Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A When Co-administered With Prevenar13 in Adults Aged 50 Years and Older
Phase: PHASE3
Conditions: Herpes Zoster
Sponsor: GlaxoSmithKline

CONFIDENTIAL
30-JAN-2018
1
Clinical Study Protocol
Sponsor:
GlaxoSmithKline Biologicals SA
Rue de l’Institut 89, 1330 Rixensart, Belgium
Primary Study vaccine
!
GlaxoSmithKline (GSK) Biologicals’ lyophilized 
formulation of the Herpes Zoster (HZ) subunit 
(HZ/su) vaccine (GSK1437173A)
Other Study vaccine
Licensed pneumococcal polysaccharide conjugate 
vaccine (13-valent, adsorbed), Prevenar13™.
eTrack study number and 
Abbreviated Title
204487 (ZOSTER-059 PRI)
Investigational New Drug 
(IND) number
BB-IND-13857
EudraCT number
2017-001220-22
Date of protocol
Final Version 2: 26 September 2017
Date of protocol 
amendment
Amendment 1 Final: 30 October 2017
Amendment 2 Final: 30 January 2018
Title
Immunogenicity and safety study of GSK Biologicals’ 
Herpes Zoster vaccine GSK1437173A when co-
administered with Prevenar13 in adults aged 50 years 
and older.
Detailed Title
A Phase IIIB, randomized, open-label, multicenter 
clinical trial to assess the immunogenicity and safety 
of GSK Biologicals’ Herpes Zoster vaccine 
GSK1437173A when co-administered with 
Prevenar13 in adults aged 50 years and older.
Co-ordinating author
, Scientific Writer, contractor for GSK 
Biologicals
Contributing authors
(Amended 30 January 2018)
!
, Clinical and Epidemiology 
Scientist
!
, Clinical and Epidemiology 
Project Lead
!
, Clinical and Epidemiology 
Project Leader
!
, Project Statistician
!
, Lead Statistician
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CONFIDENTIAL
204487 (ZOSTER-059 PRI)
Protocol Amendment 2 Final
30-JAN-2018
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eTrack study number and 
Abbreviated Title
204487 (ZOSTER-059 PRI)
Investigational New Drug 
(IND) number
BB-IND-13857
EudraCT number
2017-001220-22
Detailed Title
A Phase IIIB, randomized, open-label, multicenter 
clinical trial to assess the immunogenicity and safety 
of GSK Biologicals’ Herpes Zoster vaccine 
GSK1437173A when co-administered with 
Prevenar13 in adults aged 50 years and older.
Contributing authors
(Contd.)
(Amended 30 January 2018)
!
, Study Delivery Lead
!
, Study Delivery Lead, Synteract
Inc. for GSK Biologicals
!
, Study Delivery Associate
!
, Clinical Trial Supply Manager
!
, Clinical Safety representative
!
, Clinical Safety 
representative
!
, Study Data Manager (Tata 
Consultancy Services for GSK Biologicals)
!
 Study Data Manager (Tata 
Consultancy Services for GSK Biologicals)
!
, Oversight Data Manager
!
, Global Regulatory Affairs
!
, Global Regulatory Affairs
!
, United States Regulatory Affairs
!
, Global Patents
!
, Global Medical Affairs
!
, Clinical Readout Team Lead
!
, Laboratory Study Manager
GSK Biologicals’ Protocol DS v 15.0
©2017-2018 GSK group of companies or its licensor
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PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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PPD
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204487 (ZOSTER-059 PRI)
Protocol Amendment 2 Final
30-JAN-2018
3
Protocol Amendment 2 Sponsor Signatory Approval
eTrack study number and 
Abbreviated Title
204487 (ZOSTER-059 PRI)
IND number
BB-IND-13857
EudraCT number
2017-001220-22
Date of protocol amendment
Amendment 2 Final: 30 January 2018
Detailed Title 
A Phase IIIB, randomized, open-label, multicenter
clinical trial to assess the immunogenicity and safety 
of GSK Biologicals’ Herpes Zoster vaccine 
GSK1437173A when co-administered with 
Prevenar13 in adults aged 50 years and older.
Sponsor signatory
(Amended 30 January 2018)
Anne Schuind
Clinical and Epidemiology Project Leader, 
Zoster Program, US Research and Development 
Center (RDC)
Signature
Date
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Protocol Amendment 2 Rationale
Amendment number:
Amendment 2
Rationale/background for changes:
Major change:

This amendment is in response to the Center for Biologics Evaluation and 
Research (CBER) comments on Protocol Amendment 1, received on 09-January-
2018, requesting clarification on 1. the adjustment for baseline titers in the 
computation of the Multiplex Opsonophagocytosis Assay (MOPA) Geometric 
Mean Titers (GMT) ratios (Section 10.7.2) and 2. time points for primary 
evaluations on co-primary immunogenicity objectives (Section 10.10.1).
Other changes:

The tradename for pneumococcal polysaccharide conjugate vaccine (13-valent adsorbed)
in Canada has been corrected to Prevnar13 from Prevenar13.

The laboratory to be used for MOPA testing has been selected and is presented in 
Appendix B.

A typographical error in the estimated number of subjects in each age strata and 
study group has been corrected. Table 4 reflects the correct number of subjects for 
age stratification.
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Protocol Amendment 2 Final
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Protocol Amendment 2 Investigator Agreement
I agree:

To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (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’ study vaccine(s) 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(s) and more generally about his/her 
financial ties with the sponsor. GSK Biologicals will use and disclose the 
information solely for the purpose of complying with regulatory requirements.
Hence I:

Agree to supply GSK Biologicals with any necessary information regarding 
ownership interest and financial ties (including those of my spouse and dependent 
children).

Agree to promptly update this information if any relevant changes occur during the 
course of the study and for one year following completion of the study. 

Agree that GSK Biologicals may disclose any information it has about such 
ownership interests and financial ties to regulatory authorities.

Agree to provide GSK Biologicals with an updated Curriculum Vitae and other 
documents required by regulatory agencies for this study.
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eTrack study number and 
Abbreviated Title
204487 (ZOSTER-059 PRI)
IND number
BB-IND-13857
EudraCT number
2017-001220-22
Date of protocol amendment
Amendment 2 Final: 30 January 2018
Detailed Title
A Phase IIIB, randomized, open-label, multicenter 
clinical trial to assess the immunogenicity and safety 
of GSK Biologicals’ Herpes Zoster vaccine 
GSK1437173A when co-administered with 
Prevenar13 in adults aged 50 years and older.
Investigator name
Signature
Date
Leiter der klinischen Prüfung 
name, function and title
Signature
Date
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Sponsor Information
1.
Sponsor
GlaxoSmithKline Biologicals
Rue de l’Institut 89, 1330 Rixensart, Belgium
2.
Sponsor Medical Expert for the Study
Refer to the local study contact information document.
3.
Sponsor Study Monitor
Refer to the local study contact information document.
4.
Sponsor Study Contact for Reporting of a Serious Adverse Event
GSK Biologicals Central Back-up Study Contact for Reporting SAEs: refer to protocol 
Section 8.4.2
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SYNOPSIS
Detailed Title
A Phase IIIB, randomized, open-label, multicenter clinical 
trial to assess the immunogenicity and safety of GSK 
Biologicals’ Herpes Zoster vaccine GSK1437173A when co-
administered with Prevenar13 in adults aged 50 years and 
older.
Indication
Prevention of Herpes Zoster (HZ) and related complications 
in adults ≥50 years of age (YOA) and immunocompromized 
(IC) adults ≥18 YOA.
Rationale for the 
study and study 
design
Varicella-zoster virus (VZV) causes two distinct diseases. 
Varicella (chickenpox) occurs shortly after primary VZV 
infection and is characterized by systemic illness and a widely 
disseminated rash. Herpes zoster (HZ; shingles) occurs when 
VZV reactivates from latency and typically manifests as a 
localized, dermatomal rash.
The typical HZ rash usually lasts 2 to 4 weeks and is typically 
accompanied by pain and pruritus. The most common 
complication of HZ is postherpetic neuralgia (PHN), defined 
as pain that persists after the resolution of the HZ rash. 
Declining VZV-specific immune responses with older age are 
a clear risk factor for developing shingles and PHN.
The objective of the current phase III study is to assess 
immunogenicity, reactogenicity and safety of GSK 
Biologicals’ HZ vaccine when its first dose is co-administered 
with a pneumococcal polysaccharide conjugate vaccine 
(Prevenar13) in adults aged 50 YOA, as compared to the 
control group where the two HZ/su doses are administered 
subsequent to Prevenar13.
The two parallel arms study design was selected to allow an 
assessment of the immunogenicity, reactogenicity and safety
of HZ/su and Prevenar13 vaccines when they are co-
administered and when administered separately in a staggered 
schedule (Prevenar13 followed by HZ/su).
Objectives
Co-Primary

To determine the vaccine response rate (VRR) to HZ/su 
(based on humoral immune response) one month after the 
second vaccine dose, when the first dose of HZ/su is co-
administered with Prevenar13 (Co-Ad group).*
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Criterion to be used: 
The objective is met if the lower limit (LL) of the 95% CI 
of the VRR for anti-gE antibody concentrations in the Co-
Ad group one month after the second vaccine dose is 
≥60%.
* The VRR for anti-gE is defined as the percentage of subjects 
who have at least: a 4-fold increase in the anti-gE antibodies 
concentration as compared to the pre-vaccination anti-gE 
antibodies concentration, for subjects who are seropositive at 
baseline, or, a 4-fold increase in the anti-gE antibodies 
concentration as compared to the anti-gE antibodies cut-off 
value for seropositivity, for subjects who are seronegative at 
baseline.
If the above objective is met in the Co-Ad group, then the 
following objective will be evaluated:

To demonstrate non-inferiority of the humoral immune 
response to two doses of HZ/su at one month after the last 
vaccine dose, when the first dose of HZ/su is co-
administered with Prevenar13 (Co-Ad group) compared 
to when two doses of HZ/su are administered subsequent 
to Prevenar13 (Control Group).
Criterion for non-inferiority: 
One month after the last vaccine dose in each study 
group, the upper limit (UL) of the 95% confidence 
interval (CI) for the anti-gE antibodies Geometric Mean 
Concentration (GMC) ratio between the Control group 
and the Co-Ad group is <1.5.
If the above non-inferiority objective is met, then the 
following objective will be evaluated:

To demonstrate non-inferiority of the humoral immune 
response to Prevenar13 at one month after the vaccine 
dose, when Prevenar13 is co-administered with the first 
HZ/su dose (Co-Ad group) compared to when 
Prevenar13 is administered separately from HZ/su 
(Control group), for the 13 serotypes included in 
Prevenar13 analyzed sequentially.
Criterion for non-inferiority: 
One month after the Prevenar13 vaccine dose in each 
study group, the UL of the 95% CI for each individual 
pneumococcal conjugate serotype Geometric Mean Titer 
(GMT) ratio of the Control group over the Co-Ad group 
is <2.
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For the co-primary objectives, fixed sequence testing which 
allows for full alpha propagation in pre-ordered hypotheses 
families will be used.
Secondary

To evaluate the safety and reactogenicity following 
administration of HZ/su and Prevenar13 vaccines, up to 
one month post last vaccination and during the whole 
follow-up period, in the Control group and the Co-Ad 
group.
Study design

Experimental design: Phase IIIB, open-label, 
randomized, controlled, multi-centric, and multi-country, 
with two parallel groups. 

Duration of the study: The intended duration of the 
study per subject is approximately 14 months for subjects 
from the Co-Ad group and approximately 16 months for 
subjects from the Control group.

Epoch 001: Primary starting at Visit Day 1 and 
ending with the phone contact at Month 16.

Primary completion date (PCD): Visit Month 5. 

End of Study (EoS): Last testing results released of 
samples collected at Visit Month 3 (Co-Ad group) or at 
Visit Month 5 (Control group).

Study groups:
Synopsis Table 1
Study groups and epochs foreseen in the study
Study groups
Number of subjects
Age
Epochs
Epoch 001
Co-Ad
456
50 years
x
Control
456
50 years
x
Synopsis Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
Co-Ad
Control
HZ/su
VZV gE
X
x
AS01B
x
x
Prevenar13
Prevenar 13
x
x
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
Control: active control.

Vaccination schedule(s):
Co-Ad Group: 

at Visit Day 1: first dose of HZ/su and one dose of 
Prevenar13,

at Visit Month 2: second dose of HZ/su. 
Control Group: 

at Visit Day 1: one dose of Prevenar13, 

at Visit Month 2: first dose of HZ/su,

at Visit Month 4: second dose of HZ/su.

Treatment allocation: Subjects to be randomized in a 
1:1 ratio at Visit Day 1 to either Co-Ad or Control group. 
Subjects in each group will be stratified by age with the 
following approximate distribution (not less than 25% in 
each age strata):

171 subjects in the 50-59 YOA stratum, 

171 subjects in the 60-69 YOA stratum, and

114 subjects in the ≥70 YOA stratum.

Blinding: open-label
Synopsis Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
open

Sampling schedule: Blood samples (approximately 8 mL) 
will be collected for each group, as described below.
For Co-Ad group: 

at Visit Day 1 to assess baseline antibody 
concentrations/titers with respect to Prevenar13 and 
HZ/su vaccine antigens, prior to vaccination, 

at Visit Month 1 to assess humoral immune response 
with respect to Prevenar13 vaccine antigens, 1 month 
post-vaccination,

at Visit Month 3 to assess humoral immune response 
with respect to the HZ/su vaccine antigen, 1 month 
post-second vaccination dose.
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For Control group:

at Visit Day 1 to assess baseline antibody 
concentrations/titers with respect to Prevenar13 vaccine 
antigens, prior to vaccination, 

at Visit Month 1 to assess humoral immune response 
with respect to Prevenar13 vaccine antigens, at 1 month 
post-vaccination,

at Visit Month 2 to assess baseline antibody 
concentrations/titers with respect to the HZ/su vaccine 
antigen, prior to first vaccination dose,

at Visit Month 5 to assess humoral immune response 
with respect to the HZ/su vaccine antigen, at 1 month 
post-second vaccination dose.
For both groups:

A urine specimen will be collected from all female 
subjects of childbearing potential at Visit Day 1 and 
Visit Month 2 for Co-Ad group, and at Visit Day 1, 
Visit Month 2 and Visit Month 4 for the Control group. 
If a serum pregnancy test instead of a urine pregnancy 
test is required by country, local or ethics committee 
regulations, a blood sample will be collected from 
women of childbearing potential at these visits and will 
be used for the test as per local guidance.
Note: the result of the urine/serum pregnancy test must be 
obtained before vaccination.

Type of study: self-contained.

Data collection: Electronic Case Report Form (eCRF).
Safety monitoring: An internal GSK Safety Review Team 
(SRT) part of the HZ/su vaccine project will oversee the safety 
of the study subjects on a regular basis. Serious Adverse Events 
(SAEs) and Adverse Events (AEs) including pIMDs will be 
reviewed by the SRT at regular intervals together with data 
from other ongoing HZ/su vaccine studies. Any potential safety 
concern related to conduct of the study will be escalated to 
higher internal decision boards as per internal GSK process.
Number of subjects
Target enrollment will be approximately 912 eligible subjects, 
to obtain 820 evaluable subjects (410 in each study group).
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Endpoints
Primary

HZ/su immunogenicity:

Vaccine response for anti-gE humoral immunogenicity, 
as determined by ELISA, in subjects from the Co-Ad 
group at one month post-dose 2, at Visit Month 3.

Anti-gE antibody concentrations as determined by 
ELISA at one month post-dose 2, at Visit Month 3 for 
the Co-Ad group and Visit Month 5 for the Control 
group.

Pneumococcal vaccine immunogenicity:

Anti-pneumococcal antibody titers for the 13 following 
serotypes as determined by MOPA at one month post-
dose at Visit Month 1: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 
18C, 19A, 19F and 23F.
Secondary

Occurrence of solicited local and general symptoms: 

Occurrence, duration and intensity of each solicited 
local symptom within 7 days (Days 1 - 7) after each 
vaccination.

Occurrence, duration, intensity and relationship to 
vaccination of each solicited general symptom within 7 
days (Days 1 to 7) after each vaccination.

Occurrence of unsolicited AEs:

Occurrence, intensity and relationship to vaccination of 
unsolicited AEs within 30 days (Days 1 to 30) 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 first vaccination at Day 1 up to 30 days post last 
vaccination.

Occurrence and relationship to vaccination of all SAEs 
during the period starting after 30 days post last 
vaccination up to study end.

Occurrence of pIMDs:

Occurrence and relationship to vaccination of any 
pIMDs from first vaccination at Day 1 up to 30 days 
post last vaccination.

Occurrence of any pIMDs during the period starting 
after 30 days post last vaccination up to study end.
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TABLE OF CONTENTS
PAGE
SPONSOR INFORMATION ............................................................................................7
SYNOPSIS......................................................................................................................8
LIST OF ABBREVIATIONS...........................................................................................22
GLOSSARY OF TERMS ...............................................................................................25
TRADEMARKS .............................................................................................................30
1.
INTRODUCTION....................................................................................................31
1.1.
Background ................................................................................................31
1.2.
Rationale for the study and study design ....................................................32
1.3.
Benefit : Risk Assessment ..........................................................................32
1.3.1.
Risk Assessment .........................................................................33
1.3.2.
Benefit Assessment.....................................................................34
1.3.3.
Overall Benefit: Risk Conclusion..................................................34
2.
OBJECTIVES.........................................................................................................34
2.1.
Co-Primary objectives.................................................................................34
2.2.
Secondary objective ...................................................................................35
3.
STUDY DESIGN OVERVIEW ................................................................................36
4.
STUDY COHORT...................................................................................................39
4.1.
Number of subjects/centres ........................................................................39
4.2.
Inclusion criteria for enrolment....................................................................39
4.3.
Exclusion criteria for enrolment...................................................................40
5.
CONDUCT OF THE STUDY ..................................................................................42
5.1.
Regulatory and ethical considerations, including the informed 
consent process..........................................................................................42
5.2.
Subject identification and randomization.....................................................43
5.2.1.
Subject identification....................................................................43
5.2.2.
Randomization of treatment.........................................................43
Randomization of supplies..........................................43
5.2.2.1.
Treatment allocation to the subject.............................43
5.2.2.2.
5.2.2.2.1.
Study group and treatment 
number allocation ...................................43
5.2.2.2.2.
Treatment number allocation for 
subsequent doses ..................................44
5.3.
Method of blinding ......................................................................................44
5.4.
General study aspects ................................................................................44
5.5.
Suspected HZ cases...................................................................................45
5.6.
Outline of study procedures ........................................................................45
5.7.
Detailed description of study procedures ....................................................48
5.7.1.
Informed consent.........................................................................48
5.7.2.
Check inclusion and exclusion criteria .........................................49
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5.7.3.
Collect demographic data ............................................................49
5.7.4.
General medical history ...............................................................49
5.7.5.
History directed physical examination..........................................49
5.7.6.
Pregnancy test.............................................................................49
5.7.7.
Check contraindications, warnings and precautions to 
vaccination...................................................................................49
5.7.8.
Assess pre-vaccination body temperature ...................................50
5.7.9.
Study group and treatment number allocation..............................50
5.7.10.
Sampling......................................................................................50
Blood sampling for immune response 
5.7.10.1.
assessments ..............................................................50
5.7.11.
Study Vaccine(s) administration...................................................50
5.7.12.
Check and record concomitant medication/vaccination and 
intercurrent medical conditions ....................................................51
5.7.13.
Recording of AEs, SAEs, pregnancies and pIMDs.......................51
5.7.14.
Study conclusion..........................................................................51
5.8.
Biological sample handling and analysis.....................................................52
5.8.1.
Use of specified study materials ..................................................53
5.8.2.
Biological samples.......................................................................53
5.8.3.
Laboratory assays .......................................................................53
5.8.4.
Biological samples evaluation......................................................55
Immunological read-outs ............................................55
5.8.4.1.
5.8.5.
Immunological correlates of protection.........................................56
6.
STUDY VACCINES AND ADMINISTRATION ........................................................57
6.1.
Description of study vaccines......................................................................57
6.2.
Storage and handling of study vaccine(s) ...................................................58
6.3.
Dosage and administration of study vaccines .............................................58
6.4.
Replacement of unusable vaccine doses....................................................59
6.5.
Contraindications to subsequent vaccination ..............................................59
6.6.
Warnings and precautions ..........................................................................60
6.7.
Concomitant medications/products and concomitant vaccinations..............60
6.7.1.
Recording of concomitant medications/products and 
concomitant vaccinations.............................................................60
6.7.2.
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from per-protocol analyses............61
6.8.
Intercurrent medical conditions that may lead to elimination of a 
subject from per-protocol analyses .............................................................62
7.
HEALTH ECONOMICS ..........................................................................................62
8.
SAFETY.................................................................................................................62
8.1.
Safety definitions ........................................................................................62
8.1.1.
Definition of an adverse event......................................................62
8.1.2.
Definition of a serious adverse event ...........................................63
8.1.3.
Solicited adverse events..............................................................64
Solicited local (injection-site) adverse events..............64
8.1.3.1.
Solicited general adverse events................................65
8.1.3.2.
8.1.4.
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................65
8.1.5.
Adverse events of specific interest...............................................65
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Potential immune-mediated diseases .........................65
8.1.5.1.
8.2.
Events or outcomes not qualifying as adverse events or serious 
adverse events ...........................................................................................67
8.2.1.
Pregnancy ...................................................................................67
8.3.
Detecting and recording adverse events, serious adverse events 
and pregnancies .........................................................................................68
8.3.1.
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies.....................................68
8.3.2.
Post-Study adverse events and serious adverse events..............71
8.3.3.
Evaluation of adverse events and serious adverse events...........71
Active questioning to detect adverse events 
8.3.3.1.
and serious adverse events........................................71
Assessment of adverse events...................................71
8.3.3.2.
8.3.3.2.1.
Assessment of intensity..........................71
8.3.3.2.2.
Assessment of causality .........................73
Assessment of outcomes............................................74
8.3.3.3.
Medically attended visits.............................................74
8.3.3.4.
8.4.
Reporting of serious adverse events, pregnancies, and other events .........75
8.4.1.
Prompt reporting of serious adverse events, pregnancies, 
and other events to GSK Biologicals............................................75
8.4.2.
Contact information for reporting serious adverse events, 
pregnancies and pIMDs...............................................................76
8.4.3.
Completion and transmission of SAE reports to GSK 
Biologicals ...................................................................................76
Back-up system in case the electronic 
8.4.3.1.
reporting system does not work..................................76
8.4.4.
Completion and transmission of pregnancy reports to GSK 
Biologicals ...................................................................................77
8.4.5.
Reporting of pIMDs to GSK Biologicals........................................77
8.4.6.
Updating of SAE, pregnancy, and pIMD information after 
removal of write access to the subject’s eCRF.............................77
8.4.7.
Regulatory reporting requirements for serious adverse 
events..........................................................................................78
8.5.
Follow-up of adverse events, serious adverse events, and 
pregnancies................................................................................................78
8.5.1.
Follow-up of adverse events and serious adverse events............78
Follow-up during the study..........................................78
8.5.1.1.
Follow-up after the subject is discharged from 
8.5.1.2.
the study.....................................................................78
8.5.2.
Follow-up of pregnancies.............................................................79
8.6.
Treatment of adverse events ......................................................................79
8.7.
Subject card................................................................................................79
9.
SUBJECT COMPLETION AND WITHDRAWAL.....................................................79
9.1.
Subject completion .....................................................................................79
9.2.
Subject withdrawal......................................................................................79
9.2.1.
Subject withdrawal from the study ...............................................80
9.2.2.
Subject withdrawal from study vaccine(s) ....................................81
9.3.
Extension study ..........................................................................................81
10. STATISTICAL METHODS......................................................................................81
10.1.
Primary endpoints.......................................................................................81
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10.2.
Secondary endpoints ..................................................................................82
10.3.
Determination of sample size......................................................................82
10.4.
Cohorts for Analyses ..................................................................................84
10.4.1.
Total vaccinated cohort................................................................84
10.4.2.
Per-protocol cohort for analysis of immunogenicity......................85
10.5.
Derived and transformed data.....................................................................85
10.5.1.
Handling of missing data..............................................................85
10.6.
Analysis of demographics...........................................................................85
10.7.
Analysis of immunogenicity.........................................................................86
10.7.1.
Humoral immune response..........................................................86
10.7.2.
Statistical considerations for confirmatory objectives ...................86
10.8.
Analysis of safety........................................................................................87
10.9.
Interpretation of analyses............................................................................88
10.10. Conduct of analyses ...................................................................................88
10.10.1. Sequence of analyses..................................................................88
10.10.2. Statistical considerations for interim analyses..............................88
11. ADMINISTRATIVE MATTERS ...............................................................................89
11.1.
electronic Case Report Form instructions ...................................................89
11.2.
Study Monitoring by GSK Biologicals..........................................................89
11.3.
Record retention .........................................................................................90
11.4.
Quality assurance.......................................................................................90
11.5.
Posting of information on publicly available clinical trial registers and 
publication policy ........................................................................................91
11.6.
Provision of study results to investigators ...................................................91
11.7.
Data Sharing...............................................................................................91
12. COUNTRY SPECIFIC REQUIREMENTS...............................................................92
12.1.
Germany.....................................................................................................92
13. REFERENCES.......................................................................................................93
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LIST OF TABLES
PAGE
Table 1
Study groups and epochs foreseen in the study.....................................37
Table 2
Study groups and treatment foreseen in the study .................................37
Table 3
Blinding of study epochs ........................................................................37
Table 4
Age Stratification....................................................................................39
Table 5
Number of subjects required for enrolment.............................................44
Table 6
List of study procedures for Co-Ad Group ..............................................45
Table 7
List of study procedures for Control Group.............................................47
Table 8
Intervals between study visits/contact for Co-Ad group ..........................48
Table 9
Intervals between study visits/contact for Control group.........................48
Table 10
Biological samples .................................................................................53
Table 11
Humoral Immunity (Antibody determination)...........................................54
Table 12
Immunological read-outs for Co-Ad group..............................................55
Table 13
Immunological read-outs for Control group.............................................56
Table 14
Study vaccines.......................................................................................57
Table 15
Dosage and administration for the Co-Ad group.....................................59
Table 16
Dosage and administration for the Control group ...................................59
Table 17
Solicited local adverse events ................................................................64
Table 18
Solicited general adverse events............................................................65
Table 19
List of potential immune-mediated diseases...........................................66
Table 20
Reporting periods for collecting safety information .................................70
Table 21
Intensity scales for solicited symptoms in adults.....................................72
Table 22
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK Biologicals .................................................75
Table 23
Power to demonstrate VRR objective and non-inferiority of the 
immunogenicity of HZ/su and Prevenar13 co-administered 
compared to Control group.....................................................................84
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Table 24
GSK Biologicals’ laboratories .................................................................96
Table 25
Outsourced laboratories.........................................................................96
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LIST OF FIGURES
PAGE
Figure 1
Overview of Study Design......................................................................36
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LIST OF APPENDICES
PAGE
APPENDIX A LABORATORY ASSAYS .......................................................................95
APPENDIX B CLINICAL LABORATORIES ..................................................................96
APPENDIX C AMENDMENTS AND ADMINISTRATIVE CHANGES TO THE 
PROTOCOL...........................................................................................97
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LIST OF ABBREVIATIONS
AE:
Adverse event
ANCOVA:
Analysis of Covariance
AS01B:
MPL, QS21, liposome based Adjuvant System (50 g MPL and 50 g 
QS21)
BS:
Blood Sample
CBER:
Center for Biologics Evaluation and Research 
(Amended 30 January 2018)
CDC:
Centers for Disease Control and Prevention
CHMP:
Committee for Medicinal Products for Human Use
CI:
Confidence Interval
CLS:
Clinical Laboratory Sciences
Co-Ad:
Co-administration
CRO:
Contract Research Organization
(Amended 30 January 2018)
CSF:
Cerebrospinal fluid
eCRF:
Electronic Case Report Form
EGA:
Estimated Gestational Age
ELISA:
Enzyme-linked Immunosorbent Assay
EMA:
European Medicines Agency
EoS:
End of Study
eTDF:
Electronic Temperature excursion Decision Form
FDA:
Food and Drug Administration, United States
FU:
Follow up
GCP:
Good Clinical Practice
gE:
VZV glycoprotein E
GMC/GMT:
Geometric Mean Concentration/Titers
GSK:
GlaxoSmithKline
HIV:
Human Immunodeficiency Virus
HZ:
Herpes Zoster
HZ/su:
Herpes Zoster subunit vaccine (50 g gE/AS01B)
IB:
Investigator’s Brochure
ICF:
Informed Consent Form
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ICH:
International Conference on Harmonization
IEC:
Independent Ethics Committee
IDMC:
Independent Data Monitoring Committee
IgG:
Immunoglobulin G
IM:
Intramuscular
IND:
Investigational New Drug
IRB:
Institutional Review Board
LL:
Lower Limit
LMP:
Last Menstrual Period
LSLV:
Last Subject Last Visit
MACDP:
Metropolitan Atlanta Congenital Defects Program
MATEX:
MATerial EXcellence
MedDRA:
Medical Dictionary for Regulatory Activities
MOPA:
Multiplex Opsonophagocytosis Assay
MPL:
3-O-desacyl-4’-monophosphoryl lipid A
PCD:
Primary Completion Date
PHN:
Postherpetic Neuraligia
pIMD:
Potential Immune-Mediated Disease
PPC:
Per-protocol cohort
Pre-Vacc:
Pre-vaccination
QS21:
Quillaja saponaria Molina, fraction 21 (purified saponin extract from 
the South American tree)
SAE:
Serious Adverse Event
SAS:
Statistical Analysis System
SBIR:
Randomization System on Internet
SD:
Standard Deviation
SDV:
Source Document Verification
SmPC:
Summary of Product Characteristics
SPM:
Study Procedures Manual
SRT:
Safety Review Team
TVC:
Total Vaccinated Cohort
UL:
Upper Limit
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VRR:
Vaccine Response Rate
VZV:
Varicella-Zoster Virus
YOA:
Years of Age
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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,

Combined estrogen and progesterone oral 
contraceptives,

injectable progestogen,

implants of etenogestrel or levonorgestrel,

Contraceptive vaginal ring,

percutaneous contraceptive patches,

intrauterine device or intrauterine system,

male partner sterilization prior to the female subject’s 
entry into the study, and this male is the sole partner 
for that subject,
The information on the male sterility can come from 
the site personnel’s review of the subject’s medical 
records; or interview with the subject on her medical 
history.

male condom combined with a vaginal spermicide 
(foam, gel, film, cream or suppository), and/or 
progesterone alone oral contraceptive.
Adequate contraception does not apply to subjects of 
child bearing potential with same sex partners, or for 
subjects who are and will continue to be abstinent from 
penile-vaginal intercourse on a long term and persistent 
basis, 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.
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Blinding:
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. In an 
open-label study, no blind is used. Both the investigator 
and the subject know the identity of the treatment 
assigned.
Eligible:
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria.
End of Study:
(Synonym of End of 
Trial)
For studies without collection of human biologicals 
samples or imaging data EoS is the Last Subject Last 
Visit (LSLV). 
For studies with collection of Human Biologicals 
Samples or imaging data, EoS is defined as the date of the 
last testing/reading released of the Human Biological 
Samples or imaging data, related to primary and 
secondary endpoints. EoS must be achieved no later than 
8 months after LSLV.
Epoch:
An epoch is a set of consecutive timepoints or a single 
timepoint from a single protocol. Epochs are defined to 
support a main purpose which is either to draw 
conclusions on subject participation or to draw a 
complete conclusion to define or precise the targeted 
label of the product. Supporting means that data collected 
at the timepoints included in an epoch must be sufficient 
to fulfil the purpose of the epoch.
Typical examples of epochs are screening, primary 
vaccinations, boosters, yearly immunogenicity follow-
ups, and surveillance periods for efficacy or safety.
eTrack:
GSK’s tracking tool for clinical trials.
Evaluable:
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis (see Sections 6.7.2
and 10.4 for details on criteria for evaluability).
Immunological correlate 
of protection:
The defined immune response above which there is a high 
likelihood of protection in the absence of any host factors 
that might increase susceptibility to the infectious agent.
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Intercurrent medical 
condition:
An intercurrent medical condition is defined as a 
condition that has the capability of confounding the 
immune response to the study vaccine or its 
interpretation.
Investigational vaccine:
(Synonym of 
Investigational Medicinal 
Product)
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorisation when used in a way different 
from the approved form, or when used for an unapproved 
indication, or when used to gain further information about 
an approved use. 
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.
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Pharmacogenomics:
The International Conference on Harmonization (ICH) 
E15 Guidance for Industry defines pharmacogenomics as 
Study of variation of DNA and RNA characteristics as 
related to drug or treatment response. Pharmacogenetics, 
which is a subset of pharmacogenomics, is “the study of 
variations in DNA sequence as related to drug response.” 
Pharmacogenomic biomarkers include germline (host) 
DNA and RNA as well as somatic changes (e.g., 
mutations) that occur in cells or tissues. 
Pharmacogenomic biomarkers are not limited to human 
samples but include samples from viruses and infectious 
agents as well as animal samples. The term 
pharmacogenomic experiment includes both the 
generation of new genetic or genomic (DNA and/or 
RNA) data with subsequent analysis as well as the 
analysis of existing genetic or genomic data to understand 
drug or treatment response (pharmacokinetics, safety, 
efficacy or effectiveness, mode of action). Proteomic and 
metabolomic biomarker research are not 
pharmacogenomics.
Potential Immune-
Mediated Disease:
Potential immune-mediated diseases (pIMDs) are a subset 
of AEs that include autoimmune diseases and other 
inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology.
Primary completion 
date:
The date that the final subject was examined or received 
an intervention for the purpose of final collection of data 
for all primary outcomes, whether the clinical trial was 
concluded according to the pre-specified protocol or was 
terminated.
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.
Randomization:
Process of random attribution of treatment to subjects in 
order to reduce bias of selection.
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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.
Solicited adverse event:
AEs to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively 
solicited from the subject or an observer during a 
specified post-vaccination follow-up period.
Study vaccine/product:
Any investigational vaccine/product being tested and/or 
any authorized use of a vaccine/ product /placebo as a 
reference or administered concomitantly, in a clinical trial 
that evaluates the use of an investigational 
vaccine/product.
Sub-cohort:
A group of subjects for whom specific study procedures 
are planned as compared to other subjects or a group of 
subjects who share a common characteristic (e.g. ages, 
vaccination schedule,…) at the time of enrolment.
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(s) 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.
Treatment number:
A number identifying a treatment to a subject, according 
to treatment allocation.
Unsolicited adverse 
event:
Any AE reported in addition to those solicited during the 
clinical study. Also any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event.
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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 of the GSK group of companies
Generic description
Shingrix
Zoster Vaccine Recombinant, Adjuvanted
Trademarks not owned by the GSK group of 
companies 
Generic description
Prevenar13 (Trade name for Germany and 
Estonia)/ Prevnar13Trade name for Canada 
and United States)*
Wyeth Pharmaceuticals Inc./Pfizer Inc.
Pneumococcal polysaccharide conjugate 
vaccine (13-valent adsorbed)
Pneumovax 23 (Trade name for Canada, 
Colombia, Germany and United States)/ 
Pneumo 23(Trade name for Estonia)
Merck & Co., Inc.
Pneumococcal polysaccharide conjugate 
vaccine (23-valent adsorbed)
* For clarity and consistency, the pneumococcal vaccine has been written as Prevenar13 throughout the document
(Amended 30 January 2018)
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1.
INTRODUCTION
1.1.
Background
Varicella-zoster virus (VZV) causes two distinct diseases. Varicella (chickenpox) occurs 
shortly after primary VZV infection and is characterized by systemic illness and a widely 
disseminated rash. Herpes zoster (HZ; shingles) occurs when VZV reactivates from 
latency and typically manifests as a localized, dermatomal rash.
The typical HZ rash usually lasts 2 to 4 weeks and is typically accompanied by pain and 
pruritus. The most common complication of HZ is postherpetic neuralgia (PHN), defined 
as pain that persists after the resolution of the HZ rash. Declining VZV-specific immune 
responses with older age are a clear risk factor for developing shingles and PHN 
[Dworkin, 2007; National Network for Immunization Information (NNii), 2008].
About half of all HZ cases occur in individuals over the age of 60, and individuals who 
reach 85 YOA have a 50% chance of having HZ during their lifetime [Oxman, 2005, 
Chua, 2010]. The risk of developing PHN varied from 5% to more than 30% depending 
on the study design and age distribution [Kawai, 2014]. Since the loss of VZV-specific T-
cell responses as a result of aging is associated with a heightened susceptibility to HZ, 
vaccination is considered as a means to reduce the risk of HZ in older adults [Oxman, 
2005; Sperber, 1992].
GlaxoSmithKline (GSK) Biologicals’ vaccine (Shingrix) for the prevention of HZ is a 
recombinant subunit (su) vaccine consisting of VZV glycoprotein E (gE) as antigen and 
an adjuvant system AS01B. It has been evaluated in several studies in healthy adults and 
shown to elicit strong cellular and humoral immune responses. The safety and 
reactogenicity profile of the study vaccine was also acceptable. Based on phase II data 
from the antigen dose-ranging study ZOSTER-003 [Chlibek, 2014], and the adjuvant 
dose comparison study ZOSTER-010 [Chlibek, 2013], a gE antigen dose of 50 µg and 
the adjuvant system AS01B were selected for the final vaccine formulation. Henceforth in 
the document, the final vaccine formulation will be referred to as HZ/su. 
Two large pivotal phase III trials, ZOSTER-006 (also referred to as ZOE-50) in subjects 
≥50 YOA and ZOSTER-022 (also referred to as ZOE-70) in subjects ≥70 YOA, 
evaluated the vaccine efficacy and safety of HZ/su. These placebo-controlled trials 
enrolled more than 30,000 subjects who received either HZ/su or placebo on a 0, 2-month 
schedule. The final analysis of the ZOSTER-006 primary efficacy objective demonstrated 
that the vaccine is highly efficacious in adults ≥50 YOA, with 97.2% (95% confidence 
interval [CI] of 93.7 - 99.0) overall efficacy against HZ. In addition, vaccine efficacy 
against HZ was between 96.6% and 97.9% for all pre-specified age groups (50-59, 60-69 
and ≥70 YOA) [Lal, 2015]. The results from ZOSTER-022 demonstrated that the first 
primary objective has been successfully met, with 89.8% (95% CI of 84.3-93.7) efficacy 
against HZ in subjects ≥70 YOA, and are therefore consistent with the results of 
ZOSTER-006. In addition, the co-primary objective of a pre-specified pooled analysis of 
ZOSTER-006 and ZOSTER-022 demonstrated that HZ/su has a vaccine efficacy against 
HZ of 91.3% (with 95% CI of 86.8-94.5) and effectively prevents PHN in subjects ≥70 
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YOA (efficacy of 88.8% with 95% CI of 68.7-97.1). No safety concerns have been raised 
[Cunningham, 2016].
The immunogenicity, reactogenicity, and safety of HZ/su when co-administered with a 
23-valent pneumococcal polysaccharide conjugate vaccine (Pneumovax 23 [trade name 
for Canada, Germany and United States]/Pneumo 23 [trade name for Estonia], Merck& 
Co., Inc) have been assessed in a phase III study in subjects 50 YOA (ZOSTER-035).
The immunogenicity co-primary objectives have been met.
Please refer to the current Investigator Brochure (IB) for information regarding the pre-
clinical and clinical studies of GSK Biologicals’ study HZ/su vaccine.
1.2.
Rationale for the study and study design
The objective of the current phase III study is to assess immunogenicity, reactogenicity 
and safety of GSK Biologicals’ HZ vaccine when its first dose is co-administered with a 
pneumococcal polysaccharide conjugate vaccine (Prevenar13) in adults aged 50 YOA, 
as compared to the control group where the two HZ/su doses are administered subsequent 
to Prevenar13.
The two parallel arms study design was selected to allow an assessment of the 
immunogenicity, reactogenicity and safety of HZ/su and Prevenar13 vaccines when they 
are co-administered and when administered separately in a staggered schedule 
(Prevenar13 followed by HZ/su).
1.3.
Benefit : Risk Assessment
Please refer to the current IB for the summary of potential risks and benefits of GSK 
Biologicals’ study HZ vaccine (HZ/su).
Please refer to the Prescribing Information for information regarding the summary 
potential risks and benefits of Prevenar13.
The following section outlines the risk assessment and mitigation strategy for this study 
protocol:
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1.3.2.
Benefit Assessment
Benefits include:

Receiving HZ/su during the study may reduce the risk of HZ occurrence and HZ-
related complications.

Receiving Prevenar13 during the study may prevent occurrence of pneumococcal 
pneumonia and invasive disease caused by 13 Streptococcus pneumoniae strains (1, 
3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).

Medical evaluations/assessments associated with study procedures (e.g. physical 
examination).
1.3.3.
Overall Benefit: Risk Conclusion
Considering the measures taken to minimize risk to subjects participating in this study, 
the potential or recognized risks identified in association with the study HZ vaccine 
(HZ/su) and study procedures are justified by the potential benefits (prevention of HZ 
and related complications) that may be afforded to the subjects receiving HZ/su.
Please refer to the approved product label/package insert for the summary of potential 
risks and benefits of Prevenar13.
2.
OBJECTIVES
2.1.
Co-Primary objectives

To determine the vaccine response rate (VRR) to HZ/su (based on humoral immune
response) one month after the second vaccine dose, when the first dose of HZ/su is 
co-administered with Prevenar13 (Co-Ad group).
Criterion to be used: 
The objective is met if the lower limit (LL) of the 95% CI of the VRR for anti-gE
antibody concentrations in the Co-Ad group one month after the second vaccine dose 
is ≥60%.
If the above objective is met in the Co-Ad group, then the following objective will be 
evaluated:

To demonstrate non-inferiority of the humoral immune response to two doses of 
HZ/su at one month after the last vaccine dose, when the first dose of HZ/su is co-
administered with Prevenar13 (Co-Ad group) compared to when two doses of HZ/su 
are administered subsequent to Prevenar13 (Control Group).
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Criterion for non-inferiority: 
One month after the last vaccine dose in each study group, the upper limit (UL) of 
the 95% confidence interval (CI) for the anti-gE antibodies Geometric Mean 
Concentration (GMC) ratio between the Control group and the Co-Ad group is <1.5.
If the above non-inferiority objective is met, then the following objective will be 
evaluated:

To demonstrate non-inferiority of the humoral immune response to Prevenar13 at 
one month after the vaccine dose, when Prevenar13 is co-administered with the first 
HZ/su dose (Co-Ad group) compared to when Prevenar13 is administered separately 
from HZ/su (Control group), for the 13 serotypes included in Prevenar13 analyzed 
sequentially.
Criterion for non-inferiority: 
One month after the Prevenar13 vaccine dose in each study group, the UL of the 
95% CI for each individual pneumococcal conjugate serotype Geometric Mean Titer 
(GMT) ratio of the Control group over the Co-Ad group is <2.
For the co-primary objectives, fixed sequence testing which allows for full alpha 
propagation in pre-ordered hypotheses families will be used (see section 10.7.2).
Refer to Section 10.1 for the definition of the primary endpoints.
2.2.
Secondary objective

To evaluate the safety and reactogenicity following administration of HZ/su and 
Prevenar13 vaccines, up to one month post last vaccination and during the whole 
follow-up period, in the Control group and the Co-Ad group.
Refer to Section 10.2 for the definition of the secondary endpoints.
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3.
STUDY DESIGN OVERVIEW
Figure 1
Overview of Study Design 
Vacc: vaccination; BS: blood sample; Pre-Vacc: pre-vaccination; FU: follow-up
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. Therefore, adherence to the study design requirements, 
including those specified in the outline of study procedures (Section 5.6), are essential 
and required for study conduct. 

Experimental design: Phase IIIB, open-label, randomized, controlled, multi-centric, 
and multi-country, with two parallel groups. 

Duration of the study: The intended duration of the study per subject is 
approximately 14 months for subjects from the Co-Ad group and approximately 
16 months for subjects from the Control group.
Epoch 001: Primary starting at Visit Day 1 and ending with the phone contact at Month 
16.

Primary completion date (PCD): Visit Month 5. 
Refer to glossary of terms for the definition of PCD.

End of Study (EoS): Last testing results released of samples collected at Visit 
Month 3 (Co-Ad group) or at Visit Month 5 (Control group). 
Refer to glossary of terms for the definition of EoS.
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
Study groups:
Table 1
Study groups and epochs foreseen in the study
Study groups
Number of subjects
Age
Epochs
Epoch 001
Co-Ad
456
50 years
x
Control
456
50 years
x
Table 2
Study groups and treatment foreseen in the study
Treatment name
Vaccine/Product name
Study Groups
Co-Ad
Control 
HZ/su
VZV gE
x
x
AS01B
x
x
Prevenar13
Prevenar 13
x
x

Control: active control.

Vaccination schedule(s):
Co-Ad Group: 

at Visit Day 1: first dose of HZ/su and one dose of Prevenar13,

at Visit Month 2: second dose of HZ/su. 
Control Group: 

at Visit Day 1: one dose of Prevenar13, 

at Visit Month 2: first dose of HZ/su,

at Visit Month 4: second dose of HZ/su.

Treatment allocation: Subjects to be randomized in a 1:1 ratio at Visit Day 1 to 
either Co-Ad or Control group. Subjects in each group will be stratified by age with 
the following approximate distribution (not less than 25% in each age strata):

171 subjects in the 50-59 YOA stratum, 

171 subjects in the 60-69 YOA stratum, and

114 subjects in the ≥70 YOA stratum.

Blinding: open-label. 
Table 3
Blinding of study epochs
Study Epochs
Blinding
Epoch 001
open
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
Sampling schedule: Blood samples (approximately 8 mL) will be collected for each 
group, as described below.
For Co-Ad group: 

at Visit Day 1 to assess baseline antibody concentrations/titers with respect to 
Prevenar13 and HZ/su vaccine antigens, prior to vaccination, 

at Visit Month 1 to assess humoral immune response with respect to Prevenar13
vaccine antigens, 1 month post-vaccination,

at Visit Month 3 to assess humoral immune response with respect to the HZ/su 
vaccine antigen, 1 month post-second vaccination dose.
For Control group:

at Visit Day 1 to assess baseline antibody concentrations/titers with respect to 
Prevenar13 vaccine antigens, prior to vaccination, 

at Visit Month 1 to assess humoral immune response with respect to Prevenar13
vaccine antigens, at 1 month post-vaccination,

at Visit Month 2 to assess baseline antibody concentrations/titers with respect to 
the HZ/su vaccine antigen, prior to first vaccination dose,

at Visit Month 5 to assess humoral immune response with respect to the HZ/su 
vaccine antigen, at 1 month post-second vaccination dose.
For both groups:

A urine specimen will be collected from all female subjects of childbearing
potential at Visit Day 1 and Visit Month 2 for Co-Ad group, and at Visit Day 1, 
Visit Month 2 and Visit Month 4 for the Control group. If a serum pregnancy test 
instead of a urine pregnancy test is required by country, local or ethics committee 
regulations, a blood sample will be collected from women of childbearing
potential at these visits and will be used for the test as per local guidance.
Note: the result of the urine/serum pregnancy test must be obtained before 
vaccination.

Type of study: self-contained.

Data collection: Electronic Case Report Form (eCRF).

Safety monitoring: An internal GSK Safety Review Team (SRT) part of the HZ/su
vaccine project will oversee the safety of the study subjects on a regular basis. 
Serious Adverse Events (SAEs) and Adverse Events (AEs) including pIMDs will be 
reviewed by the SRT at regular intervals together with data from other ongoing 
HZ/su vaccine studies. Any potential safety concern related to conduct of the study 
will be escalated to higher internal decision boards as per internal GSK process.
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4.
STUDY COHORT
4.1.
Number of subjects/centres
Target enrollment will be approximately 912 eligible subjects, to obtain 820 evaluable 
subjects (410 in each study group). Detailed description of the criteria used in the 
estimation of sample size can be found in Section 10.3.
Within each study group, subjects will be stratified by age at the time of recruitment (not 
less than 25% in each age strata), as described in Table 4.
Table 4
Age Stratification
(Amended 30 January 2018)
Group
Description
Estimated number of subjects
Co-Ad
Subjects 50 to 59 YOA
171
Subjects 60 to 69 YOA
171
Subjects 70 YOA
114
Control
Subjects 50 to 59 YOA
171
Subjects 60 to 69 YOA
171
Subjects 70 YOA
114
YOA: years of age.
Overview of the recruitment plan

This study is planned to be conducted at sites in multiple countries.

The recruitment rate will be monitored using a study-specific central Randomization 
System on Internet (SBIR). 

The randomization algorithm will use a stratification procedure accounting for the 
three age strata (50-59 YOA, 60-69 YOA and ≥70 YOA).
4.2.
Inclusion criteria for enrolment
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity, regulatory acceptability of the study or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.
All subjects must satisfy ALL the following criteria at study entry:

Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary cards, return for follow-up 
visits).

Written informed consent obtained from the subject prior to performance of any 
study specific procedure.
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
A male or female, aged 50 YOA at the time of the first vaccination with the study 
vaccine(s).

Female subjects of non-childbearing potential may be enrolled in the study. Non-
childbearing potential is defined as pre-menarche, current bilateral tubal ligation or 
occlusion, hysterectomy, bilateral 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.
Please refer to the glossary of terms for the definition of adequate contraception.
4.3.
Exclusion criteria for enrolment
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential.
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study:

Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccines during the period starting 30 days before the first dose of study 
vaccines (Day -30 to Day 1), or planned use during the study period.

Any medical condition that in the judgment of the investigator would make 
intramuscular (IM) injection unsafe.

Use or anticipated use of immunosuppressants or other immune-modifying drugs 
during the period starting six months prior to study start and during the whole study 
period. This includes chronic administration of corticosteroids (>14 consecutive days 
of prednisone at a dose of ≥20 mg/day [or equivalent]), long-acting immune 
modifying agents (e.g., infliximab) or immunosuppressive/cytotoxic therapy (e.g., 
medications used during cancer chemotherapy, organ transplantation or to treat 
autoimmune disorders). Inhaled, topical and intra-articular corticosteroids are 
allowed.

Administration or planned administration of a vaccine 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 study vaccine administration. This includes any type of vaccine such 
as (but not limited to) live, inactivated and subunit vaccines (e.g., inactivated and 
subunit influenza vaccines).
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
Concurrently participating in another clinical study, at any time during the study
period, in which the subject has been or will be exposed to an investigational or a 
non-investigational vaccine/product (pharmaceutical product or device).

Previous and/or planned administration of an HZ or VZV vaccine (including an 
investigational or non-registered vaccine) other than the study vaccine during the 
study period.

History of HZ.

History of documented pneumococcal infection within 5 previous years.

Prior receipt of any pneumococcal vaccine or planned use during the study period, 
other than the study vaccines.

Any confirmed or suspected immunosuppressive or immunodeficient condition 
resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] 
infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during 
cancer chemotherapy, organ transplantation or to treat autoimmune disorders).

History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccines.

Acute disease and/or fever at the time of enrollment.

Fever is defined as temperature 38.0°C/100.4°F. The preferred location for 
measuring temperature in this study will be the oral cavity.

Subjects with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may, be enrolled at the discretion of the investigator. 

Administration of immunoglobulins and/or any blood products during the period 
starting 3 months before the first dose of study vaccine or planned administration 
during the study period.

Pregnant or lactating female.

Female planning to become pregnant or planning to discontinue contraceptive 
precautions before 2 months after the last dose of study vaccine.

Any person with cerebrospinal fluid (CSF) leaks, cochlear implants, chronic renal 
failure, nephrotic syndrome and functional or anatomic asplenia.

Any medical condition that in the judgment of the investigator would prevent the 
subject from participating in the study.
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5.
CONDUCT OF THE STUDY
5.1.
Regulatory and ethical considerations, including the 
informed consent process
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with the ICH Guideline for GCP, all 
applicable subject privacy requirements and the guiding principles of the Declaration of 
Helsinki. 
GSK will obtain favourable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country.
Conduct of the study includes, but is not limited to, the following:

Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments.

Subject informed consent.

Investigator reporting requirements as stated in the protocol.
GSK will provide full details of the above procedures to the investigator, either verbally, 
in writing, or both.
Freely given and written or witnessed/ thumb printed informed consent must be obtained 
from each subject prior to participation in the study. 
GSK Biologicals will prepare a model Informed Consent Form (ICF) which will embody 
the ICH GCP and GSK Biologicals required elements. While it is strongly recommended 
that this model ICF is to be followed as closely as possible, the informed consent 
requirements given in this document are not intended to pre-empt any local regulations 
which require additional information to be disclosed for informed consent to be legally 
effective. Clinical judgement, local regulations and requirements should guide the final 
structure and content of the local version of the ICF. 
The investigator has the final responsibility for the final presentation of the ICF, 
respecting the mandatory requirements of local regulations. The ICF generated by the 
investigator with the assistance of the sponsor’s representative must be acceptable to 
GSK Biologicals and be approved (along with the protocol, and any other necessary 
documentation) by the IRB/IEC.
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5.2.
Subject identification and randomization
5.2.1.
Subject identification
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification 
numbers allocated to each study centre.
5.2.2.
Randomization of treatment
The treatment allocation will be performed using SBIR. The treatment numbers will be 
allocated by dose. The allocation ratio will be 1:1 between each study group.
Randomization of supplies
5.2.2.1.
The randomization of supplies within blocks will be performed at GSK Biologicals, using 
MATerial EXcellence (MATEX), a program developed for use in Statistical Analysis 
System (SAS®) (Cary, NC, USA) by GSK Biologicals. Entire blocks will be shipped to 
the study centres /warehouse(s).
To allow GSK Biologicals to take advantage of greater rates of recruitment than 
anticipated at individual centres in this multi-centre study and to thus reduce the overall 
study recruitment period, an over-randomization of supplies will be prepared. 
Treatment allocation to the subject
5.2.2.2.
The treatment numbers will be allocated by dose.
5.2.2.2.1.
Study group and treatment number allocation
The target will be to enrol approximately 912 eligible subjects who will be randomly 
assigned to two study groups in a 1:1 ratio (approximately 456 in each study group).
The enrolment will be performed to ensure distribution of the population across the three 
age strata (50-59 YOA, 60-69 YOA and 70 YOA). Therefore the expected distribution 
of subjects is as shown in Table 5.
Age will be calculated as the number of years between the date of birth and the date of 
first vaccination. To ensure that the collection of date of birth will not jeopardise the 
privacy of Personally Identifiable Information (PII), only a partial date of birth*
(MMYYYY) will be collected. Therefore, the 15th of the month will be used to replace 
the missing date.
In case the month is missing, the date will be replaced by the June 30th of the year.
* In Germany, as per local regulations, only the year of birth will be collected.
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Table 5
Number of subjects required for enrolment
Age Stratum
Vaccine
N
50-59 YOA
HZ/su
342
Prevenar13
60-69 YOA
HZ/su
342
Prevenar13
≥ 70 YOA
HZ/su
228
Prevenar13
N = number of subjects to be enrolled
Allocation of the subject to a study group at the investigator site will be performed using 
SBIR. Within each age strata (50-59 YOA, 60-69 YOA and 70 YOA), the 
randomization algorithm will use a minimisation procedure accounting for centre. 
After obtaining the signed and dated ICF from the subject and having checked the 
eligibility of the subject, the study staff in charge of the vaccine administration will 
access SBIR. Upon providing the age (50-59 YOA, 60-69 YOA and 70 YOA) at the 
time of enrolment in the study and the subject identification number, the randomization 
system will determine the study group and will provide the treatment number(s) to be 
used for the first dose.
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions.
5.2.2.2.2.
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 consistent with the allocated study group.
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen.
5.3.
Method of blinding 
This study is an open-label study.
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the subject and study (without any link to the treatment 
attributed to the subject) to each sample.
5.4.
General study aspects
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects.
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5.5.
Suspected HZ cases
Suspected HZ is defined as a new rash characteristic of HZ (i.e., 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 judgment. 
Complications of HZ include, but are not limited to, PHN, HZ vasculitis, disseminated 
disease, ophthalmic disease, neurologic disease, and visceral disease. 
The occurrence of HZ is an intercurrent medical condition (see Section 6.8) which should 
be reported until study end. All other intercurrent medical conditions should be reported 
until Month 3 for subjects from the Co-Ad group and Month 5 for subjects from the 
Control group. 
The standard reporting period as specified in Section 8.4.1 for Adverse Event 
(AE)/Serious Adverse Event (SAE) should be used for HZ complications.
At Visit Day 1, all subjects will be informed of the signs and symptoms of typical HZ. 
5.6.
Outline of study procedures
The lists of study procedures are presented in Table 6 and Table 7 for Co-Ad and Control 
groups, respectively.
Table 6
List of study procedures for Co-Ad Group
Epoch
Epoch 001
Type of contact
Visit 
Visit
Visit
Visit
Phone 
contact 
Timepoint (s)
Day 1
Month 1
Month 2
Month 3
Month 
14
Sampling timepoint(s)
Pre-
vacc
Prevenar13
Post-vacc 
HZ/su Post-
vacc 2 
Informed consent
●
Inclusion/exclusion criteria
●
Collect and record demographic data
●
General Medical history
●
Vaccination history
●
General physical examination (history directed)
O
Pregnancy test 1
●
●
Check contraindications and warnings and precautions
●
●
Pre-vaccination body temperature 2
●
●
Randomization
O
Study group and treatment number allocation
O
Recording of administered treatment number
●
●
Blood sampling for antibody determination (~8 mL) in all 
subjects
●
●
●
HZ/su administration
●
●3
Prevenar13 vaccine administration
●
Post-vaccination observation (30 minutes minimum)
O
O
Training on self-reporting by subjects 4
O
O
O
O
Training on completion of diary cards
O
O
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Epoch
Epoch 001
Type of contact
Visit 
Visit
Visit
Visit
Phone 
contact 
Timepoint (s)
Day 1
Month 1
Month 2
Month 3
Month 
14
Sampling timepoint(s)
Pre-
vacc
Prevenar13
Post-vacc 
HZ/su Post-
vacc 2 
Distribution of diary cards for solicited AEs, unsolicited AEs 
and concomitant medication/vaccination to subjects
O
O
Daily recording of solicited AEs by subjects (Days 1-7 after 
each vaccination) 5
O
O
Daily recording of unsolicited AEs and concomitant 
medication/vaccination by subjects (Days 1-30 after each 
vaccination)
O
O
Return of diary cards for solicited AEs, unsolicited AEs and 
concomitant medication/vaccination
O
O
Transcription of diary cards for solicited AEs, unsolicited 
AEs and concomitant medication/vaccination by study 
staff/investigator
●
●
Recording of serious adverse event 6
●
●
●
●
●
Recording of pIMDs
●
●
●
●
●
Recording of pregnancy
●
●
●
●
●
Recording of intercurrent medical conditions other than HZ 7
●
●
●
●
Recording of HZ (intercurrent medical condition) 8
●
●
●
●
●
Recording of concomitant medication/vaccination 9
●
●
●
●
●
Study conclusion
●
Note: The double-line border following Month 3 indicates the analyses which will be performed on all data (i.e. data that 
are as clean as possible) obtained up to Month 3 for Co-Ad group.
Pre-vacc: pre-vaccination, post-vac: post-vaccination. AE: adverse event; HZ: Herpes Zoster.
● is used to indicate a study procedure that requires documentation in the individual eCRF.
○ is used to indicate a study procedure that does not require documentation in the individual eCRF.
1. For women of childbearing potential. If a serum pregnancy test instead of a urine pregnancy test is required by 
country, local or ethics committee regulations, a blood sample will be collected from women of childbearing potential.
2. Pre-vaccination temperatures should always be recorded orally at study sites. In rare situations when there is no 
other alternative, the temperature may be recorded by other route. If the temperature is taken by another route 
(axillary, rectal or tympanic), the route should be documented.
3. Any subject with a suspected HZ episode anytime following the first HZ/su dose should not receive the second HZ/su 
dose or any subject with an event of HZ between Visit Day 1 and any dose of HZ/su vaccine should not receive the 
upcoming dose(s) of the HZ/su vaccine.
4. Subjects will be instructed to contact their study site immediately if they manifest any symptoms they perceive as 
serious and, in case of pregnancy for women of childbearing potential.
5. The preferred route for the daily recording of temperature is oral. When there is no other alternative, the temperature 
may be recorded by other route. If the temperature is taken by another route (axillary, rectal or tympanic), the route 
should be documented.
6. All serious adverse events (SAEs) related to study participation or GSK concomitant medication/vaccine are to be 
recorded from the time the subject consents to participate in the study. All other SAEs are to be reported after 
administration of the first dose of vaccine.
7.According to Section 6.8
8. At Visit Day 1, all subjects will be informed of the signs and symptoms of typical HZ.
9. According to Section 6.7.1
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Table 7
List of study procedures for Control Group
Epoch
Epoch 001
Type of contact
Visit
Visit 
Visit
Visit
Visit
Phone 
contact 
Timepoint (s)
Day 1
Month 1
Month 2 Month 4 Month 5
Month 
16
Sampling timepoint(s)
Pre-vacc Prevenar13
Post-vacc
Pre-vacc
HZ/su 
Post-
vacc 2
Informed consent
●
Inclusion/exclusion criteria
●
Collect and record demographic data
●
General medical history
●
Vaccination history
●
General physical examination (history directed)
O
Pregnancy test 1
●
●
●
Check contraindications and warnings and precautions
●
●
●
Pre-vaccination body temperature 2
●
●
●
Randomization
O
Study group and treatment number allocation
O
Recording of administered treatment number
●
●
●
Blood sampling for antibody determination (~8 mL) in all 
subjects
●
●
●
●
HZ/su administration
●3
●3
Prevenar13 vaccine administration
●
Post-vaccination observation (30 minutes minimum)
O
O
O
Training on self-reporting by subjects 4
O
O
O
O
O
Training on completion of diary cards
O
O
O
Distribution of diary cards for solicited AEs, unsolicited 
AEs and concomitant medication/vaccination to subjects
O
O
O
Daily recording of solicited AEs by subjects (Days 1-7 
after each vaccination) 5
O
O
O
Daily recording of unsolicited AEs and concomitant 
medication/vaccination by subjects (Days 1-30 after 
each vaccination)
O
O
O
Return of diary cards for solicited AEs, unsolicited AEs 
and concomitant medication/vaccination
O
O
O
Transcription of diary cards for solicited AEs, unsolicited 
AEs and concomitant medication/vaccination by study 
staff/investigator
●
●
●
Recording of serious adverse event 6
●
●
●
●
●
●
Recording of pIMDs
●
●
●
●
●
●
Recording of pregnancy
●
●
●
●
●
●
Recording of intercurrent medical conditions other than 
HZ 7
●
●
●
●
●
Recording of HZ (intercurrent medical condition) 8
●
●
●
●
●
●
Recording of concomitant medication/vaccination 9
●
●
●
●
●
●
Study conclusion
●
Note: The double-line border following Month 5 indicates the analyses which will be performed on all data (i.e. data that 
are as clean as possible) obtained up to Month 5 for Control group.
Pre-vacc: pre-vaccination, post-vac: post - vaccination; AE: adverse event; HZ: Herpes Zoster.
● is used to indicate a study procedure that requires documentation in the individual eCRF .
○ is used to indicate a study procedure that does not require documentation in the individual eCRF.
1. For women of childbearing potential. If a serum pregnancy test instead of a urine pregnancy test is required by 
country, local or ethics committee regulations, a blood sample will be collected from women of childbearing potential.
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2. Pre-vaccination temperatures should always be recorded orally at study sites. In rare situations when there is no 
other alternative, the temperature may be recorded by other route. If the temperature is taken by another route 
(axillary, rectal or tympanic), the route should be documented.
3. Any subject with a suspected HZ episode anytime following the first HZ/su dose should not receive the second HZ/su 
dose or any subject with an event of HZ between Visit Day 1 and any dose of HZ/su vaccine should not receive the 
upcoming dose(s) of the HZ/su vaccine.
4. Subjects will be instructed to contact their study site immediately if they manifest any symptoms they perceive as 
serious and, in case of pregnancy for women of childbearing potential.
5. The preferred route for the daily recording of temperature is oral. When there is no other alternative, the temperature 
may be recorded by other route. If the temperature is taken by another route (axillary, rectal or tympanic), the route 
should be documented.
6. All serious adverse events (SAEs) related to study participation or GSK concomitant medication/vaccine are to be 
recorded from the time the subject consents to participate in the study. All other SAEs are to be reported after 
administration of the first dose of vaccine.
7. According to Section 6.8.
8. At Visit Day 1, all subjects will be informed of the signs and symptoms of typical HZ.
9. According to Section 6.7.1
Whenever possible the investigator should arrange study visits within the intervals 
provided in Table 8 and Table 9 for Co-Ad and Control groups, respectively.
Table 8
Intervals between study visits/contact for Co-Ad group
Interval
Optimal length of interval1
Allowed interval
Visit Day 1 Visit Month 1
1 month
30 - 42 days 1
Visit Day 1 Visit Month 2
2 months
49 - 83 days 1
Visit Month 2 Visit Month 3
1 month
30 - 48 days 1
Visit Month 2 Phone contact Month 14
12 months
335 - 395 days
1Subjects may not be eligible for inclusion in the :Per-protocol cohort (PPC) for analysis of immunogenicity if they make 
the study visit outside this interval.
Table 9
Intervals between study visits/contact for Control group
Interval
Optimal length of interval1
Allowed interval
Visit Day 1 Visit Month 1
1 month
30 - 42 days 1
Visit Day 1 Visit Month 2
2 months
60 - 83 days 1
Visit Month 2 Visit Month 4
2 months
49 - 83 days 1
Visit Month 4 Visit Month 5
1 month
30 - 48 days 1
Visit Month 4 Phone contact Month 16
12 months
335 - 395 days
1Subjects may not be eligible for inclusion in the PPC for analysis of immunogenicity if they make the study visit outside 
this interval.
5.7.
Detailed description of study procedures
5.7.1.
Informed consent
The signed/witnessed/thumb printed informed consent of the subject must be obtained 
before study participation. Refer to Section 5.1 for the requirements on how to obtain 
informed consent.
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5.7.2.
Check inclusion and exclusion criteria
Check all inclusion and exclusion criteria as described in Sections 4.2 and 4.3 before 
enrolment. 
5.7.3.
Collect demographic data
Record demographic data such as date of birth*, sex, race and ethnicity in the subject’s 
eCRF.
* In Germany, as per local regulations, only the year of birth will be collected.
5.7.4.
General medical history
Obtain the subject’s medical history by interview and/or review of the subject’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in a 
subject prior to the first study vaccination in the eCRF.
5.7.5.
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.
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.
5.7.6.
Pregnancy test
Female subjects of childbearing potential are to have a urine/blood pregnancy test prior to 
any study vaccine administration. Generally, 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. The results of the applicable test will be 
recorded in the eCRF. The study vaccine(s) may only be administered if the pregnancy 
test is negative. 
Note: Pregnancy test must be performed even if the subject is menstruating at the time of 
the study visit.
5.7.7.
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 Sections 6.5 and 6.6 for more details.
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5.7.8.
Assess pre-vaccination body temperature
The body temperature of each subjects needs to be measured prior to any study vaccine(s)
administration. The preferred location for measuring temperature in this study will be the 
oral cavity. If the subject has fever [fever is defined as temperature 38.0°C/100.4°F 
regardless the location of measurement] on the day of vaccination, the vaccination visit 
will be rescheduled within the allowed interval for this visit (see Table 8 and Table 9).
In rare situations when there is no other alternative, the temperature may be recorded by 
other route. If the temperature is taken by another route (axillary, rectal or tympanic), the 
route should be documented.
5.7.9.
Study group and treatment number allocation
Study group and treatment number allocation will be performed as described in Section 
5.2.2. The number of each administered treatment must be recorded in the eCRF.
5.7.10.
Sampling
Refer to the Investigator Lab Manual for detailed instructions for the collection, handling 
and processing of the samples.
Blood sampling for immune response assessments 
5.7.10.1.
Blood samples will be taken during certain study visits as specified in Section 5.6 List of 
Study Procedures.

A volume of at least approximately 8 mL of whole blood (to provide at least 2.8 mL 
of serum) should be drawn from all subjects for each analysis of humoral immune 
response at each pre-defined timepoint. After centrifugation, serum samples should 
be kept at –20°C/ –4°F or below until shipment. Refer to the Investigator Lab 
Manual for more details on sample storage conditions.
5.7.11.
Study Vaccine(s) administration

After completing all prerequisite procedures prior to vaccination, the dose(s) of 
vaccine(s) will be administered IM in the deltoid(s) of the arms according to the 
administration schedule (refer to Section 6.3 for detailed description of the 
vaccine(s) administration procedure). If the investigator or delegate determines that 
the subject’s health on the day of administration temporarily precludes vaccine(s)
administration, the visit will be rescheduled within the allowed interval for this visit 
(refer to Table 8 and Table 9).

The subjects will be observed closely for at least 30 minutes following the 
administration of the vaccine(s), with appropriate medical treatment readily available 
in case of anaphylaxis.

Any subjects with an event of HZ between Visit Day 1 and any dose of HZ/su 
vaccine should not receive the upcoming dose(s) of the HZ/su vaccine.
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5.7.12.
Check and record concomitant medication/vaccination and 
intercurrent medical conditions 
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 6.7.
Intercurrent medical conditions must be checked and recorded in the eCRF as described 
in Section 6.8.
5.7.13.
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 will be instructed to contact the investigator immediately should they
manifest any signs or symptoms they perceive as serious. 

At each vaccination visit, diary cards will be provided to the subject. The subject will 
be instructed to measure and record the oral body temperature, and any solicited 
local/general AEs (i.e. on the day of vaccination and during the next 6 days) or any 
unsolicited AEs (i.e. on the day of vaccination and during the next 29 days occurring
after vaccination. The subject 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 (at Visit 
Month 1 and Visit Month 3 in Co-Ad group and at Visit Month 1, Visit Month 4 and 
Visit Month 5 in Control group).

Any unreturned diary cards will be sought from the subject through telephone call(s) 
or any other convenient method. 

The investigator will transcribe the collected information into the eCRF in English.
5.7.14.
Study conclusion
The investigator will:

collect and record SAEs, pIMDs, any pregnancy cases, HZ occurences and 
concomitant medication/ vaccination taken,

review data collected to ensure accuracy and completeness,

complete the Study Conclusion screen in the eCRF.
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5.8.
Biological sample handling and analysis
Please refer to the Investigator Lab Manual for details on biospecimen management 
(handling, storage and shipment).
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the identification number for the subject (subject number).

Collected samples will be used for protocol mandated research and purposes related 
to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. This may include the management of the quality of these 
tests, the maintenance or improvement of these tests, the development of new test 
methods, as well as making sure that new tests are comparable to previous methods 
and work reliably.

It is also possible that future findings may make it desirable to use the samples 
acquired in this study for future research, not described in this protocol. Therefore, 
all subjects in countries where this is allowed will be asked to give a specific consent
to allow GSK or a contracted partner to use the samples for future research. Future 
research will be subject to the laws and regulations in the respective countries and 
will only be performed once an independent Ethics Committee or Review Board has 
approved this research.
Information on further investigations and their rationale can be obtained from GSK 
Biologicals. 
Any sample testing will be done in line with the consent of the individual subject.
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
If additional testing is performed, the marker priority ranking given in Section 5.8.4 may 
be changed.
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK Biologicals.
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5.8.1.
Use of specified study materials
When materials are provided by GSK Biologicals, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the subject from the per-protocol analysis (See Section 10.4 for the 
definition of cohorts to be analysed). The investigator must ensure that his/her personnel 
and the laboratory(ies) under his/her supervision comply with this requirement. However, 
when GSK Biologicals does not provide material for collecting and storing clinical 
samples, appropriate materials from the investigator’s site must be used. Refer to the 
Investigator Lab Manual.
5.8.2.
Biological samples
The different biological samples collected in the study, the quantity needed, the unit and 
the time points are described in Table 10.
Table 10
Biological samples
Sample type
Quantity
Unit
Timepoint Co-Ad group
Timepoint Control group
Whole blood 
Approximately 8 
mL
Visit Day 1 
Visit Month 1
Visit Month 3 
Visit Day 1
Visit Month 1 
Visit Month 2 
Visit Month 5 
5.8.3.
Laboratory assays
Please refer to APPENDIX A for a detailed description of the assays performed in the 
study. Please refer to APPENDIX B for the address of the clinical laboratories used for 
sample analysis.
Serological assays for the determination of anti-gE antibodies will be performed by 
enzyme-linked immunosorbent assay (ELISA) at a GSK Biologicals’ laboratory. 
Serological assays for the determination of pneumococcal serotype antibodies will be 
performed by multiplex opsonophagocytosis assay (MOPA) at a laboratory designated by 
GSK Biologicals using standardized and validated procedures (refer to Table 11).
(Amended 30 January 2018)
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Table 11
Humoral Immunity (Antibody determination)
System
Component
Method
Unit
Cut-off
Laboratory
Serum
Varicella Zoster Virus Glycoprotein E Ab IgG
ELISA
mlU/mL
97
GSK Biologicals*
Serum
Streptococcus pneumoniae Serotype 01/37 
Brugmann Hospital Ab
MOPA
1/dilution
14
University of 
Alabama at 
Birmingham**
Streptococcus pneumoniae Serotype 03/1 
Statens Serum Institut Ab
10
Streptococcus pneumoniae Serotype 04/2656 
Brugmann Hospital Ab
41
Streptococcus pneumoniae Serotype 05 
Ambrose- Statens Serum Institut Ab
11
Streptococcus pneumoniae Serotype 06A 
Centers for Disease Control Ab
15
Streptococcus pneumoniae Serotype 
06B/DS2212/94 Centers for Disease Control Ab
29
Streptococcus pneumoniae Serotype 07F/46 
Brugmann Hospital Ab
28
Streptococcus pneumoniae Serotype 09V/112 
161/95 Statens Serum Institut Ab
14
Streptococcus pneumoniae Serotype 14/58 
Brugmann Hospital Ab
14
Streptococcus pneumoniae Serotype 
18C/4593/40 Statens Serum Institut Ab
26
Streptococcus pneumoniae Serotype 19A/DB18 
Kansanterveyslaitos Folkhalsoinstitutet Ab
13
Streptococcus pneumoniae Serotype 19F/2737 
Brugmann Hospital Ab
15
Streptococcus pneumoniae Serotype 23F Mac-
Statens Serum Institut Ab
22
2GSK Biologicals laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium.
**Pathology Department of Professor, Moon H. Nahm, M.D, WHO Pneumococcal Serology Reference Laboratory, The 
University of Alabama at Birmingham, Bevill Building, Room 614 (BBRB 614), 845 19th Street South, Birmingham 
AL, 35294
MOPA: multiplex opsonophagocytosis assay; ELISA: enzyme-linked immunosorbent assay; Ab: antibody; IgG: 
immunoglobulin G; S pneumoniae: Streptococcus pneumoniae.
Additional exploratory testing on the vaccine and/or on the disease under study may be 
performed within the framework of the study if deemed necessary for accurate 
interpretation of the data or should such assay(s) become available at GSK. These assays 
may not be represented in the objectives/endpoints of the study protocol.
The GSK Biologicals’/ contract research organizations’ (CRO) clinical laboratories 
have established a Quality System supported by procedures. The activities of GSK 
Biologicals’/ CROs’ clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. Clinical 
laboratories contracted by GSK also conform to Good Laboratory Practice guidelines 
and operate in compliance with regulatory standards.
(Amended 30 January 2018)
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5.8.4.
Biological samples evaluation
Immunological read-outs
5.8.4.1.
The plan for immunogenicity testing on samples obtained is shown in Table 12 and Table 
13 for Co-Ad and Control groups, respectively.
Table 12
Immunological read-outs for Co-Ad group
Blood sampling timepoint
No. subjects
Component
Type of contact and timepoint
Sampling timepoint
Visit Day 1 1
Prevenar13 pre-vaccination
456
S pneumoniae 01 Ab
S pneumoniae 03 Ab
S pneumoniae 04 Ab
S pneumoniae 05 Ab
S pneumoniae 06A Ab
S pneumoniae 06B Ab
S pneumoniae 07F Ab
S pneumoniae 09V Ab
S pneumoniae 14 Ab
S pneumoniae 18C Ab
S pneumoniae 19A Ab
S pneumoniae 19F Ab
S pneumoniae 23F Ab
HZ/su pre-vaccination
456
VZV Glycoprotein E Ab IgG
Visit Month 1
Prevenar13 post-
vaccination
456
S pneumoniae 01 Ab
S pneumoniae 03 Ab
S pneumoniae 04 Ab
S pneumoniae 05 Ab
S pneumoniae 06A Ab
S pneumoniae 06B Ab
S pneumoniae 07F Ab
S pneumoniae 09V Ab
S pneumoniae 14 Ab
S pneumoniae 18C Ab
S pneumoniae 19A Ab
S pneumoniae 19F Ab
S pneumoniae 23F Ab
Visit Month 3
HZ/su post-vaccination
456
VZV Glycoprotein E Ab IgG
Ab: antibody; IgG: immunoglobulin G; S pneumoniae: Streptococcus pneumoniae; VZV: Varicella Zoster Virus.
1 In case of inadequate samples from Visit Day 1, anti-gE testing (ELISA) will be prioritized over testing for 
pneumococcal serotype antibodies (MOPA). 
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Table 13
Immunological read-outs for Control group
Blood sampling timepoint
No. subjects
Component
Type of contact and 
timepoint
Sampling timepoint
Visit Day 1
Prevenar13
pre-vaccination
456
S pneumoniae 01 Ab
S pneumoniae 03 Ab
S pneumoniae 04 Ab
S pneumoniae 05 Ab
S pneumoniae 06A Ab
S pneumoniae 06B Ab
S pneumoniae 07F Ab
S pneumoniae 09V Ab
S pneumoniae 14 Ab
S pneumoniae 18C Ab
S pneumoniae 19A Ab
S pneumoniae 19F Ab
S pneumoniae 23F Ab
Visit Month 1
Prevenar13
post-vaccination
456
S pneumoniae 01 Ab
S pneumoniae 03 Ab
S pneumoniae 04 Ab
S pneumoniae 05 Ab
S pneumoniae 06A Ab
S pneumoniae 06B Ab
S pneumoniae 07F Ab
S pneumoniae 09V Ab
S pneumoniae 14 Ab
S pneumoniae 18C Ab
S pneumoniae 19A Ab
S pneumoniae 19F Ab
S pneumoniae 23F Ab
Visit Month 2
HZ/su pre-vacc
456
VZV Glycoprotein E Ab IgG
Visit Month 5
HZ/su post-vacc
456
VZV Glycoprotein E Ab IgG
Ab: antibody; IgG: immunoglobulin G; S pneumoniae: Streptococcus pneumoniae; VZV:Varicella Zoster Virus
5.8.5.
Immunological correlates of protection
No generally accepted immunological correlate of protection against HZ has been 
demonstrated so far for the gE antigen used in the HZ/su study vaccine.
No correlate of protection for pneumococcal conjugate vaccines for use in adults has 
been established.
The investigator is encouraged to share the immunological assay results for non-
responders with the study subjects.
For the subjects identified as non-responders, it remains the responsibility of the 
investigator in charge of the subject’s clinical management to determine the medical need 
for re-vaccination and to re-vaccinate the subjects as per local/regional practices.
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6.
STUDY VACCINES AND ADMINISTRATION
6.1.
Description of study vaccines
The study vaccine to be used has been developed and manufactured by GSK Biologicals. 
The Prevenar13 vaccine is marketed by Pfizer Inc..
The Quality Control Standards and Requirements for the study vaccine are described in 
separate Quality Assurance documents (e.g. release protocols, certificate of analysis) and 
the required approvals have been obtained.
The vaccines are labelled and packed according to applicable regulatory requirements.
Commercial vaccine(s) are assumed to comply with the specifications given in the 
manufacturer’s Summary of Product Characteristics.
The characteristics of the study vaccines are presented in Table 14.
Table 14
Study vaccines
Treatment 
name
Vaccine 
name
Formulation
Presentation
Volume to be 
administered
No. of 
doses
HZ/su 
VZV gE 
gE=50µg per 0.5 mL of 
reconstituted vaccine
Lyophilized pellet in 
a monodose vial
0.5 mL
2
AS01B
MPL=50µg; QS21=50µg; 
Liposomes per 0.5 mL of 
reconstituted vaccine
Liquid in a 
monodose vial
Prevenar13
Prevenar13 
13 pneumococcal 13 
polysaccharides (1, 3, 4, 5, 6A, 
6B, 7F, 9V, 14, 18C, 19A, 19F, 
23F), conjugated to cross-
reactive material 197 carrier 
protein and adsorbed on 
aluminum phosphate 
(PS1=2.2µg CRM197; 
PS3=2.2µg CRM197; 
PS4=2.2µg CRM197; 
PS5=2.2µg CRM197; 
PS6A=2.2µg CRM197; 
PS6B=4.4µg CRM197; 
PS7F=2.2µg CRM197; 
PS9V=2.2µg CRM197; 
PS14=2.2µg CRM197; 
PS18C=2.2µg CRM197; 
PS19A=2.2µg CRM197; 
PS19F=2.2µg CRM197; 
PS23F=2.2µg CRM197; 
AlPO₄=125µg Al3+ )
Homogenous white 
suspension after 
shaking (in pre-
filled syringe) 
0.5 mL
1
HZ/su = Herpes Zoster subunit vaccine; VZV = Varicella Zoster Virus; gE = recombinant purified envelope glycoprotein
E; μg = microgram; mL = milliliter; AS01B = Adjuvant System AS01B; MPL: 3-O-desacyl-4’-monophosphoryl lipid A.
*QS21: Quillaja saponaria Molina, fraction 21 (Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation).
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6.2.
Storage and handling of study vaccine(s)
The study vaccine(s) 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 SPM for more details on storage of the study 
vaccine(s).
Temperature excursions must be reported in degree Celsius.
Any temperature excursion outside the range of 0.0 to +8.0C (for +2 to +8°C/+36 to 
+46°F label storage condition) impacting investigational medicinal products (IMPs) must 
be reported in the appropriate (electronic) temperature excursion decision form ([e]TDF). 
The impacted IMPs must not be used and must be stored in quarantine at label 
temperature conditions until usage approval has been obtained from the sponsor.
In case of temperature excursion below +2.0°C down to 0.0°C impacting IMP(s) there is 
no need to report in (e)TDF, but adequate actions must be taken to restore the +2 to 
+8°C/+36 to +46°F label storage temperature conditions. The impacted IMP(s) may still 
be administered, but the site should avoid re-occurrence of such temperature excursion.
Refer to the SPM for more details on actions to take.
Refer to the SPM for details and instructions on the temperature excursion reporting and 
usage decision process, packaging and accountability of the study vaccine(s).
6.3.
Dosage and administration of study vaccines
For HZ/su:
After reconstitution, the vaccine should be used promptly; if this is not possible, the 
vaccine should be stored in a refrigerator (2°C – 8°C). If not used within 6 hours it should 
be discarded. 
For Prevenar13:
Prevenar13 is a commercially available vaccine and should be administered in 
accordance with the instructions provided in the manufacturer’s product label/packaging 
insert.
Both vaccines will be administered as indicated in Table 15 and Table 16. The vaccines 
should be administered by IM injection into the deltoid muscle of different arms, using a 
standard aseptic technique. For subjects in the Co-Ad group at Visit Day 1, the HZ/su and 
Prevenar13 vaccinations must be administered in different arms. 
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Table 15
Dosage and administration for the Co-Ad group
Type of 
contact and 
timepoint
Treatment 
name
Volume to be 
administered
Route
Site
Location
Laterality
Visit Day 1 
HZ/su
0.5 ml
IM
Deltoid
Non-dominant
Prevenar13
0.5 ml
IM
Deltoid
Dominant
Visit Month 2
HZ/su
0.5 ml
IM
Deltoid
Non-dominant 1
IM: Intramuscular.
1 In rare situations when there is no alternative, the injection may be given in the other arm.
Table 16
Dosage and administration for the Control group
Type of 
contact and 
timepoint
Treatment 
name
Volume to be 
administered
Route
Site
Location
Laterality1
Visit Day 1
Prevenar13
0.5 ml
IM
Deltoid
Dominant
Visit Month 2
HZ/su
0.5 ml
IM
Deltoid
Non-dominant
Visit Month 4
HZ/su
0.5 ml
IM
Deltoid
Non-dominant
IM: Intramuscular.
1 In rare situations when there is no alternative, the injection may be given in the other arm
6.4.
Replacement of unusable vaccine doses
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomization when applicable), at least 30% additional vaccine doses will be 
supplied to replace those that are unusable. 
6.5.
Contraindications to subsequent vaccination
The following events constitute absolute contraindications to further administration of the 
HZ vaccine. 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(s).

Pregnancy.

If the subject experiences an SAE judged to be vaccine-related by the investigator.

The occurrence of a new potential immune-mediated diseases (pIMDs) or the 
exacerbation of an existing pIMD that, in the opinion of the investigator, expose the 
subject to unacceptable risk from subsequent vaccination. In such cases, the 
investigator should use his/her clinical judgement prior to administering the next 
dose of the vaccine(s)/product(s). 
Refer to Section 8.1.5.1 for the definition of pIMDs.

Any confirmed or suspected immunosuppressive or immunodeficient condition, 
including HIV infection. 
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
Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe.

If the subject experiences an event of HZ between the first and the second dose of 
HZ/su or between Visit Day 1 and any dose of HZ/su vaccine (Refer Section 5.5 and 
6.8).
The following events constitute contraindications to administration of HZ/su study 
vaccine 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, or withdrawn at the discretion of the investigator (Time 
windows between visits are given in Table 8 and Table 9).

Acute disease and/or fever at the time of vaccination. 

Fever is defined as temperature 38.0°C / 100.4°F. The preferred location for 
measuring 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/products.
6.6.
Warnings and precautions
Refer to the approved product label/package insert of Prevenar13.
6.7.
Concomitant medications/products and concomitant 
vaccinations
At each study visit/contact, the investigator or delegate should question the subject about 
any medications/products taken and vaccinations received by the subject.
6.7.1.
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 dose of study vaccine (Day 1 to Day 
30).

Relevant medications/products administered during the period.

Any concomitant vaccination administered in the period starting 30 days before the 
first dose of study vaccine and ending 30 days after the last dose, and any 
concomitant vaccination against HZ or pneumococcal vaccine (other than the study 
vaccines) during the study period.

Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination).
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E.g. an anti-pyretic is considered to be prophylactic when it is given in the absence 
of fever and any other symptom, to prevent fever from occurring [fever is defined as 
temperature 38.0°C/100.4°F regardless the location of measurement]. The 
preferred location for measuring temperature in this study will be the oral cavity.

Any concomitant medications/products/vaccines listed in Section 6.7.2.

Any concomitant medications/products/vaccines relevant to a SAE/pIMD to be 
reported as per protocol or administered 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.

Any concomitant medication administered for the treatment of confirmed or 
suspected HZ or any HZ-related complications (including pain) at any time during 
the study period. 
6.7.2.
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from per-protocol analyses
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
per-protocol analysis. See Section 10.4 for cohorts to be analysed.

Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine(s) used during the study period. 

Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. >14 days in total) up to the last blood sampling. For corticosteroids, this will 
mean prednisone 20 mg/day, or equivalent. Inhaled and topical steroids are 
allowed.

Long-acting immune-modifying drugs administered at any time during the study 
period up to the last blood sampling (e.g. infliximab).

A vaccine not foreseen by the study protocol administered during the period starting 
30 days before and ending 30 days after the last dose of study vaccine 
administration. 
In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a 
pandemic) is organized by the public health authorities, outside the routine 
immunization program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to its Prescribing 
Information and according to the local governmental recommendations and provided 
a written approval of the Sponsor is obtained.

Immunoglobulins and/or any blood products administered during the study period up 
to the last blood sampling.

Receipt of a vaccine against HZ or VZV or pneumococcal vaccine other than the 
study vaccine during the study period.
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6.8.
Intercurrent medical conditions that may lead to elimination 
of a subject from per-protocol analyses
At each study visit subsequent to the first vaccination/the vaccination visit, it must be 
verified if the subject has experienced or is experiencing any intercurrent medical 
condition (IMC). If it is the case, the condition(s) must be recorded in the eCRF. An IMC 
is defined as a condition that has the capability of confounding the immune response to 
the study vaccine or its interpretation. Subjects may be eliminated from the Per-protocol 
cohort for immunogenicity if, during the study, they incur an IMC. 
Examples of IMCs include cases of HZ or a confirmed or suspected immunosuppressive 
or immunodeficient condition resulting from disease (e.g., malignancy, HIV infection).
All IMCs including HZ will be recorded until Visit Month 3 for subjects in the Co-Ad 
group and Visit Month 5 for subjects in the Control group. All IMCs will be recorded in 
AE/SAE screens as appropriate. 
Occurrences of HZ from Visit Month 3 (Co-Ad group) and Visit Month 5 (Control 
group) are to be reported till study end (phone contact at Month 14 for the Co-Ad group 
and Month 16 for the Control group) but will not be considered as IMCs.
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 adverse event (AE) or serious 
adverse event (SAE) as provided in this protocol. 
Each subject will be instructed to contact the investigator immediately should they 
manifest any signs or symptoms they perceive as serious.
8.1.
Safety definitions
8.1.1.
Definition of an adverse event
An AE is any untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. 
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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 study vaccine(s) 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 study
vaccine(s) or a concurrent medication (overdose per se should not be reported as an 
AE/SAE).

Signs, symptoms temporally associated with study vaccine(s) administration.

Significant failure of expected pharmacological or biological action. 

Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen).
AEs to be recorded as endpoints (solicited AEs) are described in Section 8.1.3. All other 
AEs will be recorded as UNSOLICITED AEs.
Examples of an AE DO NOT include:

Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that 
leads to the procedure is an AE/SAE.

Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

Pre-existing conditions or signs and/or symptoms present in a subject prior to the 
first study vaccination. These events will be recorded in the medical history section 
of the eCRF.
8.1.2.
Definition of a serious adverse event 
A SAE is any untoward medical occurrence that:
a.
Results in death,
b.
Is life-threatening,
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe.
c.
Requires hospitalization or prolongation of existing hospitalization,
Note: In general, hospitalization signifies that the subject has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
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been appropriate in the physician’s office or in an out-patient setting. Complications 
that occur during hospitalization are also considered AEs. If a complication prolongs 
hospitalization or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalization’ occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline is 
NOT considered an AE.
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 hospitalization 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 hospitalization.
8.1.3.
Solicited adverse events
Solicited local (injection-site) adverse events
8.1.3.1.
The following local (injection-site) AEs will be solicited:
Table 17
Solicited local adverse events
Pain at injection site
Redness at injection site
Swelling at injection site
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Solicited general adverse events
8.1.3.2.
The following general AEs will be solicited:
Table 18
Solicited general adverse events
Fatigue
Fever
Gastrointestinal symptoms †
Headache
Myalgia
Shivering
†Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain.
Note: Subjects will be instructed to measure and record the oral body temperature in the 
evening. Should additional temperature measurements be performed at other times of
day, subjects will be instructed to record the highest temperature in the diary card.
8.1.4.
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events 
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
haematology, urinalysis) or other abnormal assessments 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. However, clinically significant abnormal laboratory findings or other abnormal 
assessments that are associated with the disease being studied, unless judged by the 
investigator as more severe than expected for the subject’s condition, or that are present 
or detected at the start of the study and do not worsen, will not be reported as AEs or 
SAEs.
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant.
8.1.5.
Adverse events of specific interest
Potential immune-mediated diseases
8.1.5.1.
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 19.
However, the investigator will exercise his/her medical and scientific judgement in 
deciding whether other diseases have an autoimmune origin (i.e. pathophysiology 
involving systemic or organ-specific pathogenic autoantibodies) and should also be 
recorded as a pIMD.
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Table 19
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/cardiomyopathySarco
idosis

Stevens-Johnson syndrome

Sjögren’s syndrome

Idiopathic pulmonary fibrosis

Goodpasture syndrome

Raynaud’s phenomenon
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Liver disorders
Gastrointestinal disorders
Endocrine disorders

Autoimmune hepatitis

Primary biliary 
cirrhosis

Primary sclerosing 
cholangitis

Autoimmune 
cholangitis

Inflammatory Bowel disease, 
including Crohn’s disease, 
ulcerative colitis,
microscopic colitis, 
ulcerative proctitis 

Celiac disease

Autoimmune pancreatitis

Autoimmune thyroiditis (including 
Hashimoto thyroiditis)

Grave's or Basedow’s disease

Diabetes mellitus type I

Addison’s disease

Polyglandular autoimmune 
syndrome

Autoimmune hypophysitis
When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as a pIMD. Symptoms, signs or conditions which might (or might not) represent 
the above diagnoses, should be recorded and reported as AEs but not as pIMDs until the 
final or definitive diagnosis has been determined, and alternative diagnoses have been 
eliminated or shown to be less likely.
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire and a list of preferred terms (PTs) and PT codes corresponding to the above 
diagnoses will be available to investigators at study start.
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(s) 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 
EMA Guideline on pregnancy exposure [EMA, 2006]. It is recognized that national 
regulations might be different.

Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life). 
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
Any congenital anomaly or birth defect (as per [CDC MACDP] 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 study vaccine(s) 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 within 30 days following administration of each dose of study vaccine 
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 approximately 12 months following administration of the last dose 
of study vaccine for each subject. See Section 8.4 for instructions on reporting of SAEs.
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the first receipt of study vaccine.
SAEs that are related to the study vaccine(s) will be collected and recorded from the time 
of the first receipt of study vaccine(s) until the subject is discharged from the study.
In addition to the above-mentioned reporting requirements and in order to fulfil 
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) or are 
related to a concurrent GSK medication/vaccine will be collected and recorded from the 
time the subject consents to participate in the study until she/he is discharged from the 
study.
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccine and will end approximately 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 approximately 12 months following administration of the last 
dose of study vaccine. See section 8.4 for instructions on reporting of pIMDs.
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Intercurrent medical conditions other than HZ (see Section 6.8) will be recorded from 
Day 1 until Month 3 for subjects from the Co-Ad group and Month 5 for subjects from 
the Control group. Intercurrent medical conditions will be recorded in AE/SAE screens as 
appropriate.
The occurrence of HZ will constitute an AE/SAE as appropriate. The reporting period for 
cases of HZ will be from Day 1 to study end.
An overview of the protocol-required reporting periods for AEs, SAEs, pIMDs, 
pregnancies, and intercurrent medical conditions (including HZ) is given in Table 20.
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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 20. 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 study vaccine(s), the investigator will promptly notify the 
Study Contact for Reporting SAEs.
8.3.3.
Evaluation of adverse events and serious adverse events
Active questioning to detect adverse events and serious adverse 
8.3.3.1.
events
As a consistent method of collecting AEs, the subject should be asked a non-leading 
question such as:
‘Have you felt different in any way since receiving the vaccine(s) or since the previous 
visit?’
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK Biologicals instead of appropriately completing the 
eCRF. However, there may be instances when copies of medical records for certain cases 
are requested by GSK Biologicals. In this instance, all subject identifiers will be blinded 
on the copies of the medical records prior to submission to GSK Biologicals.
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms.
Assessment of adverse events
8.3.3.2.
8.3.3.2.1.
Assessment of intensity
The intensity of the following solicited AEs will be assessed as described:
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Table 21
Intensity scales for solicited symptoms in adults 
Adults
Adverse Event
Intensity grade
Parameter
Pain at injection site
0
None
1
Mild: Any pain neither interfering with nor preventing 
normal every day activities.
2
Moderate: Painful when limb is moved and 
interferes with every day activities.
3
Severe: Significant pain at rest. Prevents normal 
every day activities.
Redness at injection site
Record greatest surface diameter in mm
Swelling at injection site
Record greatest surface diameter in mm
Fever*
Record temperature in °C/°F
Headache
0
Normal
1
Mild: Headache that is easily tolerated
2
Moderate: Headache that interferes with normal 
activity
3
Severe: Headache that prevents normal activity
Fatigue
0
Normal
1
Mild: Fatigue that is easily tolerated
2
Moderate: Fatigue that interferes with normal activity
3
Severe: Fatigue that prevents normal activity
Gastrointestinal symptoms
0
Gastrointestinal symptoms normal
(nausea, vomiting, diarrhoea and/or 
abdominal pain)
1
Mild: Gastrointestinal symptoms that are easily 
tolerated
2
Moderate: Gastrointestinal symptoms that interfere 
with normal activity
3
Severe: Gastrointestinal symptoms that prevent 
normal activity
Myalgia
0
Normal
1
Mild: Myalgia that is easily tolerated
2
Moderate: Myalgia that interferes with normal 
activity
3
Severe: Myalgia that prevents normal activity
Shivering
0
None
1
Shivering that is easily tolerated
2
Shivering that interferes with normal activity
3
Shivering that prevents normal activity
*Fever is defined as temperature 38.0°C / 100.4°F. The preferred location for measuring temperature in this study 
will be the oral cavity. When there is no other alternative, the temperature may be recorded by other route. If the 
temperature is taken by another route (axillary, rectal or tympanic), the route should be documented.
The maximum intensity of local injection site redness/swelling will be scored at GSK 
Biologicals using GSK Biologicals’ standard grading scale base on the US FDA 
guidelines for Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
enrolled in Preventive Vaccine Clinical Trials [FDA, 2007].
0
:
< 20 mm diameter
1
:
20 mm to 50 mm diameter
2
:
> 50 mm to 100 mm diameter
3
:
> 100 mm diameter
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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/school 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 study vaccine(s) and the 
occurrence of each AE/SAE using clinical judgement. In case of concomitant 
administration of multiple vaccines/products, if possible, the investigator should specify 
if the AE could be causally related to a specific vaccine/product administered (i.e 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine(s)/product(s) cannot be determined the investigator should indicate the 
AE to be related to all products.
Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study vaccine(s) will be considered and investigated. The investigator will also consult 
the IB and/or and/or SmPC and/or Prescribing Information for marketed products to 
determine his/her assessment.
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK 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.
All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question:
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Is there a reasonable possibility that the AE may have been caused by the study vaccine?
YES
:
There is a reasonable possibility that the study vaccine(s)
contributed to the AE. 
NO
:
There is no reasonable possibility that the AE is causally related to 
the administration of the study vaccine(s). There are other, more 
likely causes and administration of the study vaccine(s) 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(s), if applicable.

Erroneous administration.

Other cause (specify).
Assessment of outcomes
8.3.3.3.
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).
Medically attended visits
8.3.3.4.
For each solicited and unsolicited symptom the subject experiences, the subject will be 
asked if he/she received medical attention defined as hospitalization, or an otherwise 
unscheduled visit to or from nurses practitioners, health care workers or medical 
personnel for any reason, including emergency room visits. This information will be 
recorded in the in the eCRF. 
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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 22, 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 22, 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 22, once the investigator determines that 
the event meets the protocol definition of a pIMD.
Table 22
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
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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 22.
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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 study vaccine(s) 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 
Follow-up during the study
8.5.1.1.
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 22).
All SAEs and pIMDs (serious or non-serious) documented at a previous visit/contact and 
designated as not recovered/not resolved or recovering/resolving will be reviewed at 
subsequent visits/contacts until the last visit of the subject.
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until 30
days after the last vaccination.
Follow-up after the subject is discharged from the study
8.5.1.2.
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.
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK Biologicals using a paper/ electronic 
Expedited Adverse Events Report and/or pregnancy report as applicable.
GSK Biologicals may request that the investigator performs or arranges the conduct of 
additional clinical examinations/tests and/or evaluations to elucidate as fully as possible 
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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 a SAE / pIMDs
should be recorded in Expedited Adverse Event Report of the subject’s eCRF (refer to 
Section 6.7).
8.7.
Subject card
Study subjects 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. 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.
9.
SUBJECT COMPLETION AND WITHDRAWAL
9.1.
Subject completion
A subject who returns for the concluding visit/is available for the concluding contact 
foreseen in the protocol is considered to have completed the study.
9.2.
Subject withdrawal
Withdrawals will not be replaced.
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9.2.1.
Subject withdrawal from the study
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did 
not come back for the concluding visit/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, or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal:

Serious adverse event.

Unsolicited non-serious adverse event.

Solicited adverse event

Protocol violation (specify).

Consent withdrawal, not due to an adverse event*.

Moved from the study area.

Lost to follow-up.

Other (specify).
*In case a subject is withdrawn from the study because he/she has withdrawn consent, the 
investigator will document the reason for withdrawal of consent, if specified by the 
subject, in the eCRF .
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 8.5.1.2).
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9.2.2.
Subject withdrawal from study vaccine(s)
A ‘withdrawal’ from the study vaccine(s) refers to any subject who does not receive the 
complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A subject withdrawn from the study vaccine(s) 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. 
Information relative to premature discontinuation of the study vaccine(s) will be 
documented on the Vaccine Administration screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination/treatment was made by 
the subject himself/herself, or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal:

Serious adverse event.

Unsolicited non-serious adverse event.

Solicited adverse event

Not willing to be vaccinated

Other (specify).
9.3.
Extension study
During the study conclusion visit/contact, the investigator will ask each subject if he/she 
is interested in participating in a long-term study. If a subject is not interested in 
participating in the long-term study the reason for refusal will be documented in the 
subject’s eCRF.
10.
STATISTICAL METHODS
10.1.
Primary endpoints

HZ/su immunogenicity:

Vaccine response for anti-gE humoral immunogenicity, as determined by ELISA, 
in subjects from the Co-Ad group at one month post-dose 2, at Visit Month 3.

Anti-gE antibody concentrations as determined by ELISA at one month post-
dose 2, at Visit Month 3 for the Co-Ad group and Visit Month 5 for the Control 
group.

Pneumococcal vaccine immunogenicity:

Anti-pneumococcal antibody titers for the 13 following serotypes as determined 
by MOPA at one month post-dose at Visit Month 1: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 
14, 18C, 19A, 19F and 23F.
The criteria used to define the VRR is given in Section 10.7.1.
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10.2.
Secondary endpoints

Occurrence of solicited local and general symptoms: 

Occurrence, duration and intensity of each solicited local symptom within 7 days 
(Days 1 - 7) after each vaccination,

Occurrence, duration, intensity and relationship to vaccination of each solicited 
general symptom within 7 days (Days 1 to 7) after each vaccination.

Occurrence of unsolicited AEs:

Occurrence, intensity and relationship to vaccination of unsolicited AEs within 
30 days (Days 1 to 30) 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 first vaccination at 
Day 1 up to 30 days post last vaccination.

Occurrence and relationship to vaccination of all SAEs during the period starting 
after 30 days post last vaccination up to study end.

Occurrence of pIMDs:

Occurrence and relationship to vaccination of any pIMDs from first vaccination 
at Day 1 up to 30 days post last vaccination.

Occurrence of any pIMDs during the period starting after 30 days post last 
vaccination up to study end.
10.3.
Determination of sample size
Assumptions used for the sample-size calculations come from data available from study 
Zoster-010 (112077) and the Prevenar13 assessment report [EMA, 2011] which provides 
a summary of the data used by the Committee for Medicinal Products for Human Use 
(CHMP) of the European Medicines Agency (EMA) to extend the indication of 
Prevenar13 to include adults aged 50 YOA.
The evaluation of the VRR following administration of two doses of HZ/su will be one of 
the co-primary objectives. The objective will be met if the LL of the 95% CI of VRR is 
equal to or more than 60% (criterion used in other studies in the HZ/su vaccine program). 
In the absence of correlate of protection or threshold level, this criterion ensures that an 
acceptable percentage of subjects meet GSK definition of responder (a 4-fold increase in 
anibody concentration/titer). Based on ZOSTER-010 (112077) study results, the vaccine 
response assumed in healthy adults (50 years of age) is 95%.
The humoral immune responses to the 13 serotypes of Prevenar13 one month post-dose 
and to HZ/su (anti-gE) one month post-dose 2 will be the two other co-primary objectives 
and will be compared to demonstrate non-inferiority of the Co-Ad to the Control groups.
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Non-inferiority with respect to the antibody responses to gE will be demonstrated if the 
ULs of the 95% CIs of the GMC ratios (Control group divided by Co-Ad group) are 
below the pre-defined clinical limit of 1.5 (based on variability of the assays used in the 
HZ/su vaccine program), one month post-dose 2 (Visit Month 3 for the Co-Ad group and 
Visit Month 5 for the Control group).
Non-inferiority with respect to the immune responses to the 13 vaccine pneumococcal 
serotypes will be demonstrated if the UL of the 95% CI of the MOPA GMTs ratios 
(Control group divided by Co-Ad group) is below the pre-defined clinical limit of 2 
(based on variability of the assays used ) for each of 13 pneumococcal vaccine serotypes, 
one month post-dose (Month 1).
No adjustment is needed for the type I error due to multiple comparison since fixed 
sequence test which allows full alpha propagation in pre-ordered family of hypotheses 
will be used.
The global power to meet all co-primary objectives with 410 evaluable subjects in Co-Ad 
and Control groups is approximately 91% (Table 23). Assuming that about 10% of the 
subjects enrolled are non-evaluable (e.g. due to dropout, bad sample), approximately 912 
subjects will need to be enrolled (456 subjects in each treatment group).
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Table 23
Power to demonstrate VRR objective and non-inferiority of the 
immunogenicity of HZ/su and Prevenar13 co-administered 
compared to Control group
Family 1: HZ/su: VVR*(1-sided test with alpha = 2.5%) 
Endpoint
Threshold
VR assumed
Total 
Power
VRR in Co-Ad group
0.60
95%
0.001%
99.99%
Family 2: HZ/su: non-inferiority* (1-sided test with alpha = 2.5%) N=410 
Endpoint
Standard deviation

Total 
Power
Anti-gE GMC ratio
0.35
1.5
0.001 %
99.99 %
Family 3: Prevenar13: Non-inferiority* (1-sided test with alpha = 2.5%)  N=410
Endpoint (13 vaccine 
pneumococcal serotypes)
Standard deviation

Total 
Power
3 GMT ratio
0.660 
2
0.001%
99.99%
19A GMT ratio
0.644 
2
0.001%
99.99%
1 GMT ratio
0.798 
2
0.029%
99.97%
18C GMT ratio
0.891 
2
0.203%
99.80%
4 GMT ratio
0.906 
2
0.260%
99.74%
6A GMT ratio
0.919 
2
0.320%
99.68%
5 GMT ratio
0.931 
2
0.383%
99.62%
19F GMT ratio
0.971 
2
0.664%
99.33%
6B GMT ratio
0.995 
2
0.891%
99.11%
7F GMT ratio
1.014 
2
1.107%
98.89%
9V GMT ratio
1.021 
2
1.194%
98.81%
14 GMT ratio
1.045 
2
1.530%
98.47%
23F GMT ratio
1.094 
2
2.398%
97.60%
Global to show non-inferiority
~9%
Global power
~91%
VRR: vaccine response rate; gE: Varicella Zoster Virus glycoprotein E; GMT: geometric mean titer; GMC: geometric 
mean concentration.
* Pass 12, alpha = 2.5%, for VRR: Exact test, for non-inferiority one-sided equivalence of means.
For gE: non-inferiority limit = 0.176 (=log10(1.5)), power under equal GMC
For each pneumococcal serotype: non-inferiority limit = 0.301 (=log10(2)), variability for each of the 13 vaccine 
pneumococcal serotype taken from the EMA assessment report for Prevenar13 and multiplied by 1.1, power 
under equal GMT.
10.4.
Cohorts for Analyses
10.4.1.
Total vaccinated cohort
The Total vaccinated cohort (TVC) will include all subjects with at least one vaccine 
administration documented:

The TVC for analysis of reactogenicity will include all subjects with at least one 
vaccine administered.

The TVC for analysis of safety will include all subjects with at least one vaccine 
administered.

The TVC for analysis of immunogenicity will include vaccinated subjects for whom 
immunogenicity data are available.
The TVC analysis will be performed per treatment actually administered (at Dose 1).
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10.4.2.
Per-protocol cohort for analysis of immunogenicity
The Per-protocol cohort for analysis of immunogenicity will include all evaluable 
subjects: 

who meet all eligibility criteria,

who comply with the procedures and intervals allowed for the analysis,

who do not meet any of the criteria for elimination during the study,

for whom data concerning immunogenicity endpoint measures are available.
10.5.
Derived and transformed data

Immunogenicity
The cut-off value is defined by the laboratory before the analysis and is described in 
Section 5.8.3.
10.5.1.
Handling of missing data
For the analysis of solicited symptoms, missing or non-evaluable measurements will not 
be imputed. Therefore, the analysis of the solicited symptoms based on the TVC will 
include only subjects/doses with documented safety data (i.e. symptom screen 
completed).
For the analysis of unsolicited AEs/SAEs/pIMDs/concomitant medication, all vaccinated 
subjects will be considered and subjects who did not report an event will be considered as 
subjects without an event.
For a given subject and a given immunogenicity measurement, missing or non-evaluable 
measurements will not be replaced. Therefore, a subject will be excluded from an 
analysis if all measurements are missing or non-evaluable.
10.6.
Analysis of demographics
Demographic characteristics (age, sex, race and ethnicity) will be tabulated per treatment 
group. 
The mean age (plus range and standard deviation [SD]) of the enrolled subjects, as a 
whole, and per treatment group will be calculated. The distribution of subjects enrolled 
among the study sites will be tabulated as a whole and per treatment group.
The same tabulations might be performed by age category if deemed necessary.
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10.7.
Analysis of immunogenicity
The primary analysis will be based on the per-protocol cohort for analysis of 
immunogenicity. If, in any study group, the percentage of enrolled subjects with 
serological results excluded from the per-protocol cohort for analysis of immunogenicity 
is 5% or more, a second analysis based on the Total vaccinated cohort will be performed 
to complement the per-protocol analysis.
10.7.1.
Humoral immune response

A seronegative subject is a subject whose antibodies concentration/titer is below the 
cut-off value (cut-off value is defined by the laboratory prior to the analysis).

A seropositive subject is a subject whose antibodies concentration/titer is greater 
than or equal to the assay cut-off value.

The seropositivity rate is defined as the percentage of seropositive subjects.

The VRR for anti-gE is defined as the percentage of subjects who have at least:

a 4-fold increase in the anti-gE antibodies concentration as compared to the pre-
vaccination anti-gE antibodies concentration, for subjects who are seropositive at 
baseline, or,

a 4-fold increase in the anti-gE antibodies concentration as compared to the anti-
gE antibodies cut-off value for seropositivity, for subjects who are seronegative 
at baseline.

The GMC/GMT calculations are performed by taking the anti-log of the mean of the 
log concentration transformations. Antibody concentrations below the cut-off of the 
assay will be given an arbitrary value equal to half the cut-off for the purpose of 
GMC/GMT calculation.
10.7.2.
Statistical considerations for confirmatory objectives
All analyses will be performed overall and by age stratum, if the number of subjects 
enrolled is sufficient in each stratum.
For the multiplicity adjustment, all hypotheses will be ranked into three families and one 
subfamily according to the power of test (Table 23). Fixed sequence testing which allows 
for full alpha propagation in pre-ordered hypotheses families will be applied in the 
following manner:
Family 1:
In the Co-Ad group, for anti-gE, at one month post-dose 2:

The VRR and 95% CI will be computed.
The objective is met if the LL of the 95% CI is 60%. 
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Family 2:
For anti-gE, at one month post-dose 2:

The 95% CI of the group GMCs ratio will be computed using an analysis of 
covariance (ANCOVA) model on the log10 transformation of the concentrations. 
The pre-vaccination log-transformed antibody concentrations will be included as 
continuous covariate and the ANCOVA model will include the vaccine group and 
age strata as fixed effects. 
In terms of concentrations, the Co-Ad group will be considered non-inferior to the 
Control group if the UL of the 95% CI for the GMC ratio of the Control group to the Co-
Ad group is <1.5.
Family 3:
For each vaccine pneumococcal serotype (according to the order in Table 23), one month 
post-dose:

The 95% CI of the group MOPA GMT ratios will be computed using an ANCOVA 
model on the log10 transformation of the titers. The pre-vaccination log-
transformed antibody titers will be included as a continuous covariate. The 
ANCOVA model will include the vaccine group and age strata as fixed effects. 
(Amended 30 January 2018)
In terms of MOPA GMTs, the Co-Ad group will be considered non-inferior to the Control 
group if the UL of the 95% CI for the MOPA GMTs ratio of the Control group to the Co-
Ad group is <2 for each of the 13 vaccine serotypes.
10.8.
Analysis of safety
The analysis for safety will be based on the TVC; all safety analyses may also be 
performed by age strata (50-59, 60-69 and ≥70 YOA).
When appropriate, tabulations will be presented overall and by time of occurrence 
relative to last vaccination (e.g. using windows such as Days 1 to 7, Days 1 to 30 and 
more than 30 days post-vaccination).
The results for the analysis of safety will be tabulated as follows:

The number and percentage of subjects with at least one local solicited AE, with at 
least one general solicited AE, and with any solicited AE during the 7-day follow-up 
period with exact 95% CIs after each vaccine dose and overall by vaccination group
will be provided;

The percentage of subjects reporting each individual solicited local and general AE 
during the solicited 7-day follow-up period will be tabulated with exact 95% CI;

For all solicited symptoms, the same tabulation will be performed for grade 3 
solicited AEs and for solicited general AEs with relationship to vaccination;
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
Number of days with each individual solicited local and general AE during the 
solicited 7-day follow-up period;

The proportion of subjects with at least one report of unsolicited AE classified by the 
MedDRA preferred term and reported up to 30 days after each vaccination will be 
tabulated with exact 95% CI;

The same tabulation will be performed for grade 3 unsolicited AEs and for 
unsolicited AEs with a relationship to vaccination. The proportion of AEs resulting 
in a medically attended visit will also be tabulated;

Total number/percentages of doses (per dose and overall) followed by AEs will be 
tabulated;

Number of subjects with pIMDs will be tabulated;

SAEs, including fatalities and withdrawal due to AE(s) will be described in detail.
10.9.
Interpretation of analyses
All co-primary objectives will be evaluated using a one-sided Type I error of 2.5% (as 
already justified by fixed sequential testing procedure, no alpha adjustment needed). The 
trial will be considered conclusive if all co-primary objectives criteria are met.
10.10.
Conduct of analyses
Any deviation(s) or change(s) from the original statistical plan outlined in this protocol 
will be described and justified in the final study report.
10.10.1.
Sequence of analyses
The analysis will be performed in the following steps:
1.
Analysis of the co-primary immunogenicity objectives will be performed at the end 
of the active phase on data as clean as possible. A confirmatory re-analysis will be 
done at the end of the study using the final database. In addition, analyses of 
secondary objectives will also be performed at the end of the active phase. 
(Amended 30 January 2018)..
2.
Analyses on safety data will be performed when all data up to study end (i.e., phone 
contact at Month 14 for Co-Ad group and phone contact at Month 16 for Control 
group) will be available and cleaned. (Amended 30 January 2018)
An integrated clinical study report containing all data will be written and made available 
to the investigators.
10.10.2.
Statistical considerations for interim analyses
No interim analyses are planned.
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11.
ADMINISTRATIVE MATTERS
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality, public disclosure requirements 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 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 other items, the: 

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents.
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits.
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform an eCRF review and a Source Document 
Verification (SDV). By SDV we understand verifying eCRF entries by comparing them 
with the source data that will be made available by the investigator for this purpose. 
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The Source Documentation Agreement Form describes the source data for the different 
data in the eCRF. This document should be completed and signed by the site monitor and 
investigator and should be filed in the 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. 
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. 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, 
otherwise, the minimum retention period will default to 25 years after completion of the 
study report.
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.
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11.5.
Posting of information on publicly available clinical trial 
registers and publication policy
GSK assures that the key design elements of this protocol will be posted on the GSK 
website and in publicly accessible database(s) such as clinicaltrials.gov, in compliance 
with the current regulations.
GSK also assures that results of this study will be posted on the GSK website and in 
publicly accessible regulatory registry(ies) within the required time-frame, in compliance 
with the current regulations. The minimal requirement is to have primary endpoint 
summary results disclosed at latest 12 months post primary completion date (PCD) and to 
have secondary endpoint disclosed at latest 12 months after the last subject last visit 
(LSLV) as described in the protocol.
As per EU regulation, summaries of the results of GSK interventional studies (phase I-
IV) in adult population conducted in at least one EU member state will be posted on 
publicly available EMA registers within 12 months of EoS (as defined in the protocol) in 
the concerned EU member state. However, where, for scientific reasons detailed in the 
protocol, it is not possible to submit a summary of the results one year in the concerned 
EU member state, the summary of results shall be submitted as soon as it is available. In 
this case, the protocol shall specify when the results are going to be submitted, together 
with a justification. 
GSK also aims to publish the results of these studies in searchable, peer reviewed 
scientific literature and follows the guidance from the International Committee of 
Medical Journal Editors.
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.
11.7.
Data Sharing
Under the framework of the SHARE initiative, results of GSK studies may be combined 
with non- GSK studies, to investigate further about the study product(s) and other 
product(s), and /or the disease/condition under investigation and related diseases and 
conditions.
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12.
COUNTRY SPECIFIC REQUIREMENTS
12.1.
Germany
Explanatory statement concerning Gender Distribution
(Article 7, paragraph 2 (12) of the German GCP ORDER)
EudraCT Number: 2017-001220-22
Study Identifier: 
204487 (ZOSTER-059 PRI)
Compound Number:GSK1437173A
Title of Study:
A Phase IIIB, randomized, open-label, multicenter clinical trial to 
assess the immunogenicity and safety of GSK Biologicals’ Herpes 
Zoster vaccine GSK1437173A when co-administered with 
Prevenar13™in adults aged 50 years and older.
There is no intention to conduct specific analyses investigating the relationship between 
gender of subjects and the immunogenicity and safety of GSK Biologicals’ lyophilized 
formulation of the Herpes Zoster (HZ) subunit (HZ/su) vaccine (GSK1437173A). The 
ratio of male to female subjects recruited into study Zoster-059 PRI is expected to be in 
line with the demographics of the population aged 50 years and older in the Member 
State.
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13.
REFERENCES
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; 
http://www.cdc.gov/ncbddd/birthdefects/documents/MACDPcode0807.pdf
Chlibek R, Bayas JM, Collins H, de la Pinta MLR, Ledent E, Mols JF, et al. Safety and 
Immunogenicity of an AS01-adjuvanted Varicella-zoster Virus Subunit Candidate 
Vaccine Against Herpes Zoster in Adults ≥50 Years of Age. J Infect Dis. 2013; 
208(12):1953-61.
Chlibek R, Smetana J, Pauksens K, Rombo L, Van den Hoek JAR, Richardus JH, et al. 
Safety and immunogenicity of three different formulations of an adjuvanted varicella-
zoster virus subunit candidate vaccine in older adults: A phase II, randomized, controlled 
study. Vaccine. 2014 3/26/;32(15):1745-53.
Chua JV, Chen WH. Herpes zoster vaccine for the elderly: boosting immunity. Aging 
health. 2010;6(2):169-176.
Cunningham, AL; Lal, H; Kovac, M; et al. Efficacy of the Herpes Zoster Subunit 
Vaccine in Adults 70 Years of Age or Older. N Engl J Med. 2016, 375 (11), 1019-1032.
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
EMA Prevenar13 pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) 
(Doc. Ref. EMEA/H/C/001104/II/0028), 2011 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Assessment_Report_-_Variation/human/001104/WC500119784.pdf
FDA, U.S. Department of Health and Human Services, Center for Biologics Evaluation 
and Research. Guidance for Industry: Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Version of 
September 2007.
Kawai K, Gebremeskel BG et al. Systematic review of incidence and complications of 
Herpes Zoster: towards a global perspective. BMJ Open. 2014; 4:e004833.
Lal H, Cunningham AL, Godeaux O et al. Efficacy of an Adjuvanted Herpes Zoster 
Subunit Vaccine in Older Adults. N Engl J Med. 2015; 372:2087-2096. 
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National Network for Immunization Information (NNii). Herpes Zoster. Updated: April 
2008. http://www.immunizationinfo.org/vaccines/shingles-herpes-zoster. Accessed on 17 
November 2012.
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.
Romero-Steiner S, Libutti D, Pais LB et al. Standardization of an Opsonophagocytic 
Assay for the Measurement of Functional Antibody Activity against Streptococcus 
pneumoniae Using Differentiated HL-60 Cells. Clin Diagn Lab Immunol. 1997;4(4):415-
422.
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.
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APPENDIX A
LABORATORY ASSAYS
Specific antibody measurements:
Anti-gE ELISA: Anti-gE antibody concentrations will be measured using an anti-gE 
ELISA. Diluted blood serum samples of study subjects will be added to microtiter wells 
pre-coated with gE antigen. Secondary peroxidase-conjugated anti-human Abs will be 
added, which bind to the primary human anti-gE Abs. After incubation of the microtiter 
wells with a chromogen substrate solution, the enzymatic reaction will be stopped. 
Optical densities will be recorded and anti-gE antibody concentrations are calculated 
from a standard curve. The assay cut-off is 97 mIU/mL. 
(Amended 30 January 2018)
Pneumococcal serotype antibodies OPA: Opsonophagocytic activity for antibodies 
against each of the pneumococcal serotype will be measured by an opsonophagocytosis 
mulitplex killing-assay (MOPA) using the HL 60 cell line as the phagocytic effector cell 
[Romero-Steiner, 1997]. The results will be presented as the dilution of serum (opsonic 
titer) able to sustain 50% killing of live pneumococci under the assay conditions.
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APPENDIX B
CLINICAL LABORATORIES
Table 24
GSK Biologicals’ laboratories
(Amended 30 January 2018)
Laboratory
Address
GSK Biological’s Clinical Laboratory 
Sciences, Rixensart 
Rue de l'Institut, 89 - B-1330 Rixensart – Belgium 
Table 25
Outsourced laboratories
Laboratory
Address
University of Alabama at 
Birmingham
Pathology Department of Professor, Moon H. 
Nahm, M.D, WHO Pneumococcal Serology 
Reference Laboratory, The University of Alabama 
at Birmingham, Bevill Building, Room 614 (BBRB 
614), 845 19th Street South, Birmingham AL, 
35294
Q2 Solutions Clinical Trials (US)
27027 Tourney Road, Suite 2E
Valencia, CA 91355
USA
Q2 Solutions Clinical Trials (UK)
Unit B1, Parkway West Industrial Estate
Cranford Lane – Heston, 
Middlesex TW5 9QA
UK
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APPENDIX C
AMENDMENTS AND ADMINISTRATIVE 
CHANGES TO THE PROTOCOL
GlaxoSmithKline Biologicals
Vaccine Value & Health Science (VVHS)
Protocol Amendment 1
eTrack study number 
and Abbreviated Title
204487 (ZOSTER-059 PRI)
EudraCT number
2017-001220-22
Amendment number:
Amendment 1
Amendment date:
30 October 2017
Co-ordinating author:
, Scientific Writer, contractor for GSK 
Biologicals
Rationale/background for changes:
!
Following the initial approval of the GlaxoSmithKline (GSK) Biologicals’ HZ/su 
vaccine, this protocol was amended to indicate that the Trademark is Shingrix. In 
addition, the term “candidate” vaccine has been replaced by “study” vaccine 
throughout the protocol in Sections 1.1, 1.3, 5.8.5 and 6.1; and the term 
“investigational” vaccine has been replaced by “study” vaccine in Sections 1.3.1 
and 1.3.3.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
TRADEMARKS:
Trademarks of the GSK group of companies
Generic description
Shingrix
Zoster Vaccine Recombinant, Adjuvanted
Section 1.1 1.1 Background:
GlaxoSmithKline (GSK) Biologicals’ candidatestudyvaccine (Shingrix) for the 
prevention of HZ is a recombinant subunit (su) vaccine consisting of VZV glycoprotein E 
(gE) as antigen and an adjuvant system AS01B. It has been evaluated in several studies in 
healthy adults and shown to elicit strong cellular and humoral immune responses. The 
safety and reactogenicity profile of the candidatestudy vaccine was also acceptable.
Please refer to the current Investigator Brochure (IB) for information regarding the pre-
clinical and clinical studies of GSK Biologicals’ candidatestudy HZ/su vaccine.
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GlaxoSmithKline Biologicals
Vaccine Value & Health Science (VVHS)
Protocol Amendment 2
eTrack study number 
and Abbreviated Title
204487 (ZOSTER-059 PRI)
EudraCT number
2017-001220-22
Amendment number:
Amendment 2
Amendment date:
30 January 2018
Co-ordinating author:
, Scientific Writer, contractor for GSK 
Biologicals
Contributing authors
!
, Clinical and Epidemiology 
Scientist G Clinical Research and Development 
Lead, Business & Decision Life Sciences for GSK 
Biologicals
!
, Clinical and Epidemiology Project 
Leader
!
, Study Delivery Lead, Synteract Inc. 
for GSK Biologicals
!
, Global Regulatory Affairs
!
, Clinical Safety 
representative
!
 Study Data Manager (Tata 
Consultancy Services for GSK Biologicals)
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Rationale/background for changes:
Major change
!
This amendment is in response to the Center for Biologics Evaluation and 
Research (CBER) comments on Protocol Amendment 1, received on 09-January-
2018, requesting clarification on 1. the adjustment for baseline titers in the 
computation of the Multiplex Opsonophagocytosis Assay (MOPA) Geometric 
Mean Titers (GMT) ratios (Section 10.7.2) and 2. time points for primary 
evaluations on co-primary immunogenicity objectives (Section 10.10.1).
Other changes
!
The tradename for pneumococcal polysaccharide conjugate vaccine (13-valent adsorbed)
in Canada has been corrected to Prevnar13 from Prevenar13.
!
The laboratory to be used for MOPA testing has been selected and is presented in 
Appendix B.
!
A typographical error in the estimated number of subjects in each age strata and 
study group has been corrected. Table 4 reflects the correct number of subjects for 
age stratification.
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections:
Protocol Amendment 2 Sponsor Signatory Approval
Sponsor signatory
Clinical and Epidemiology Project Leader (CEPL),
Zoster Program, Beligian Research and Development 
Center (RDC)
Clinical and Epidemiology Project Leader, 
Zoster Program, US Research and Development 
Center (RDC)
List of abbreviations:
CBER:
Center for Biologics Evaluation and Research 
CRO:
Contract Research Organization
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Trademarks
Trademarks not owned by the GSK group of 
companies 
Generic description
Prevenar13 (Trade name for Canada, Germany 
and Estonia)/ Prevnar13Trade name for 
Canada and United States)*
Wyeth Pharmaceuticals Inc./Pfizer Inc.
Pneumococcal polysaccharide conjugate 
vaccine (13-valent adsorbed)
Section 4.1 Number of subjects/centers
Table 4
Age Stratification
Group
Description
Estimated number of subjects
Co-Ad
Subjects 50 to 59 YOA
342 171
Subjects 60 to 69 YOA
342 171
Subjects 70 YOA
228 114
Control
Subjects 50 to 59 YOA
342 171
Subjects 60 to 69 YOA
342 171
Subjects 70 YOA
228 114
YOA: years of age.
Section 5.8.3 Laboratory assays
Serological assays for the determination of pneumococcal serotype antibodies will be 
performed by multiplex opsonophagocytosis assay (MOPA) at a GSK Biologicals’ 
laboratory or in a laboratory designated by GSK Biologicals using standardized and 
validated procedures (refer to Table 11).
The GSK Biologicals’/ contract research organizations’ (CRO) clinical laboratories 
have established a Quality System supported by procedures. The activities of GSK 
Biologicals’/ CROs’ clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. Clinical 
laboratories contracted by GSK also conform to Good Laboratory Practice guidelines 
and operate in compliance with regulatory standards.
Section 10.7.2 Statistical considerations for confirmatory objectives
Family 3:
The 95% CI of the group MOPA GMT ratios will be computed using an analysis of 
variance (ANCOVA) model on the log10 transformation of the concentrations/ titers. The 
pre-vaccination log-transformed antibody titers will be included as a continuous 
covariate. The ANCOVA model will include the vaccine group and age strata as fixed 
effects.
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Section 10.10.1 Sequence of analyses
The analysis will be performed in the following steps:
1.
Analyses after end of active phase at Visit Month 3 for Co Ad group and Visit 
Month 5 for Control group will be performed on data as clean as possible, in order to 
explore the demography as well as reactogenicity and safety. Analysis on the 
humoral response may also be performed at this point in time if the data is available..
These data will also be available for the purpose of public data disclosure.
Analysis of the co-primary immunogenicity objectives will be performed at the end 
of the active phase on data as clean as possible. A confirmatory re-analysis will be 
done at the end of the study using the final database. In addition, analyses of 
secondary objectives will also be performed at the end of the active phase.
2.
Analyses on immunogenicity and safety data will be performed when all data up to 
study end (i.e., phone contact at Month 14 for Co-Ad group and phone contact at 
Month 16 for Control group) will be available and cleaned. After the study 
completion, results from both analyses will be presented in a single study report.
APPENDIX A
LABORATORY ASSAYS
Specific antibody measurements:
Anti-gE ELISA: Anti-gE antibody concentrations will be measured using an anti-gE 
ELISA. Diluted blood serum samples of study subjects will be added to microtiter wells 
pre-coated with gE antigen. Secondary peroxidase-conjugated anti-human Abs will be 
added, which bind to the primary human anti-gE Abs. After incubation of the microtiter 
wells with a chromogen substrate solution, the enzymatic reaction will be stopped. 
Optical densities will be recorded and anti-gE antibody concentrations are calculated 
from a standard curve. The assay cut-off is 97 mIU/mL. The assay will be performed on 
human serum at GSK Biologicals’ laboratory or another laboratory designated by GSK 
Biologicals.
APPENDIX B
CLINICAL LABORATORIES
Table 24
GSK Biologicals’ laboratories
Laboratory
Address
GSK Biological’s Clinical Laboratory 
Sciences, Rixensart 
Rue de l'Institut, 89 - B-1330 Rixensart – Belgium 
GSK Biological’s Clinical Laboratory 
Sciences, Wavre Nord Noir Epine
Avenue Fleming, 20 B 1300 Wavre Belgium
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