Cross-vaccination Study of GSK Biologicals' Lyophilized Formulation of the Herpes Zoster Subunit (HZ/su) Vaccine (GSK 1437173A) in Subjects Who Previously Received Placebo in ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) Studies
Phase: PHASE3
Conditions: Herpes Zoster
Sponsor: GlaxoSmithKline

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
1
Clinical Study Protocol
Sponsor:
GlaxoSmithKline Biologicals
Rue de l’Institut 89, 1330 Rixensart, Belgium
Primary Study vaccine and 
number
GlaxoSmithKline (GSK) Biologicals’ Lyophilized 
formulation of the Herpes Zoster subunit (HZ/su) 
vaccine (GSK 1437173A)
eTrack study number and 
Abbreviated Title
204486 (ZOSTER-056)
Investigational New Drug 
(IND) number
BB-IND-13857
EudraCT number
2015-000965-30
Date of protocol
Final Version 1: 09 November 2015
Date of protocol 
amendment
Amendment 1 Final: 17 December 2015
Amendment 2 Final: 11 January 2017
Amendment 3 Final: 30 May 2017
Title
Cross-vaccination study of GSK Biologicals’ 
Lyophilized formulation of the Herpes Zoster subunit 
(HZ/su) vaccine (GSK 1437173A) in subjects who 
previously received placebo in ZOSTER-006 and 
ZOSTER-022 studies.
Detailed Title
A Phase IIIB, non-randomized, open-label, multi-
country, multi-centric cross-vaccination study to 
evaluate the safety of GSK Biologicals' Herpes Zoster 
subunit (HZ/su) vaccine when administered 
intramuscularly on a two-dose schedule to subjects 
who previously received placebo in ZOSTER-006 and 
ZOSTER-022 studies.
Co-ordinating authors
 Scientific Writer;
, Scientific Writer (XPE Pharma and 
Science for GSK Biologicals)
Contributing authors
!
, Clinical Research and Development 
Lead
!
, Project Statistician
!
, Study Delivery Lead
!
, Vice President, Vaccine 
Development Lead
!
, Vaccine Supply Coordinator

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
1
30-MAY-2017
PPD
PPD
PPD
PPD
PPD
PPD
PPD

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
2
eTrack study number and 
Abbreviated Title
204486 (ZOSTER-056)
Investigational New Drug 
(IND) number
BB-IND-13857
EudraCT number
2015-000965-30
Detailed Title
A Phase IIIB, non-randomized, open-label, multi-
country, multi-centric cross-vaccination study to 
evaluate the safety of GSK Biologicals' Herpes 
Zoster subunit (HZ/su) vaccine when administered 
intramuscularly on a two-dose schedule to subjects 
who previously received placebo in ZOSTER-006 
and ZOSTER-022 studies.
Contributing authors
!
, Clinical Safety 
representative
!
, Oversight Data Manager
!
 and 
 (USA), Global 
Regulatory Affairs
!
, Global Patent
!
, Lead Statistician
!
, 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.

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
2
30-MAY-2017
PPD
PPD
PPD
PPD
PPD
PPD
PPD

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
3
Protocol Amendment 3 Sponsor Signatory Approval
eTrack study number and 
Abbreviated Title
204486 (ZOSTER-056)
IND number
BB-IND-13857
EudraCT number
2015-000965-30
Date of protocol amendment
Amendment 3 Final: 30 May 2017
Detailed Title
A Phase IIIB, non-randomized, open-label, multi-
country, multi-centric cross-vaccination study to 
evaluate the safety of GSK Biologicals' Herpes Zoster 
subunit (HZ/su) vaccine when administered 
intramuscularly on a two-dose schedule to subjects 
who previously received placebo in ZOSTER-006 
and ZOSTER-022 studies.
Sponsor signatory
Lidia Oostvogels, Clinical and Epidemiology Project 
Lead for Zoster, Belgian RDC
Signature
Date
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
3
30-MAY-2017
- ----------------Checksum----------------!Ver.!Created On -   -
c07d97e55cdd80c89a37b72805073d69201142a4 2.0 6/6/2017 6:22:42 AM -   -
---------------------------------------------------------------------------- -
For internal use only

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
4
Protocol Amendment 3 Rationale
Amendment number:
Amendment 3
Rationale/background for changes:

This country specific protocol amendment was developed in order to remove the 
Voice of the Patient (VoP) initiative text from Section 12.3 since this initiative was 
not adopted in Japan.

This is a country specific administrative change for the US since the back-up study 
contact telephone number for reporting SAEs, pregnancies and pIMDs in the US 
was removed from Section 8.4.2. This US telephone number, which was originally 
provided to the US sites as a courtesy, became inactivated over the course of the 
study and the US Fax number is retained as the back-up study contact number for 
reporting SAEs, pregnancies and pIMDs.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
4
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
5
Protocol Amendment 3 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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
5
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
6
eTrack study number and 
Abbreviated Title
204486 (ZOSTER-056)
IND number
BB-IND-13857
EudraCT number
2015-000965-30
Date of protocol amendment
Amendment 3 Final: 30 May 2017
Detailed Title
A Phase IIIB, non-randomized, open-label, multi-
country, multi-centric cross-vaccination study to 
evaluate the safety of GSK Biologicals' Herpes 
Zoster subunit (HZ/su) vaccine when administered 
intramuscularly on a two-dose schedule to subjects 
who previously received placebo in ZOSTER-006 
and ZOSTER-022 studies.
Investigator name
Signature
Date
Leiter der klinischen 
Prüfung name, function and 
title
Signature
Date
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
6
30-MAY-2017
- ----------------Checksum----------------!Ver.!Created On -   -
c07d97e55cdd80c89a37b72805073d69201142a4 2.0 6/6/2017 6:22:42 AM -   -
---------------------------------------------------------------------------- -
For internal use only

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
7
eTrack study number and 
Abbreviated Title
204486 (ZOSTER-056)
IND number
BB-IND-13857
EudraCT number
2015-000965-30
Date of protocol amendment
Amendment 3 Final: 30 May 2017
Detailed Title
A Phase IIIB, non-randomized, open-label, multi-
country, multi-centric cross-vaccination study to 
evaluate the safety of GSK Biologicals' Herpes 
Zoster subunit (HZ/su) vaccine when administered 
intramuscularly on a two-dose schedule to subjects 
who previously received placebo in ZOSTER-006 
and ZOSTER-022 studies.
GSK Japan study 
representative/Joint Vaccine 
Co representative name, 
function and title
Signature
Date
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
7
30-MAY-2017
- ----------------Checksum----------------!Ver.!Created On -   -
c07d97e55cdd80c89a37b72805073d69201142a4 2.0 6/6/2017 6:22:42 AM -   -
---------------------------------------------------------------------------- -
For internal use only

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
8
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 8.4.2.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
8
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
9
SYNOPSIS
Detailed Title
A Phase IIIB, non-randomized, open-label, multi-country, 
multi-centric cross-vaccination study to evaluate the safety of 
GSK Biologicals' Herpes Zoster subunit (HZ/su) vaccine 
when administered intramuscularly on a two-dose schedule to 
subjects who previously received placebo in ZOSTER-006 
and ZOSTER-022 studies.
Indication
Prevention of Herpes Zoster (HZ) and related complications 
in adults aged 50 years and older and in immunocompromised
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 HZ, a recombinant subunit (su) vaccine 
consisting of Varicella-zoster Virus (VZV) glycoprotein E 
(gE) as antigen and an adjuvant system (AS01), has been 
evaluated in previous studies in healthy 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, a 
gE antigen dose of 50 µg and the adjuvant system AS01B
were selected for the final vaccine formulation. Henceforth, 
the final vaccine formulation will be referred to as HZ/su.
Two large pivotal Phase III trials (ZOSTER-006 enrolling 
subjects ≥ 50 Years Of Age [YOA], and ZOSTER-022 
enrolling subjects ≥ 70 YOA,) are being conducted to evaluate 
the Vaccine Efficacy (VE) and safety of GSK Biologicals’ 
HZ/su vaccine. These trials 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 
VE results from the ZOSTER-006 Phase III trial demonstrated 
the HZ/su vaccine to be highly efficacious in the prevention of 
HZ with no safety concerns raised in this population of 
subjects ≥ 50 YOA. Results received up to date from the 
ZOSTER-022 Phase III trial and from a prespecified pooled 
analysis over both studies confirmed these findings.
According to the ZOSTER-006/ZOSTER-022 protocol and 
Informed Consent form (ICF), once these studies are
concluded and HZ/su vaccine proved to be efficacious and 
safe, the control vaccine group would be offered the HZ/su 
vaccine in a cross-vaccination setting.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
9
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
10
Potentially eligible subjects who previously received placebo
in ZOSTER-006/ZOSTER-022 will now be offered cross-
vaccination.
In a previously completed study (ZOSTER-033) conducted in 
older adults (≥ 50 YOA) with a history of previous HZ, the 
immunogenicity profile and the safety profile of HZ/su did not 
appear to be different from what has been observed in other 
studies in older adults with no previous history of HZ. Clinical 
efficacy against recurrent HZ, was not evaluated in this 
population. However based on the very high efficacy observed 
in the phase III clinical efficacy studies in individuals without 
previous HZ (ZOE-50 and ZOE-70) who received the HZ/su 
vaccine, anticipated benefits against recurrence of HZ may be 
expected.

Rationale for the study design
Since the HZ/su vaccine has not yet been licensed and 
marketed, this study is being conducted to enable potentially 
eligible subjects who previously received placebo in 
ZOSTER-006 or ZOSTER-022 to receive the HZ/su vaccine.
Study ZOSTER-056 is an open-label, multi-centric and single 
arm study to cross-vaccinate and collect safety data from 
subjects ≥ 50 YOA who previously received placebo.
Objective
Primary

To evaluate the safety, in terms of unsolicited Adverse 
Events (AEs), Serious Adverse Events (SAE) and 
potential Immune Mediated Disease (pIMD) in all 
subjects, following administration of each dose of the 
HZ/su vaccine.
Secondary

To evaluate the incidence of suspected HZ episodes (self-
reported or medically diagnosed) during the entire study 
period.
Study design

Experimental design: Phase IIIB open-label, non-
randomised, multi-centric , multi-country cross-
vaccination study, with a single group.

Duration of the study: Approximately 14 months. Each 
subject will be followed for safety for approximately 12 
months after the second vaccine dose.

Epoch 001: Primary starting at Visit 1 (Month 0) and 
ending at final phone contact (Month 14, i.e. 12 
months post dose 2).
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
10
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
11

Study groups:
Synopsis Table 1
Study groups and epochs foreseen in the study
Study Groups
Number of 
subjects
Age (Min - Max)
Epochs
Epoch 001
HZ/su Group
~ 14,550
> 50 YOA
x
Synopsis Table 2
Study groups and treatment foreseen in the study
Treatment name
Product name
Study Group
HZ/su Group
HZ/su
VZV gE
x
AS01B

Control: uncontrolled.

Vaccination schedule: 0, 2 months.

Treatment allocation: non-randomised.

Blinding: open-label.
Synopsis Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
open

Sampling schedule: no sampling.

Type of study: self-contained.

Data collection: electronic Case Report Form (eCRF).
Number of subjects
Target enrolment will be approximately 14,550 potentially 
eligible subjects (all in one vaccine group).
Endpoints
Primary

Occurrence of unsolicited 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.

Occurrence of SAEs.

Occurrence and relationship to vaccination of all SAEs 
from Month 0 until study end (Month 14, i.e. 12 
months post dose 2).

Occurrence of AEs of special interest.

Occurrence of any pIMDs from Month 0 until study 
end (Month 14, i.e. 12 months post dose 2).
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
11
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
12
Secondary

Occurrence of suspected HZ cases.

Occurrence of suspected HZ cases from Month 0 to 
study end.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
12
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
13
TABLE OF CONTENTS
PAGE
SPONSOR INFORMATION ............................................................................................8
SYNOPSIS......................................................................................................................9
LIST OF ABBREVIATIONS (AMENDED 30 MAY 2017)................................................19
GLOSSARY OF TERMS ...............................................................................................21
TRADEMARKS .............................................................................................................25
1.
INTRODUCTION....................................................................................................26
1.1.
Background ................................................................................................26
1.2.
Rationale for the study and study design ....................................................27
1.2.1.
Rationale for the study.................................................................27
1.2.2.
Rationale for the study design......................................................28
1.3.
Benefit : Risk Assessment ..........................................................................28
1.3.1.
Risk Assessment .........................................................................28
1.3.2.
Benefit Assessment.....................................................................28
1.3.3.
Overall Benefit : Risk Conclusion.................................................29
2.
OBJECTIVE ...........................................................................................................29
2.1.
Primary objective ........................................................................................29
2.2.
Secondary objective ...................................................................................29
3.
STUDY DESIGN OVERVIEW ................................................................................29
4.
STUDY COHORT...................................................................................................30
4.1.
Number of subjects/centres ........................................................................30
4.2.
Inclusion criteria for enrolment....................................................................31
4.3.
Exclusion criteria for enrolment...................................................................32
5.
CONDUCT OF THE STUDY ..................................................................................33
5.1.
Regulatory and ethical considerations, including the informed 
consent process..........................................................................................33
5.2.
Subject identification and randomisation of treatment .................................34
5.2.1.
Subject identification....................................................................34
5.2.2.
Randomisation of treatment.........................................................34
5.2.2.1.
Treatment allocation to the subject.............................34
5.2.2.1.1.
Study group and treatment 
number allocation ...................................34
5.2.2.1.2.
Treatment number allocation for 
subsequent doses ..................................34
5.3.
Method of blinding ......................................................................................35
5.4.
General study aspects ................................................................................35
5.4.1.
Data collection .............................................................................35
5.5.
Outline of study procedures ........................................................................36
5.6.
Detailed description of study procedures ....................................................37
5.6.1.
Informed consent.........................................................................37
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
13
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
14
5.6.2.
Check inclusion and exclusion criteria .........................................39
5.6.3.
Collect demographic data ............................................................39
5.6.4.
Medical history.............................................................................39
5.6.5.
History directed physical examination..........................................39
5.6.6.
Pregnancy test.............................................................................39
5.6.7.
Check contraindications, warnings and precautions to 
vaccination...................................................................................40
5.6.8.
Assess pre-vaccination body temperature ...................................40
5.6.9.
Treatment number allocation .......................................................40
5.6.10.
Study Vaccine administration.......................................................40
5.6.11.
Training on self-reporting by subjects ..........................................40
5.6.12.
Training and reporting signs/symptoms of typical HZ...................41
5.6.13.
Check and record concomitant medication/vaccination................41
5.6.14.
Recording of AEs, SAEs, pregnancies and pIMDs.......................41
5.6.15.
Recording of suspected HZ episodes ..........................................41
5.6.15.1.
Suspected HZ.............................................................41
5.6.15.2.
Study procedures in case of suspected HZ ................42
5.6.16.
Reminder for follow-up contact ....................................................42
5.6.17.
Study conclusion..........................................................................42
6.
STUDY VACCINE AND ADMINISTRATION...........................................................43
6.1.
Description of study vaccine .......................................................................43
6.2.
Storage and handling of study vaccine .......................................................43
6.3.
Dosage and administration of study vaccine...............................................44
6.4.
Replacement of unusable vaccine doses....................................................44
6.5.
Contraindications to subsequent vaccination ..............................................44
6.6.
Concomitant medications/products and concomitant vaccinations..............45
6.6.1.
Recording of concomitant medications/products and 
concomitant vaccinations.............................................................46
6.6.2.
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from According-To-Protocol 
(ATP) analyses ............................................................................46
7.
HEALTH ECONOMICS ..........................................................................................46
8.
SAFETY.................................................................................................................46
8.1.
Safety definitions ........................................................................................46
8.1.1.
Definition of an adverse event......................................................46
8.1.2.
Definition of a serious adverse event ...........................................47
8.1.3.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................48
8.1.4.
Adverse events of specific interest...............................................49
8.1.4.1.
Potential immune-mediated diseases .........................49
8.2.
Events or outcomes not qualifying as adverse events or serious 
adverse events ...........................................................................................51
8.2.1.
Pregnancy ...................................................................................51
8.3.
Detecting and recording adverse events, serious adverse events 
and pregnancies .........................................................................................52
8.3.1.
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies.....................................52
8.3.2.
Post-Study adverse events and serious adverse events..............55
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
14
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
15
8.3.3.
Evaluation of adverse events and serious adverse events...........55
8.3.3.1.
Active questioning to detect adverse events 
and serious adverse events........................................55
8.3.3.2.
Assessment of adverse events...................................56
8.3.3.2.1.
Assessment of intensity..........................56
8.3.3.2.2.
Assessment of causality .........................56
8.3.3.3.
Assessment of outcomes............................................57
8.4.
Reporting of serious adverse events, pregnancies, and other events .........58
8.4.1.
Prompt reporting of serious adverse events, pregnancies, 
and other events to GSK Biologicals............................................58
8.4.2.
Contact information for reporting serious adverse events, 
pregnancies and pIMDs...............................................................59
8.4.3.
Completion and transmission of SAE reports to GSK 
Biologicals ...................................................................................59
8.4.3.1.
Back-up system in case the electronic 
reporting system does not work..................................59
8.4.4.
Completion and transmission of pregnancy reports to GSK 
Biologicals ...................................................................................60
8.4.5.
Reporting of pIMDs to GSK Biologicals........................................60
8.4.6.
Updating of SAE, pregnancy, and pIMD information after 
removal of write access to the subject’s eCRF.............................60
8.4.7.
Regulatory reporting requirements for serious adverse 
events..........................................................................................61
8.5.
Follow-up of adverse events, serious adverse events, and 
pregnancies................................................................................................61
8.5.1.
Follow-up of adverse events and serious adverse events............61
8.5.1.1.
Follow-up during the study..........................................61
8.5.1.2.
Follow-up after the subject is discharged from 
the study.....................................................................61
8.5.2.
Follow-up of pregnancies.............................................................62
8.6.
Treatment of adverse events ......................................................................62
8.7.
Subject card................................................................................................62
9.
SUBJECT COMPLETION AND WITHDRAWAL.....................................................62
9.1.
Subject completion .....................................................................................62
9.2.
Subject withdrawal......................................................................................63
9.2.1.
Subject withdrawal from the study ...............................................63
9.2.2.
Subject withdrawal from investigational vaccine...........................64
10. STATISTICAL METHODS......................................................................................64
10.1.
Primary endpoints.......................................................................................64
10.2.
Secondary endpoints ..................................................................................64
10.3.
Determination of sample size......................................................................65
10.4.
Cohorts for Analyses ..................................................................................65
10.4.1.
Total vaccinated cohort................................................................65
10.5.
Derived and transformed data.....................................................................65
10.6.
Analysis of demographics...........................................................................65
10.7.
Analysis of safety........................................................................................65
10.8.
Analysis of suspected HZ incidence............................................................66
10.9.
Interpretation of analyses............................................................................66
10.10. Conduct of analyses ...................................................................................66
10.10.1. Sequence of analyses..................................................................66
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
15
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
16
10.10.2. Statistical considerations for interim analyses..............................66
11. ADMINISTRATIVE MATTERS ...............................................................................67
11.1.
electronic Case Report Form instructions ...................................................67
11.2.
Study Monitoring by GSK Biologicals..........................................................67
11.3.
Record retention .........................................................................................68
11.4.
Quality assurance.......................................................................................68
11.5.
Posting of information on publicly available clinical trial registers and 
publication policy ........................................................................................69
11.6.
Provision of study results to investigators ...................................................69
12. COUNTRY SPECIFIC REQUIREMENTS...............................................................69
12.1.
Requirements for France ............................................................................69
12.2.
Requirements for Germany.........................................................................74
12.3.
Requirements for Japan (Amended 30 May 2017)......................................74
13. REFERENCES.......................................................................................................78
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
16
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
17
LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study.....................................30
Table 2
Study groups and treatment foreseen in the study .................................30
Table 3
Blinding of study epochs ........................................................................30
Table 4
List of study procedures .........................................................................36
Table 5
Intervals between study visits.................................................................37
Table 6
Guidelines on the consent process ........................................................38
Table 7
Study vaccine.........................................................................................43
Table 8
Dosage and administration.....................................................................44
Table 9
List of potential immune-mediated diseases...........................................50
Table 10
Reporting periods for collecting safety information .................................54
Table 11
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK Biologicals .................................................58
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
17
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
18
LIST OF APPENDICES
PAGE
APPENDIX A AMENDMENTS AND ADMINISTRATIVE CHANGES TO THE 
PROTOCOL...........................................................................................80
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
18
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
19
LIST OF ABBREVIATIONS (Amended 30 May 2017)
AE:
Adverse Event
ANCA:
Anti-Neutrophil Cytoplasmic Antibody
ANSM:
Agence Nationale de Sécurité du Médicament
AS01B:
MPL, QS21, liposome based Adjuvant System (50 μg 
MPL and 50 μg QS21)
ATP:
According-To-Protocol
CDC:
Centres for Disease Control
CNIL:
Commission Nationale de l'Informatique et des Libertés
CRA:
Clinical Research Assistant
eCRF:
electronic Case Report Form
CTR:
Clinical Trials Register
eTDF:
Electronic Temperature excursion Decision Form
EDD:
Estimated Date of Delivery
EGA:
Estimated Gestational Age
EMA:
European Medicines Agency
GCP:
Good Clinical Practice
gE:
Glycoprotein E
GSK:
GlaxoSmithKline
HIV:
Human Immunodeficiency Virus
HZ:
Herpes Zoster
IAF:
Informed Assent Form
IB:
Investigator Brochure
ICF:
Informed Consent Form
ICH:
International Conference on Harmonisation
(I)EC:
(Independent) Ethics Committee
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
19
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
20
IM:
Intramuscular/Intramuscularly
IMP:
Investigational Medicinal Product
IND:
Investigational New Drug
(I)RB:
(Institutional) Review Board
LAR:
Legally Acceptable Representative
LMP:
Last Menstrual Period
MACDP:
Metropolitan Atlanta Congenital Defects Program
MedDRA:
Medical Dictionary for Regulatory Activities
PHN:
Postherpetic Neuralgia 
PID:
Personal Identification Number
PT:
Preferred Terms
pIMD:
Potential Immune-Mediated Disease
QS-21:
Quillaja saponaria Molina, fraction 21 (Licensed by GSK 
from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation) 
RDC:
Research and Development Centre
SAE:
Serious Adverse Event
SBIR:
Randomisation System on Internet
SDV:
Source Document Verification
SPM:
Study Procedures Manual
su:
Subunit
TVC:
Total Vaccinated Cohort
US:
United States
VE:
Vaccine Efficacy
VZV:
Varicella-zoster Virus
YOA:
Years of Age
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
20
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
21
GLOSSARY OF TERMS
Adequate contraception:
Adequate contraception is defined as a contraceptive 
method with failure rate of less than 1% per year when 
used consistently and correctly and when applicable, in 
accordance with the product label for example:

abstinence from penile-vaginal intercourse, when this 
is their preferred and usual lifestyle,

oral contraceptives, either combined or progestogen 
alone,

injectable progestogen,

implants of etenogestrel or levonorgestrel,

estrogenic vaginal ring,

percutaneous contraceptive patches,

intrauterine device or intrauterine system,

male partner sterilisation prior to the female subject’s 
entry into the study, and this male is the sole partner 
for that subject,
The information on the male sterility can come from 
the site personnel’s review of the subject’s medical 
records; or interview with the subject on her medical 
history.

male condom combined with a vaginal spermicide 
(foam, gel, film, cream or suppository),

male condom combined with a female diaphragm, 
either with or without a vaginal spermicide (foam, 
gel, film, cream, or suppository).
Adequate contraception does not apply to subjects of 
child bearing potential with same sex partners, when this 
is their preferred and usual lifestyle.
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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
21
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
22
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.
Caregiver
Someone who lives in the close surroundings of a subject 
having a continuous caring role or may be someone 
having substantial periods of contact with a subject and is 
engaged in his/her daily health care (e.g. a relative of the 
subject, a nurse who helps with daily activities in case of 
residence in a nursing home). In a context of a clinical 
study, a caregiver could include an individual appointed 
to oversee and support the subject's compliance with 
protocol specified procedures.
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.
Investigational vaccine
(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. 
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
22
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
23
Legally acceptable 
representative
(The terms legal 
representative or legally 
authorized 
representative are used 
in some settings.)
An individual or juridical or other body authorized under 
applicable law to consent, on behalf of a prospective 
subject, to the subject's participation in the clinical trial.
Menarche:
Menarche is the onset of menses for the first time in a 
young female and is preceded by several changes 
associated with puberty including breast development and 
pubic hair growth. Menarche usually occurs within 1-2 
years of breast development, thelarche. However, a young 
female can become pregnant before her first menses. 
Thus, a conservative definition of non-childbearing 
potential in a pre-menarcheal female is a young female 
who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue).
Menopause:
Menopause is the age associated with complete cessation 
of menstrual cycles, menses, and implies the loss of 
reproductive potential by ovarian failure. A practical 
definition accepts menopause after 1 year without menses 
with an appropriate clinical profile at the appropriate age 
e.g. > 45 years.
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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
23
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
24
Self-contained study:
Study with objectives not linked to the data of another 
study.
Site Monitor:
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites.
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 during the clinical study.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
24
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
25
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 descriptions
Varivax® (Merck & Co)
Varicella vaccine consisting of live 
attenuated varicella-zoster virus (Oka strain)
Zostavax® (Merck & Co )
Herpes zoster vaccine consisting of high-
titre live attenuated Varicella-zoster virus 
(Oka strain)
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
25
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
26
1.
INTRODUCTION
1.1.
Background
Varicella-Zoster Virus (VZV) causes two distinct diseases. Varicella (chickenpox) 
shortly occurs after primary VZV infection and is characterised by systemic illness and a 
widely disseminated rash. Herpes zoster (shingles) occurs when VZV reactivates from 
latency and typically manifests as a localised, dermatomal rash.
The typical Herpes Zoster (HZ) rash usually lasts 2 to 4 weeks and is usually 
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. 
Older age is a clear risk factor for PHN. Other risk factors may include a severe HZ rash 
and a painful HZ prodrome. PHN tends to improve over a period of months. About 70-
80% of cases resolve within 1 year, however, in some persons PHN persists for many 
years [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]. The risk 
for PHN is also highest in older people with HZ, occurring in 18-50% of those aged 70 
years and older [Oxman, 2005; Scott, 2006]. Patients with impaired cell-mediated 
d immunity 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 
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
26
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
27
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, a 
recombinant subunit (su) vaccine consisting of VZV glycoprotein E (gE) as antigen and 
an adjuvant system (AS01), has been evaluated in previous studies in healthy 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, a gE antigen dose of 50 µg and 
the adjuvant system AS01B were selected for the final vaccine formulation. Henceforth, 
the final vaccine formulation will be referred to as HZ/su. 
Two large pivotal Phase III trials (ZOSTER-006 enrolling subjects ≥ 50 YOA, and 
ZOSTER-022 enrolling subjects ≥ 70 YOA,) are being conducted to evaluate the Vaccine 
Efficacy (VE) and safety of GSK Biologicals’ HZ/su vaccine. These trials 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 VE results from the ZOSTER-006 Phase III trial 
demonstrated the HZ/su vaccine to be highly efficacious in the prevention of HZ subjects 
≥ 50 YOA, 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.
In a previously completed study (ZOSTER-033) conducted in older adults (≥ 50 YOA) 
with a history of previous HZ, the immunogenicity profile and the safety profile of HZ/su 
did not appear to be different from what has been observed in other studies in older adults 
with no previous history of HZ. Clinical efficacy against recurrent HZ, was not evaluated 
in this population. However based on the very high efficacy observed in the phase III 
clinical efficacy studies in individuals without previous HZ (ZOE-50 and ZOE-70) who 
received the HZ/su vaccine, anticipated benefits against recurrence of HZ may be 
expected.
Please refer to the current Investigator Brochure (IB) 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
According to the ZOSTER-006/ZOSTER-022 protocol and Informed Consent Form 
(ICF), once these studies are concluded and HZ/su vaccine proven to be efficacious and 
safe, the control vaccine group would be offered the HZ/su vaccine in a cross-vaccination 
setting. Potentially eligible subjects who previously received placebo in ZOSTER-
006/ZOSTER-022 will now be offered cross-vaccination.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
27
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
28
1.2.2.
Rationale for the study design
Since the HZ/su vaccine has not yet been licensed and marketed, this study is being 
conducted to enable potentially eligible subjects who previously received placebo in 
ZOSTER-006 or ZOSTER-022 to receive the HZ/su vaccine.
Study ZOSTER-056 is an open-label, multi-centric and single arm study to cross-
vaccinate and collect safety data from subjects ≥ 50 YOA who previously received 
placebo.
1.3.
Benefit : Risk Assessment
Please refer to the current IB 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:
1.3.1.
Risk Assessment
Important Potential Risk
Data/Rationale for Risk
Mitigation Strategy
Investigational study vaccine Hz/su
Theoretical risk of acquiring 
a vaccine induced 
autoimmune disease after 
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 potential 
Immune-Mediated Diseases 
(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 
may be serious.
1.3.2.
Benefit Assessment
Benefits include:

Benefit of receiving HZ/su vaccine during the study that may have clinical utility.

Medical evaluations/assessments associated with study procedures (e.g. physical 
examination)
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
28
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
29
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 study procedures are offset by the potential benefits (prevention of HZ and 
related complications) that may be afforded to the subject(s).
2.
OBJECTIVE
2.1.
Primary objective

To evaluate the safety, in terms of unsolicited Adverse Events (AEs), Serious 
Adverse Events (SAEs) and pIMD in all subjects, following administration of each 
dose of the HZ/su vaccine. 
Refer to Section 10.1 for the definition of the primary endpoint(s).
2.2.
Secondary objective 

To evaluate the incidence of suspected HZ episodes (self-reported or medically 
diagnosed) during the entire study period.
Refer to Section 10.2 for the definition of the secondary endpoint.
3.
STUDY DESIGN OVERVIEW
*Could be a visit or a phone contact. Operational details will be defined in the Study Procedure Manual (SPM)
# i.e. 12 months post dose 2
n: number of subjects
Vacc: vaccination
SFU: Safety follow-up
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, non-randomised, multi-centric , multi-
country cross-vaccination study, with a single group.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
29
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
30

Duration of the study: Approximately 14 months. Each subject will be followed for 
safety approximately 12 months after the second vaccine dose

Epoch 001: Primary starting at Visit 1 (Month 0) and ending at final phone 
contact (Month 14, i.e. 12 months post dose 2)

Study groups:
Table 1
Study groups and epochs foreseen in the study
Study Groups
Number of 
subjects
Age (Min – Max)
Epochs
Epoch 001
HZ/su Group
max 14,550
> 50 YOA
x
Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product 
name
Study Groups
HZ/su
VZV gE
HZ/su Group
AS01B

Control: uncontrolled.

Vaccination schedule: 0, 2 months.

Treatment allocation: non-randomised. 

Blinding: open-label.
Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
open

Sampling schedule: no sampling.

Type of study: self-contained.

Data collection: electronic Case Report Form (eCRF).
4.
STUDY COHORT
4.1.
Number of subjects/centres
Approximately 14,550 potentially eligible subjects who received placebo in the 
ZOSTER-006/ZOSTER-022 studies will be contacted and invited to participate in this 
cross-vaccination study with GSK Biologicals’ HZ/su vaccine. Refer to Section 4.2 and 
Section 4.3 for eligibility criteria.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
30
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
31
Overview of the recruitment plan 
Potentially eligible subjects who participated and received placebo in ZOSTER-
006/ZOSTER-022 studies will be contacted and considered for entry in ZOSTER-056 
study. The rationale for not enrolling any of these subjects will be recorded 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, vaccination visits, 
follow-up contacts). Or subjects’ Legally Acceptable Representative(s) 
[LAR(s)]/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/LAR(s) of the subject prior to 
performing any study specific procedure. If the subject is not capable of giving 
consent, his/her assent to participate should be obtained to the extent possible.

Subject who previously participated in ZOSTER-006 or ZOSTER-022 studies and 
received at least one dose of placebo.

Female subjects of non-childbearing potential may be enrolled in the study.

Non-childbearing potential is defined as pre-menarche, current tubal ligation, 
hysterectomy, ovariectomy or post-menopause. 
Please refer to the glossary of terms for the definition of menarche and menopause.

Female subjects of childbearing potential may be enrolled in the study, if the subject:

has practiced adequate contraception for 30 days prior to vaccination, and

has a negative pregnancy test on the day of vaccination and

has agreed to continue adequate contraception during the entire treatment 
period* and for 2 months after completion of the vaccination series. 
*treatment period refers to vaccination days and the interval between them.
Please refer to the glossary of terms for the definition of adequate contraception.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
31
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
32
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 dose of study 
vaccine (Day -29 to Day 0), or planned use up to 30 days post Dose 2.

Previous vaccination against VZV or HZ.

Planned administration of VZV or HZ vaccination during the study (including an 
investigational or non-registered vaccine), with the exception of the study vaccine.

Planned administration/administration of a vaccine/product not foreseen by the study 
protocol in the period starting 30 days before the first dose and ending 30 days after 
the last dose of vaccine administration, with the exception of 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). These 
vaccines 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.

Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting six 
months prior to the first vaccine dose and up to 30 days post Dose 2. For
corticosteroids, this will mean prednisone 20 mg/day or equivalent. Inhaled, topical 
and intra-articular corticosteroids are allowed.

Administration of long-acting immune-modifying drugs (e.g. infliximab, rituximab) 
within six months prior to the first vaccine dose up to 30 days post Dose 2.

Concurrently participating in another clinical study, at the time of enrolment or 
planned participation up to the 30 days post second dose, in which the subject has 
been or will be exposed to an investigational or a non-investigational vaccine/product 
(pharmaceutical product or device).

Any confirmed or suspected immunosuppressive or immunodeficient condition 
resulting from disease (e.g., malignancy, Human Immunodeficiency Virus [HIV]
infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during 
cancer chemotherapy, organ transplantation or to treat autoimmugne disorders).

History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine.

Active HZ infection at the time of enrolment (i.e. HZ lesions not completely crusted 
over).

Pregnant or lactating female.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
32
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
33

Any condition which, in the opinion of the investigator, prevents the subject from 
participating in the study.

Any condition which in the judgment of the investigator would make intramuscular 
injection unsafe.
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 International Conference on 
Harmonisation (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/subject’s (LAR[s]) 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 and/or each subject’s LAR(s) and subject informed assent, as 
appropriate, prior to participation in the study.
GSK Biologicals will prepare a model 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. 
In accordance with the ICH Harmonised Tripartite Guidelines for Good Clinical Practice, 
those subjects who can only be enrolled in the study with the consent of the subject’s 
LAR, should be informed about the study to the extent compatible with the subject’s 
understanding and, if capable, the subject should sign and personally date a written 
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
33
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
34
Informed Assent Form (IAF). It is required that the assent be signed by each subject, if 
capable, in addition to the informed consent that is to be signed by his/her legal 
representative.
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.
5.2.
Subject identification and randomisation of treatment
5.2.1.
Subject identification
Subjects who have consented to participate in the study will be assigned a subject 
identification number linked to those used in ZOSTER-006/ZOSTER-022.
5.2.2.
Randomisation of treatment
Even though there will be no randomisation of treatment, randomisation system on 
internet (SBIR) will be used for treatment number allocation and for enrolment tracking 
purposes.
5.2.2.1.
Treatment allocation to the subject
The treatment numbers will be allocated by dose.
5.2.2.1.1.
Study group and treatment number allocation
There is only one study group, and the target to be enrolled is approximately 14,550 
potentially eligible subjects.
After obtaining the signed/thumb printed and dated ICF (and IAF if applicable and 
possible) from the subject/subject’s LAR and having checked the eligibility of the 
subject, the site staff in charge of the vaccine administration will access SBIR. Upon
providing the subject identification number, the randomisation system will provide the 
treatment number to be used for the first dose.
The number of each administered treatment must be recorded in eCRF on the Vaccine 
Administration screen.
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions.
5.2.2.1.2.
Treatment number allocation for subsequent doses 
For each dose subsequent to the first dose, the study staff in charge of the vaccine
administration will access SBIR, provide the subject identification number, and the 
system will provide a treatment number to be used for the second dose.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
34
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
35
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 a single treatment group, no blinding will be applied.
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 2, there will be 3 contacts between the subject/subject’s LAR/caregiver and 
the investigator and/or his delegate for the purpose of collecting information on any event 
of interest (see Table 4 and Section 5.6.16 for details). Month 3 contact will either be a 
site visit or a phone contact depending on the needs of the subject. Logistical details 
pertaining to Month 3 contact will be included in the SPM. Months 8 and 14 will be 
phone contacts. The phone contacts will take place using the most convenient method 
suited for the sites (e.g., telephone calls by site staff or designee, and/or by call centre). 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 LAR/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.
30-day diary cards will be completed by all subjects/subject’s LAR/caregiver for 
unsolicited AEs (from Day 0 to Day 29 after each vaccination), including episodes of 
suspected HZ (self-reported or medically diagnosed) and any concomitant medication 
and vaccination taken from Day 0 to Day 29 after each vaccination.
Episodes of suspected HZ occurring from Day 0 to Day 29 after each vaccination should 
be collected in the diary cards (by subject/LAR/caregiver) and in the HZ section of the 
eCRF (if considered an AE by the investigator and/or his delegate) or in the SAE and HZ
section of the eCRF (if considered an SAE by the investigator and/or his delegate). 
Episodes of suspected HZ occurring outside of this period should be reported in the HZ 
section (if a Non-Serious AE) or in the SAE and HZ section of the eCRF (if an SAE). If 
the investigators become aware of an HZ episode between study visits, they should report 
it at that time in the eCRF, as per above.
The diary cards to be completed will be distributed and explained by the investigator or 
his/her delegate. Any supplied diary cards should be completed by the subject/subject’s 
LAR/caregiver.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
35
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
36
5.5.
Outline of study procedures
Table 4
List of study procedures
Epoch
Primary
Type of contact
visit
visit
contact 1
phone 
contact
phone 
contact
Timepoint identification
Visit 1
Visit 2
Visit 
3/Month 3 
Phone 
contact
Month 8 
Phone 
contact
Month 14*
Phone 
contact
Time value
Month 0
Month 2
Month 3
Month 8
Month 14*
Sampling timepoints
Vacc 1
Vacc 2
Post-Vacc 2
SFU
SFU
Informed consent (and assent if applicable)
●
Check inclusion/exclusion criteria
●
Collect demographic data 2
●
Medical history
●
History directed physical examination
O
O
Pregnancy test if applicable 3
●
●
Check contraindications and warnings and 
precautions
O
O
Pre-vaccination body temperature
●
●
Treatment number allocation
O
Treatment number allocation for subsequent 
dose
O
Recording of administered treatment number
●
●
Vaccine administration
●
●
Distribution of diary cards for the recording 
unsolicited AEs and concomitant 
medications/vaccinations by the 
subject/LAR/caregiver 4
O
O
Training of subjects/LAR/caregiver on 
completion of diary cards
O
O
Training on self-reporting by 
subjects/LAR/caregiver 5
O
O
O
O
Training on signs/symptoms of typical HZ
O
O
O
O
O
Reminder for follow-up contact
O
O
O
Return of diary cards
O
O6
Reception of diary cards 7
O
O
Diary card transcription by study 
staff/investigator
●
●
Record any concomitant 
medications/vaccinations
●
●
●
●
●
Recording of unsolicited AEs within 30 days 
post-vaccination
●
●
●
Recording of suspected HZ episodes
●
●
●
●
●
Recording of SAEs, pregnancies, pIMDs and 
AEs leading to withdrawal
●
●
●
●
●
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine
●
●
●
●  
●
Study Conclusion
●
Vacc: vaccination; SFU: safety follow-up
● 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
* i.e. 12 months post dose 2
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
36
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
37
1 At Month 3 contact, the subject will either come to the study site or be contacted by phone. Operational details will be 
defined in the SPM.
2Subjects will be assigned the same PID numbers as those used in ZOSTER-006/ZOSTER-022
3Only applicable for females of childbearing potential. A urine pregnancy test is sufficient. A serum pregnancy test 
instead of a urine pregnancy test should only be considered if required by country, local or ethics committee 
regulations.
4One diary card for unsolicited AEs up to 30 days post vaccination
5Subject will be instructed to contact their study site immediately if he/she manifests any symptoms he/she perceives 
as serious and, in case of pregnancy for women of childbearing potential
6Subjects will be asked to mail the diary cards 30 days after Visit 2 if their Month 3 contact will be by phone or to bring 
along their diary card if their Month 3 contact will be a site visit. Operational details will be defined in the SPM
7It is the responsibility of the site to follow up until the diary cards are received
Table 5
Intervals between study visits
Interval
Optimal length of interval 1
Allowed interval
Visit 1Visit 2
60 days (2 months)
49 days - 83 days
Visit 2 Visit 3/Month 3
Phone contact
30 days (1 month)
30 - 48  days
Visit 2  Month 8 Phone 
contact
180 days (6 months)
180 - 240 days
Visit 2 Month 14* Phone 
contact
365 days (12 months)
335 –395 days
1 Whenever possible the investigator should arrange study visits within this interval
*i.e. 12 months post dose 2
5.6.
Detailed description of study procedures
5.6.1.
Informed consent
The signed/witnessed/thumb printed informed consent of the subject must be obtained 
before study participation. A signed informed assent should preferably be obtained from 
subjects who are not capable of consenting and for whom a LAR would sign the ICF (as 
assessed by the investigator). Refer to Table 6 and 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 should be confirmed during 
informed consent process by the subject or his/her LAR. In addition, the caregiver 
should also provide his/her agreement for the role that he/she is playing in the study,
(helping the subject to comply with study procedures). The role of the caregiver 
should be fully explained to him/her and the caregiver should confirm his/her 
agreement by signing the dedicated part of the ICF. In case the LAR takes the 
supplementary role to act as a caregiver, the LAR will sign as well the part dedicated 
for caregiver (Table 6). If required by local regulations, the witness signature is also 
obtained, confirming the fact that the study procedures were explained appropriately 
to the caregiver.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
37
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
38

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. Any change of the caregiver should be documented in the eCRF. 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/subject’s LAR(s)* (Table 6).
* Note that in this case, the subject/subject’s LAR(s) 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/subject’s LAR re-consent to study participation.

At the start of the study, the subject/subject’s LAR(s)/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/subject's LAR/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. 
Table 6
Guidelines on the consent process
    Who signs what
Situation
Consent
Assent
ICF 
Caregiver 
statement
Annex part of the ICF in case 
the caregiver changes during 
the study period
(to study 
participation)
(to study 
participation)
(to help with 
study 
procedures)
(to be helped 
with study 
procedures)
(to help with 
study 
procedures)
Subject able to consent and 
to comply with study 
procedures
Subject
-
-
-
-
Subject unable to consent but 
able to comply with study 
procedures
LAR
Subject
-
-
-
Subject able to consent and 
unable to comply with study 
procedures alone
Subject
-
Caregiver
-
-
Subject unable to consent 
and unable to comply with 
study procedures alone
LAR
Subject
Caregiver
-
-
Subject with caregiver 
changed during the study 
period
-
-
-
Subject or 
LAR
New 
Caregiver
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
38
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
39
5.6.2.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.2 and 4.3 before 
enrolment. 
5.6.3.
Collect demographic data
Record demographic data such as year of birth, gender in the subject’s eCRF.
5.6.4.
Medical history
Obtain the subject’s clinically relevant medical history by interview and/or review of the 
subject’s medical records and record any pre-existing medical conditions or signs and/or 
symptoms present in a subject prior to the first study vaccination in the eCRF.
Clinically relevant prior medical history is defined as: chronic disease or medical 
conditions requiring continued or chronic treatment (e.g. diabetes, psoriasis), any 
previous malignant cancer, acute disease resolved with sequelae (e.g. hemiplegia due to 
cerebrovascular accident), pIMD (see Table 9). 
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 categories and diseases will be available in the 
eCRF.
In addition, history of prior HZ episodes must be recorded (from HZ collected during the 
ZOSTER-006/ZOSTER-022 studies until the first visit in the study ZOSTER-056).
5.6.5.
History directed physical examination
Perform a history directed physical examination. If the investigator determines that the 
subject’s health on the day of vaccination temporarily precludes vaccination, the visit will 
be rescheduled. Collected information needs to be recorded in the eCRF.
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.
Pregnancy test 
Female subjects of childbearing potential are to have a urine or serum pregnancy test 
prior to any study vaccine administration. The study vaccines may only be administered 
if the pregnancy test is negative. Note: The urine pregnancy test must be performed even 
if the subject is menstruating at the time of the study visit.
A urine pregnancy test is sufficient. A serum pregnancy test instead of a urine pregnancy 
test should only be considered if required by country, local or ethics committee 
regulations.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
39
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
40
5.6.7.
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 Section 6.5 for more details. 
5.6.8.
Assess pre-vaccination body temperature
The axillary, oral or tympanic body temperature of all subjects needs to be measured 
prior to any study vaccines 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).
5.6.9.
Treatment number allocation
At each vaccination visit, the subject will be assigned a treatment number which must be 
recorded in the eCRF.
If there is a need for a site to use a replacement vaccine, then that treatment number needs 
to be transcribed into the eCRF (see Section 6.4).
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.
Training on self-reporting by subjects
Subjects/subject’s LAR/caregiver will be instructed at Visit 1 (and will be reminded at 
each subsequent visit or phone contact) to contact their study site immediately 

should the subject manifest any signs or symptoms he/she perceive as serious;

should the subject become pregnant (for women of childbearing potential)
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
40
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
41
5.6.12.
Training and reporting signs/symptoms of typical HZ
Subjects/subject’s LAR/caregiver will be instructed at Visit 1 and Visit 2 to:

recognize the signs and symptoms of typical HZ 

to record in the diary card information related to suspected HZ (Day 0 to Day 29 
post-vaccination).
At each subsequent visit and contact until study end at Month 14, subjects will be 
reminded of the signs and symptoms of typical HZ and will be questioned about 
occurrence of a suspected HZ episode from previous study visit or contact.
5.6.13.
Check and record concomitant medication/vaccination
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 6.6.
5.6.14.
Recording of AEs, SAEs, pregnancies and pIMDs

Refer to Section 8.3 for procedures for the investigator to record AEs, SAEs, 
pregnancies and pIMDs. Refer to Section 8.4 for guidelines and how to report SAE, 
pregnancy and pIMD reports to GSK Biologicals.

The subjects/subjects’LAR(s)/caregiver will be instructed to contact the investigator 
immediately should 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 
LAR(s)/caregiver. The subjects/subject’s LAR/caregiver will be trained on how to 
complete the diary cards The subject/subject’s LAR(s)/caregiver will record any 
unsolicited AEs (i.e. occurring on the day of vaccination and during the next 29 days
after vaccination).

All subjects/subject’s LARs/caregivers will be instructed to return the completed 
diary card to the investigator at the next study visit. Collect and verify completed 
diary cards during discussion with the subject/subject’s LAR(s)/caregiver on Visit 2
and Visit 3/Month 3 phone contact.

Any unreturned diary cards will be sought from the subject/subject’s 
LAR(s)/caregiver through telephone call(s) or any other convenient procedure. The 
investigator will transcribe the collected information into the eCRF in English.
5.6.15.
Recording of suspected HZ episodes
5.6.15.1.
Suspected HZ
A suspected case of HZ is defined as a new rash characteristic of HZ (e.g., unilateral, 
dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or 
other sensations).
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
41
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
42
A diagnosis of suspected HZ will be based upon investigator or the attending physician
judgment. The occurrence of suspected HZ will be reported as an AE/SAE, as 
appropriate. The reporting period for cases of suspected HZ will be from Day 0 to study 
end.
5.6.15.2.
Study procedures in case of suspected HZ
The subject card will include a request to the attending physician to provide information 
about the clinical diagnosis of a case of suspected HZ, when contacted by the investigator 
or delegate. When a clinical diagnosis of suspected HZ has been made by an attending 
physician, the subject should ensure the study site is informed about the case.
When the investigator or delegate becomes aware that a clinical diagnosis of suspected 
HZ has been made by an attending physician, he/she will contact the attending physician. 
The investigator or delegate will obtain the relevant information from the attending 
physician and this information will be recorded in the HZ section or SAE and HZ section 
of eCRF, as applicable.
When the suspected HZ cases is self-reported, the investigator or his delegate will collect 
all information regarding the suspected HZ episode and this will be recorded in the HZ 
section or SAE and HZ section of eCRF, as applicable.
Note: Non-serious episodes of suspected HZ do not require immediate reporting to the 
site. The investigator/study staff will question the subject at each scheduled visit and 
contact regarding the onset of signs and symptoms of the suspected HZ.
5.6.16.
Reminder for follow-up contact
The subject/subject’s LAR/caregiver will be reminded that, after Visit 2, three contacts 
between the subjects/subject’s LAR/caregiver and the investigator and/or his delegate 
will take place in order to collect all relevant information on any event of interest that 
may have occurred (including SAEs, pIMDs, suspected HZ [Section 8.3], the use of 
concomitant medications and/or vaccinations [Section 6.6] or pregnancy [Section 8.3]), 
and that information will be recorded in the appropriate section of the subject’s eCRF.
5.6.17.
Study conclusion
At the study conclusion contact, the following procedures will take place:

Recording of all suspected HZ episodes and SAEs (including related to study 
participation, or to a concurrent GSK medication/vaccine).

Recording of pIMDs.

Recording of pregnancies.

Checking and recording specific concomitant medication/vaccination.

Reviewing of the data collected to ensure accuracy and completeness and completing
the Study Conclusion screen in the eCRF by the investigator.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
42
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
43
6.
STUDY VACCINE AND ADMINISTRATION
6.1.
Description of study vaccine
The candidate vaccine/product 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 7
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: Quillaja saponaria Molina, fraction 21 (purified saponin extract from the 
South American tree)
6.2.
Storage and handling of study vaccine
The study vaccine 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 
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
43
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
44
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.
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). Refer to the SPM for details on 
vaccine reconstitution.
Vaccine will be administered as indicated in Table 8.
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.
Table 8
Dosage and administration
Type of contact 
and timepoint
Volume to be 
administered
Study group
Treatment 
name
Route 1
Site
Side2
Visit 1 (Month 0)
0.5 ml
HZ/su Group
HZ/su
IM
Deltoid
Non-
dominant
Visit 2  (Month 2)
1 Intramuscular (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-randomisation when applicable), 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 8.5). 

Anaphylaxis following the administration of vaccine Dose 1.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
44
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
45

Pregnancy (see Section 8.2.1).

An SAE judged to be vaccine-related by the investigator.

An episode of suspected HZ at Visit 1 (Month 0, Vaccination 1) and/or Visit 2 
(Month 2, Vaccination 2).

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. Also, for corticosteroids, prednisone < 20 mg/day, or equivalent, is 
allowed. Inhaled and topical steroids are allowed.

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, exposes the subject to unacceptable risk from 
subsequent vaccination. In such cases, the investigator should use his/her 
clinical judgement prior to administering the next dose of the vaccine. Refer to 
Section 8.1.4.1 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 8.5). 

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.

Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe.
6.6.
Concomitant medications/products and concomitant 
vaccinations
At each study visit/contact the investigator should question the subject and/or the 
subject’s LAR(s)/caregiver about any medications/products taken and vaccinations
received by the subject.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
45
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
46
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 medications/products, except vitamins and dietary supplements, 
administered during 30 days following each study vaccine dose.

Any concomitant vaccination administered in the period starting 30 days before the 
first dose of study vaccine and ending 30 days following the second dose of study 
vaccine.

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.
6.6.2.
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from According-To-Protocol (ATP)
analyses
Not applicable.
7.
HEALTH ECONOMICS
Not applicable.
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 AE or SAE as provided in 
this protocol. 
Each subject/subject’s LAR(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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
46
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
47
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).
All 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).

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 clinical 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.
Refer to Section 5.6.4 for the definition of pre-existing clinical conditions.
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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
47
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
48
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.
8.1.3.
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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
48
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
49
8.1.4.
Adverse events of specific interest
8.1.4.1.
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 9.
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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
49
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
50
Table 9
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
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
50
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
51
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.
Events or outcomes not qualifying as adverse events or 
serious adverse events
8.2.1.
Pregnancy
Female subjects who are pregnant or lactating at the time of vaccination must not receive 
additional doses of study vaccine but may continue other study procedures at the 
discretion of the investigator.
While pregnancy itself is not considered an AE or SAE, any adverse pregnancy outcome 
or complication or elective termination of a pregnancy for medical reasons will be 
recorded and reported as an AE or a SAE.
Note: The pregnancy itself should always be recorded on an electronic pregnancy report.
The following should always be considered as SAE and will be reported as described in 
Sections 8.4.1 and 8.4.3:

Spontaneous pregnancy loss, including:

spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation)

ectopic and molar pregnancy

stillbirth (intrauterine death of foetus after 22 weeks of gestation).
Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the 
European Medicines Agency (EMA) Guideline on pregnancy exposure [EMA, 
2006]. It is recognized that national regulations might be different.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
51
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
52

Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life).

Any congenital anomaly or birth defect (as per [Centers for Disease Control 
Metropolitan Atlanta Congenital Defects Program CDC MACDP, 2007] guidelines) 
identified in the offspring of a study subject (either during pregnancy, at birth or 
later) regardless of whether the foetus is delivered dead or alive. This includes 
anomalies identified by prenatal ultrasound, amniocentesis or examination of the 
products of conception after elective or spontaneous abortion.
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the investigator to be reasonably related to the investigational vaccine will be reported 
to GSK Biologicals as described in Section 8.4.3. While the investigator is not obligated 
to actively seek this information from former study participants, he/she may learn of a 
pregnancy through spontaneous reporting.
8.3.
Detecting and recording adverse events, serious adverse 
events and pregnancies
8.3.1.
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies
All AEs starting 30 days following administration of each 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 receipt of study 
vaccine and will end 12 months following administration of the last dose of study vaccine 
for each subject. See Section 8.4 for instructions on reporting of SAEs.
The occurrence of suspected HZ will constitute an AE or SAE, as appropriate (and shall 
be reported in the HZ section of the eCRF [if an AE] or in the SAE and HZ section of the 
eCRF [if an SAE]). During the study, the time period for collecting and recording of 
suspected HZ will range from first receipt of study vaccine to study end. When a
suspected HZ episode has been reported, specific clinical information about the case, 
following the first vaccination visit (Month 0) until study end (Month 14), will be entered 
into the eCRF. Please refer to the SPM for information about recording the details of 
suspected HZ cases.
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the first receipt of study vaccine.
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 
time the subject consents to participate in the study until she/he is discharged from the 
study.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
52
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
53
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccine and will end 12 Months following administration of the last dose of study 
vaccine. See Section 8.4 for instructions on reporting of pregnancies.
The time period for collecting and recording of pIMDs will begin at the first receipt of 
study vaccine and will end 12 Months following administration of the last dose of study 
vaccine. See Section 8.4 for instructions on reporting of pIMDs.
An overview of the protocol-required reporting periods for AEs, SAEs, and pregnancies 
is given in Table 10 (see also reporting methods below).
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
53
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
54
Table 10
Reporting periods for collecting safety information
Study 
activity
Pre-
Vacc 
1*
Visit 1
(Vacc 1)
Visit 2
(Vacc 2)
Visit 
3/Month 3 
phone 
contact
(Post-
vacc 2)
Month 8 
phone 
contact
SFU
Month 
14#
phone 
contact 
SFU
Time of 
reporting
Day 
0/Month 
0
Day 29 
post 
Dose 1
Day 
0/Month 
2
Day 29 
post 
Dose 2
Month 3
Month 8
Month 
14#
Reporting of 
unsolicited 
AEs1
Reporting of 
suspected HZ
2
Reporting of 
AEs/SAEs 
leading to 
withdrawal 
from the study
Reporting of 
all SAEs2
Reporting of 
SAEs related 
to study 
participation 
or GSK 
concomitant 
medication/
vaccine
Reporting of 
pregnancies
Reporting of 
pIMDs
AE: Adverse Event; SAE: Serious Adverse Event; pIMD: potential Immune-Mediated Disease; Vacc: Vaccination; M: 
Month
* i.e. consent obtained;
# i.e. 12 months post dose 2
1Unsolicited AEs will be recorded in 30 day diary card
2 At pre-vaccination, suspected HZ episodes will be collected as medical history (see section 5.6.4.). Post vaccination, 
suspected HZ will be recorded in the diary card as an AE/SAE within the Day 0 –Day 29 period and will also be 
reported during the Month 3, 8 and 14 contacts.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
54
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
55
Type
Unsolicited adverse events/ SAEs, SAEs related to 
study participation or to GSK concomitant 
medication/vaccine; AEs/SAEs leading to withdrawal 
from the study.
Method of ‘unsolicited’ follow-up
including suspected HZ
Diary cards
Method for reporting SAEs, SAEs 
related to study participation or 
to GSK concomitant 
medication/vaccine, Serious 
suspected HZ cases and pIMDs,
Electronic Expedited Adverse Events Report.
Suspected HZ cases (non-serious 
or serious)
HZ (if an AE)/HZ and SAE (if an SAE) screen of the 
eCRF
AEs/SAEs leading to withdrawal 
from the study
AEs/SAE screen of the eCRF
8.3.2.
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 10. 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.
8.3.3.
Evaluation of adverse events and serious adverse events
8.3.3.1.
Active questioning to detect adverse events and serious adverse 
events
As a consistent method of collecting AEs, the subject or the subject’s LAR(s) should be 
asked a non-leading question such as:
‘Have you felt different in any way since receiving the vaccine or since the previous 
visit?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK 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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
55
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
56
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.
8.3.3.2.
Assessment of adverse events
8.3.3.2.1.
Assessment of intensity
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. Such an AE 
would, for example prevent attendance at work and would 
necessitate the administration of corrective therapy.
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets one of the pre-
defined outcomes as described in Section 8.1.2.
8.3.3.2.2.
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 and/or summary of product 
characteristics 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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
56
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
57
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/product administered. The investigator should, therefore, assess whether the AE 
could be causally related to vaccination rather than to the individual vaccines.
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).
8.3.3.3.
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).
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
57
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
58
8.4.
Reporting of serious adverse events, pregnancies, and 
other events
8.4.1.
Prompt reporting of serious adverse events, pregnancies, and 
other events to GSK Biologicals
SAEs that occur in the time period defined in Section 8.3 will be reported promptly to 
GSK within the timeframes described in Table 11, once the investigator determines that 
the event meets the protocol definition of a SAE.
Pregnancies that occur in the time period defined in Section 8.3 will be reported promptly 
to GSK within the timeframes described in Table 11, once the investigator becomes 
aware of the pregnancy. 
pIMDs that occur in the time period defined in Section 8.3 will be reported promptly to 
GSK within the timeframes described in Table 11, once the investigator determines that 
the event meets the protocol definition of a pIMD.
Note: the procedure described in this section will also apply to suspected HZ episodes 
qualifying as SAEs.
Table 11
Timeframes for submitting serious adverse event, pregnancy 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*
electronic Expedited Adverse 
Events Report
Pregnancies 
2 weeks*
electronic pregnancy report
2 weeks*
electronic pregnancy report
pIMDs
24 hours**‡
electronic Expedited 
Adverse Events Report
24 hours*
electronic Expedited Adverse 
Events Report
* Timeframe allowed after receipt or awareness of the information
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD
‡ The investigator will be required to confirm review of the SAE/pIMD causality by ticking the ‘reviewed’ box in the 
electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/pIMD
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
58
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
59
8.4.2.
Contact information for reporting serious adverse events,
pregnancies and pIMDs
Study Contact for Reporting SAEs, pIMDs and pregnancies 
Refer to the local study contact information document.
Back-up Study Contact for Reporting SAEs, pIMDs and pregnancies 
24/24 hour and 7/7 day availability:
GSK Biologicals Clinical Safety & Pharmacovigilance
Outside US & Canada sites:
Fax: 
 or 
Email address:
US sites only:
Fax: 
(Amended 30 May 2017)
Canadian sites only:
Fax: 
8.4.3.
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.
8.4.3.1.
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. 

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
59
30-MAY-2017
PPD
PPD
PPD
PPD
PPD

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
60
8.4.4.
Completion and transmission of pregnancy reports to GSK 
Biologicals
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 2 WEEKS.
Note: Conventionally, the Estimated Gestational Age (EGA) of a pregnancy is dated 
from the first day of the Last Menstrual Period (LMP) of the cycle in which a woman 
conceives. If the LMP is uncertain or unknown, dating of EGA and the Estimated Date of 
Delivery (EDD) should be estimated by ultrasound examination and recorded in the 
pregnancy report.
8.4.5.
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 8.4.3.1 for back-up system in case the electronic reporting system does 
not work.
8.4.6.
Updating of SAE, pregnancy, and pIMD information after removal 
of write access to the subject’s eCRF
When additional SAE, pregnancy, or pIMD information is received after removal of the 
write access to the subject’s eCRF, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
Sponsor Information) or to GSK Biologicals Clinical Safety and Pharmacovigilance 
department within the designated reporting time frames specified in Table 11.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
60
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
61
8.4.7.
Regulatory reporting requirements for serious adverse events
The investigator will promptly report all SAEs to GSK in accordance with the procedures 
detailed in Section 8.4.1. 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.
8.5.
Follow-up of adverse events, serious adverse events, and 
pregnancies
8.5.1.
Follow-up of adverse events and serious adverse events 
8.5.1.1.
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 11).
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 
days after the last vaccination.
8.5.1.2.
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 an electronic Expedited 
Adverse Events Report and/or pregnancy report as applicable.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
61
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
62
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.
8.5.2.
Follow-up of pregnancies
Pregnant subjects will be followed to determine the outcome of the pregnancy. At the end 
of the pregnancy, whether full-term or premature, information on the status of the mother 
and child will be forwarded to GSK Biologicals using the electronic pregnancy report and 
the Expedited Adverse Events Report if applicable. Generally, the follow-up period 
doesn’t need to be longer than six to eight weeks after the estimated date of delivery.
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE.
8.6.
Treatment of adverse events
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of an AE should 
be recorded in the subject’s eCRF (refer to Section 6.6).
8.7.
Subject card
Study subjects/subjects’ LAR(s)/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 LAR(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’ LAR(s)/caregiver must be instructed to keep subject cards in their 
possession at all times.
9.
SUBJECT COMPLETION AND WITHDRAWAL
9.1.
Subject completion
A subject who is available for the concluding contact foreseen in the protocol is 
considered to have completed the study.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
62
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
63
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 
was not available for the concluding contact 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, by the subject’s LAR(s), 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/the subject’s LAR(s) has 
withdrawn consent, the investigator will document the reason for withdrawal of consent, 
if specified by the subject/subject’s LAR(s), in the eCRF.
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 8.5.1.2).
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
63
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
64
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 screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination was made by the 
subject himself/herself by the subject’s LAR(s), 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

Occurrence of unsolicited 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.

Occurrence of SAEs.

Occurrence and relationship to vaccination of all SAEs from Month 0 until study 
end (Month 14, i.e. 12 months post dose 2).

Occurrence of AEs of special interest.

Occurrence of any pIMDs from Month 0 until study end (Month 14, i.e. 12 
months post dose 2).
10.2.
Secondary endpoints

Occurrence of suspected HZ cases.

Occurrence of suspected HZ cases from Month 0 to study end.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
64
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
65
10.3.
Determination of sample size
No sample size is calculated for this study. Potentially eligible subjects who received 
placebo in the ZOSTER-006/ZOSTER-022 studies will be invited to participate in this 
cross-vaccination study. An estimate of the maximum number to be potentially enrolled 
can be calculated by considering for both studies the currently placebo vaccinated 
subjects that are still alive. This gives a maximum number of approximately 14,550.
10.4.
Cohorts for Analyses
This study will collect only safety data. The statistical analysis of the safety endpoints 
will be based on the Total Vaccinated Cohort (TVC); hence no elimination criteria or 
ATP cohorts are defined for the purpose of statistical analysis. 
10.4.1.
Total vaccinated cohort
The Total vaccinated cohort will include all subjects with at least one HZ/su vaccine 
administration documented for whom data are available:

A safety analysis based on the Total vaccinated cohort will include all vaccinated 
subjects.
10.5.
Derived and transformed data

Safety

For the analysis of unsolicited AEs, SAEs and pIMDs, missing or non-evaluable 
measurements will not be replaced. Subjects who missed reporting of 
unsolicited AEs (including SAEs/pIMDs) will be treated as subjects who did not 
report an event. In case of significant non-compliance of study procedures for 
reporting events, the analysis plan will be reassessed to ensure more accurate 
reporting of study data by further analysis.
10.6.
Analysis of demographics
Demographic characteristics (age at first study vaccination in years, gender), withdrawal 
status will be summarised using descriptive statistics:

Frequency tables will be generated for categorical variable such as centre.

Mean, median, standard deviation will be provided for continuous data such as age. 
10.7.
Analysis of safety
The primary analysis for safety will be based on the TVC.
All analysis may be performed by age group at inclusion in the ZOSTER-006/022 (50-59, 
60-69 and ≥70 YOA).
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
65
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
66
When appropriate, tabulations will be presented overall and by time of occurrence related 
to last vaccination (e.g. using windows such as Days 0-29 and more than 30 days post-
vaccination.
The results for the analysis of safety will be tabulated as follows:

The proportion of subjects with at least one report of an unsolicited AE during the 
30-day (Days 029) follow-up period after each vaccination classified according to 
the MedDRA System Organ Class and Preferred Terms 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.

SAEs and withdrawal due to AE(s) will be described in detail.

Number of subjects with pIMDs will be tabulated.
10.8.
Analysis of suspected HZ incidence
Descriptive statistics
The number of suspected HZ cases will be tabulated.
10.9.
Interpretation of analyses
Not applicable, all analyses will be descriptive.
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
All analyses will be conducted on cleaned data. There will be an analysis at the end of the 
study and a study report will also be written.
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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
66
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
67
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.
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 a 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 
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
67
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
68
investigator and should be filed in the monitor’s and investigator’s study file. Any data 
item for which the eCRF will 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.
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.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
68
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
69
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. 
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
All countries will comply with AE and SAE reporting as described in Section 8.4 of the 
protocol. Additionally, countries and sites will follow all applicable local regulations and 
guidelines for AE and SAE reporting as required by their respective healthcare authorities 
and ethics committees.
12.1.
Requirements for France
This section includes all the requirements of the French law (n⁰ 2004-806 of 09 August 
2004), and identifies, item per item, the mandatory modifications or additional 
information to the study protocol.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
69
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
70
Concerning the « STUDY POPULATION » 

In line with the local regulatory requirements, the following text about «PAYMENT 
TO SUBJECTS » is added: 
Subjects will be paid for the inconvenience of participating in the study. The amount 
of payment is stated in the ICF. Subjects not completing the study for whatever 
reason could be paid at the discretion of the Investigator, generally on a pro rata
basis.

In line with the local regulatory requirements, the following text about  
« NATIONAL FILE » is added:
All subjects who will be paid, will be recorded into the “national File” by the 
investigator. They could be identified and monitored under the « Fichier national ».
The following details will be described:

Reference of the study

Surname and first name,

Date and place of birth

Sex

Dates of beginning and termination of the study,

Exclusion period,

The total amount of allowance.

In line with the local regulatory requirements, the following text in section  «OTHER 
STUDY ELIGIBILITY CRITERIA CONSIDERATIONS » is added:
A subject will be eligible for inclusion in this study if he/she is either affiliated to or 
beneficiary of a social security category.
It is the investigator’s responsibility to ensure and to document (in source document -
patient notes) that the patient is either affiliated to or beneficiary of a social security 
category.
Concerning the “DATA ANALYSIS AND STATISTICAL CONSIDERATIONS” 
and specially in the “SAMPLE SIZE ASSUMPTION”

The expected number of patients to be recruited in France is declared to the French 
regulatory authority.
Concerning the “STUDY CONDUCT CONSIDERATIONS”

In section “Regulatory and Ethical Considerations, Including the Informed Consent 
Process”
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
70
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
71
Concerning the process for informing the patient or his/her legally 
authorized representative, the following text is added: 

French Patient ICF is a document which summarizes the main features of the study 
and allows collection of the patient's written consent in triplicate. It also contains a 
reference to the authorisation of ANSM and the approval from the French Ethic 
committee and the maintenance of confidentiality of the returned consent form by 
GSK France.
Concerning the process for obtaining subject informed consent:

When biomedical research is carried out on an adult in the care of a “tutelle” 
guardian, consent is given by their legal representative and, if the committee 
mentioned in article L. 1123-1 considers that the research in question, because of the 
gravity of the restraints or the specificity of the medical acts involved, entails a 
serious risk of affecting their private life or the integrity of their body, by the family 
council if it has been instated, or by the judge of “tutelle” guardians.

When biomedical research is carried out on an adult in the care of a "curatelle" 
guardian, consent is given by the subject assisted by his guardian.
However, if the adult in the care of a "curatelle" guardian is invited to participate in 
research which the committee mentioned in article L. 1123-1 considers, because of 
the gravity of the restraints or the specificity of the medical acts involved, to entail a 
serious risk of affecting their private life or the integrity of their body, the matter is 
submitted to the judge of guardians who decides whether the adult is capable of 
giving his consent. In the case of incapacity, the judge will decide whether or not to 
authorise the biomedical research.

When biomedical research, which complies with the conditions laid down in article 
L. 1121-8, is considered for an adult incapable of expressing his consent and not 
under a legal protection order, consent is given by a person of confidence as defined 
in article L. 1111-6 and, failing this, by a person who maintains close and stable 
links with the subject. However, if the committee mentioned in article L. 1123-1 
considers that the research in question, because of the gravity of the restraints or the 
specificity of the medical acts involved, entails a serious risk of affecting their 
private life or the integrity of their body, consent is given by the judge of guardians.
Concerning the management of the Patient ICFs, the following text is 
added:

The first copy of the Patient ICF is kept by the investigator. The second copy is kept 
by the Director of the Medical Direction of GSK France and the last copy is given to 
the patient or his/her legally authorized representative.

The second copy of all the consent forms will be collected by the investigator at the 
end of the trial under the Clinical Research Assistant’s (CRA's) control, and placed 
in a sealed envelope bearing only:

the study number, 

the identification of the Centre : name of the principal investigator and number of 
centre),
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
71
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
72

the number of informed consents,

the date, 

and the principal investigator’s signing.
Then, the CRA hands the sealed envelope over to the Medical Direction, for 
confidential recording, under the responsibility of the Medical Director.
In section concerning the “ NOTIFICATION TO THE HOSPITAL DIRECTOR ” 
the following text is added (if applicable)

In accordance with Article L1123-13 of the Public Health Code, the Hospital 
Director is informed of the commitment to the trial in his establishment. The 
Hospital Director is supplied with the protocol and any information needed for the 
financial disposition, the name of the investigator(s), the number of sites involved in 
his establishment and the estimated time schedule of the trial (R.1123-63).
In section concerning the “ INFORMATION TO THE HOSPITAL 
PHARMACIST ” the following text is added (if applicable)

In accordance with Article R.1123-64 of the Public Health Code, the Hospital 
Pharmacist is informed of the commitment to the trial in his establishment. The 
Pharmacist is supplied with a copy of the protocol (which allows him to dispense the 
drug(s) of the trial according to the trial methodology), all information concerning 
the product(s) of the trial (e.g. included in the CIB), the name of the investigator(s), 
the number of sites involved in his establishment and the estimated time schedule of 
the trial.
In section “ DATA MANAGEMENT ” the following text is added

" Within the framework of this clinical trial, data regarding the identity of the 
investigators and/or co-investigators and/or the pharmacist if applicable, involved in 
this clinical trial, and data regarding the patients recruited in this clinical trial (patient 
number, treatment number, patient status with respect to the clinical trial, dates of 
visit, medical data) will be collected and computerized in GSK data bases by GSK 
Laboratory or on its behalf, for reasons of follow up, clinical trial management and 
using the results of said clinical trial. According to the Act n° 78-17 of 6th January 
1978 further modified, each of these people aforesaid has a right of access, 
correction and opposition on their own data through GSK Laboratory (Clinical
Operations Department)."
Concerning Monitoring visits

The Health Institution and the Investigator agree to receive on a regular basis a CRA 
of GSK or of a service provider designated by GSK. The Health Institution and the 
Investigator agree to be available for any phone call and to systematically answer to 
all correspondence regarding the Study from GSK or from a service provider 
designated by GSK. In addition, the Health Institution and the Investigator agree that 
the CRA or the service provider designated by GSK have direct access to all the data 
concerning the Study (test results, medical record, etc …). This consultation of the 
information by GSK is required to validate the data registered in the eCRF, in 
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
72
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
73
particular by comparing them directly to the source data. In accordance with the 
legal and regulatory requirements, the strictest confidentiality will be respected.
Concerning Data entry into the eCRF
The Health Institution and the Investigator agree to meet deadlines, terms and conditions 
of the Study’s eCRF use here below :
The Health Institution and the Investigator undertake:
1. That the Investigator and the staff of the investigator centre make themselves 
available to attend the training concerning the computer system dedicated to the 
eCRF of the Study provided by GSK or by a company designated by GSK.
2. That the Investigator and the staff of the investigator centre use the IT Equipment 
loaned and/or the access codes only for the purpose of which they are intended and 
for which they have been entrusted to them, namely for the Study achievement, to the 
exclusion of any other use.
3. That the Investigator and the staff of the investigator centre use the IT Equipment 
loaned according to the specifications and manufacturer’s recommendations which 
will have been provided by GSK.
4. To keep the IT Equipment and/or access codes in a safe and secure place and to only 
authorize the use of this IT Equipment by investigator centre staff designated by the 
principal investigator to enter the data of the Study.
5. That the Investigator and the staff of the investigator centre enter the data of the 
eCRF related to a patient visit in the 3 days following the date of the patient visit or, 
for the patient test results, in the 3 days following the reception of the results of such 
tests.
6. That the Investigator resolves and returns to GSK the data queries issued by GSK or a 
service provider designated by GSK within 7 days after the reception of the request of 
clarification or in a period of one (1) day during the final stage of clarification of the 
data base or in such other period as provided by GSK and/or a company designated 
by GSK.
7. To be responsible for the installation and payment of the required Internet 
connections needed for the use of the IT Equipment, Computer systems and/or access 
codes.
8. To return at the end of the Study the IT Equipment and/or access codes to GSK or to 
any company designated by GSK and any training material and documentation. The 
IT Equipment cannot under any circumstances be kept by the Health Institution or the 
Investigator for any reason whatsoever. 
Concerning Clinical Trials Register (CTR) publication

It is expressly specified that GSK and/or the Sponsor can make available to the 
public the results of the Study by the posting of the said results on a website of the 
GSK Group named CTR including the registration of all the clinical trials conduct by 
the GSK Group and this before or after the publication of such results by any other 
process.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
73
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
74
Concerning Data Protection French Law of 6 January 1978 (CNIL)

In accordance with the Data Protection French Law of 6 January 1978 as modified, 
computer files used by GSK to monitor and follow the implementation and the 
progress of the Study are declared with the CNIL by GSK. The Investigator has 
regarding the processing data related to him a right of access, of rectification and of 
opposition with GSK in accordance with the legal provisions. This information can 
be transferred or be accessed to other entities of GSK Group in France, Britain or 
United States, what the Investigator agrees by the signature of the present Protocol.
12.2.
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 safety of the GSK Biologicals’ HZ/su 
vaccine. 
Note: The study can only enrol placebo subjects from ZOSTER-006/ZOSTER-022 
studies who are willing to return for vaccination with HZ/su, regardless of gender, 
race or male/female ratio.
12.3.
Requirements for Japan (Amended 30 May 2017)
Regulatory and Ethical Considerations
The study will be conducted in accordance with “the Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (Ministry of Health 
and Welfare/Ministry of Health, Labour and Welfare Notification No.28 dated 27th 
March, 1997)” GCP, Article 14-3 and 80-2 of the Pharmaceutical Affairs Law and 
Evaluation and Licensing Division, Pharmaceutical Safety Bureau of MHW, Notification 
No. 1061, 1998.
Clinical Trial Notification to Regulatory Authority
Japan Vaccine Co.,Ltd. will submit the CTN to the regulatory authorities in accordance 
with Article 80-2 of the Pharmaceutical Affairs Law before conclusion of any contract 
for the conduct of the study with study sites.
Informed Consent of Subjects
Informed consent will be obtained before the subject can participate in the study. The 
contents and process of obtaining informed consent will be in accordance with all 
applicable regulatory requirements.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
74
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
75
Informed Consent
Prior to the start of the study, the investigator (or sub-investigator) should fully inform 
the potential subject of the study including the written information given approval by the 
IRB. The investigator (or sub-investigator) should provide the subject ample time and 
opportunity to inquire about details of the study and to decide whether or not to 
participate in the study. After giving informed consent based on his/her free will, the 
subject should sign and personally date the consent form. If the subject wishes to 
consider the content of the written information at home, he/she may sign the consent 
form at home. The person who conducted the informed consent discussion should sign 
and personally date the consent form. If the subject  is unable to read, an impartial 
witness should be present during the entire informed consent discussion, and the witness 
should sign and personally date the consent form. The investigator (or sub-investigator)
should retain this signed and dated form (and other written information) together with the 
source medical records, such as clinical charts (in accordance with the rules for records 
retention, if any, at each medical institution) and give a copy to the subject.
If information becomes available that may be relevant to the subject's  
willingness to continue participation in the study (revision of ICF and other 
written information)
If information becomes available that may be relevant to the subject's willingness to 
continue participation in the study, the investigator (or sub-investigator) should 
immediately inform the subject of it to confirm the willingness to continue participation 
in the study, and document the communication of this information (in medical records). If 
necessary, the investigator should revise the written information to be provided to 
subjects, promptly report it to the sponsor, and obtain approval from the IRB. The 
investigator should not enrol any new subject in the study before the IRB’s approval. 
After the IRB approves the revision of the written information to be provided to subjects, 
the investigator (or sub-investigator) should inform each subject participating in the study 
of the revised written information, and obtain written informed consent.
Study Monitoring
By monitoring the parties involved in the study including medical institutions, 
investigators, sub-investigators, study collaborators, and storage managers, monitors will:
1.
Oversee the process of obtaining written informed consent, the control of 
investigational products and the progress of the study (including withdrawals and 
adverse events, and ensure that the conduct of the study is in compliance with GCP, 
Revised GCP, this protocol, and any other written agreement between the sponsor 
and the investigator/institution.
2.
Collect and provide information that is necessary to conduct the study properly 
(information on investigational products’ safety, efficacy and quality).
3.
Verify that the investigator/institution has adequate qualifications and resources and 
remain adequate throughout the study period, and that facilities, including 
laboratories, equipment, and staff, are adequate to safely and properly conduct the 
study and remain adequate throughout the study period.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
75
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
76
4.
Verify that source documents and other study records are accurate, complete, kept 
up-to-date and maintained.
5.
Determine whether the person responsible for retaining records is maintaining the 
essential documents at each medical institution.
6.
Check the accuracy and completeness of the CRF entries, source documents and 
other study-related records against each other.
The investigator and institution should agree to allow the monitor direct access to 
essential documents and other relevant documents.
Direct access to essential documents by monitors and the scope of those documents will 
be specified separately in the written procedures for monitoring prepared for this study.
Source Data Recorded Directly on CRF
The following data may be recorded directly on the CRFs and considered to be source 
data.
1.
Assessment of causality between adverse events and the investigational product.
Deviations from and Changes of Protocol
Deviations from Protocol
The investigator (or sub-investigator) may implement a deviation from, or a change of, 
the protocol to eliminate an immediate hazard(s) to subjects without agreement by the 
sponsor or prior IRB approval. As soon as possible, the implemented deviation or change 
and the reasons for it should be submitted to the head of the medical institution and the 
IRB for approval, and via the head of the medical institution to the sponsor for 
agreement.
The investigator (or sub-investigator) should document all deviations from the approved 
protocol. The investigator should document the reason only for the deviation from, or the
change of, the protocol to eliminate an immediate hazard(s) to subjects, and submit it to 
the sponsor and the head of the medical institution, and retain its copy.
Changes of Protocol
1.
If it becomes necessary to make any changes significantly affecting the conduct of 
the study, and/or increasing the risk to subjects, the sponsor should promptly 
document the changes and reasons for them and amend the protocol after discussion 
with the (coordinating [investigator, committee members] and) investigators, and 
notify the heads of the medical institutions and investigators of the changes of the 
protocol (sample ICF and other written information, if necessary). The investigator 
should not implement any significant changes without approval from the IRB.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
76
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
77
2.
For changes other than the above 1), the sponsor should document the changes and 
reasons for them and inform the heads of the medical institutions and investigators of 
the changes of the protocol. Such changes require prior approval from the IRB, 
except where necessary to eliminate an immediate hazard(s), or when the change(s) 
involves only logistical or administrative aspects of the study. The investigator 
should promptly report the changes implemented without prior approval to the IRB 
for approval.
Study Period
The study period has not been confirmed at the time of this protocol. When needed and 
available, the study period can be communicated at local level, outside of this protocol.
If during the conduct of the study the HZ/su vaccine (GSK 1437173A) is approved in 
Japan, the study will then be locally amended to be conducted as a post-marketing study.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
77
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
78
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.
Centers for Disease Control and  Prevention Metropolitan Atlanta Congenital Defects 
Program (CDC MACDP) guidelines. Birth defects and genetic diseases branch 6-digit 
code for reportable congenital anomalies; (2007) 
http://www.cdc.gov/ncbddd/birthdefects/documents/MACDPcode0807.pdf
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.
EMA Guideline on the exposure to medicinal products during pregnancy: need for post-
authorization data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community level 
in May 2006);
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_g
uideline/2009/11/WC500011303.pdf
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): 245–247.
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
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: 2271–2284.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
78
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
79
Schmader KE, Dworkin RH. Natural history and treatment of herpes zoster. The Journal 
of pain. 2008; 9(1): S3–S9.
Scott F, Johnson R, Leedham-Green M, et al. The burden of herpes zoster: A prospective 
population based study. Vaccine. 2006; 24: 1308–1314.
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: 213–222.
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): 2053–2058.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
79
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
80
APPENDIX A
AMENDMENTS AND ADMINISTRATIVE 
CHANGES TO THE PROTOCOL
GlaxoSmithKline Biologicals
Vaccine Value & Health Science (VVHS)
Protocol Amendment 1
eTrack study number 
and Abbreviated Title
204486 (ZOSTER-056)
IND number
BB-IND-13857
EudraCT number
2015-000965-30
Amendment number:
Amendment 1
Amendment date:
17 December 2015
Co-ordinating author:
, Scientific Writer (XPE Pharma and 
Science for GSK Biologicals)
Rationale/background for changes: 
!
Occurrence of suspected Herpes Zoster (HZ) episodes during the entire study 
period will be evaluated as secondary objective. Therefore, wording related to 
collection, reporting and recording of HZ was added where applicable throughout 
the protocol.
!
Other minor changes were done.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
Cover page:
Contributing authors
!
, Study Delivery Manager
SYNOPSIS and Section 2.2. Secondary objective
!
To evaluate the incidence of suspected HZ episodes (self-reported or medically 
diagnosed) during the entire study period.
SYNOPSIS and Section 10.2. Secondary endpoints
!
Occurrence of suspected HZ cases.
∀
Occurrence of suspected HZ cases from Month 0 to study end.

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
80
30-MAY-2017
PPD
PPD

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
81
LIST OF ABBREVIATIONS
QS-21
Quillaja saponaria Molina, fraction 21 (Licensed by 
GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation)
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., a Delaware, USA corporation)
Triterpene glycoside immune enhancer
Section 2.2. Secondary objective
Refer to Section 10.2 for the definition of the secondary endpoint.
Section 5.4.1. Data collection
After Visit 2, there will be 3 contacts between the subject/subject’s LAR/caregiver and 
the investigator and/or his delegate for the purpose of collecting information on any event 
of interest (see Table 4 and Section 5.6.14 for details). Month 3 contact will either be a 
site visit or a phone contact depending on the needs of the subject. Logistical details 
pertaining to Month 3 contact will be included in the SPM. Months 8 and 14 will be 
phone contacts. The phone contacts will take place using the most convenient method 
suited for the sites (e.g., telephone calls by site staff or designee, and/or by call centre). 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 LAR/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. 
30-day diary cards will be completed by all subjects/subject’s LAR/caregiver for 
unsolicited AEs (from Day 0 to Day 29 after each vaccination), including episodes of 
suspected HZ (self-reported or medically diagnosed) and any concomitant medication 
and vaccination taken from Day 0 to Day 29 after each vaccination.
Episodes of suspected HZ occurring from Day 0 to Day 29 after each vaccination 
should be collected in the diary cards (by subject/LAR/caregiver) and in the HZ section 
of the eCRF (if considered an AE by the investigator and/or his delegate) or in the SAE 
and HZ section of the eCRF (if considered an SAE by the investigator and/or his 
delegate). Episodes of suspected HZ occurring outside of this period should be reported 
in the HZ section (if a Non-Serious AE) or in the SAE and HZ section of the eCRF (if 
an SAE). If the investigators become aware of an HZ episode between study visits, they 
should report it at that time in the eCRF, as per above.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
81
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
82
Section 5.5. Outline of study procedures
Table 4 List of study procedures
Epoch
Primary
Type of contact
visit
visit
contact 1
phone 
contact
phone 
contact
Timepoint identification
Visit 1
Visit 2
Visit 
3/Month 3 
Phone 
contact
Month 8 
Phone 
contact
Month 14* 
Phone 
contact
Time value
Month 0
Month 2
Month 3
Month 8
Month 14*
Sampling timepoints
Vacc 1
Vacc 2
Post-Vacc 2
SFU
SFU
Training on self-reporting by 
subjects/LAR/caregiver 5
O
O
O
O
Training on signs/symptoms of typical HZ
O
O
O
O
O
Recording of suspected HZ episodes
●
●
●
●
●
Section 5.6.4. Medical history
In addition history of prior HZ episodes must be recorded (from HZ collected during the 
ZOSTER-006/ZOSTER-022 studies until the first visit in the study ZOSTER-056)
Section 5.6.11.Training on self-reporting by subjects was moved (previously having been 
section 5.6.13)
Section 5.6.12. Training and reporting signs/symptoms of typical HZ
Subjects/subject’s LAR/caregiver will be instructed at Visit 1 and Visit 2 to:

recognize the signs and symptoms of typical HZ 

to record in the diary card information related to suspected HZ (Day 0 to Day 29 
post-vaccination)
At each subsequent visit and contact until study end at Month 14, subjects will be 
reminded of the signs and symptoms of typical HZ and will be questioned about 
occurrence of a suspected HZ episode from previous study visit or contact.  
Section 5.6.15. Recording of suspected HZ episodes was added with the wording below:
5.6.15.1. Suspected HZ
A suspected case of HZ is defined as a new rash characteristic of HZ (e.g., unilateral, 
dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or 
other sensations).
A diagnosis of suspected HZ will be based upon investigator or the attending physician
judgment. The occurrence of suspected HZ will be reported as an AE/SAE, as 
appropriate. The reporting period for cases of suspected HZ will be from Day 0 to study 
end.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
82
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
83
5.6.15.2. Study procedures in case of suspected HZ
The subject card will include a request to the attending physician to provide 
information about the clinical diagnosis of a case of suspected HZ, when contacted by 
the investigator or delegate. When a clinical diagnosis of suspected HZ has been made 
by an attending physician, the subject should ensure the study site is informed about 
the case.
When the investigator or delegate becomes aware that a clinical diagnosis of suspected 
HZ has been made by an attending physician, he/she will contact the attending 
physician. The investigator or delegate will obtain the relevant information from the 
attending physician and this information will be recorded in the HZ section or SAE 
and HZ section of eCRF, as applicable.
When the suspected HZ cases is self-reported, the investigator or his delegate will 
collect all information regarding the suspected HZ episode and this will be recorded in 
the HZ section or SAE and HZ section of eCRF, as applicable.
Note: Non-serious episodes of suspected HZ do not require immediate reporting to the 
site. The investigator/study staff will question the subject at each scheduled visit and 
contact regarding the onset of signs and symptoms of the suspected HZ.
Section 5.6.16. Reminder for follow-up contact
The subject/subject’s LAR/caregiver will be reminded that, after Visit 2, three contacts 
between the subjects/subject’s LAR/caregiver and the investigator and/or his delegate 
will take place in order to collect all relevant information on any event of interest that 
may have occurred (including SAEs, pIMDs, suspected HZ [Section 8.3], the use of 
concomitant medications and/or vaccinations (Section 6.6) or pregnancy [Section 8.3]), 
and that information will be recorded in the appropriate section of the subject’s eCRF.
Section 5.6.17. Study conclusion
At the study conclusion contact, the following procedures will take place:
Recording of all suspected HZ episodes and SAEs (including related to study 
participation, or to a concurrent GSK medication/vaccine).
Section 6.5. Contraindications to subsequent vaccination
An episode of suspected HZ at between Visit 1 (Month 0, Vaccination 1) and/or Visit 2 
(Month 2, Vaccination 2).
Section 8.3.1. Time period for detecting and recording adverse events, serious adverse 
events and pregnancies
The occurrence of suspected HZ will constitute an AE or SAE, as appropriate (and 
shall be reported in the HZ section of the eCRF [if an AE] or in the SAE and HZ 
section of the eCRF [if an SAE]). During the study, the time period for collecting and 
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
83
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
84
recording of suspected HZ will range from first receipt of study vaccine to study end. 
When a suspected HZ episode has been reported, specific clinical information about 
the case, following the first vaccination visit (Month 0) until study end (Month 14), will 
be entered into the eCRF. Please refer to the SPM for information about recording the 
details of suspected HZ cases. 
Table 10
Reporting periods for collecting safety information
Study activity
Pre-
Vacc 
1*
Visit 1
(Vacc 1)
Visit 2
(Vacc 2)
Visit 
3/Month 3 
phone 
contact
(Post-
vacc 2)
Month 8 
phone 
contact
SFU
Month 
14#
phone 
contact 
SFU
Time of 
reporting
Day 0/
Month 0
Day 29 
post 
Dose 1
Day 0/
Month 2
Day 29 
post 
Dose 2
Month 3
Month 8
Month 
14#
Reporting of 
suspected HZ2
Reporting of all 
SAEs2
2 At pre-vaccination, suspected HZ episodes will be collected as medical history (see section 5.6.4.). Post 
vaccination, suspected HZ will be recorded in the diary card as an AE/SAE within the Day 0 –Day 29 
period and will also be reported during the Month 3, 8 and 14 contacts.
Type
Unsolicited adverse events/SAEs, SAEs related to 
study participation or to GSK concomitant 
medication/vaccine; AEs/SAEs leading to withdrawal 
from the study.
Method of ‘unsolicited’ follow-up 
including suspected HZ
Diary cards
Method for reporting SAEs, SAEs 
related to study participation or 
to GSK concomitant 
medication/vaccine, Serious 
suspected HZ cases and pIMDs,
Electronic Expedited Adverse Events Report. 
Suspected HZ cases (non 
serious or serious)
HZ (if an AE)/HZ and SAE (if an SAE) screen of the 
eCRF
AEs/SAEs leading to withdrawal 
from the study
AEs/SAE screen of the eCRF
Section 8.4.1. Prompt reporting of serious adverse events, pregnancies, and other events 
to GSK Biologicals
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
84
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
85
Note: the procedure described in this section will also apply to suspected HZ episodes 
qualifying as SAEs. 
Section 10.8. Analysis of suspected HZ incidence was added with the wording below: 
Descriptive statistics
The number of suspected HZ cases will be tabulated.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
85
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
86
GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Amendment 2
eTrack study number 
and Abbreviated Title
204486 (ZOSTER-056)
IND number
BB-IND-13857
EudraCT number
2015-000965-30
Amendment number:
Amendment 2
Amendment date:
11 January 2017
Co-ordinating author:
 Scientific Writer (XPE Pharma and Science 
for GSK Biologicals)
Rationale/background for changes:
!
This Country Specific Protocol Amendment was developed in order to implement 
the Voice of the Patient initiative in Japan.
!
The following statement was added in Section 12.3: “If during the conduct of the 
study the HZ/su vaccine (GSK 1437173A) is approved in Japan, the study will 
then be locally amended to be conducted as a post-marketing study”.
!
The list of the contributing authors was updated.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
Cover page:
Contributing authors
!
, Clinical Research and 
Development Lead
!
, Clinical Research and 
Development Lead
!
, Clinical Research and 
Development Lead (Chiltern International for 
GSK Biologicals)
!
, Study 
Delivery Lead
!
 and 
, Study 
Delivery Managers (SynteractHCR for GSK 
Biologicals)
!
, Vice President, VDL
!
, Study Delivery Manager

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
86
30-MAY-2017
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
87
!
, Vaccine Supply 
Coordinator
!
, 
Clinical Safety Representative
!
, Project
Oversight Data Manager
!
 and 
 
 and 
(USA), Global 
Regulatory Affairs
!
 Project level Clinical Research and 
Development Lead, Belgian RDC
!
, Zoster Portfolio level Clinical 
and Epidemiology Project Research and 
Development Lead for Zoster, Belgian RDC
Copyright 2015-2017 the GlaxoSmithKline group of companies. All rights reserved. Unauthorised 
copying or use of this information is prohibited.
Sponsor signatory
!
, Zoster Portfolio level Clinical 
and Epidemiology Project Research and 
Development Lead for Zoster, Belgian RDC
LIST OF ABBREVIATIONS
PA:
Polling Agency
VCSP:
Vaccines Clinical Safety and Pharmacovigilance
12.3.   Requirements for Japan
Regulatory and Ethical Considerations
The study will be conducted in accordance with “the Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (Ministry of Health 
and Welfare/Ministry of Health, Labour and Welfare Notification No.28 dated 27th 
March, 1997)” GCP and, Article 14-3 and 80-2 of the Pharmaceutical Affairs Law and 
Evaluation and Licensing Division, Pharmaceutical Safety Bureau of MHW, 
Notification No. 1061, 1998.
Study Period
The study period has not been confirmed at the time of this protocol. When needed and 
available, the study period can be communicated at local level, outside of this protocol.
If during the conduct of the study the HZ/su vaccine (GSK 1437173A) is approved in 
Japan, the study will then be locally amended to be conducted as a post-marketing 
study. 

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
87
30-MAY-2017
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
88
Voice of the Patient (VoP) Initiative
Subjects who are participating in the Zoster-056 study will be invited for a qualitative 
survey conducted by Polling Agency (PA) to better understand their own experience 
after the administration of HZ/su vaccine and what impact it may have had on their 
daily life, their perception of HZ/su and stated willingness to receive additional dose.
Contact details of the PA will be provided to the subjects by the investigators. Subjects 
who are willing to participate in this survey, can contact the PA at all stages during the 
study - after the first, second dose and also when full vaccination course was not 
completed.
Participation in the survey will be optional and will not impact subject's participation 
in the study.
Results of this research as well as proposal, interviews and market research material 
(questionnaire) are for internal use only and will not be published.
The survey is likely to elicit safety information and robust safety reporting process will 
be followed.
Safety reporting process:
Adverse Event (AE) Reporting:
Any AE linked to the HZ/su vaccine reported by the interviewees must be reported by 
the PA to the trial investigator within 24 hours of initial receipt (or next working day if 
over a weekend or a national holiday).
Investigator's responsibilities are as follows:

The investigator will have the responsibility to review the AE reported by the PA 
and reconcile with the AE/SAE reported in the eCRF. In case of discrepancy 
between the AE/SAE reported through the PA and the AE/SAE reported in the 
eCRF, the Investigator will have to contact the subject to request more information 
regarding the reported AE/SAE and correct the eCRF, if needed (see Section 8).

The Investigator will have to assess whether the AE/SAE reports should be 
submitted within eCRF according to protocol requirements (see Section 8).

Each investigator site will have to track and document the AE/SAE reconciliation.
Any AE linked to other GSK vaccine/product must be reported to Vaccines Clinical 
Safety and Pharmacovigilance (VCSP) Department according to spontaneous 
reporting process. VCSP will process such AE/SAE (linked to marketed products) 
according to standard processes.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
88
30-MAY-2017

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
89
GlaxoSmithKline Biologicals SA
Vaccines R &D
Protocol Amendment 3
eTrack study number 
and Abbreviated Title
204486 (ZOSTER-056)
IND number
BB-IND-13857
EudraCT number
2015-000965-30
Amendment number:
Amendment 3
Amendment date:
30 May 2017
Co-ordinating author:
, Scientific Writer
Rationale/background for changes:
!
This country specific protocol amendment was developed in order to remove the 
Voice of the Patient (VoP) initiative text from Section 12.3 since this initiative was 
not adopted in Japan.
!
This is a country specific administrative change for the US since the back-up study 
contact telephone number for reporting SAEs, pregnancies and pIMDs in the US 
was removed from Section 8.4.2. This US telephone number, which was originally 
provided to the US sites as a courtesy, became inactivated over the course of the 
study and the US Fax number is retained as the back-up study contact number for 
reporting SAEs, pregnancies and pIMDs.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
LIST OF ABBREVIATIONS
PA:
Polling Agency
VCSP:
Vaccines Clinical Safety and Pharmacovigilance
Section 8.4.2 Contact information for reporting serious adverse events, pregnancies 
and pIMDs
Study Contact for Reporting SAEs, pIMDs and pregnancies 
Back-up Study Contact for Reporting SAEs, pIMDs and pregnancies 
24/24 hour and 7/7 day availability:
GSK Biologicals Clinical Safety & Pharmacovigilance
US sites only:
Fax: 
 Tel: 

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
89
30-MAY-2017
PPD
PPD
PPD

CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
30-MAY-2017
90
12.3.   Requirements for Japan
Voice of the Patient (VoP) Initiative
Subjects who are participating in the Zoster-056 study will be invited for a qualitative 
survey conducted by Polling Agency (PA) to better understand their own experience after 
the administration of HZ/su vaccine and what impact it may have had on their daily life, 
their perception of HZ/su and stated willingness to receive additional dose.
Contact details of the PA will be provided to the subjects by the investigators. Subjects 
who are willing to participate in this survey, can contact the PA at all stages during the 
study - after the first, second dose and also when full vaccination course was not 
completed.
Participation in the survey will be optional and will not impact subject's participation in 
the study.
Results of this research as well as proposal, interviews and market research material 
(questionnaire) are for internal use only and will not be published.
The survey is likely to elicit safety information and robust safety reporting process will 
be followed.
Safety reporting process:
Adverse Event (AE) Reporting:
Any AE linked to the HZ/su vaccine reported by the interviewees must be reported by the 
PA to the trial investigator within 24 hours of initial receipt (or next working day if over 
a weekend or a national holiday).
Investigator's responsibilities are as follows:

The investigator will have the responsibility to review the AE reported by the PA 
and reconcile with the AE/SAE reported in the eCRF. In case of discrepancy 
between the AE/SAE reported through the PA and the AE/SAE reported in the eCRF, 
the Investigator will have to contact the subject to request more information 
regarding the reported AE/SAE and correct the eCRF, if needed (see Section 8).

The Investigator will have to assess whether the AE/SAE reports should be 
submitted within eCRF according to protocol requirements (see Section 8).

Each investigator site will have to track and document the AE/SAE reconciliation.
Any AE linked to other GSK vaccine/product must be reported to Vaccines Clinical 
Safety and Pharmacovigilance (VCSP) Department according to spontaneous reporting 
process. VCSP will process such AE/SAE (linked to marketed products) according to 
standard processes.
 
CONFIDENTIAL
204486 (ZOSTER-056)
Protocol Amendment 3 Final
c07d97e55cdd80c89a37b72805073d69201142a4
90
30-MAY-2017