ......................................................73
10.5.
Derived and transformed data.....................................................................73
10.5.1.
Handling of missing data..............................................................73
10.5.2.
Humoral immune response..........................................................74
10.5.3.
CMI response ..............................................................................74
10.6.
Analysis of demographics...........................................................................75
10.7.
Analysis of immunogenicity.........................................................................76
 
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10.7.1.
Assessment of follow-up of persistence phase Months 108 
and 120 post first dose of initial vaccination course. ....................76
10.7.2.
Assessment of re-vaccination phase............................................77
10.7.3.
Assessment of persistence (Post re-vaccination).........................78
10.8.
Analysis of safety........................................................................................79
10.8.1.
Persistence phase .......................................................................79
10.8.2.
Re-vaccination phase ..................................................................80
10.9.
Interpretation of analyses............................................................................81
10.10. Conduct of analyses ...................................................................................81
10.10.1. Sequence of analyses..................................................................81
10.10.2. Statistical considerations for interim analyses..............................81
11. ADMINISTRATIVE MATTERS ...............................................................................81
11.1.
electronic Case Report Form instructions ...................................................81
11.2.
Study Monitoring by GSK Biologicals..........................................................82
11.3.
Record retention .........................................................................................83
11.4.
Quality assurance.......................................................................................83
11.5.
Posting of information on publicly available clinical trial registers and 
publication policy ........................................................................................83
11.6.
Provision of study results to investigators ...................................................84
12. COUNTRY SPECIFIC REQUIREMENTS...............................................................84
12.1.
Requirements for Germany.........................................................................84
13. REFERENCES.......................................................................................................85
 
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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study.....................................33
Table 2
Study groups and treatment foreseen in the study .................................33
Table 3
Blinding of study epochs ........................................................................33
Table 4
List of study procedures .........................................................................39
Table 5
Intervals between study visits.................................................................40
Table 6
Biological samples .................................................................................46
Table 7
Humoral Immunity (Antibody determination)...........................................46
Table 8
Cell-Mediated Immunity (CMI)................................................................47
Table 9
Immunological read-outs........................................................................47
Table 10
Study vaccine.........................................................................................48
Table 11
Dosage and administration.....................................................................49
Table 12
Solicited local adverse events ................................................................55
Table 13
Solicited general adverse events............................................................55
Table 14
List of potential immune-mediated diseases...........................................57
Table 15
Reporting periods for collecting safety information .................................60
Table 16
Intensity scales for solicited symptoms in adults.....................................62
Table 17
Timeframes for submitting serious adverse event and other 
events reports to GSK Biologicals ..........................................................65
Table 18
GSK Biologicals’ laboratories .................................................................88
Table 19
Outsourced laboratories.........................................................................88
 
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LIST OF FIGURES
PAGE
Figure 1
Study design overview ...........................................................................32
 
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LIST OF APPENDICES
PAGE
APPENDIX A LABORATORY ASSAYS .......................................................................87
APPENDIX B CLINICAL LABORATORIES ..................................................................88
APPENDIX C AMENDMENTS AND ADMINISTRATIVE CHANGES TO THE 
PROTOCOL...........................................................................................89
 
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LIST OF ABBREVIATIONS
Ab:
Antibody
AE:
Adverse Event
AIC:
Akaike’s Information Criterion
AS01B:
MPL, QS21 Stimulon®, liposome based Adjuvant 
System [50g MPL and 50g QS21]
ATP:
According-To-Protocol
CD40L:
CD40 Ligand
CDC:
Centers for Disease Control
CMI:
Cell-Mediated Immunity
eCRF:
electronic Case Report Form
ELISA:
Enzyme-Linked Immunosorbent Assay
FDA:
Food and Drug Administration, United States of America
GCP:
Good Clinical Practice
gE:
Glycoprotein E
GMC:
Geometric Mean Concentration
GSK:
GlaxoSmithKline
HZ:
Herpes Zoster
IB:
Investigator Brochure
ICF:
Informed Consent Form
ICH:
International Conference on Harmonisation
IEC:
Independent Ethics Committee
IFN-:
Interferon gamma
IL-2:
Interleukin- 2
IMC:
Intercurent Medical Condition
IMP:
Investigational Medicinal Product
 
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IRB:
Institutional Review Board
LSLV:
Last Subject Last Visit
LTFU:
Long-Term Follow-up
MedDRA:
Medical Dictionary for Regulatory Activities
mIU:
Milli International Unit
MPL:
3-O-desacyl-4’-Monophosphoryl Lipid A
PBMC:
Peripheral Blood Mononuclear Cells
PHN:
Postherpetic Neuralgia
pIMD:
Potential Immune-Mediated Disease
RDC:
Research and Development Centre
QS21:
(Amended 18 August
2017)
Quillaja saponaria Molina, fraction 21 (Licensed by 
GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., Lexington, MA, USA)
SAE:
Serious Adverse Event
SBIC:
Schwarz’ Bayesian Information Criterion
SBIR:
Randomisation System on Internet
SDV:
Source Document Verification
SPM:
Study Procedures Manual
su:
Subunit
TNF-:
Tumor Necrosis Factor alpha
VZV:
Varicella-Zoster virus
YOA:
Years of Age
 
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GLOSSARY OF TERMS
Adverse event:
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product. 
An adverse event (AE) can therefore be any unfavourable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse.
Blinding:
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. In an 
open-label study, no blind is used. Both the investigator 
and the subject know the identity of the treatment 
assigned. 
Eligible:
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria.
Epoch:
An epoch is a self-contained set of consecutive 
timepoints or a single timepoint from a single protocol. 
Self-contained means that data collected for all subjects 
at all timepoints within that epoch allows to draw a 
complete conclusion to define or precise the targeted 
label of the product. Typical examples of epochs are 
primary vaccinations, boosters, yearly immunogenicity 
follow-ups, and surveillance periods for efficacy or 
safety.
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 according-to-protocol (ATP) analysis (see 
Sections 6.6.2 and 10.4 for details on criteria for 
evaluability).
 
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Immunological correlate 
of protection:
The defined immune response above which there is a high 
likelihood of protection in the absence of any host factors 
that might increase susceptibility to the infectious agent.
Intercurrent Medical 
Condition:
It is defined as a condition with onset during the study 
period that has the capability of confounding the immune 
response to the study vaccine or its interpretation. 
Examples of IMCs include a confirmed or suspected 
immunosuppressive or immunodeficient condition 
resulting from disease (e.g., HIV infection, malignancy), 
occurrence of a suspected case of HZ during this study 
will be considered an intercurrent medical condition 
(IMC).
Investigational 
vaccine/product:
(Synonym of 
Investigational Medicinal 
Product)
A pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in a clinical trial, 
including a product with a marketing authorisation when 
used in a way different from the approved form, or when 
used for an unapproved indication, or when used to gain 
further information about an approved use. 
Potential Immune-
Mediated Disease:
Potential immune-mediated diseases (pIMDs) are a subset 
of AEs that include autoimmune diseases and other 
inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology.
Primary completion 
date:
The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for the primary outcome, whether the clinical trial 
concluded according to the pre-specified protocol or was 
terminated.
Protocol amendment:
The International Conference on Harmonisation (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK Biologicals further details this to include a change 
to an approved protocol that affects the safety of subjects, 
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 treatment to subjects in 
order to reduce bias of selection.
 
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Site Monitor:
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites.
Solicited adverse event:
AEs to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively 
solicited from the subject or an observer during a 
specified post-vaccination follow-up period.
Subject:
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the vaccine or as a control.
Subject number:
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study.
Treatment:
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject, 
identified by a unique number, according to the study 
randomisation or treatment allocation.
Treatment number:
A number identifying a treatment to a subject, according 
to the study randomisation or treatment allocation.
Unsolicited adverse 
event:
Any AE reported in addition to those solicited during the 
clinical study. Also any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event.
 
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TRADEMARKS
The following trademarks are used in the present protocol.
Note: In the body of the protocol (including the synopsis), the names of the 
vaccines/products and/or medications will be written without the superscript symbol ™ 
or ® and in italics.
Trademarks not owned by the 
GlaxoSmithKline group of companies
Generic description
QS-21
(Amended 18 August 2017)
(Quillaja saponaria Molina, fraction 21) 
(Licensed by GSK from Antigenics Inc, a 
wholly owned subsidiary of Agenus Inc., 
Lexington, MA, USA).
 
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1.
INTRODUCTION
1.1.
Background
Varicella-zoster Virus (VZV) causes two distinct diseases. Varicella (chickenpox) occurs 
shortly after primary VZV infection and is characterised by systemic illness and a widely 
disseminated rash. Herpes zoster (HZ), commonly called shingles, occurs when VZV 
reactivates from latency and typically manifests as a localised, dermatomal rash.
The typical HZ rash usually lasts 2 to 4 weeks and is typically accompanied by pain that 
is often described as burning, shooting, or stabbing. In some patients, even touching the 
affected area lightly may cause pain, a phenomenon known as allodynia. This HZ-
associated pain may be severe, and pruritus, which can also be severe, may be as 
common as pain.
The most common complication of HZ is postherpetic neuralgia (PHN). PHN is defined 
as pain that persists after the resolution of the HZ rash. Affected patients typically report 
constant burning, throbbing, intermittent sharp or electric shock-like pain, or allodynia 
[Dworkin, 2007]. Other complications of HZ include ophthalmologic, neurological, 
cutaneous and visceral disease, which can result in severe disability. The most common 
ocular complications of HZ are keratitis and uveitis; other ophthalmologic complications 
include ptosis, episcleritis/scleritis, retinitis, secondary glaucoma and cataract [Schmader, 
2008; Carter, 2008]. Neurologic complications associated with HZ include myelitis, 
motor neuropathy, ischaemic infarction of the brain and spinal cord, aneurysm, and 
subarachnoid and cerebral haemorrhage [Gilden, 2009; Schmader, 2008].
Age is the most common risk factor for developing HZ. The incidence of HZ is relatively 
constant at 2-3 cases per 1000 persons per year until age 40, and then increases 
progressively with age: at 50-59 years of age (YOA) the incidence is about 5 cases per 
1000 persons per year, and it increases to 10 cases per 1000 persons per year in people ≥
60 YOA [CDC, 2008; Oxman, 2005]. While most HZ incidence data come from the 
e United States (US) and Europe, available data indicate similar incidences of HZ in 
other parts of the world including Japan, Korea, Australia and Latin America [Araújo, 
2007; Garcia Cenoz, 2008; Kang, 2008; Toyama, 2009].
Half of all HZ cases occur in patients over the age of 60, and individuals who reach 85 
years old have a 50% chance of having HZ during their lifetime [Oxman, 2005]. Patients 
with impaired cell-mediated immunity (CMI) due to disease, drug treatment, medical 
interventions or advanced age are at increased risk for the development of HZ [Cohen, 
2007]. Since the loss of VZV-specific T cell responses as a result of aging or 
immunosuppression leads to heightened susceptibility to HZ, vaccination is considered as 
a means to reduce the risk of HZ in older adults and immunocompromised persons 
[Oxman, 2005; Sperber, 1992].
GlaxoSmithKline (GSK) Biologicals’ candidate vaccine for the prevention of HZ, HZ/su, 
a recombinant subunit (su) vaccine consisting of VZV glycoprotein E (gE) as antigen and 
an adjuvant system (AS01), has been and is being evaluated in several studies in older
adults and immunocompromised adults. In these studies it was shown to elicit strong 
 
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cellular and humoral immune responses. Furthermore, the safety and reactogenicity 
profile of the candidate vaccine was acceptable. Based on phase II data from the antigen 
dose-ranging study, ZOSTER-003, and the adjuvant dose comparison study, ZOSTER-
010, the formulation using gE antigen dose of 50 g and the adjuvant system AS01B 
(HZ/su vaccine) was selected for the final vaccine and for use in all future studies.
Henceforth, the final vaccine formulation will be referred to as HZ/su. The results of the 
previous studies in older adults demonstrated strong vaccine-induced immune responses 
following HZ/su administration at 0 and 2 months, supporting the selection of a 2-dose 
vaccine schedule.
Two large pivotal Phase III trials (ZOSTER-006 enrolled subjects ≥ 50 YOA and 
ZOSTER-022 enrolled subjects ≥ 70 YOA) are ongoing to evaluate the vaccine efficacy 
(VE) and safety of HZ/su vaccine. These trials have enrolled more than 30,000 subjects 
who either received the HZ/su vaccine or placebo control vaccine on a 0, 2-month 
schedule. The final HZ/su vaccine efficacy results from the ZOSTER-006 Phase III trial 
demonstrated an overall vaccine efficacy against HZ of 97.2% [95% CI: 93.7-99.0], with 
no safety concerns raised [Lal, 2015]. Results received up to date from the ZOSTER-022 
Phase III trial and from a prespecified pooled analysis over both studies confirmed these 
findings.
Please refer to the current Investigator Brochure for information regarding the pre-
clinical and clinical studies of HZ/su vaccine.
1.2.
Rationale for the study and study design
1.2.1.
Rationale for the study
In study ZOSTER-003, subjects were randomized into 5 groups and were administered 
different formulations including the candidate HZ/su vaccine. These subjects were then 
followed at Month 12 (ZOSTER-011), Month 24 (ZOSTER-012), and Month 36 
(ZOSTER-013) for safety and immunogenicity of the different formulations. Study 
ZOSTER-024 followed all subjects who received 2 doses of the selected formulation 
(50µg gE/AS01B [HZ/su vaccine]) in study ZOSTER-003, at Months 48, 60 and 72. The 
results indicated that HZ/su-induced immune responses remained above baseline levels at 
Month 72. The current long-term follow-up (LTFU) study (ZOSTER-060) is planned to 
evaluate the persistence of immune response to the HZ vaccine as well as safety up to 10 
years after the first dose of initial vaccination course. This study will also assess immune 
responses after re-vaccination with 2 additional doses of the HZ/su administered at ten 
years after the initial vaccination course from study ZOSTER-003. If the immune 
responses wane over time, the increase in immunogenicity following revaccination with 2 
additional doses of HZ/su vaccine could support the concept of administering additional 
doses with the expectation that this may translate into preserving VE.
Even though an immunologic threshold of protection has not been identified, these data 
may provide information that will help us to evaluate the potential of HZ/su to provide 
long-term protection against HZ.
 
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1.2.2.
Rationale for the study design
In this LTFU study (ZOSTER-060), subjects who received 2 doses of HZ/su in the earlier 
ZOSTER-003 study will be followed up at Month 108/Year 9 and Month 120/Year 10 
post first dose of vaccine for safety and immunogenicity. 
In order to assess the effect of re-vaccination with 2 additional doses of HZ/su vaccine, 
all the subjects will receive 2 additional doses of the HZ/su vaccine, on a 0, 2-month 
schedule at ten years after the initial vaccination course in study ZOSTER-003.
In alignment with the previous persistence studies, this study has no control group.
Blood samples for the evaluation of persistence of humoral and cellular immunogenicity 
as well immunogenicity after re-vaccination will be taken from all subjects who 
participate in the study.
1.3.
Benefit : Risk Assessment
Please refer to the current Investigator Brochure for the summary of potential risks and 
benefits of HZ/su vaccine.
The following section outlines the risk assessment and mitigation strategy for this study 
protocol:
 
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1.3.1.
Risk Assessment (Amended 18 August 2017)
Important 
Potential/Identified Risk
Data/Rationale for Risk
Mitigation Strategy
Investigational HZ/su vaccine
Risk of pIMD following the 
HZ/su vaccination.
No confirmed signals related to 
this potential risk have been 
identified during the clinical 
program. Available clinical data do 
not highlight any concern.
Close monitoring of pIMDs as per 
study protocol.
The potential risk of events of 
possible autoimmune aetiology to 
occur is mentioned in the ICF. In 
addition, the ICF advises subjects 
to contact the study doctor or the 
study staff immediately, should 
they get any symptoms that they 
feel maybe serious.
Hypersensitivity reactions 
(including anaphylaxis)
No confirmed signals related to 
this potential risk have been 
identified during the clinical 
program. Available clinical data 
do not highlight any concern.
Administration of the study 
vaccination is to be preceded 
by a review of the subjects’ 
medical history (especially with 
regard to previous vaccination 
and possible occurrence of 
undesirable events) and a 
clinical examination.
As with all injectable vaccines, 
appropriate medical treatment 
and supervision should always 
be readily available in case of 
an anaphylactic event following 
the administration of the 
vaccine.
Study procedures (LTFU study)
Risk of blood sampling
Blood sampling associated risk of 
syncope, dizziness, infection at 
the site after or during 
venipuncture
Blood samples will be obtained 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 subject’s 
health.
 
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1.3.2.
Benefit Assessment
Benefits include:

Potential benefit of receiving the study vaccine that may provide a clinical benefit in 
reducing the risk of developing HZ.

Medical evaluations/assessments associated with study procedures (e.g. physical 
examination).
1.3.3.
Overall Benefit: Risk Conclusion
Taking into account the measures to minimize risk to subjects participating in this study, 
the potential or recognized risks identified in association with the investigational HZ/su 
vaccine and the study procedures are offset by the potential benefits (prevention of HZ 
and related complications) that may be afforded to the subject(s).
2.
OBJECTIVES
2.1.
Primary objective

To evaluate persistence of humoral and cell mediated immune responses overall at 
Months 108 and 120 post first dose of initial vaccination course in study ZOSTER-
003.
Refer to Section 10.1 for the definition of the primary endpoints.
2.2.
Secondary objectives
For the persistence phase Months 108 and 120 post first dose of initial vaccination in 
study ZOSTER-003:

To evaluate the persistence of humoral and cell mediated immune responses within 
each age cohort (60-69 YOA and ≥70 YOA at the time of the initial vaccination) at 
Months 108 and 120 post first dose of initial vaccination course.

To evaluate the safety of the study vaccine from Months 108 to Months 120 post first 
dose of initial vaccination course.
For the re-vaccination phase:

To evaluate humoral and cell mediated immune responses to a two dose re-
vaccination course at one month after each dose (Months 121 and 123) and 12 
months after last dose (Month 134) when administered 10 years after the initial 
vaccination course.

To evaluate the reactogenicity and safety of the study vaccine after re-vaccination 
with two additional doses.
Refer to Section 10.2 for the definition of the secondary endpoints.
 
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3.
STUDY DESIGN OVERVIEW
Figure 1
Study design overview
* Visits only performed by initial 104 subjects enrolled in Germany
** In ZOSTER-003, subjects received vaccination at Month 0 and Month 2. Months 48, 60, 72, 108 and 120 are respectively 48, 60, 72, 108 and 120 after first dose of vaccination.
# Months 120, 121, 122, 123 and 134 correspond to Month 0, 1, 2, 3 and 14 of the re-vaccination course.
§ N is the number of subjects that were planned to be enrolled in ZOSTER-003
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Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the outline of study procedures (Section 5.5), are essential and required for 
study conduct. 

Experimental design: Phase IIIB, open-label, multi-centric, single group.

Duration of the study: The intended duration of the study per subject is 
approximately 26 months.

Epoch 001: Long-term follow-up starting at Visit 1 (Month 108, Year 9) and 
ending at Visit 6 (Month 134).

Study group: Subjects vaccinated with 2 doses of HZ/su (group 50µg gE/AS01B) in 
study ZOSTER-003 will be offered participation in this study.
Table 1
Study groups and epochs foreseen in the study
Study Groups
Number of 
subjects
Epochs
Epoch 001
50µg gE/AS01B
~100
x
Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product 
name
Study Groups
HZ/su
VZV gE
50µg gE/AS01B
AS01B

Control: Uncontrolled.

Vaccination schedule: Visit 2 (Month 120) and Visit 4 (Month 122) in the re-
vaccination phase.

Treatment allocation: All subjects will receive HZ/su and will be assigned to the two 
age cohorts (60-69 years of age [YOA] and ≥ 70 YOA at the time of the initial
vaccination) as defined in the ZOSTER-003 study.

Blinding: Open-label.
Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
Open-label

Sampling schedule: Blood samples for immunogenicity evaluation will be collected 
at the following study visits:

Visit 1 (Month 108/Year 9), Visit 2 (Month 120/Year 10), Visit 3 (Month 121/ 
one month after re-vaccination dose 1), Visit 5 (Month 123/ one month after re-
vaccination dose 2) and Visit 6 (Month 134/ 12 months after re-vaccination dose 
2).

Type of study: extension of other protocols, i.e., ZOSTER-003.

Data collection: Electronic Case Report Form (eCRF).
 
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4.
STUDY COHORT
4.1.
Number of subjects/centres
Subjects who participated in study ZOSTER-003, in group 50 µg gE / AS01B, and had 
complete vaccination vaccination course (2 doses of HZ/su) in study ZOSTER-003 will 
be offered enrolment into this LTFU study.
All subjects willing to participate in the ZOSTER-060 study will be enrolled and 
assigned to the two age cohorts (60-69 years of age [YOA] and ≥ 70 YOA at the time of 
the initial vaccination) as defined in the ZOSTER-003 study. Refer to Sections 4.1 and 
4.3 for inclusion/exclusion criteria, respectively.
Overview of the recruitment plan 
The study will include subjects in multiple centres in selected countries that previously 
participated in study ZOSTER-003.
At the time of initiation of the long-term follow-up study, the investigator will contact 
those subjects from his site who completed the study ZOSTER-003, were vaccinated with 
HZ/su and for whom he/she believes the subject can be eligible for and interested in 
participation in the ZOSTER-060 study. The reason for non-participation in the long-term 
follow-up study will be documented in the site’s screening log.
4.2.
Inclusion criteria for enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
All subjects must satisfy ALL the following criteria at study entry:

Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g., completion of the diary cards, return for follow-up 
visits, ability to have scheduled contacts to allow evaluation during the study). Or 
subjects with a caregiver who, in the opinion of the investigator, can and will comply 
with the requirements of the protocol (e.g., completion of the diary cards, 
vaccination visits, availability for follow-up contacts).

Written informed consent obtained from the subject prior to performance of any 
study specific procedure.

Previous participation in study ZOSTER-003, in group 50 µg gE / AS01B, and who
completed vaccination course (2 doses of HZ/su) in study ZOSTER-003.

Subjects who can complete Visit 1 between 108 and 111 months after the first HZ/su
dose of the previous vaccination course in study ZOSTER-003.
 
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4.3.
Exclusion criteria for enrolment
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential.
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study:

Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine during the period starting 30 days before the first study visit (Day -29 
to Day 0), or planned use during the study period.

Use or anticipated use of immunosuppressants or immune-modifying drugs during 
the period starting six months prior to study start and during the whole study period. 
This includes chronic administration of corticosteroids (>14 consecutive days of 
prednisone at a dose of ≥20 mg/day [or equivalent]), long-acting immune-modifying 
agents (e.g., infliximab) or immunosuppressive/cytotoxic therapy (e.g., medications 
used during cancer chemotherapy, organ transplantation or to treat autoimmune 
disorders).

Any confirmed or suspected immunosuppressive or immunodeficient condition 
resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] 
infection).

Administration or planned administration of a live vaccine in the period starting 30 
days before the first dose of study vaccine and ending 30 days after the last dose of 
study vaccine, or, administration or planned administration of a non-replicating 
vaccine* within 8 days prior to or within 14 days after either dose of study vaccine.
E.g., inactivated and subunit vaccines, including inactivated and subunit influenza 
vaccines and pneumococcal conjugate vaccines.

Previous vaccination against HZ since initial vaccination in ZOSTER-003.

Administration of immunoglobulins and/or any blood products during the period 
starting 3 months before study start, or planned administration during the study 
period.

History of previous HZ.
 
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5.
CONDUCT OF THE STUDY
5.1.
Regulatory and ethical considerations, including the 
informed consent process
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with the ICH Guideline for Good Clinical 
Practice (GCP), all applicable subject privacy requirements and the guiding principles of 
the Declaration of Helsinki. 
GSK will obtain favourable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country.
Conduct of the study includes, but is not limited to, the following:

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments.

Subject informed consent and subject informed assent, as appropriate.

Investigator reporting requirements as stated in the protocol.
GSK will provide full details of the above procedures to the investigator, either verbally, 
in writing, or both.
Freely given and written or witnessed/ thumb printed informed consent must be obtained 
from each subject prior to participation in the study. 
GSK Biologicals will prepare a model Informed Consent Form (ICF) which will embody 
the ICH GCP and GSK Biologicals required elements. While it is strongly recommended 
that this model ICF is to be followed as closely as possible, the informed consent 
requirements given in this document are not intended to pre-empt any local regulations 
which require additional information to be disclosed for informed consent to be legally 
effective. Clinical judgement, local regulations and requirements should guide the final 
structure and content of the local version of the ICF. 
The investigator has the final responsibility for the final presentation of the ICF and IAF, 
respecting the mandatory requirements of local regulations. The ICF and IAF generated 
by the investigator with the assistance of the sponsor’s representative must be acceptable 
to GSK Biologicals and be approved (along with the protocol, and any other necessary 
documentation) by the IRB/IEC.
 
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5.2.
Subject identification and randomisation of treatment
Subjects will keep the subject numbers that they were assigned in study ZOSTER-003.
5.2.1.
Treatment allocation 
The treatment allocation will be performed using SBIR. The treatment numbers will be 
allocated by dose.
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
5.3.
Method of blinding 
This is an open-label study with only one treatment group.
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the subject and study (without any link to the treatment 
attributed to the subject) to each sample.
5.4.
General study aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects.
5.4.1.
Data collection
After Visit 5, there will be 3 contacts between the subjects/subject’s caregiver and the 
investigator and/or his delegate for the purpose of collecting information on any event of 
interest (see Table 4 and Section 5.6.8.1 for details). The contacts will take place using 
the most convenient method suited for the sites (e.g., telephone calls by site staff or 
designee, or visit by the study staff to the subject's home). A guidance document 
outlining the information that needs to be collected at each contact will be provided to 
each country, and will serve as a guidance to develop the local script. The logistic details 
on the set-up of the contacts will be documented by each site/country. At each contact, 
the subjects/subject’s caregiver will respond to a standard set of questions in a language 
that is understandable to them. The investigator and/or his delegate will transcribe the 
relevant information or any event of interest in the appropriate section of the subject’s 
eCRF, in English.
Diary cards to be completed by the subject/ subject’s caregiver will be distributed and 
explained by the investigator or his/her delegate. Any supplied diary cards should be 
preferably completed by the subject themselves. In case of difficulty in self-completion 
of the diary cards, an aide (such as a family member or caregiver who is not involved in 
the study) may provide assistance with transcribing the subject’s information in the diary 
cards.
 
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The 7-day and 30-day diary cards will be dispensed on the day of vaccination to be 
completed by the subjects/ subjects’ caregiver. The 7-day diary cards will be completed 
for solicited AEs (from Day 0 to Day 6 after each vaccination) and the 30-day diary cards 
will be completed for unsolicited AEs (from Day 0 to Day 29 after each vaccination) and 
any concomitant medication and vaccination taken from Day 0 to Day 29 after each 
vaccination (see Table 4 and Table 15).
When the completed diary cards are returned to the study staff, the study staff will ask the 
subject (at the time of return or at subsequent contact) if he/she received any assistance in 
completing diary cards. If the subject had assistance completing the diary card (e.g., by a 
caregiver), it should be noted in the eCRF.
 
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5.5.
Outline of study procedures
Table 4
List of study procedures
Epoch 001
Type of contact
Visit 1
Visit 2
Visit 3
Visit 4 Visit 5 Contacts Visit 6
Timepoints
Year 9‡
Month 
108 §
Year 10‡
Month 
120 # 
Month 
121 #
Month 
122 #
Month 
123 #
Month 
126
Month 
129
Month 
132
Month 
134 #
Sampling timepoints for Long-Term Follow-up 
Phase
Post-
Vacc
Post-
Vacc
Sampling timepoints for Re-vaccination Phase
Pre-
Vacc1 
Post-
Vacc1
Post-
Vacc2
Post-
Vacc2
Informed consent
●
Check inclusion/exclusion criteria
●
Collect demographic data
●
Medical history
●
●
History directed physical examination
O
O
Check contraindications and warnings and 
precautions
●
●
Pre-vaccination body temperature
●
●
Vaccine administration
●
●
Blood sampling for antibody determination ((5 ml)
●
●*
●
●
●
Blood sampling for CMI response ((20 ml)
●
●*
●
●
●
Record any concomitant medications/vaccinations
●
●
●
●
●
●
●
Distribution of diary cards
O
O
Return of diary cards
O
O
Transcribing of solicited symptoms reported within 
7 days post-vaccination
●
●
Transcribing of non-serious adverse events 
reported within 30 days post-vaccination
●
●
Recording of Intercurent Medical Conditions 
(IMCs)
●
●
●
●
●
●
●
Recording of any SAEs after the first dose from 
the re-vaccination course at Visit 2
(Amended 18 August 2017)
●
●
●
●
●
●
Recording of any AEs/SAEs leading to 
withdrawal from the study
(Amended 18 August 2017)
●
●
●
●
●
●
●
Recording of SAEs related to investigational 
vaccine, study participation or to a concurrent GSK 
medication/vaccine †
●
●
●
●
●
●
●
Recording of any pIMDs
●
●
●
●
●
●
Recording of HZ cases **
●
●
●
●
●
●
●
Study Conclusion
●
Note: The double-line border following Month 108 and Month 123 indicates the analyses which will be performed on all 
data (i.e. data that are as clean as possible) obtained up to Month 108/123.
Vacc: vaccination
● is used to indicate a study procedure that requires documentation in the individual eCRF
O is used to indicate a study procedure that does not require documentation in the individual eCRF 
§ Subjects can complete Visit 1 between 108 and 111 months after the first HZ/su dose of the previous vaccination 
course in ZOSTER-003.
‡ Months 108 and 120 after first dose of initial vaccination course in study ZOSTER-003
 
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#  Months 120, 121, 122, 123 and 134 correspond to Month 0, 1, 2, 3 and 14 of the re-vaccination course.
* Before vaccine administration.
** HZ cases will be collected in HZ specific screen in the eCRF.
† SAEs related to investigational vaccine include SAEs occurring between V1 and V2 considered as related to initial 
vaccination in ZOSTER-003 study and SAEs related to re-vaccination course occurring after administration of the 1st
dose from re-vaccination course.
Table 5
Intervals between study visits
Interval
Length of interval
Maximum interval allowed1
Visit 1Visit 2
12 months
365 - 401 days
Visit 2Visit 3
1 months
28 - 48 days
Visit 2Visit 4
2 months
49 - 83 days
Visit 4Visit 5
1 months
28 - 48 days
Contacts between Visit 5 and Visit 6
3 months between each
75-105 days2
Visit 4Visit 6
12 months
327 - 401 days
Whenever possible the investigator should arrange study visits within this interval.
1 The investigator should endeavour to have the subjects come in for the visits within this interval. However subjects 
may not be excluded from the ATP cohort for analysis of immunogenicity if they make the study visit outside this 
interval.
2 The phone contacts are to be as evenly spaced throughout time as possible. Phone contacts which are not at the 
intervals as specified in this table will not necessary result in elimination from the ATP cohort.
5.6.
Detailed description of study procedures
5.6.1.
Informed consent
The signed/witnessed informed consent of the subject must be obtained before study 
participation. Refer to Section 5.1 for the requirements on how to obtain informed 
consent and assent, as appropriate.
Local laws and regulations (EC/RB recommendations and/or approvals) should be 
followed when a subject needs the assistance of a caregiver in completing study 
procedures.
The following are recommended and can be used as guidance in such cases: 

The need of a caregiver in completing study procedures will be confirmed during the 
informed consent process by the subject. In addition, the caregiver will also provide 
his/her agreement to be involved in the study and express willingness to act in a 
support role during the conduct of study specific procedures. The agreement of the 
caregiver to participate to the study will be included in the subject’s ICF in a separate 
dedicated paragraph. The role of the caregiver will be fully explained in the ICF or 
annex where the subject and the caregiver will confirm their involvement in the 
study.
 
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
The caregiver can stop assisting the subject in completing study procedures for any 
reason at any time, and he/she should be replaced by another caregiver, if still 
needed. The former caregiver must not be involved in the consent process and the 
appointment of a new caregiver. The new caregiver should confirm his/her 
willingness to assist the subject in completing study procedures by signing the annex 
part of the ICF together with the subject.
* Note that in this case, the subject would sign the annex part of the ICF to confirm 
his/her agreement with the new caregiver’s assistance in completing study 
procedures. The signature would not be considered as a subject re-consent to study 
participation.

At the start of the study, the subject/caregiver should be instructed to announce when 
the caregiver stops his/her involvement in the study (if possible, beforehand) and 
whether he/she will be replaced by another caregiver.

The signature of the new caregiver can be obtained on study site. When the 
subject/caregiver are unable to visit the investigational site to sign the annex part of 
the ICF, other more convenient means are acceptable*, provided that they are in 
accordance with the protocol and local laws and regulations (local/regional/national 
EC/RB). 
*When explanation of the study procedures given to the new caregiver is done solely 
by telephone, proper documentation of the process (information provided, name of 
individual obtaining the annex of ICF, date annex obtained) should be included in 
the study records. 

If non-compliance with study procedures (as assessed by the investigator) results 
from changing the caregiver, the subject would be considered as a withdrawal.
5.6.2.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.1 and 4.3 before 
enrolment. 
5.6.3.
Collect demographic data
Record demographic data such as date of birth and gender in the subject’s eCRF.
5.6.4.
Medical history
Obtain the subject’s medical history by interview and/or review of the subject’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in the 
subject prior to the study start and to the first study re-vaccination dose in the CRF/eCRF.
Below is a list of the type of medical conditions that should be collected as part of the 
medical history:

Acute on-going medical conditions

Chronic on-going medical conditions
 
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
Serious medical conditions that happened in the past even if not currently on-going.  
The following criteria should be taken into account to assess a medical condition as 
serious:

A medical condition for which hospitalization was required;

A medical condition for which surgery was performed;

Life-threatening medical condition.
A condition that doesn’t meet any of the criteria above but that the investigator considers 
to be serious or relevant, taking into account the population under study and the medical 
circumstances of subjects in that population.
Excluded from recording are: acute infections that have resolved (e.g., lobar pneumonia, 
influenza), medical events that have resolved (e.g., hip fracture with replacement, cataract 
treated with surgery). A predefined list of excluded categories and diseases will be 
available in the eCRF.
In addition, history of prior HZ episode must be recorded.
5.6.5.
History directed physical examination
Visit 1: Perform a history directed physical examination. Collected information needs to 
be recorded in the source document.
Visit 2: Perform a history directed physical examination. If the investigator determines 
that the subject’s health on the day of vaccination temporarily precludes vaccination, the 
visit will be rescheduled. Collected information needs to be recorded in the source 
document.
Medical information collected at both visits needs to be recorded in the source document. 
Treatment of any abnormality observed during this examination has to be performed
according to local medical practice outside this study or by referral to an appropriate 
health care provider.
5.6.6.
Check contraindications, warnings and precautions to 
vaccination 
Contraindications, warnings and precautions to vaccination must be checked at the 
beginning of each vaccination visit. Refer to Sections 6.5 for more details. 
5.6.7.
Assess pre-vaccination body temperature
The axillary, oral or tympanic body temperature of all subjects needs to be measured 
prior to any study vaccine administration. The preferred route for recording temperature 
in this study will be oral. If the subject has fever (fever is defined as temperature 
37.5°C/99.5°F for oral, axillary or tympanic route, or 38.0°C/100.4°F for rectal route)
on the day of vaccination, the vaccination visit will be rescheduled within the allowed 
interval for this visit (see Table 5).
 
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5.6.8.
Training on self-reporting by subjects
Subjects/ subject’s caregiver will be instructed at Visit 1 (and will be reminded at each
visit or contact) to contact their study site immediately:

should the subject manifest any signs or symptoms he/she perceive as serious;

should the subject develop any symptoms suggestive of HZ. The subject/subject’s 
caregiver must complete the HZ-specific diary card immediately upon development 
of these symptoms prior to visiting the study site for evaluation of the suspected HZ;

if the subject has been diagnosed by an attending physician as having suspected HZ.
5.6.8.1.
Reminder for follow-up contacts between Visit 5 and Visit 6
The subject/ subject’s caregiver will be reminded that, after Visit 5, contacts between the 
subjects and the investigator and/or his delegate will take place in order to collect all 
relevant information on occurrence of a suspected episode of HZ, SAEs (Section 8.2), 
pIMDs, IMCs (Section 6.7) or the use of concomitant medications and/or vaccinations 
(Section 6.6.2), and that information will be recorded in the appropriate section of the 
subject’s eCRF.
5.6.9.
Sampling
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples.
5.6.9.1.
Blood sampling for safety or immune response assessments
Blood samples will be taken during certain study visits as specified in Section 5.5 List of 
Study Procedures.

A volume of about 5 mL of whole blood should be drawn from all subjects for each 
analysis of humoral immune response at each pre-defined timepoint. After 
centrifugation, serum samples should be kept at -20°C/-4°F (-80°C/-112°F is also 
acceptable) until shipment. Refer to the SPM for more details on sample storage 
conditions.

A volume of about 20 mL of whole blood should be drawn from all subjects for 
analysis of cell-mediated immune (CMI) response at each pre-defined timepoint. The 
blood should be stored at the investigator’s site at room temperature and it must not 
be centrifuged. Samples will be shipped at room temperature (15 to 25°C/68 to 77°F) 
to the designated laboratory for cell separation to be performed within 24 hours.
Refer to the SPM for more details on sample storage conditions.
 
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5.6.10.
Study Vaccine administration

After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine will be administered intramuscularly (IM) in the deltoid of the non-dominant 
arm (refer to Section 6.3 for detailed description of the vaccine administration 
procedure). If the investigator or delegate determines that the subject’s health on the 
day of administration temporarily precludes vaccine administration, the visit will be 
rescheduled within the allowed interval for this visit (refer to Table 5).

The subjects will be observed closely for at least 30 minutes following the 
administration of the vaccine, with appropriate medical treatment readily available in 
case of anaphylaxis.
5.6.11.
Check and record concomitant medication/vaccination and 
intercurrent medical conditions
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 6.6.
Intercurrent medical conditions must be checked and recorded in the eCRF as described 
in Section 6.7.
5.6.12.
Recording of AEs, SAEs and pIMDs

Refer to Section 8.2 for procedures for the investigator to record AEs, SAEs and 
pIMDs. Refer to Section 8.3 for guidelines and how to report SAE and pIMD reports 
to GSK Biologicals.

The subjects/subjects’ caregiver will be instructed to contact the investigator 
immediately should they/the subjects manifest any signs or symptoms they perceive 
as serious. 

At each vaccination visit, diary cards will be provided to the subject/subject’s 
caregiver. The subject/subject’s caregiver will record body (oral) temperature and 
any solicited local/general AEs (i.e. on the day of vaccination and during the next 6 
days) or any unsolicited AEs (i.e. on the day of vaccination and during the next 29
days occurring after vaccination. 

The subject/ subject’s caregiver will be instructed to return the completed diary cards 
to the investigator at the next study visit. The study staff/investigator will collect and 
verify completed diary cards during discussion with the subject/ subject’s caregiver 
on Visit 3 and Visit 5.

Any unreturned diary cards will be sought from the subject/subject’s caregiver 
through telephone call(s) or any other convenient procedure. The investigator will 
transcribe the collected information into the eCRF in English.
 
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5.6.13.
Study conclusion
At the study conclusion visit, the investigator will:

collect a blood sample;

collect and record SAEs, pIMDs, HZ cases, concomitant medications/vaccinations;

review data collected to ensure accuracy and completeness;

complete the Study Conclusion screen in the eCRF.
5.7.
Biological sample handling and analysis
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment).
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the identification number for the subject (subject number).

Collected samples will be used for protocol mandated research and purposes related 
to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. This may include the management of the quality of these 
tests, the maintenance or improvement of these tests, the development of new test 
methods, as well as making sure that new tests are comparable to previous methods 
and work reliably.

It is also possible that future findings may make it desirable to use the samples 
acquired in this study for future research, not described in this protocol. Therefore, 
all subjects in countries where this is allowed, will be asked to give a specific 
consent to allow GSK or a contracted partner to use the samples for future research. 
Future research will be subject to the laws and regulations in the respective countries 
and will only be performed once an independent Ethics Committee or Review Board 
has approved this research.
Information on further investigations and their rationale can be obtained from GSK 
Biologicals.
Any sample testing will be done in line with the consent of the individual subject.
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK Biologicals.
 
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5.7.1.
Use of specified study materials
When materials are provided by GSK Biologicals, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the ATP analysis (See Section 10.4 for the definition of 
cohorts to be analysed). The investigator must ensure that his/her personnel and the 
laboratory(ies) under his/her supervision comply with this requirement. However, when 
GSK Biologicals does not provide material for collecting and storing clinical samples, 
appropriate materials from the investigator’s site must be used. Refer to the Module on 
Clinical Trial Supplies in the SPM.
5.7.2.
Biological samples
The biological samples collected in the study, the quantities needed, the units and the 
timepoints are described in Table 6.
Table 6
Biological samples
Sample type
Quantity
(approximate volume)
Unit
Timepoint(s)
Blood
(Humoral immunity)
5
mL
Visits 1, 2, 3, 5 and 6
Blood
(Cell-mediated immunity)
20
mL
Visits 1, 2, 3, 5 and 6
mL = Millilitre
5.7.3.
Laboratory assays
Please refer to APPENDIX A for a detailed description of the assays performed in the 
study. Please refer to APPENDIX B for the address of the clinical laboratories used for 
sample analysis 
Laboratory assays, which will be used in this study, are summarised in respectively in 
Table 7 (Humoral Immunity) and Table 8 (CMI).
Table 7
Humoral Immunity (Antibody determination)
System
Component
Method
Kit / 
Manufacturer
Unit
Cut-
off
Laboratory*
Serum
Varicella Zoster 
Virus.Glycoprotein E 
Ab.IgG
ELISA
NA
mIU/ml
97
GSK 
Biologicals**
*GSK Biologicals laboratory refers to the Clinical Laboratory in Rixensart, Belgium.
VZV = Varicella Zoster Virus; gE = Glycoprotein E; Ab = Antibody; IgG = Immunoglobulin class G; ELISA = Enzyme-
linked Immunosorbent Assay; NA = Not applicable; ml = milliliter; mIU = milli international unit.
 
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Table 8
Cell-Mediated Immunity (CMI)
System
Component
Challenge
Method
Unit
Laboratory*
PBMC
CD4.polypositives CD40L+IL-
2+TNFα+IFNγ*
gE
ICS
Events
CEVAC+
IL-2 = Interleukin 2; TNFα = Tumor Necrosis Factor-alpha; IFNγ = Interferon-gamma; gE = Glycoprotein E; ICS = 
Intracellular cytokine staining.
* CD4.polypositives CD40L+IL2+TNFα+IFNγ = CD4+ T-cells expressing at least 2 activation markers (from among 
IFN-γ, IL-2, TNF-α and CD40L)
+ Centre for Vaccinology (CEVAC), Ghent University, Building A, 1st Floor, De Pintelaan, 185, 9000 Gent, Belgium
The GSK Biologicals’ clinical laboratories have established a Quality System supported 
by procedures. The activities of GSK Biologicals’ clinical laboratories are audited 
regularly for quality assessment by an internal (sponsor-dependent) but laboratory-
independent Quality Department.
5.7.4.
Biological samples evaluation
5.7.4.1.
Immunological read-outs
Table 9
Immunological read-outs
Blood sampling timepoint
No. subjects
Component
Type of contact and timepoint
Sampling timepoint
Visit 1 (Month 108/Year 9)
Post-Initial Vacc
All
ICS gE
All
Ab gE ELISA
Visit 2 (Month 120/Year 10)
Post-Initial Vacc
All
ICS gE
All
Ab gE ELISA
Visit 3 (Month 121)
Month 1 Post-Re-Vacc 1
All
ICS gE
All
Ab gE ELISA
Visit 5 (Month 123)
Month 1 Post-Re-Vacc 2
All
ICS gE
All
Ab gE ELISA
Visit 6 (Month 134)
Month 12 Post-Re-Vacc 2
All
ICS gE
All
Ab gE ELISA
ICS = Intracellular Cytokine Staining; gE = Glycoprotein E; Ab = Antibody; ELISA = Enzyme-linked Immunosorbent 
Assay.
5.7.5.
Immunological correlates of protection
No generally accepted immunological correlate of protection against HZ has been 
demonstrated so far for the gE antigen used in the HZ/su candidate vaccine.
 
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6.
STUDY VACCINE AND ADMINISTRATION
6.1.
Description of study vaccine
The candidate vaccine to be used has been developed and manufactured by GSK 
Biologicals.
The Quality Control Standards and Requirements for the candidate vaccine are described 
in separate Quality Assurance documents (e.g. release protocols, certificate of analysis) 
and the required approvals have been obtained. 
The vaccine is labelled and packed according to applicable regulatory requirements.
Table 10
Study vaccine
Treatment 
name
Vaccine 
name
Formulation
Presentation
Volume to be 
administered*
Number of 
doses
HZ/su
VZV gE
gE=50µg
Lyophilized pellet 
in a monodose vial
0.5 mL
2
AS01B
MPL=50µg; 
QS21=50µg; 
Liposomes
Liquid in a 
monodose vial
*Refer to the SPM for the volume after reconstitution.
VZV = Varicella Zoster Virus, gE = recombinant purified Glycoprotein E; AS01B = Adjuvant System AS01B;  MPL = 3-
O-desacyl-4’-monophosphoryl lipid A; QS21 Stimulon® = Quillaja saponaria Molina, fraction 21 (purified saponin 
extract from the South American tree).
6.2.
Storage and handling of study vaccine
The study vaccines must be stored at the respective label storage temperature conditions 
in a safe and locked place. Access to the storage space should be limited to authorized 
study personnel. The storage conditions will be assessed during pre-study activities under 
the responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccine.
Temperature excursions must be reported in degree Celsius.
Any temperature excursion outside the range of 0.0 to +8.0C (for +2 to +8°C/+36 to 
+46°F label storage condition) impacting investigational medicinal products (IMPs) must 
be reported in the appropriate (electronic) temperature excursion decision form ([e]TDF). 
The impacted IMPs must not be used and must be stored in quarantine at label 
temperature conditions until usage approval has been obtained from the sponsor.
In case of temperature excursion below +2.0°C down to 0.0°C impacting IMP(s) there is 
no need to report in (e)TDF, but adequate actions must be taken to restore the +2 to 
+8°C/+36 to +46°F label storage temperature conditions. The impacted IMP(s) may still 
be administered, but the site should avoid re-occurrence of such temperature excursion.
Refer to the Module on Clinical Trial Supplies in the SPM for more details on actions to 
take.
 
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Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on 
the temperature excursion reporting and usage decision process, packaging and 
accountability of the study vaccine.
6.3.
Dosage and administration of study vaccine
After removal of the vaccine components from the temperature monitored refrigerator, 
the vaccine should be reconstituted and administered within 6 hours, and should be kept 
at room temperature (between 2°C/36°F and 30°C/86°F).
Vaccine will be administered as indicated in Table 11.
The reconstituted vaccine (0.5 mL) should be administered by IM injection into the 
deltoid muscle of the non-dominant arm using a standard aseptic technique.
Refere to the SPM for more details on vaccine reconstitution and administration.
Table 11
Dosage and administration
Type of contact 
and timepoint
Volume to be 
administered
Study group
Treatment 
name
Route 1
Site
Side2
Visit 2 (Month 
120)
0.5 ml
50µg 
gE/AS01B
HZ/su
IM
Deltoid
Non-
Dominant
Visit 4 (Month 
122)
1Intramuscular (IM)
2 In rare situations when there is no other alternative, the injection may be given in the dominant arm.
6.4.
Replacement of unusable vaccine doses
In addition to the vaccine doses provided for the planned number of subjects (including 
over supply), at least 5 % additional vaccine doses will be supplied to replace those that 
are unusable. 
Additional doses of the study vaccine will be supplied if necessary.
6.5.
Contraindications to subsequent vaccination
The following events constitute absolute contraindications to (further) administration of 
HZ/su. If any of these events occur during the study, the subject must not receive 
additional doses of vaccine but may continue other study procedures at the discretion of 
the investigator (see Section 8.4). 

Anaphylaxis following the administration of any previous dose of HZ/su.

An SAE judged to be related to HZ/su by the investigator.

Active HZ infection i.e. HZ lesions not completely crusted over at the moment of 
Visit 2 or an episode of HZ between Visit 2 (Month 120: re-vaccination dose1) and 
Visit 4 (Month 122: re-vaccination dose 2).
 
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
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
resulting from disease (e.g., malignancy, HIV infection) or 
immunosuppressive/cytotoxic therapy (e.g., medications used during cancer 
chemotherapy, organ transplantation or to treat autoimmune disorders). However 
subjects who have received less than 15 days of immunosuppressants or other 
immune modifying drugs should not be contraindicated from receiving subsequent 
vaccinations. Corticosteroids, prednisone < 20 mg/day, or equivalent, as well as 
inhaled and topical steroids are allowed.

Administration of a vaccine not foreseen by the study protocol within the period 
starting 30 days before the first dose of study vaccine, and ending 30 days after the 
last dose of study vaccine. However, licensed non-replicating vaccines (i.e. 
inactivated and subunit vaccines, including inactivated and subunit influenza 
vaccines, with or without adjuvant for seasonal or pandemic flus) may be 
administered up to 8 days prior to dose 1 and/or dose 2 and/or at least 14 days after 
any dose of study vaccine.

Administration of vaccine against HZ or varicella (including an investigational or 
non-registered vaccine) other than the study vaccine.

Participating or planned participation in another clinical study, from 30 days before 
Visit 2 up to 30 days post second dose, in which the subject is or will be exposed to 
an investigational or a non-investigational vaccine/product (pharmaceutical product 
or device).

Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe.

Other events that constitute contraindications to administration of HZ/su vaccine.

Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the 
opinion of the investigator, expose the subject to unacceptable risk from 
subsequent vaccination. In such cases, the investigator should use his/her 
clinical judgement prior to administering the next dose of the 
vaccine(s)/product(s). Refer to Section 8.1.5.1 for the definition of pIMDs.
The following events constitute contraindications to administration of HZ/su at that point 
in time; if any of these events occur at the time scheduled for vaccination, the subject 
may be vaccinated at a later date, within the time window specified in the protocol (see 
Section 5.5), or the subject may be withdrawn at the discretion of the investigator (see 
Section 8.4). 

Acute disease and/or fever at the time of vaccination. 

Fever is defined as temperature 37.5°C/99.5°F for oral, axillary or tympanic 
route, or 38.0°C/100.4°F for rectal route. The preferred route for recording 
temperature in this study will be oral.

Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever can be administered all vaccines.
 
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6.6.
Concomitant medications/products and concomitant 
vaccinations
At each study visit/contact, the investigator should question the subject and/or the 
subject’s caregiver about any medications/products taken and vaccinations received by 
the subject.
6.6.1.
Recording of concomitant medications/products and 
concomitant vaccinations
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in 
the eCRF.

All concomitant medication/vaccination, with the exception of vitamins and/or 
dietary supplements, administered at ANY time during the period starting with the 
administration of each dose of study vaccine and ending 30 days (Days 0-29) after 
each dose of study vaccine must be recorded in the eCRF. 

Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination).
E.g. an anti-pyretic is considered to be prophylactic when it is given in the absence 
of fever and any other symptom, to prevent fever from occurring [fever is defined as 
temperature ≥37.5°C/99.5°F on oral, axillary or tympanic setting, or 
≥38.0°C/100.4°F on rectal setting].

Any vaccine not foreseen in the study protocol administered at any time during the 
period starting with the administration of each dose of study vaccine and ending 30 
days (Days 0-29) after each dose of study vaccine must be recorded in the eCRF.

Any investigational medication or vaccine administered throughout the study (i.e. 
from V1 through study conclusion) must be recorded in the eCRF.

Concomitant medication, administered for the treatment of HZ or any related 
HZcomplications, from V1 until study conclusion, must be recorded in the eCRF.

Any concomitant medications/products/vaccines listed in Section 6.6.2.

Any concomitant medications/products/vaccines relevant to a SAE/pIMD to be 
reported as per protocol or administered at any time during the study period for the 
treatment of a SAE /pIMD. In addition, concomitant medications relevant to SAEs 
and pIMD need to be recorded on the expedited Adverse Event report.
 
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6.6.2.
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from ATP analyses
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
ATP analysis.

Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this will 
mean prednisone 20 mg/day for adult subjects), or equivalent. Inhaled, topical and 
intra-articular steroids are allowed.

Long-acting immune-modifying drugs administered at any time during the study 
period (e.g. infliximab).

Immunoglobulins and/or any blood products administered during the study period.

A vaccine against HZ or varicella (including an investigational or non-registered 
vaccine) other than the study vaccine during the study period.
6.7.
Intercurrent medical conditions that may lead to elimination 
of a subject from ATP analyses
At each study visit, it must be verified if the subject has experienced or is experiencing 
any intercurrent medical condition. If it is the case, the condition(s) must be recorded in 
the eCRF.
Subjects may be eliminated from the ATP cohort for immunogenicity if, during the study, 
they incur a condition that has the capability of altering their immune response (i.e. 
varicella or suspected HZ episode) or are confirmed to have an immunocompromising 
condition (e.g. HIV, cancer). HZ cases will be collected/reported in HZ specific screen in 
the eCRF.
Subjects who experience an episode of suspected HZ during the study will be eliminated 
from the ATP cohort for immunogenicity. These subjects will be analysed separately.
IMCs will be reported either as AE or SAEs (as appropriate) in the eCRF.
7.
HEALTH ECONOMICS
Not applicable.
 
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8.
SAFETY
The investigator or site staff is/are responsible for the detection, documentation and 
reporting of events meeting the criteria and definition of an adverse event (AE) or serious 
adverse event (SAE) as provided in this protocol. 
Each subject/ subject’s caregiver will be instructed to contact the investigator 
immediately should they/the subject manifest any signs or symptoms they perceive as 
serious.
8.1.
Safety definitions
8.1.1.
Definition of an adverse event
An AE is any untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 
Examples of an AE include:

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 investigational vaccine administration 
even though they may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
investigational vaccine or a concurrent medication (overdose per se should not be 
reported as an AE/SAE).

Signs, symptoms temporally associated with vaccine administration.

Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen).
AEs to be recorded as endpoints (solicited AEs) are described in Section 8.1.3. All other 
AEs will be recorded as UNSOLICITED AEs.
Examples of an AE DO NOT include:

Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that 
leads to the procedure is an AE/SAE.

Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination).
 
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
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

Pre-existing conditions or signs and/or symptoms present in a subject prior to the 
first study vaccination. These events will be recorded in the medical history section 
of the eCRF.
8.1.2.
Definition of a serious adverse event 
A SAE is any untoward medical occurrence that:
a.
Results in death,
b.
Is life-threatening,
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe.
c.
Requires hospitalisation or prolongation of existing hospitalisation,
Note: In general, hospitalisation signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or in an out-patient setting. Complications 
that occur during hospitalisation are also considered AEs. If a complication prolongs 
hospitalisation or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalisation’ occurred or was necessary, the 
AE should be considered serious.
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline is 
NOT considered an AE.
d.
Results in disability/incapacity, OR
Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhoea, influenza like illness, and accidental trauma (e.g. sprained 
ankle) which may interfere or prevent everyday life functions but do not constitute a 
substantial disruption.
e.
Is a congenital anomaly/birth defect in the offspring of a study subject.
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise the
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalisation.
 
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8.1.3.
Solicited adverse events
8.1.3.1.
Solicited local (injection-site) adverse events
The following local (injection-site) AEs will be solicited:
Table 12
Solicited local adverse events
Pain at injection site
Redness at injection site
Swelling at injection site
8.1.3.2.
Solicited general adverse events
The following general AEs will be solicited:
Table 13
Solicited general adverse events
Fatigue
Fever
Gastrointestinal symptoms †
Headache
Myalgia
Shivering
†Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain.
Note: Temperature will be recorded in the evening. Should additional temperature 
measurements be performed at other times of day, the highest temperature will be 
recorded in the eCRF. The preferred route for recording temperature in this study will be 
oral.
8.1.4.
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events 
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
haematology, urinalysis) or other abnormal assessments (e.g. imaging studies) that are 
judged by the investigator to be clinically significant will be recorded as AE or SAE if 
they meet the definition of an AE or SAE (refer to Sections 8.1.1 and 8.1.2). Clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen following the start of the study will also be reported as 
AEs or SAEs. 
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant.
 
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8.1.5.
Adverse events of specific interest
8.1.5.1.
Potential immune-mediated diseases
Potential immune-mediated diseases (pIMDs) are a subset of AEs that include 
autoimmune diseases and other inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology. AEs that need to be recorded and 
reported as pIMDs include those listed in Table 14.
However, the investigator will exercise his/her medical and scientific judgement in 
deciding whether other diseases have an autoimmune origin (i.e. pathophysiology 
involving systemic or organ-specific pathogenic autoantibodies) and should also be 
recorded as a pIMD.
 
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Table 14
List of potential immune-mediated diseases
Neuroinflammatory disorders
Musculoskeletal disorders
Skin disorders

Cranial nerve disorders, including 
paralyses/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 

Immune-mediated peripheral 
neuropathies and plexopathies, 
(including chronic inflammatory 
demyelinating polyneuropathy, 
multifocal motor neuropathy and 
polyneuropathies associated with 
monoclonal gammopathy).

Narcolepsy

Systemic lupus erythematosus 
and associated conditions

Systemic scleroderma (Systemic 
sclerosis), including diffuse 
systemic form and CREST 
syndrome
Idiopathic inflammatory 
myopathies, including 
dermatomyositis 

Polymyositis 

Antisynthetase syndrome

Rheumatoid arthritis, and 
associated conditions including 
juvenile chronic arthritis and 
Still’s disease

Polymyalgia rheumatica

Spondyloarthritis, including 
ankylosing spondylitis, reactive 
arthritis (Reiter's Syndrome) and 
undifferentiated spondyloarthritis 

Psoriatic arthropathy

Relapsing polychondritis

Mixed connective tissue disorder

Psoriasis

Vitiligo

Erythema nodosum

Autoimmune bullous 
skin diseases 
(including 
pemphigus, 
pemphigoid and 
dermatitis 
herpetiformis)

Alopecia areata

Lichen planus

Sweet’s syndrome

Localised 
Scleroderma 
(Morphoea)
Vasculitides
Blood disorders
Others

Large vessels vasculitis including: 
giant cell arteritis such as 
Takayasu's arteritis and temporal 
arteritis. 

Medium sized and/or small 
vessels vasculitis including: 
polyarteritis nodosa, Kawasaki's 
disease, microscopic polyangiitis, 
Wegener's granulomatosis, 
Churg–Strauss syndrome (allergic 
granulomatous angiitis), Buerger’s 
disease (thromboangiitis 
obliterans), necrotizing vasculitis 
and anti-neutrophil cytoplasmic 
antibody (ANCA) positive 
vasculitis (type unspecified), 
Henoch-Schonlein purpura, 
Behcet's syndrome, 
leukocytoclastic vasculitis.

Autoimmune 
hemolytic anemia

Autoimmune 
thrombocytopenia

Antiphospholipid 
syndrome

Pernicious anemia

Autoimmune 
aplastic anaemia

Autoimmune 
neutropenia 

Autoimmune 
pancytopenia

Autoimmune glomerulonephritis 
(including IgA nephropathy, 
glomerulonephritis rapidly 
progressive, membranous 
glomerulonephritis, 
membranoproliferative 
glomerulonephritis, and 
mesangioproliferative 
glomerulonephritis)

Ocular autoimmune diseases 
(including autoimmune uveitis and 
autoimmune retinopathy)

Autoimmune 
myocarditis/cardiomyopathySarcoido
sis

Stevens-Johnson syndrome

Sjögren’s syndrome

Idiopathic pulmonary fibrosis

Goodpasture syndrome

Raynaud’s phenomenon
 
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Liver disorders
Gastrointestinal disorders
Endocrine disorders

Autoimmune hepatitis

Primary biliary cirrhosis

Primary sclerosing 
cholangitis

Autoimmune cholangitis

Inflammatory Bowel disease, 
including Crohn’s disease, 
ulcerative colitis, microscopic 
colitis, ulcerative proctitis 

Celiac disease

Autoimmune pancreatitis

Autoimmune thyroiditis (including 
Hashimoto thyroiditis)

Grave's or Basedow’s disease

Diabetes mellitus type I

Addison’s disease

Polyglandular autoimmune 
syndrome

Autoimmune hypophysitis
When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as a pIMD. Symptoms, signs or conditions which might (or might not) represent 
the above diagnoses, should be recorded and reported as AEs but not as pIMDs until the 
final or definitive diagnosis has been determined, and alternative diagnoses have been 
eliminated or shown to be less likely.
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire and a list of preferred terms (PTs) and PT codes corresponding to the above 
diagnoses will be available to investigators at study start.
Once a pIMD is diagnosed (serious or non-serious) in a study subject, the investigator (or 
designate) must complete, date and sign an electronic Expedited Adverse Events Report.
8.2.
Detecting and recording adverse events and serious 
adverse events
8.2.1.
Time period for detecting and recording adverse events and
serious adverse events (Amended 18 August 2017)
All AEs starting 30 days following administration of each dose/the dose of study vaccine
(Day 0 to Day 29) must be recorded into the appropriate section of the eCRF, irrespective 
of intensity or whether or not they are considered vaccination-related.
All SAEs will be collected and recorded from the time of the first receipt of study 
vaccine at Visit 2 until the subject is discharged from the study or until the end of the 
study (Table 15). See Section 8.3 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 study visit up to the last study visit at the end of the study.
SAEs related to initial vaccination course from study ZOSTER-003 will be collected 
and recorded from the time of the first study visit and will end at the time of the first 
receipt of dose one of re-vaccination course.
In addition to the above-mentioned reporting requirements and in order to fulfil 
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) or are 
related to a concurrent GSK medication/vaccine will be collected and recorded from the 
 
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time the subject consents to participate in the study until she/he is discharged from the 
study.
The time period for collecting and recording of pIMDs will begin at Visit 2, the first
receipt of study vaccine and will end 365 days following administration of the last dose 
of study vaccine. See section 8.3 for instructions on reporting of pIMDs.
An overview of the protocol-required reporting periods for AEs, SAEs, IMCs and pIMDs 
is given in Table 15.
 
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Table 15
Reporting periods for collecting safety information
Event
Visit 1*
Visit 2
Visit 3
Visit 4
Visit 5
Contacts
Visit 6
Timepoint
Year 9
Year 10
Vacc 1
Post 
Vacc
Post 
Vacc
Post Vacc
Vacc 2
Post-
Vacc
Post 
Vacc
Month 108
Month 120
6 days 
post V1
29 days 
post V1
Month 121
Month 122
6 days 
post V2
29 days 
post V2
Month 123 Month 126, 
129 and 132
Month 134
Solicited local and general AEs
Reporting of unsolicited AE
Reporting of any SAEs after the first 
dose from the re-vaccination course
at Visit 2
(Amended 18 August 2017)
Reporting of any AEs/SAEs leading 
to withdrawal from the study
(Amended 18 August 2017)
Reporting of all SAEs related to 
investigational vaccine, study 
participation or to a concurrent GSK 
medication/vaccine†
(Amended 18 August 2017)
Reporting of pIMDs 
Reporting of intercurrent medical 
conditions‡
* i.e. consent obtained; Vacc 1- re-vaccination dose 1; Vacc 2- re-vaccination dose 2
† SAEs related to investigational vaccine include SAEs occurring between V1 and V2 considered as related to initial vaccination  in ZOSTER-003 study and SAEs related to re-
vaccination course occurring after administration of the 1st dose from re-vaccination course.
‡Including suspected cases of HZ
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8.2.2.
Post-Study adverse events and serious adverse events
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 15. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE at 
any time after a subject has been discharged from the study, and he/she considers the 
event reasonably related to the investigational vaccine, the investigator will promptly 
notify the Study Contact for Reporting SAEs.
8.2.3.
Evaluation of adverse events and serious adverse events
8.2.3.1.
Active questioning to detect adverse events and serious adverse 
events
As a consistent method of collecting AEs, the subject or the subject should be asked a 
non-leading question such as:
‘Have you felt different in any way since receiving the vaccine or since the previous 
visit?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK Biologicals instead of appropriately completing the 
eCRF. However, there may be instances when copies of medical records for certain cases 
are requested by GSK Biologicals. In this instance, all subject identifiers will be blinded 
on the copies of the medical records prior to submission to GSK Biologicals.
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
 
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8.2.3.2.
Assessment of adverse events
8.2.3.2.1.
Assessment of intensity
The intensity of the following solicited AEs will be assessed as described:
Table 16
Intensity scales for solicited symptoms in adults
Adults
Adverse Event
Intensity grade
Parameter
Pain at injection site
0
None
1
Mild: Any pain neither interfering with nor preventing 
normal every day activities.
2
Moderate: Painful when limb is moved and interferes with 
every day activities.
3
Severe: Significant pain at rest. Prevents normal every 
day activities.
Redness at injection site
Record greatest surface diameter in mm
Swelling at injection site
Record greatest surface diameter in mm
Fever*
Record temperature in °C/°F
Temperature will be analysed in 0.5°C increments from ≥ 
37.5°C
Grade 3 fever is defined as > 39.0°C.
Headache
0
Normal
1
Mild: Headache that is easily tolerated
2
Moderate: Headache that interferes with normal activity
3
Severe: Headache that prevents normal activity
Fatigue
0
Normal
1
Mild: Fatigue that is easily tolerated
2
Moderate: Fatigue that interferes with normal activity
3
Severe: Fatigue that prevents normal activity
Gastrointestinal symptoms
0
Normal
(nausea, vomiting, diarrhoea and/or 
abdominal pain)
1
Mild: Gastrointestinal symptoms that are easily tolerated
2
Moderate: Gastrointestinal symptoms that interfere with 
normal activity
3
Severe: Gastrointestinal symptoms that prevent normal
activity
Myalgia
0
Normal
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 37.5°C / 99.5°F for oral, axillary or tympanic route. The preferred route for 
recording temperature in this study will be oral.
 
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The maximum intensity of local injection site redness/swelling will be scored at GSK 
Biologicals as follows using GSK Biologicals’ standard grading scale based on the US 
Food and Drug Administration (FDA) guidelines for Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers enrolled in Preventive Vaccine Clinical Trials [FDA, 
2007]:
0
:
< 20 mm diameter
1
:
20 mm to 50 mm diameter
2
:
> 50 mm to 100 mm diameter
3
:
> 100 mm diameter
The preferred route for recording temperature in this study is oral.
Grade 3 fever will be defined as temperature > 39.0C (regardless the route used).
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 one of the following categories:
1 (mild)
=
An AE which is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
2 (moderate)
=
An AE which is sufficiently discomforting to interfere with 
normal everyday activities.
3 (severe)
=
An AE which prevents normal, everyday activities 
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets one of the pre-
defined outcomes as described in Section 8.1.2.
8.2.3.2.2.
Assessment of causality
The investigator is obligated to assess the relationship between investigational vaccine
and the occurrence of each AE/SAE. The investigator will use clinical judgement to 
determine the relationship. Alternative plausible causes, such as natural history of the 
underlying diseases, concomitant therapy, other risk factors, and the temporal 
relationship of the event to the investigational vaccine will be considered and 
investigated. The investigator will also consult the IB to determine his/her assessment.
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK Biologicals. However, it is very 
important that the investigator always makes an assessment of causality for every event 
prior to submission of the Expedited Adverse Events Report to GSK Biologicals. The 
investigator may change his/her opinion of causality in light of follow-up information and 
update the SAE information accordingly. The causality assessment is one of the criteria 
used when determining regulatory reporting requirements.
 
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In case of concomitant administration of multiple vaccines/products, it may not be 
possible to determine the causal relationship of general AEs to the individual vaccine
administered. The investigator should, therefore, assess whether the AE could be causally 
related to vaccination rather than to the individual vaccine.
All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question:
Is there a reasonable possibility that the AE may have been caused by the investigational 
vaccine?
YES
:
There is a reasonable possibility that the vaccine contributed to the 
AE. 
NO
:
There is no reasonable possibility that the AE is causally related to 
the administration of the study vaccine. There are other, more 
likely causes and administration of the study vaccine is not 
suspected to have contributed to the AE.
If an event meets the criteria to be determined as ‘serious’ (see Section 8.1.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE.
Possible contributing factors include:

Medical history.

Other medication.

Protocol required procedure.

Other procedure not required by the protocol.

Lack of efficacy of the vaccine, if applicable.

Erroneous administration.

Other cause (specify).
8.2.3.3.
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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8.3.
Reporting of serious adverse events and other events
8.3.1.
Prompt reporting of serious adverse events and other events to 
GSK Biologicals
SAEs that occur in the time period defined in Section 8.2 will be reported promptly to 
GSK within the timeframes described in Table 17, once the investigator determines that 
the event meets the protocol definition of a SAE.
pIMDs that occur in the time period defined in Section 8.2 will be reported promptly to 
GSK within the timeframes described in Table 17, once the investigator determines that 
the event meets the protocol definition of a pIMD.
Table 17
Timeframes for submitting serious adverse event and other events 
reports to GSK Biologicals
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*
paper Expedited Adverse Events 
Report
pIMDs
24 hours**‡
electronic Expedited 
Adverse Events Report
24 hours*
paper Expedited Adverse Events 
Report
* Timeframe allowed after receipt or awareness of the information.
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD
‡ The investigator will be required to confirm review of the SAE/pIMD causality by ticking the ‘reviewed’ box in the 
electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/pIMD
8.3.2.
Contact information for reporting serious adverse events and 
pIMDs
Study Contact for Reporting SAEs and pIMDs
Refer to the local study contact information document.
Back-up Study Contact for Reporting SAEs and pIMDs
24/24 hour and 7/7 day availability:
GSK Biologicals Clinical Safety & Pharmacovigilance
Outside US & Canada sites:
Fax: 
or 
Email address: 
 
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PPD
PPD
PPD

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8.3.3.
Completion and transmission of SAE reports to GSK Biologicals
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event. Even if the investigator does 
not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated 
WITHIN 24 HOURS.
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE.
8.3.3.1.
Back-up system in case the electronic reporting system does not work
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the Sponsor Information) or to GSK 
Biologicals Clinical Safety and Pharmacovigilance department within 24 hours. 
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system. 
8.3.4.
Reporting of pIMDs to GSK Biologicals
Once a pIMD is diagnosed (serious or non-serious) in a study subject, the investigator (or 
designate) must complete the information in the electronic Expedited Adverse Events 
Report WITHIN 24 HOURS after he/she becomes aware of the diagnosis. The report 
allows to 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 8.3.3.1 for back-up system in case the electronic reporting system does 
not work.
 
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8.3.5.
Updating of SAE and pIMD information after removal of write 
access to the subject’s eCRF
When additional SAE or pIMD information is received after removal of the write access 
to the subject’s eCRF, new or updated information should be recorded on the appropriate
paper report, with all changes signed and dated by the investigator. The updated report 
should be faxed to the Study Contact for Reporting SAEs (refer to the Sponsor 
Information) or to GSK Biologicals Clinical Safety and Pharmacovigilance department 
within the designated reporting time frames specified in Table 17.
8.3.6.
Regulatory reporting requirements for serious adverse events
The investigator will promptly report all SAEs to GSK in accordance with the procedures 
detailed in Section 8.3.1. GSK Biologicals has a legal responsibility to promptly notify, 
as appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to the Study Contact for Reporting SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of other subjects are met.
Investigator safety reports are prepared according to the current GSK policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the investigational vaccine and unexpected. The 
purpose of the report is to fulfil specific regulatory and GCP requirements, regarding the 
product under investigation.
8.4.
Follow-up of adverse events and serious adverse events
8.4.1.
Follow-up of adverse events and serious adverse events 
8.4.1.1.
Follow-up during the study
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide additional relevant information on the subject’s condition to GSK 
Biologicals (within 24 hours for SAEs; refer to Table 17).
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 end of the study.
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 
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8.4.1.2.
Follow-up after the subject is discharged from the study
The investigator will follow subjects:

with SAEs, pIMDs (serious or non-serious), or subjects withdrawn from the study as 
a result of an AE, until the event has resolved, subsided, stabilised, disappeared, or 
until the event is otherwise explained, or the subject is lost to follow-up. 

with other non-serious AEs until 30 days after the last vaccination or they are lost to 
follow-up.
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK Biologicals using a paper/ electronic 
Expedited Adverse Events Report as applicable.
GSK Biologicals may request that the investigator performs or arranges the conduct of 
additional clinical examinations/tests and/or evaluations to elucidate as fully as possible 
the nature and/or causality of the AE or SAE. The investigator is obliged to assist. If a 
subject dies during participation in the study or during a recognised follow-up period, 
GSK Biologicals will be provided with any available post-mortem findings, including 
histopathology.
8.5.
Treatment of adverse events
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of an AE should 
be recorded in the subject’s eCRF (refer to Section 6.6).
8.6.
Subject card
Study subjects / subjects’ caregiver must be provided with the address and telephone 
number of the main contact for information about the clinical study.
The investigator (or designate) must therefore provide a “subject card” to each subject/ 
subject’s caregiver. In an emergency situation this card serves to inform the responsible 
attending physician that the subject is in a clinical study and that relevant information 
may be obtained by contacting the investigator.
Subjects / subjects’ caregiver must be instructed to keep subject cards in their possession 
at all times.
 
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9.
SUBJECT COMPLETION AND WITHDRAWAL
9.1.
Subject completion
A subject who returns for the concluding visit foreseen in the protocol is considered to 
have completed the study.
9.2.
Subject withdrawal
Withdrawals will not be replaced.
9.2.1.
Subject withdrawal from the study
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did 
not come back for the concluding visit foreseen in the protocol. 
All data collected until the date of withdrawal/last contact of the subject will be used for 
the analysis.
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact.
Investigators will make an attempt to contact those subjects who do not return for
scheduled visits or follow-up.
Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself, or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal:

Serious adverse event.

Non-serious adverse event.

Protocol violation (specify).

Consent withdrawal, not due to an adverse event*.

Moved from the study area.

Lost to follow-up.

Other (specify).
*In case a subject is withdrawn from the study because he/she has withdrawn consent, the 
investigator will document the reason for withdrawal of consent, if specified by the 
subject, in the eCRF.
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 8.4.1.2).
 
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9.2.2.
Subject withdrawal from investigational vaccine
A ‘withdrawal’ from the investigational vaccine refers to any subject who does not 
receive the complete treatment, i.e. when no further planned dose is administered from 
the date of withdrawal. A subject withdrawn from the investigational vaccine may not 
necessarily be withdrawn from the study as further study procedures or follow-up may be 
performed (safety or immunogenicity) if planned in the study protocol. 
All data collected until the date of withdrawal/last contact of the subject will be used for 
the analysis.
Information relative to premature discontinuation of the investigational vaccine will be 
documented on the Vaccine Administration page/screen of the eCRF. The investigator 
will document whether the decision to discontinue further vaccination was made by the 
subject himself/herself or by the investigator, as well as which of the following possible 
reasons was responsible for withdrawal:

Serious adverse event.

Non-serious adverse event.

Other (specify).
10.
STATISTICAL METHODS
10.1.
Primary endpoints

Antigen-specific antibody (Ab) concentrations at Months 108 and 120 post first dose 
of initial vaccination course in study ZOSTER-003.

Anti-gE Ab concentrations as determined by ELISA at Months 108 and 120.

Cell-Mediated Immunity (CMI) in terms of frequencies of antigen-specific CD4 T-
cells at Months 108 and 120 post first dose of initial vaccination course in study 
ZOSTER-003.

Frequencies of CD4+ T cells with antigen-specific Interferon gamma (IFN-γ) 
and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) 
and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by 
Intracellular Cytokine Staining (ICS) at Months 108 and 120.
10.2.
Secondary endpoints
For the follow-up of persistence phase Months 108 and 120 post first dose of initial 
vaccination course in study ZOSTER-003:

Antigen-specific antibody (Ab) concentrations within each age cohort (60-69 YOA 
and ≥70 YOA at the time of initial vaccination) at persistence Months 108 and 120.

Anti-gE Ab concentrations as determined by ELISA at Months 108 and 120.
 
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
Cell-Mediated Immunity (CMI) in terms of frequencies of antigen-specific CD4 T-
cells within each age cohort (60-69 YOA and ≥70 YOA at the time of initial 
vaccination) at persistence Months 108 and 120 post first dose of initial vaccination 
course.

Frequencies of CD4+ T cells with antigen-specific Interferon gamma (IFN-γ) 
and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) 
and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by 
Intracellular Cytokine Staining (ICS) at Months 108 and 120.

Serious Adverse events:

Occurrence of all serious adverse events (SAEs) related to study participation or 
to a concurrent GSK medication/vaccine (including HZ/su administered during 
the ZOSTER-003 study) between Months 108 and 120.
For the re-vaccination phase:

Antigen-specific antibody (Ab) concentrations post re-vaccination.

Anti-gE antibody concentrations as determined by ELISA in all subjects at one 
month after each vaccine dose (Months 121 and 123) and 12 months after last 
dose (Month 134).

Cell-Mediated Immunity (CMI) in terms of frequencies of antigen-specific CD4 T-
cells at one month after each vaccine dose (Months 121 and 123) and 12 months 
after last dose (Month 134).

Frequencies of CD4+ T cells with antigen-specific Interferon gamma (IFN-γ) 
and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) 
and/or CD40 Ligand (CD40L) secretion/expression to gE as determined by 
Intracellular Cytokine Staining (ICS) at Months 121, 123 and 134.

Solicited local and general symptoms:

Occurrence and intensity of each solicited local symptom within 7 days (Days 0-
6) after each vaccination in all subjects;

Occurrence, intensity and relationship to vaccination of each solicited general 
symptom within 7 days (Days 0-6) after each vaccination, in all subjects;

Unsolicited adverse events (AEs)

Occurrence, intensity and relationship to vaccination of unsolicited Aes during 
30 days (Days 0-29) after each vaccination, according to the Medical Dictionary 
for Regulatory Activities (MedDRA) classification in all subjects

SAEs

Occurrence and relationship to vaccination of all SAEs from dose 1 of re-
vaccination until study end.

Occurrence of any fatal SAEs from dose 1 of re-vaccination until study end.
 
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
Potential immune-mediated diseases (pIMDs)

Occurrence and relationship to vaccination of any pIMDs from dose 1 of re-
vaccination until study end in all subjects.
10.3.
Determination of sample size
Subjects who participated in study ZOSTER-003, in group 50 µg gE / AS01B, and had 
complete vaccination course (2 doses of HZ/su) will be offered enrolment into this LTFU 
study.
10.4.
Cohorts for Analyses
10.4.1.
Total enrolled cohort
Total enrolled cohort will include all subjects enrolled in to the study.
10.4.2.
ATP cohort for analysis of persistence (LTFU)
The According To Protocol (ATP) cohort for analysis of persistence will include all 
evaluable subjects i.e, those who were included in the ATP cohort for immunogenicity in 
the initial ZOSTER-003 study, or were excluded from this cohort solely because they had 
no blood samples taken or because of incompliance with blood sample schedule, and:

Who did not receive a concomitant medication/ product leading to elimination from 
the ATP analysis for immunogenicity up to the considered time point of study 
ZOSTER-060 (see Section 6.6.2).

Who did not present with an intercurrent medical condition leading to elimination 
from the ATP analysis for immunogenicity (including herpes zoster) up to the 
considered time point of study ZOSTER-060 (see Section 6.7).

For whom persistence immunogenicity results are available at the considered time 
point.
10.4.3.
Total Vaccinated cohort for re-vaccination phase
The Total Vaccinated Cohort (TVC) will include all subjects vaccinated with HZ/su in 
the ZOSTER-060 study.
The TVC for analysis of immunogenicity will include subjects vaccinated with HZ/su in 
the ZOSTER-060 study for whom immunogenicity data are available.
The TVC for analysis of safety will include all subjects with at least one HZ/su 
administration in the ZOSTER-060 study documented.
 
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10.4.3.1.
According-to-protocol (ATP) cohort for analysis of immunogenicity
The ATP cohort for analysis of immunogenicity will include all evaluable subjects from 
the TVC:

Who meet all eligibility criteria.

Who have received one or two doses of re-vaccination schedule up to the time point 
considered.

For whom administration site of study vaccine is known/ and correct, as per protocol.

Who have not received any vaccine forbidden in the protocol up to the timepoint 
considered.

Who comply with the procedures and intervals defined in the protocol up to the 
timepoint considered.

Who did not receive a medication/ product leading to exclusion from the ATP 
analysis (see Section 6.6.2) up to the timepoint considered.

Who did not present with an intercurrent medical condition (including herpes zoster) 
leading to elimination from the ATP analysis (see Section 6.7) up to the timepoint 
considered.

Who complied with the vaccination schedule up to the timepoint considered.

Who complied with the blood sample schedule up to the timepoint considered.

Who had immunogenicity results available up to the timepoint considered.
Subjects who experience an episode of suspected HZ up to the considered time point of 
study ZOSTER-060 will be eliminated from the ATP cohort for immunogenicity
subsequent to that time point. These subjects will be analysed separately.
10.5.
Derived and transformed data
10.5.1.
Handling of missing data

For the analysis of solicited symptoms, missing or non-evaluable measurements will 
not be replaced. Therefore, the analysis of the solicited symptoms based on the TVc 
will include only subjects/doses with documented safety data (i.e. symptom screen
completed).

For the analysis of unsolicited symptoms/SAEs/pIMDs/concomitant medication, all 
vaccinated subjects will be considered and subjects who did not report an event will 
be considered as subjects without an event.

For the analysis of immunogenicity, missing or non-evaluable measurements will not 
be replaced. Therefore, a subject will be excluded from an analysis timepoint if any 
measurements are missing or non-evaluable for that timepoint.
 
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10.5.2.
Humoral immune response
A seronegative subject is a subject whose Ab concentration is below the cut-off value.
A seropositive subject is a subject whose Ab concentration is greater than or equal to the 
cut-off value.
The seropositivity rate is defined as the percentage of seropositive subjects.
The Vaccine Response Rate (VRR) for anti-gE is defined as the percentage of subjects 
who have at least:

a 4-fold increase in the anti-gE Ab concentration as compared to the 
pre-vaccination anti-gE Ab concentration, for subjects who are seropositive at 
baseline, or,

a 4-fold increase in the anti-gE Ab concentration as compared to the anti-gE Ab 
cut-off value for seropositivity, for subjects who are seronegative at baseline.
Note: Baseline is the pre-vaccination titre in the initial study ZOSTER-003.
The GMC calculations are performed by taking the anti-log of the mean of the log 
concentration transformations. Ab concentrations below the cut-off of the assay will be 
given an arbitrary value equal to half the cut-off for the purpose of GMC calculation.
The Mean Geometric Increase (MGI) is defined as the geometric mean of the within 
subject ratios of the post-vaccination titre to the Day 0 titre (pre-vaccination titre in the 
initial study).
10.5.3.
CMI response
For the descriptive analyses, the frequency of CD4[2+] T-cells upon in vitro stimulation 
with the gE-antigen (induction condition) is calculated by dividing the number of 
activated CD4[2+] T-cells (numerator) over the total number of CD4 T-cells involved 
(denominator). The same calculation will be performed for the frequency computation for 
any kinds of cells and for each individual activation marker as appropriate.
The frequency of gE-specific CD4 T-cells for each individual subject is calculated as the 
difference between the frequency of CD4[2+] T-cells, upon in vitro stimulation with the 
gE antigen (induction condition) minus the frequency of CD4[2+] T-cells upon in vitro 
stimulation in medium only (background condition). The differences less or equal to one 
are imputed to one gE-specific CD4[2+] T-cell per 106 CD4+ T-cells. The same 
calculation will be performed for the frequency computation for any kind of cells and for 
each individual activation marker as appropriate.
 
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
The GM frequency calculations are performed by taking the anti-log of the mean of 
the log frequency transformations.

The CMI vaccine response to gE will be based on the gE-specific data as computed 
above. The lower limit of linearity (LLL) for the assay will be used as threshold for 
vaccine response assessment and the estimated value will be detailed in the 
Statistical Analysis Plan (SAP). The Vaccine Response (VR) is defined as the 
percentage of subjects who have:

at least a 2-fold increase as compared to the LLL, for subjects with pre-
vaccination T-cell frequencies below the LLL;

at least a 2-fold increase as compared to pre-vaccination T-cell frequencies, for 
subjects with pre-vaccination above the LLL.
10.6.
Analysis of demographics
The analysis of demography for the persistence phase at Month 108 and Month 120 post 
first dose of initial vaccination course will be performed on the Total enrolled cohort and 
the ATP cohort for persistence.

Demographic characteristics (age at Month 108 and Month 120 persistence phase 
respectively, gender, geographic ancestry, race and ethnicity), cohort description and 
withdrawal status will be summarized overall.

The mean age at Month 108 and Month 120 (plus range and standard deviation) of 
the enrolled subjects, as a whole, and stratified by age group will be calculated.

The distribution of subjects enrolled among the study sites will be tabulated.

Frequency tables will be generated for categorical variables such as gender.

Mean, median and standard error will be provided for continuous data such as age.
The analysis of demography for the re-vaccination phase will be performed on the Total 
vaccinated cohort and ATP cohort for immunogenicity.

Demographic characteristics (age at first re- vaccination dose, gender, geographic 
ancestry, race and ethnicity), cohort description and withdrawal status will be 
summarized overall.

The mean age at first study re-vaccination dose (plus range and standard deviation) 
of the enrolled subjects, as a whole, and stratified by age group will be calculated.

The distribution of subjects enrolled among the study sites will be tabulated.
 
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
Frequency tables will be generated for categorical variables such as gender.

Mean, median and standard error will be provided for continuous data such as age.
10.7.
Analysis of immunogenicity
10.7.1.
Assessment of follow-up of persistence phase Months 108 and 
120 post first dose of initial vaccination course.
The analysis for the persistence phase at Month X (Month 108 and Month 120) post first 
dose of initial vaccination course will be performed on the ATP cohort for persistence at 
Month X – adapted for each time point. If, the percentage of subjects with serological 
results excluded from the ATP cohort for analysis of persistence is 5% or more, a second 
analysis based on the Total enrolled cohort will be performed to complement the ATP 
analysis.
All analyses will be performed overall and by age stratum if the number of subjects is 
sufficient in each stratum.
Humoral Immune response endpoint
For the humoral immune response, at each timepoint that a blood sample is available (at 
Months 0, 3, 12, 24, 36, 48, 60, 72, 108 and 120) post initial vaccination, the following 
parameters (with 95% CIs) will be tabulated overall, and by age group:

Geometric mean concentrations (GMCs) of anti-gE Ab with 95% confidence 
interval (CIs).

Humoral seropositivity rates with exact 95% confidence interval (CIs); 

Descriptive statistics of the fold over pre-vaccination in the initial study at 
months 3, 12, 24, 36, 48, 60, 72, 108 and 120 (Mean, Standard deviation, Min, 
Q1, Median, Q3, Max).

The geometric mean of the ratio Post month x over pre-vaccination in the initial 
study with 95% CI.

The distribution of antibody titres will be tabulated and also presented using 
reverse cumulative curves.
CMI endpoint
For CMI response, the following parameters (for gE specific CD4[2+] frequency and 
CD4[+2] T-cell following induction with gE) will be tabulated overall and by age group 
[60-69,>=70 YOA at time of initial vaccination in study ZOSTER-003] at Months 0, 3, 
12, 24, 36, 48, 60, 72, 108 and 120 post first dose of initial vaccination:
 
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Descriptive statistics (N, mean, SD, min, Q1, median, Q3, max) of the following 
parameters will be tabulated:

Descriptive statistics of the frequency of CD4+ T-cells secreting at least two 
activation markers (from among IFN-, IL-2, TNF-, CD40L) for gE-specific 
stimulation.

Descriptive statistics of the fold over pre-vaccination in the initial study at 
months 3, 12, 24, 36, 48, 60, 72, 108 and 120.
Exploratory analysis
A piece-wise linear mixed model and modified power law model for repeated 
measurements (all data available from month 0, 3, 12, 24, 36, 48, 60, 72, 108 and 120 
post first dose of initial vaccination) will be used to model over time the frequency of
CD4 T-cells producing at least 2 immunological activation markers following stimulation 
with gE [Ledent, 2009] and gE antibody concentrations. The covariates for the frequency 
of CD4 T-cells will include background CD4 frequency, log transformed prevaccination 
response and the log-transformed of the time elapsed (measured in months) following the 
initial vaccination. The covariates for the anti-gE will include log transformed 
prevaccination response. The model allows for random individual deviations from the 
overall mean response (random intercept) and, if necessary according to Schwarz’ 
Bayesian Information Criterion (SBIC) and Akaike’s Information Criterion (AIC) 
goodness-of-fit statistics , for a random individual deviation from the overall CD4-
frequency decay over time (random coefficient [slope]).
10.7.2.
Assessment of re-vaccination phase
The analysis of re-vaccination phase will be based on the ATP cohort for analysis of 
immunogenicity. If, the percentage of vaccinated subjects with serological results 
excluded from the ATP cohort for analysis of immunogenicity is 5% or more, a second 
analysis based on the TVc will be performed to complement the ATP analysis.
All analyses will be performed overall and by age stratum (60-69, 70 YOA at time of 
initial vaccination in study ZOSTER-003) if the number of subjects is sufficient in each 
stratum.
Humoral Immune response endpoint
For the humoral immune response, at each timepoint that a blood sample is available (at 
Months 120, 121 and 123) post-revaccination, the following parameters (with 95% CIs) 
will be tabulated overall, and by age group (60-69, 70 YOA at time of initial 
vaccination in study ZOSTER-003):

Geometric mean concentrations (GMCs) of anti-gE Ab with 95% confidence interval 
(CIs); 

Humoral seropositivity rates with exact 95% confidence interval (CIs);

Vaccine response rates [post re-vaccination over pre-vaccination in the initial study] 
with 95% confidence interval (CIs);
 
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
The geometric mean of the ratio Post Month 1 (Month 121) and post Month 3 
(Month 123) post re-vaccination (current study) over Visit Month 0 (Month 120), in 
the current study with 95% CI;

The geometric mean of the ratio Post Month 1 (Month 121) and post Month 3 
(Month 123) post re-vaccination (current study) over pre-vaccination in the initial 
study with 95% CI;

The distribution of antibody titres will be tabulated and also presented using reverse 
cumulative curves.
CMI endpoint
For CMI response, the following parameters (for gE specific CD4[2+] frequency and 
CD4[+2] T-cell following induction with gE) will be tabulated overall and by age group 
(60-69, 70 YOA at time of initial vaccination in study ZOSTER-003) at Months M0 
(Month 120), M1 (Month 121) and M3 (Month 123) post re-vaccination:
Descriptive statistics (N, mean, SD, min, Q1, median, Q3, max) of the following 
parameters will be tabulated:

Descriptive statistics of the frequency of CD4+ T-cells secreting at least two 
activation markers (from among IFN-, IL-2, TNF-, CD40L) for gE-specific 
stimulation.
10.7.3.
Assessment of persistence (Post re-vaccination)
Persistence data will be analyzed at Month 134 (i.e. 12 months after last dose of re-
vaccination) timepoint after re-vaccination.
The analysis of antibody persistence (post re-vaccination) at Month 134 will be based on 
the ATP cohort for analysis of immunogenicity at month 134. If the percentage of 
subjects who come back for this follow-up with serological results excluded from the 
ATP cohort is higher than 5%, a second analysis based on the Total Vaccinated Cohort at 
Month 134 will be performed to complement the ATP analysis.
Humoral immune response endpoint:
For the humoral immune response, if a blood sample is available at Month 134, the 
following parameters (with 95% CIs) will be tabulated overall and by age group (60-69, 
70 YOA at time of initial vaccination in study ZOSTER-003):

GMC of anti-gE Ab with 95% CI; 

Humoral seropositivity rate with 95% CI;

Vaccine response rates [Month 134 over pre-vaccination in the initial study] with
95% CI;

The geometric mean of the ratio Month 134 over Visit Month 0 (Month 120), in the 
current study with 95% CI;
 
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
The geometric mean of the ratio Month 134 over pre-vaccination in the initial study 
with 95% CI;

The distribution of antibody titres will be tabulated and also presented using reverse 
cumulative curves.
CMI endpoint:
For CMI response, the following parameters (for gE specific CD4[2+] frequency and 
CD4[+2] T-cell following induction with gE) will be tabulated overall and by age group 
(60-69, 70 YOA at time of initial vaccination in study ZOSTER-003) at M134 (12 
months after last dose of re-vaccination):
Descriptive statistics (N, mean, SD, min, Q1, median, Q3, max) of the following 
parameters will be tabulated:

Descriptive statistics of the frequency of CD4+ T-cells secreting at least two 
activation markers (from among IFN-, IL-2, TNF-, CD40L) for gE-specific 
stimulation.
10.8.
Analysis of safety
10.8.1.
Persistence phase
Analyses in the follow-up of persistence phase will be performed on the Total enrolled 
cohort.
All safety analyses might be performed by age stratum (60-69 and ≥ 70 YOA at the time 
of initial vaccination course in study ZOSTER-003) when the size of the category is 
considered meaningful.
Proportion of subjects reporting at least one serious adverse events classified by 
MedDRA Primary System Organ Class and Preferred Term related to study participation 
or to a concurrent GSK medication/vaccine between Month 108 and Month 120 post first 
dose of initial vaccination will be tabulated, with exact 95% CI.
Proportion of subjects reporting at least one serious adverse events related to initial 
vaccination from study ZOSTER-003 classified by MedDRA Primary System Organ 
Class and Preferred Term between Month 108 and Month 120 post first dose of initial
vaccination will be tabulated with exact 95% CI.
Proportion of subjects experiencing a suspected HZ episode between Month 108 and 
Month 120 post first dose of initial vaccination will be tabulated with exact 95% CI.
 
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10.8.2.
Re-vaccination phase
Analyses post the re-vaccination phase will be performed on the Total vaccinated cohort.
All safety analyses might be performed by age stratum (60-69 and ≥ 70 YOA at the time 
of initial vaccination as in ZOSTER-003 study) when the size of the category is 
considered meaningful.

The percentage of subjects with at least one local solicited AE, with at least one 
general solicited AE and with any solicited AEs during the solicited 7-day follow-up 
period will be tabulated with exact 95% CI after each vaccine dose and overall. The 
same tabulation will be performed for grade 3;

The percentage of subjects reporting each individual solicited local and general AE 
during the solicited 7-day follow-up period will be tabulated with exact 95% CI. For 
all solicited symptoms, the same tabulation will be performed for grade 3 solicited 
AEs and for solicited general AEs with relationship to vaccination ;

The percentage of subjects reporting temperature by half degree (°C) cumulative 
increments. Similar tabulations will be performed for any fever with a causal 
relationship to vaccination and for any fever resulting in a medically attended visit ;

The proportion of subjects with at least one report of unsolicited AE classified by the 
MedDRA Preferred Terms and reported up to 30 days after each vaccination will be 
tabulated with exact 95% CI;

The same tabulation will be performed for grade 3 unsolicited AEs and for 
unsolicited AEs with a relationship to vaccination. The proportion of AEs resulting 
in a medically attended visit will also be tabulated ;

Total number/percentages of doses (per dose and overall) followed by AEs will be 
tabulated;

Number of subjects with pIMDs will be tabulated;

All SAEs will be tabulated;

SAEs related to vaccine will be tabulated and described;

SAEs related to study participation or to GSK concomitant medication/vaccine will 
be tabulated and described;

Adverse events (AEs)/SAEs leading to withdrawal from the study will be tabulated;

Intercurrent medical conditions will be tabulated.
 
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10.9.
Interpretation of analyses
Long term follow-up phase:
All the analyses will be descriptive with the aim to characterize the long-term immune 
profile.
Re-vaccination phase:
All the analyses will be descriptive with the aim to characterize the immune profile after 
2 additional doses of HZ/su vaccine.
10.10.
Conduct of analyses
Any deviation(s) or change(s) from the original statistical plan outlined in this protocol 
will be described and justified in the final study report.
10.10.1.
Sequence of analyses
The analysis will be performed in the following steps:

Intermediate Month 108 analysis will be performed in order to explore the 
immunological response. No clinical report will be written at that time.

Intermediate analysis after the active phase (one month after last dose of re-
vaccination) will be performed. An intermediate clinical study report (CSR) will be 
written at this point of time. This report will also include the Month 108 analysis.

A final analysis on immunogenicity and safety will be performed at the time of study 
end (Visit 6, Month 134), once all data are available and cleaned. An integrated 
clinical CSR will be written at this point of time. 
10.10.2.
Statistical considerations for interim analyses
All analyses will be conducted on final data and therefore no statistical adjustment for 
interim analyses is required. Because the analysis is purely descriptive, no adjustment on 
type I error is foreseen.
11.
ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality and publications must be fulfilled. 
11.1.
electronic Case Report Form instructions
A validated GSK defined electronic data collection tool will be used as the method for 
data collection. 
 
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In all cases, subject initials will not be collected nor transmitted to GSK. Subject data 
necessary for analysis and reporting will be entered/transmitted into a validated database 
or data system. Clinical data management will be performed in accordance with 
applicable GSK standards and data cleaning procedures.
While completed eCRFs are reviewed by a GSK Biologicals’ Site Monitor at the study 
site, omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction of omissions or inconsistencies with documentation and 
approval by the investigator or appropriately qualified designee. In all cases, the 
investigator remains accountable for the study data. 
The investigator will be provided with a CD-ROM of the final version of the data 
generated at the investigational site once the database is archived and the study report is 
complete and approved by all parties.
11.2.
Study Monitoring by GSK Biologicals
GSK will monitor the study to verify that, amongst others, the: 

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits.
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform an eCRF review and a Source Document 
Verification (SDV). By SDV we understand verifying eCRF entries by comparing them 
with the source data that will be made available by the investigator for this purpose. 
The Source Documentation Agreement Form describes the source data for the different 
data in the eCRF. This document should be completed and signed by the site monitor and 
investigator and should be filed in the monitor’s and investigator’s study file. Any data 
item for which the eCRFwill serve as the source must be identified, agreed and 
documented in the source documentation agreement form. 
For eCRF, the monitor freezes completed and approved screens at each visit.
Upon completion or premature discontinuation of the study, the monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations, GCP, and GSK procedures.
 
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11.3.
Record retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere) in a safe and 
secure location. The records must be easily accessible, when needed (e.g. audit or 
inspection), and must be available for review in conjunction with assessment of the 
facility, supporting systems, and staff. Where permitted by applicable laws/regulations or 
institutional policy, some or all of these records can be maintained in a validated format 
other than hard copy (e.g. microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions 
are legible and are a true and accurate copy of the original and meet accessibility and 
retrieval standards, including re-generating a hard copy, if required. Furthermore, the 
investigator must ensure that an acceptable back-up of the reproductions exists and that 
there is an acceptable quality control procedure in place for making these reproductions.
GSK will inform the investigator/institution of the time period for retaining these records 
to comply with all applicable regulatory requirements. However, the 
investigator/institution should seek the written approval of the sponsor before proceeding 
with the disposal of these records. The minimum retention time will meet the strictest 
standard applicable to a particular site, as dictated by ICH GCP, any institutional 
requirements, applicable laws or regulations, or GSK standards/procedures. 
The investigator/institution must notify GSK of any changes in the archival 
arrangements, including, but not limited to archival at an off-site facility, transfer of 
ownership of the records in the event the investigator leaves the site. 
11.4.
Quality assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 
inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution 
agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
his/her time and the time of his/her staff to the auditor/inspector to discuss findings and 
any relevant issues.
11.5.
Posting of information on publicly available clinical trial 
registers and publication policy
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of subjects begins.
Summaries of the results of GSK interventional studies (phase I-IV) are posted on 
publicly available results registers within 12 months of the primary completion date for 
studies of authorised vaccines and 18 months for studies of non-authorised vaccines. 
 
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GSK also aims to publish the results of these studies in the searchable, peer reviewed 
scientific literature. Manuscripts are submitted for publication within 24 months of the 
last subject’s last visit. At the time of publication, this protocol will be fully disclosed.
Study information from this protocol will be posted on publicly available clinical trial 
registers following finalization of the protocol and, whenever possible, before the 
initiation of the analysis/study. 
Results are publicly registered within 8 months of the completion of the analysis. GSK 
also aims to publish the results of these studies in the searchable, peer reviewed scientific 
literature. Manuscripts are submitted within 18 months of the completion of the analysis.
At the time of publication, this protocol will be fully disclosed.
11.6.
Provision of study results to investigators
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location.
GSK Biologicals will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the study 
subjects, as appropriate.
12.
COUNTRY SPECIFIC REQUIREMENTS
12.1.
Requirements for Germany
EXPLANATORY STATEMENT CONCERNING GENDER DISTRIBUTION 
(ARTICLE 7, PARAGRAPH 2 (12) OF THE GERMAN GCP ORDER)

There is no intention to conduct specific analyses investigating the relationship 
between the gender of the subjects and the efficacy, immunogenicity or safety of the 
GSK Biologicals’ gE/AS01B vaccine. 
 
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13.
REFERENCES
Araújo LQ, MacIntyre CR, Vujacich C. Epidemiology and burden of herpes zoster and 
post-herpetic neuralgia in Australia, Asia and South America. Herpes 2007; 14(Suppl 2): 
40A–44A.
Carter WP, Germann CA, Baumann MR. Ophthalmic diagnoses in the ED: herpes zoster 
ophthamicus. Am. J. Ophthalmol. 2008; 612– 617.
CDC. Prevention of herpes zoster. Recommendations of the Advisory Committee on 
Immunization Practices (ACIP). MMWR. 2008; 57: 1-30.
Cohen JI, Straus SE, Arvin AM. Varicella zoster virus and its replication. 2007; p. 2774-
2818. In D. M. Knipe and P. M. Howley (ed.), Fields virology, 5th ed. Lippincott/The 
Williams & Wilkins Co., Philadelphia, PA.
Dworkin RH, Johnson RW, Breuer J, et al. Recommendations for the management of 
herpes zoster. Clin Infect Dis. 2007;44 Suppl 1:S1–26.
FDA, U.S. Department of Health and Human Services, Center for Biologics Evaluation 
and Research. Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Version of 
September 2007.
Garcia Cenoz M, Castilla J, Montes Y, et al. Varicella and herpes zoster incidence prior 
to the introduction of systematic child vaccination in Navarre, 2005-2006. An Sist Sanit 
Navar. 2008; 31: 71-80.
Gilden D, Cohrs RJ, Mahalingam R, et al. Varicella zoster virus vasculopathies: diverse 
clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet 
Neurology. 2009;8(8):731–740.
Kang CI, Choi CM, Park TS, et al. Incidence of herpes zoster and seroprevalence of 
varicella-zoster virus in young adults of South Korea. Int J Inf Dis. 2008; 12(3): 245-7.
Lal H, Cunningham AL, Godeaux O et al. Efficacy of an Adjuvanted Herpes Zoster 
Subunit Vaccine in Older Adults. N Engl J Med. 2015: DOI: 10.1056/NEJMoa1501184.
Ledent E., Van-der-Most, R. Vaccine Effect on Cell-Mediated Immunity Accounting for 
Undesired Background Response in Intracellular Cytokine Staining, Poster presented at 
BDS conference October 2009. 
Oxman MN, Levin MJ, Johnson GR, et al. Shingles Prevention Study Group. A vaccine 
to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005; 
352: 2271-84.
Schmader KE, Dworkin RH. Natural history and treatment of herpes zoster. The Journal 
of pain. 2008;9(1):S3–S9.
 
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Sperber SJ, Smith BV, Hayden FG. Serologic response and reactogenicity to booster 
immunization of healthy seropositive adults with live or inactivated varicella vaccine. 
Antiviral Res. 1992; 17: 213-22.
Toyama N, Shiraki K, and Members of the Society of the Miyazaki Prefecture 
Dermatologists. Epidemiology of herpes zoster and its relationship to varicella in Japan: 
A 10-year survey of 48,388 herpes zoster cases in Miyazaki prefecture. J Med Virol.
2009; 81(12): 2053-58.
 
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APPENDIX A
LABORATORY ASSAYS
Specific Ab (anti-gE) measurements:
Anti-gE ELISA: Anti-gE Ab concentrations will be measured using an anti-gE ELISA. 
Diluted blood serum samples of study subjects will be added to microtitre wells pre-
coated with gE antigen. Secondary peroxidase-conjugated anti-human Abs will be added, 
which bind to the primary human anti-gE Abs. After incubation of the microtitre 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.
Intracellular cytokine staining (ICS):
CMI responses will be performed by GSK Biologicals (or designated laboratory) on 
thawed Peripheral Blood Mononuclear Cells (PBMCs) by ICS. The assay will be 
performed on samples collected during the course of the study. This assay provides 
information on the frequency of CD4 T cells responding to culture medium or antigens 
(gE peptide pool) by secreting cytokine molecules involved in immunity such as IFN-, 
IL-2, TNF-, and CD40L.
Briefly, PBMC collected from the subjects are stimulated for two hours using culture 
medium (for evaluation of the non-specific response), a pool of overlapping peptides 
covering the entire sequence of the vaccine antigen gE. Then, an intracellular block 
(brefeldin A) is added to inhibit cytokine secretion for a subsequent overnight incubation. 
Cells are then harvested, stained for surface markers (CD3, CD4 and CD8) and fixed. 
The fixed cells are then permeabilised and stained with anti-cytokine Abs, washed and 
analyzed by cytofluorometry.
The results of ICS assays are expressed as the frequency of specific CD4 T cells per 
million total CD4 T cells.
 
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APPENDIX B
CLINICAL LABORATORIES
Table 18
GSK Biologicals’ laboratories
Laboratory
Address
GSK Biologicals Global Vaccine Clinical 
Laboratory, Rixensart
Biospecimen Reception - B7/44
Rue de l'Institut, 89 - B-1330 Rixensart - Belgium
GSK = GlaxoSmithKline
Table 19
Outsourced laboratories
Laboratory
Address
CEVAC - University of Ghent
De Pintelaan, 185 - B-9000 Ghent - Belgium
CEVAC = Centre for Vaccination
 
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APPENDIX C
AMENDMENTS AND ADMINISTRATIVE 
CHANGES TO THE PROTOCOL
GlaxoSmithKline Biologicals
Vaccine Value & Health Science (VVHS)
Protocol Amendment 1
eTrack study number 
and Abbreviated Title
204926 (ZOSTER-060 EXT:003)
EudraCT number
2015-004400-30
Amendment number:
Amendment 1
Amendment date:
18 August 2017
Co-ordinating author:
 Scientific Writer
Rationale/background for changes:

This protocol amendment was developed to clarify in Section 8.2.1 that:

All SAEs will be collected and recorded from the time of the first receipt of 
study vaccine at Visit 2 until the subject is discharged from the study or until 
the end of the study;

All AEs/SAEs leading to withdrawal from the study will be collected and 
recorded from Visit 1 up to the last study visit at the end of the study;
and by aligning Table 4 and Table 15 with the text in Section 8.2.1.

Although no confirmed signals related to hypersensitivity reactions (including 
anaphylaxis) have been identified during the HZ/su clinical program, a mitigation 
strategy for the potential risk has been added to the Risk Assessment Section 1.3.1.

The list of the contributing authors was updated and minor typographic errors were 
corrected.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
Cover page:
Co-ordinating authors

 Scientific Writer
Contributing authors

 Clinical Research and 
Development Lead

 Study Delivery Lead

 Project Statistician
 
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PPD
PPD
PPD
PPD
PPD

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
 Clinical Safety representative

 Zoster Portfolio level Clinical 
and Epidemiology Project Research and 
Development Lead for Zoster, Belgian RDC
Sponsor page:
Sponsor signatory
Lidia Oostvogels, Zoster Portfolio level Clinical and 
Epidemiology Project Research and Development
Lead for Zoster, Belgian RDC
LIST OF ABBREVIATIONS
QS21 Stimulon®:
Quillaja saponaria Molina, fraction 21) (Licensed by 
GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., Lexington, MA, USA)
TRADEMARKS
Trademarks not owned by the 
GlaxoSmithKline group of companies
Generic descriptions
QS-21 Stimulon®:
(Quillaja saponaria Molina, fraction 21) 
(Licensed by GSK from Antigenics Inc, a 
wholly owned subsidiary of Agenus Inc., 
Lexington, MA, USA).
Section 1.3.1 Risk Assessment
Important 
Potential/Identified Risk
Data/Rationale for Risk
Mitigation Strategy
Investigational HZ/su vaccine
Theoretical risk of acquiring a 
vaccine induced autoimmune 
disease after vaccinationRisk 
of pIMD following the HZ/su 
vaccination.
No confirmed signals related 
to this potential risk have 
been identified during the 
clinical program. Available 
clinical data do not highlight 
any concern.
Close monitoring of pIMDs as per 
study protocol.
The potential risk of events of possible 
autoimmune aetiology to occur is 
mentioned in the ICF. In addition, the 
ICF advises subjects to contact the 
study doctor or the study staff 
immediately, should they get any 
symptoms that they feel maybe 
serious.
Hypersensitivity reactions 
(including anaphylaxis.
No confirmed signals 
related to this potential risk 
have been identified during 
the clinical program. 
Available clinical data do 
not highlight any concern.
Administration of the study 
vaccination is to be preceded by a 
review of the subjects’ medical 
history (especially with regard to 
previous vaccination and possible 
occurrence of undesirable events) 
 
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Important 
Potential/Identified Risk
Data/Rationale for Risk
Mitigation Strategy
and a clinical examination.
As with all injectable vaccines, 
appropriate medical treatment and 
supervision should always be 
readily available in case of an 
anaphylactic event following the 
administration of the vaccine.
Section 5.5
Outline of study procedures
Table 4
List of study procedures
Epoch 001
Type of contact
Visit 1 
Visit 2 
Visit 3 Visit 4 Visit 5 Contacts Visit 6 
Timepoints
Year 9‡
Month 
108 § 
Year 10‡
Month 
120 # 
Month 
121 #
Month 
122 #
Month 
123 #
Month 
126 
Month 
129 
Month 
132
Month 
134 #
Sampling timepoints for Long-Term Follow-up 
Phase
Post-
Vacc 
Post-
Vacc 
Sampling timepoints for Re-vaccination Phase
Pre-
Vacc1 
Post-
Vacc1 
Post-
Vacc2 
Post-
Vacc2 
Recording of any SAEs after the first dose from 
the re-vaccination course at Visit 2
●
●
●
●
●
●
Recording of any AEs/SAEs leading to 
withdrawal from the study
●
●
●
●
●
●
●
Section 8.2.1 Time period for detecting and recording adverse events and serious 
adverse events
All AEs starting 30 days following administration of each dose/the dose of study vaccine 
(Day 0 to Day 29) must be recorded into the appropriate section of the eCRF, irrespective 
of intensity or whether or not they are considered vaccination-related.
The time period for collecting and recording SAEs will begin at the first study visit and 
will end at the end of the study for each subject. SAEs that are related to the 
investigational vaccine administered during re-vaccination phase will be collected and 
recorded from the time of the first receipt of study vaccine at Visit 2 until the subject is 
discharged from the study or until the end of the study (Table 15). See Section 8.3 for 
instructions on reporting of SAEs.
SAEs related to initial vaccination course from study ZOSTER-003 will be collected and 
recorded from the time of the first study visit and will end at the time of the first receipt 
of dose one of re-vaccination course.
SAEs that are related to the investigational vaccine administered during re-vaccination 
phase will be collected and recorded from the time of the first receipt of study vaccine 
until the subject is discharged from the study.
 
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All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the first study visit up to the last study visit at the end of the study.
SAEs related to initial vaccination course from study ZOSTER-003 will be collected 
and recorded from the time of the first study visit and will end at the time of the first 
receipt of dose one of re-vaccination course.
 
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Table 15
Reporting periods for collecting safety information
Event
Visit 1*
Visit 2
Visit 3
Visit 4
Visit 5
Contacts
Visit 6
Timepoint
Year 9
Year 10
Vacc 1
Post 
Vacc
Post 
Vacc
Post Vacc
Vacc 2
Post-
Vacc
Post 
Vacc
Month 108
Month 120
6 days 
post V1
29 days 
post V1
Month 121
Month 122
6 days 
post V2
29 days 
post V2
Month 123 Month 126, 
129 and 132
Month 134
Reporting of any SAEs after the first 
dose from the re-vaccination course
at Visit 2
Reporting of any AEs/SAEs leading 
to withdrawal from the study
Reporting of all serious adverse events 
(SAEs) related to investigational 
vaccine, study participation or to a 
concurrent GSK medication/vaccine†
CONFIDENTIAL
204926 (ZOSTER-060 EXT:003)
Protocol Amendment 1 Final
be4a47156c7472c04f2d2d28f64476e1f625754a
93
18-AUG-2017

PPD