Long-term Immunogenicity Study of Herpes Zoster Subunit Vaccine (GSK1437173A) and Immunogenicity and Safety Assessment of Revaccination With Two Additional Doses in Adults With Renal Transplant From Study ZOSTER-041
Phase: PHASE3
Conditions: Herpes Zoster
Sponsor: GlaxoSmithKline

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
1  
 
Cli ni c al St u d y Pr ot o c ol  
S p o n s or:  
Gl a x o S mit h Kli n e Bi ol o gi c al s S A  
R u e d e l’I n stit ut 8 9, 1 3 3 0 Ri x e n s art, B el gi u m  
Pri m ar y St u d y v acci ne  
a n d n u m ber   
Gla x o S mit h Kli ne Bi ol o gicals S A ( G S K) L y o p hilize d  
f or m ulati o n of t he Her pes Z oster s u b u nit  vacci ne 
( G S K 1 4 3 7 1 7 3 A) 
e Tr ac k st u d y n u m ber 
a n d a b bre vi ate d title  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 )  
I n vesti g ati o n al Ne w 
Dr u g (I N D) n u m ber  
B B -I N D 1 3 8 7 9 
E u dr a C T n u m ber  
2 0 1 9‐ 0 0 1 8 1 5‐ 2 1  
D ate of pr ot oc ol  
Fi nal Versi o n 1 : 0 7 J u ne 2 0 1 9  
D ate of pr ot oc ol 
a me n d me nt  
A me n d me nt 1 Fi nal: 1 5  J u ne 2 0 2 0  
Title  
L o n g -t er m i m m u n o ge ni cit y st u d y of Her pes Z oster s u b u nit 
vacci ne ( G S K 1 4 3 7 1 7 3 A) a n d i m m u n o ge ni cit y a n d safet y 
assess me nt of re v acci nati o n wit h t w o a d diti o nal d oses i n 
a d ults wit h re nal tra ns pla nt fr o m st u d y Z O S T E R -0 4 1.  
Det aile d  title 
A p hase III B, o pe n la bel, l o n g ter m f oll o w -u p st u d y t o 
assess persiste nce of i m m u ne res p o nses t o G S K’s H Z/s u 
vacci ne 4 -7 years aft er pri mar y v acci n ati o n; a n d 
i m m u n o ge nicit y a n d safet y assess me nt of re v acci n ati o n 
wit h 2 a d diti o nal d oses of H Z/s u vacci n e, a d mi nistere d 1 -2 
m o nt hs a part, 6 -8 years after pri mar y v acci nati o n of a d ults 
wit h re nal tra ns pla nt fr o m st u d y Z O S T E R -0 4 1.  
C o -or di n ati n g a ut h or  
 (M o dis Life Scie nces, c o ntract or f or G S K)  
C o ntri b uti n g a ut h ors  
( A me n de d: 1 5  J u ne  
2 0 2 0)  
•  
, 
, Se ni or Cli nical E x pert, Z oster 
•  
, Cli nical Researc h a n d De vel o p me nt 
Lea d , Z oster 
•  
, St u d y Statisticia n 
•  
, Lea d Statisticia n  
•  
, St u d y 
Deli ver y Lea d s 
•  
 La b orat or y St u d y M a na ger 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
2  
e Tr ac k st u d y n u m ber 
a n d a b bre vi ate d title  
2 1 2 3 4 0 (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0)  
I n vesti g ati o n al Ne w 
Dr u g (I N D) n u m ber  
B B -I N D 1 3 8 7 9 
E u dr a C T n u m ber  
2 0 1 9‐ 0 0 1 8 1 5‐ 2 1  
D ate of pr ot oc ol  
Fi nal Versi o n 1 : 0 7 J u ne 2 0 1 9 
D ate of pr ot oc ol 
a me n d me nt  
A me n d me nt 1 Fi nal: 1 5 J u ne 2 0 2 0  
Det aile d title  
A p hase III B, o pe n la bel, l o n g ter m f oll o w -u p st u d y t o 
assess persiste nce of i m m u ne res p o nses t o G S K’s H Z/s u 
vacci ne 4 -7 years aft er pri mar y v acci n ati o n; a n d 
i m m u n o ge nicit y a n d safet y assess me nt of re v acci n ati o n 
wit h 2 a d diti o nal d oses of H Z/s u vacci n e, a d mi nistere d 1 -2 
m o nt hs a part, 6 -8 years after pri mar y v acci nati o n of a d ults 
wit h re nal tra ns pla nt fr o m st u d y Z O S T E R -0 4 1.  
C o ntri b uti n g a ut h ors 
( C o nt d.) 
( A me n de d: 1 5 J u ne 
2 0 2 0)  
•  
, Cli nical 
Rea d o ut Tea m Lea ds  
•  
, S E R M 
E x pert Scie ntists  
•  
, O versi g ht Data 
Ma na gers  
•  
, Se ni or Ma na ger, Gl o bal Re g ulat or y 
Affairs  
•  
, Gl o bal Pate nt 
•  
 Cli nical a n d E pi de mi ol o g y Pr oject 
Lea d, Z oster Pr o gra m, U S R D C  
G S K Pr ot oc ol W S v 1 6. 0. 1  
© 2 0 1 9  G S K g r o u p of c o m p a nies or its lice ns or.  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
P P D
P P D
P P D
P P D
P P D
P P D

CONFIDENTIAL 
212340 (ZOSTER-073 EXT:041 Y4-10) 
Protocol Amendment 1 Final 
15-JUN-2020 
3 
Protocol Amendment 1 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
212340 (ZOSTER-073 EXT:041 Y4-10)  
IND number 
BB-IND 13879  
EudraCT number 
2019‐001815‐21  
Date of protocol amendment 
Amendment 1 Final: 15 June 2020 
Detailed Title  
A phase IIIB, open label, long term follow-up study 
to assess persistence of immune responses to GSK’s 
HZ/su vaccine 4-7 years after primary vaccination; 
and immunogenicity and safety assessment of 
revaccination with 2 additional doses of HZ/su 
vaccine, administered 1-2 months apart, 6-8 years 
after primary vaccination of adults with renal 
transplant from study ZOSTER-041.  
Sponsor signatory 
Anne Schuind, Clinical and Epidemiology Project 
Lead (CEPL) for Zoster, Clinical R&D 
 
 
Signature 
 
 
 
Date 
 
 
 
 
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4 
Protocol Amendment 1 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline Biologicals SA (GSK). 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.  
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study vaccine and other study-related duties and functions as described in 
the protocol. 
• 
To supervise any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site. 
• 
To ensure that any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site are qualified to perform those trial-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the subject.  
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).  
• 
To co-operate with a representative of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine, and more generally about his/her financial 
ties with the sponsor. GSK will use and disclose the information solely for the 
purpose of complying with regulatory requirements. 
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CONFIDENTIAL 
212340 (ZOSTER-073 EXT:041 Y4-10) 
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5 
Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
course of the study and for 1 year following completion of the study.  
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and other documents 
required by regulatory agencies for this study. 
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Protocol Amendment 1 Final 
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6 
eTrack study number and 
Abbreviated Title 
212340 (ZOSTER-073 EXT:041 Y4-10)  
IND number  
BB-IND 13879  
EudraCT number 
2019‐001815‐21 
Date of protocol amendment 
Amendment 1 Final: 15 June 2020 
Detailed Title 
A phase IIIB, open label, long term follow-up study 
to assess persistence of immune responses to GSK’s 
HZ/su vaccine 4-7 years after primary vaccination; 
and immunogenicity and safety assessment of 
revaccination with 2 additional doses of HZ/su 
vaccine, administered 1-2 months apart, 6-8 years 
after primary vaccination of adults with renal 
transplant from study ZOSTER-041.  
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
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CONFIDENTIAL 
212340 (ZOSTER-073 EXT:041 Y4-10) 
Protocol Amendment 1 Final 
15-JUN-2020 
7 
SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut 89, 1330 Rixensart, Belgium 
2. Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
3. Sponsor Study Monitor 
Refer to the local study contact information document. 
4. Sponsor Study Contact for Reporting of a Serious Adverse Event 
GSK Central Back-up Study Contact for Reporting SAEs: refer to protocol Section 
12.5.10.3  
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
GSK Central Safety Physician and Back-up Phone contact: refer to protocol Section 
8.4.4.1. 
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8 
PROTOCOL AMENDMENT 1 SUMMARY OF CHANGES TABLE 
Table 1 
Document history 
Document 
Date 
Amendment 1 
15-JUN-2020 
Protocol Version 1 
07-JUN-2019 
Amendment 1: 15-JUN-2020 
Overall rationale for the current Amendment: 
The purpose of the amendment is to: 
• 
Outline measures to be applied during special circumstances (e.g., COVID-19 
pandemic), to protect participant’s welfare and safety, and, as far as possible, to 
ensure the potential benefit to the participant and promote study integrity.  
• 
Define study procedures / assessments to allow participation of non-revaccinated 
subjects in an extended long-term follow-up phase. 
• 
Minor corrections and clarifications 
Table 2 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief rationale 
Section 8.1.16 Study 
procedures during special 
circumstances  
Added new 
To provide guidance on adapting study 
procedures during special 
circumstances, such as COVID-19 
pandemic 
Across the document, including 
objectives and endpoints 
sections 
Revised text or added new text for 
non-revaccinated subjects 
To nuance differences in study 
procedures / assessments for non-
revaccinated subjects 
Amended text is indicated in bold italics in the body of the protocol. Detailed description 
of the main change is provided in Appendix 9.  
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9 
TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT 1 SPONSOR SIGNATORY APPROVAL ............................. 3 
PROTOCOL AMENDMENT 1 INVESTIGATOR AGREEMENT ....................................... 4 
SPONSOR INFORMATION ............................................................................................ 7 
PROTOCOL AMENDMENT 1 SUMMARY OF CHANGES TABLE .................................. 8 
1. 
SYNOPSIS ............................................................................................................. 16 
2. 
SCHEDULE OF ACTIVITIES (SOA) ....................................................................... 21 
3. 
INTRODUCTION .................................................................................................... 26 
3.1. Study rationale ....................................................................................... 26 
3.2. Background ............................................................................................ 28 
3.2.1. 
Herpes Zoster .............................................................................. 28 
3.2.2. 
Herpes Zoster in Solid Organ Transplant subjects ....................... 28 
3.3. Benefit/Risk assessment ........................................................................ 29 
3.3.1. 
Risk assessment .......................................................................... 30 
3.3.2. 
Benefit assessment ..................................................................... 32 
3.3.3. 
Overall Benefit: Risk conclusion ................................................... 32 
4. 
OBJECTIVES AND ENDPOINTS ........................................................................... 32 
5. 
STUDY DESIGN .................................................................................................... 36 
5.1. Scientific rationale for study design......................................................... 36 
5.2. Scientific rationale for the non-use of control group ................................ 37 
5.3. Overall design ........................................................................................ 38 
5.4. Number of subjects ................................................................................. 40 
5.5. Subject and study completion ................................................................. 41 
6. 
STUDY POPULATION ........................................................................................... 41 
6.1. Inclusion criteria...................................................................................... 41 
6.1.1. 
Inclusion criteria for enrollment (to be checked at Visit 1) ............ 41 
6.1.2. 
Inclusion criteria for revaccination (to be checked at 
Visit 3) ......................................................................................... 42 
6.2. Exclusion criteria .................................................................................... 42 
6.2.1. 
Exclusion criteria for enrollment (to be checked at Visit 1) ........... 42 
6.2.2. 
Exclusion criteria for revaccination (to be checked at 
Visit 3) ......................................................................................... 43 
6.2.3. 
Other exclusion criteria for revaccination ..................................... 44 
6.3. Criteria for temporary delay for revaccination ......................................... 44 
7. 
TREATMENTS ....................................................................................................... 45 
7.1. Treatments administered ........................................................................ 45 
7.2. Method of treatment assignment ............................................................ 46 
7.2.1. 
Subject identification .................................................................... 46 
7.2.2. 
Randomization of treatment ......................................................... 46 
7.2.3. 
Allocation of subjects to CMI sub-cohort ...................................... 46 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
1 0  
7. 3.  Bli n di n g a n d u n bli n di n g ........................................................................... 4 6  
7. 4.  H a n dli n g, st or a g e a n d r e pl a c e m e nt of st u d y v a c ci n e  .............................. 4 7  
7. 4. 1.  
St or a g e a n d h a n dli n g of st u d y v a c ci n e  ........................................ 4 7  
7. 4. 2.  
R e pl a c e m e nt of u n u s a bl e v a c ci n e d o s e s  ..................................... 4 7  
7. 5.  C o n c o mit a nt m e di c ati o n( s)/ pr o d u ct( s) a n d c o n c o mit a nt 
v a c ci n ati o n s  ......................................................................................... 4 8  
7. 5. 1.  
R e c or di n g of c o n c o mit a nt m e di c ati o n s/ pr o d u ct s a n d 
c o n c o mit a nt v a c ci n ati o n s  ............................................................. 4 8  
7. 5. 2.  
C o n c o mit a nt m e di c ati o n s/ pr o d u ct s/ v a c ci n e s t h at m a y l e a d 
t o t h e eli mi n ati o n of a s u bj e ct fr o m p er-pr ot o c ol a n al y s e s  ............ 4 9  
7. 6.  I nt er c urr e nt m e di c al c o n diti o n s t h at m a y l e a d t o eli mi n ati o n of a 
s u bj e ct fr o m p er -pr ot o c ol a n al y s e s  ....................................................... 5 0  
7. 7.  C o ntr ai n di c ati o n s t o s u b s e q u e nt v a c ci n e a d mi ni str ati o n  ......................... 5 0  
7. 8.  Tr e at m e nt aft er c o m pl eti o n of t h e st u d y  .................................................. 5 1  
8.  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ..................................................... 5 1  
8. 1.  G e n er al st u d y a s p e ct s  ............................................................................ 5 2  
8. 1. 1.  
I nf or m e d c o n s e nt ......................................................................... 5 2  
8. 1. 2.  
C oll e cti o n of d e m o gr a p hi c d at a  .................................................... 5 2  
8. 1. 3.  
M e di c al hi st or y  ............................................................................. 5 2  
8. 1. 4.  
I nt eri m m e di c al hi st or y ................................................................. 5 3  
8. 1. 5.  
R e c or d tr a n s pl a nt -s p e cifi c i nf or m ati o n i n c a s e of n e w 
tr a n s pl a nt r e c ei v e d si n c e t h e l a st vi sit i n Z O S T E R-0 4 1.  ............... 5 3  
8. 1. 6.  
P h y si c al e x a mi n ati o n s a n d hi st or y dir e ct e d p h y si c al 
e x a mi n ati o n  ................................................................................. 5 5  
8. 1. 7.  
Pr e g n a n c y t e st  ............................................................................. 5 5  
8. 1. 8.  
Pr e -r e v a c ci n ati o n b o d y t e m p er at ur e ............................................ 5 5  
8. 1. 9.  
R e c or d s er u m cr e ati ni n e m e a s ur e s  ............................................. 5 6  
 
 ........................................................ 5 7  
8. 1. 1 1.  
R e c or d a n y c o n c o mit a nt m e di c ati o n s/ v a c ci n ati o n s a n d 
a n y i nt er c urr e nt m e di c al c o n diti o n s  .............................................. 5 7  
8. 1. 1 2.  
D at a c oll e cti o n  ............................................................................. 5 7  
8. 1. 1 3.  
R e c or d pr e g n a n ci e s a n d pr e g n a n c y o ut c o m e s  ............................ 5 8  
8. 1. 1 4.  
R e n al all o gr aft r ej e cti o n  ............................................................... 5 8  
8. 1. 1 5.  
A d -h o c  H Z vi sit a n d p h o n e c all f or e v al u ati o n of s u s p e ct e d 
H Z  ................................................................................................ 6 0  
8. 1. 1 6.  
St u d y pr o c e d ur e s d uri n g s p e ci al cir c u m st a n c e s 
( A m e n d e d: 1 5 J u n e 2 0 2 0) ........................................................... 6 1  
8. 2.  Effi c a c y a s s e s s m e nt s  ............................................................................. 6 3  
8. 3.  I m m u n o g e ni cit y a s s e s s m e nt s ................................................................. 6 3  
8. 3. 1.  
U s e of s p e cifi e d st u d y m at eri al s  .................................................. 6 4  
8. 3. 2.  
Bi ol o gi c al s a m pl e s  ....................................................................... 6 4  
8. 3. 3.  
L a b or at or y a s s a y s  ....................................................................... 6 6  
8. 3. 4.  
B i ol o gi c al s a m pl e s e v al u ati o n ...................................................... 6 8  
8. 3. 5.  
I m m u n ol o gi c al c orr el at e s of pr ot e cti o n ......................................... 6 9  
8. 4.  S af et y A s s e s s m e nt s  ............................................................................... 6 9  
8. 4. 1.  
S af et y d efi niti o n s  ......................................................................... 6 9  
8. 4. 2.  
T i m e p eri o d a n d fr e q u e n c y f or c oll e cti n g A E a n d s eri o u s 
a d v er s e e v e nt ( S A E) i nf or m ati o n  ................................................. 6 9  
8. 4. 3.  
M et h o d of d et e cti n g A E s a n d S A E s  ............................................. 7 1  
8. 4. 4.  
R e p orti n g of s eri o u s a d v er s e e v e nt s, pr e g n a n ci e s, a n d 
ot h er e v e nt s  ................................................................................. 7 1  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

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8.4.5. 
Follow-up of AEs and SAEs ......................................................... 72 
8.4.6. 
Treatment of adverse events ....................................................... 73 
8.4.7. 
Subject card ................................................................................. 73 
8.4.8. 
Evaluation and confirmation of suspected HZ cases .................... 73 
9. 
DISCONTINUATION CRITERIA ............................................................................. 76 
9.1. Discontinuation from the study ................................................................ 76 
9.2. Discontinuation of study vaccine ............................................................. 77 
9.3. Lost to follow-up ..................................................................................... 78 
10. STATISTICAL CONSIDERATIONS ........................................................................ 78 
10.1. Sample size determination ..................................................................... 78 
10.1.1. 
Sample size calculation ............................................................... 78 
10.2. Populations for analyses ......................................................................... 79 
10.3. Statistical analyses ................................................................................. 79 
10.3.1. 
Subjects disposition ..................................................................... 79 
10.3.2. 
Demography and baseline characteristics analyses ..................... 80 
10.3.3. 
Immunogenicity analyses ............................................................. 80 
10.3.4. 
Safety analyses ........................................................................... 84 
10.3.5. 
Interim analyses ........................................................................... 86 
10.4. Sequence of analyses ............................................................................ 86 
11. REFERENCES ....................................................................................................... 87 
12. APPENDICES ........................................................................................................ 90 
12.1. Appendix 1: Abbreviations, glossary of terms and trademarks ................ 90 
12.1.1. 
List of abbreviations ..................................................................... 90 
12.1.2. 
Glossary of terms ......................................................................... 93 
12.1.3. 
Trademarks ................................................................................. 98 
12.2. Appendix 2: Clinical laboratory tests ....................................................... 99 
12.2.1. 
Clinical laboratory tests ................................................................ 99 
12.2.2. 
Ascertainment of HZ CASES including PCR testing 
algorithm to classify suspected HZ cases .................................. 100 
12.3. Appendix 3: Clinical laboratories ........................................................... 103 
12.4. Appendix 4: Study governance considerations ..................................... 104 
12.4.1. 
Regulatory and ethical considerations ....................................... 104 
12.4.2. 
Financial disclosure ................................................................... 104 
12.4.3. 
Informed consent process .......................................................... 105 
12.4.4. 
Data protection .......................................................................... 105 
12.4.5. 
Committees structure ................................................................. 106 
12.4.6. 
Publication policy ....................................................................... 107 
12.4.7. 
Dissemination of clinical study data ........................................... 107 
12.4.8. 
Data quality assurance .............................................................. 108 
12.4.9. 
Source documents ..................................................................... 109 
12.4.10. Study and site closure ................................................................ 109 
12.5. Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting ................................... 110 
12.5.1. 
Definition of AE .......................................................................... 110 
12.5.2. 
Definition of SAE ........................................................................ 111 
12.5.3. 
Solicited adverse events ............................................................ 112 
12.5.4. 
Unsolicited adverse events ........................................................ 112 
12.5.5. 
Adverse events of special interest .............................................. 113 
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12.5.6. 
COVID-19 (Amended: 15 June 2020) ........................................ 117 
12.5.7. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events .......................................................................... 117 
12.5.8. 
Events or outcomes not qualifying as adverse events or 
serious adverse events .............................................................. 118 
12.5.9. 
Detecting and recording adverse events, serious adverse 
events and pregnancies ............................................................. 119 
12.5.10. Reporting of SAEs, pregnancies, and other events .................... 125 
12.5.11. Updating of SAE, pregnancy, and AESI information after 
removal of write access to the subject’s eCRF ........................... 126 
12.5.12. Follow-up of adverse events, serious adverse events, and 
pregnancies ............................................................................... 127 
12.6. Appendix 6: Contraceptive guidance and collection of pregnancy 
information 
129 
12.6.1. 
Definitions .................................................................................. 129 
12.6.2. 
Contraception guidance ............................................................. 130 
12.6.3. 
Collection of pregnancy information ........................................... 131 
12.7. Appendix 8: Country-specific requirements ........................................... 132 
12.8. Appendix 9: Case Definition for COVID-19 Coronavirus Infection 
(Amended: 15 June 2020) .................................................................. 133 
12.9. Appendix 10: Amendments and Administrative Changes to the 
Protocol .............................................................................................. 134 
 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
1 3  
LI S T O F T A B L E S  
P A G E  
T a bl e 1  
D o c u m e nt hi st or y  ..................................................................................... 8  
T a bl e 2  
Li st of m ai n c h a n g e s i n t h e pr ot o c ol a n d t h eir r ati o n al e ............................ 8  
T a bl e 3  
S c h e d ul e of a cti viti e s .............................................................................. 2 1  
T a bl e 4  
I nt er v al s b et w e e n st u d y vi sit s ................................................................. 2 6  
T a bl e 5  
St u d y o bj e cti v e s a n d e n d p oi nt s ( A m e n d e d: 1 5 J u n e 2 0 2 0)  .................... 3 2  
T a bl e 6  
St u d y gr o u p, tr e at m e nt a n d e p o c h s f or e s e e n i n t h e st u d y  ...................... 3 9  
T a bl e 7  
Tr e at m e nt s a d mi ni st er e d  ........................................................................ 4 5  
T a bl e 8  
I nt er v al s b et w e e n st u d y vi sit s d uri n g s p e ci al cir c u m st a n c e s 
( A m e n d e d: 1 5 J u n e 2 0 2 0) ...................................................................... 6 3  
T a bl e 9  
Bi ol o gi c al s a m pl e s  ................................................................................. 6 6  
T a bl e 1 0  
H u m or al I m m u nit y ( A nti b o d y d et er mi n ati o n)  ........................................... 6 6  
T a bl e 1 1  
C ell -m e di at e d I m m u nit y ( C MI) u si n g c yt o ki n e fl o w c yt o m etr y  ................. 6 7  
T a bl e 1 2  
M ol e c ul ar Bi ol o g y ( P C R t e st s)  ................................................................ 6 7  
 
 6 7  
T a bl e 1 4  
I m m u n ol o gi c al r e a d-o ut s  ........................................................................ 6 8  
T a bl e 1 5  
E v al u ati o n of s u s p e ct e d H Z c a s e s  ......................................................... 6 9  
T a bl e 1 6  
R e p orti n g p eri o d s f or c oll e cti n g s af et y i nf or m ati o n  ................................. 7 0  
T a bl e 1 7  
Ti m efr a m e s f or s u b mitti n g s eri o u s a d v er s e e v e nt, pr e g n a n c y a n d 
ot h er e v e nt s r e p ort s t o G S K  ................................................................... 7 1  
T a bl e 1 8  
C o nt a ct i nf or m ati o n f or r e p orti n g of s eri o u s a d v er s e e v e nt s 
( S A E s), A E SI s a n d pr e g n a n ci e s ............................................................. 7 2  
T a bl e 1 9  
G S K l a b or at ori e s  .................................................................................. 1 0 3  
T a bl e 2 0  
O ut s o ur c e d l a b or at ori e s  ....................................................................... 1 0 3  
T a bl e 2 1  
S oli cit e d l o c al a d v er s e e v e nt s  .............................................................. 1 1 2  
T a bl e 2 2  
S oli cit e d g e n er al a d v er s e e v e nt s  .......................................................... 1 1 2  
T a bl e 2 3  
Li st of p ot e nti al i m m u n e -m e di at e d di s e a s e s  ......................................... 1 1 4  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

CONFIDENTIAL 
212340 (ZOSTER-073 EXT:041 Y4-10) 
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15-JUN-2020 
14 
Table 24 
Intensity scales for solicited adverse events ......................................... 122 
Table 25 
Highly Effective Contraceptive Methods ............................................... 130 
 
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212340 (ZOSTER-073 EXT:041 Y4-10) 
Protocol Amendment 1 Final 
15-JUN-2020 
15 
LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 38 
Figure 2 
Algorithm for HZ case definition by PCR .............................................. 102 
 
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212340 (ZOSTER-073 EXT:041 Y4-10) 
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16 
1. 
SYNOPSIS 
Indication:  
The target indication for Shingrix is prevention of Herpes Zoster (HZ) and related 
complications in adults aged 50 years and older, and in immunocompromised adults aged 
18 years and older. 
Rationale: 
In the study ZOSTER-041, GSK’s adjuvanted recombinant HZ subunit vaccine (HZ/su) 
demonstrated a clinically acceptable safety profile and induced significant and durable 
humoral and cell-mediated immune responses up to 1 year of follow-up when given as a 
2-dose primary vaccination series, 1 to 2-month apart, in renal transplant (RT) subjects 
(18 years of age [YOA]) taking daily chronic immunosuppressive (CIS) therapy [Vink, 
2019]. 
Study ZOSTER-073 is designed to provide data on the persistence of HZ/su vaccine-
induced immune response at 4 – 7 years after a 2-dose primary HZ/su vaccination in RT 
subjects on CIS therapy. This study will also investigate the immune response after 
revaccination with HZ/su vaccine.  
In studies in subjects 50 YOA, a single revaccination dose of HZ/su was shown to boost 
the HZ/su immune responses when given at 10 years after the 2-dose primary vaccination 
series [ZOSTER-060 study]. In a CIS-treated IC population, a single revaccination dose 
might be insufficient and 2 additional doses may be required to boost and maintain the 
immune response to HZ. 
Therefore, study ZOSTER-073 is designed to assess the immunogenicity and safety of 
two revaccination doses of HZ/su, when given 1-2 month apart, approximately 7 years 
after primary vaccination of RT subjects taking daily CIS therapy.  
Study ZOSTER-073 will provide insights into HZ/su-induced immune responses in the 
RT population and, potentially, in other immunocompromised populations including 
SOT, AID, IID subjects receiving CIS.  
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212340 (ZOSTER-073 EXT:041 Y4-10) 
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17 
Objectives and Endpoints (Amended: 15 June 2020):  
Objectives 
Endpoints 
Primary 
LTFU phase - Immunogenicity 
assessment  
• 
To evaluate persistence of 
humoral immunity after primary 
vaccination course. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by ELISA at Day 1, 
Month 12 and Month 24. 
Revaccination active phase - 
Immunogenicity assessment 
• 
To evaluate humoral immunity of 
HZ/su vaccine post-revaccination 
Doses 1 & 2. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by ELISA at pre-
revaccination (Month 24) and at 1-month post-revaccination Dose 1 
(Month 25) and Dose 2 (Month 26). 
Secondary 
LTFU phase - Immunogenicity 
assessment 
• 
To evaluate persistence of 
cellular immunity after primary 
vaccination course. 
In CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T-cells expressing two or more 
markers such as IFN-γ, IL-2, TNF-α, CD40L as determined by ICS at 
Day 1, Month 12 and Month 24. 
LTFU phase - safety assessment 
• 
To evaluate safety of HZ/su 
vaccine from the study ZOSTER-
041 last visit to study ZOSTER-
073 Visit 3. 
In all subjects: 
• 
Related-SAEs 
− 
Occurrence of SAEs related to primary vaccination as assessed 
by the investigator from the study ZOSTER-041 last visit (Month 
13) to study ZOSTER-073 Visit 3 (Month 24). 
• 
HZ episodes 
− 
Occurrence of suspected or confirmed HZ cases from the study 
ZOSTER-041 last visit (Month 13) to study ZOSTER-073 Visit 1 
(Day 1).  
− 
Occurrence of confirmed HZ cases from Day 1 through Month 
24. 
• 
AESIs 
− 
Occurrence of suspected or biopsy-proven allograft rejections 
from the study ZOSTER-041 last visit (Month 13) to study 
ZOSTER-073 Visit 1 (Day 1).  
− 
Occurrence of biopsy-proven allograft rejections from Day 1 
through Month 24. 
• 
Allograft function for episode(s) of allograft rejection. 
− 
Occurrence of allograft dysfunction through assessment of all 
clinically obtained serum creatinine measures from 2 months 
prior to an episode of biopsy-proven rejection and up to 2 months 
after rejection resolution and cessation of therapeutic 
immunosuppressive therapy for the time period from study 
ZOSTER-041 last visit (Month 13) to study ZOSTER-073 Visit 3 
(Month 24).  
• 
Allograft function for episode(s) of HZ 
− 
Occurrence of allograft dysfunction through assessment of all 
clinically obtained serum creatinine measures from 2 months 
prior to an episode of HZ and up to 2 months after HZ rash 
resolution for the time period from study ZOSTER-041 last visit 
(Month 13) to study ZOSTER-073 Visit 3 (Month 24). 
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CONFIDENTIAL 
212340 (ZOSTER-073 EXT:041 Y4-10) 
Protocol Amendment 1 Final 
15-JUN-2020 
18 
Objectives 
Endpoints 
Revaccination active phase - 
Immunogenicity assessment 
• 
To evaluate cell-mediated 
immunity post- revaccination 
Doses 1 & 2. 
In revaccinated subjects in CMI sub-cohort: 
 
• 
Frequencies of gE-specific CD4+ T-cells expressing two or more 
markers such as IFN-γ, IL-2, TNF-α, CD40L as determined by ICS at 
pre-vaccination (Month 24) and at 1-month post-revaccination Dose 1 
(Month 25) and Dose 2 (Month 26). 
Revaccination follow-up phase – 
Immunogenicity assessment 
• 
To evaluate persistence of 
humoral and cell-mediated 
immune responses post-
revaccination Dose 2. 
In all revaccinated subjects: 
• 
Anti-gE antibody concentrations as determined by ELISA at 12 months 
and 24 months post-revaccination Dose 2. 
In revaccinated subjects in CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T- cells expressing two or more 
markers such as IFN-γ, IL-2, TNF-α, CD40L as determined by ICS at 
12 months and 24 months post-revaccination Dose 2 in a CMI sub-
cohort of subjects. 
Revaccination active and follow-up 
phases - Safety assessment 
• 
To evaluate reactogenicity and 
safety of the HZ/su vaccine after 
each revaccination. 
In all revaccinated subjects: 
• 
Solicited local and general AEs: 
− 
Occurrence, duration and intensity of solicited local AEs within 7 
days after each revaccination (i.e., the day of revaccination and 6 
subsequent days);  
− 
Occurrence, duration and intensity of solicited general AEs within 
7 days after each revaccination dose (i.e., the day of 
revaccination and 6 subsequent days) and causal relationship to 
revaccination by investigator assessment.  
• 
Unsolicited AEs  
− 
Occurrence, intensity of unsolicited AEs during 30 days after 
each revaccination (i.e., the day of revaccination and 29 
subsequent days) and causal relationship to revaccination by 
investigator assessment.  
• 
SAEs  
− 
Occurrence of SAEs (including fatal SAEs) from Dose 1 of 
revaccination (Month 24) until 12 months post-last revaccination 
dose (Month 37).  
− 
Occurrence of related-SAEs (including related-fatal SAEs) as per 
investigator assessment from Dose 1 of revaccination (Month 24) 
up to study end (Month 49).  
• 
AESIs   
− 
Occurrence of all biopsy-proven allograft rejections from Dose 1 
of revaccination (Month 24) up to study end (Month 49) and 
causal relationship to revaccination by investigator assessment.  
− 
Occurrence of pIMDs from Dose 1 of revaccination (Month 24) 
up to 12 months post-last revaccination dose (Month 37) and 
causal relationship by investigator assessment. 
• 
HZ episodes  
− 
Occurrence of confirmed HZ cases from Dose 1 of revaccination 
(Month 24) up to study end (Month 49).  
• 
Allograft function following revaccination  
− 
Occurrence of allograft dysfunction through assessment of all 
clinically obtained serum creatinine measures from 3 months 
before the first revaccination dose until 3 months after the last 
revaccination dose. 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
1 9  
O bj e cti v e s  
E n d p oi nt s  
•  
All o gr aft f u ncti o n f or e pis o d e(s) of all o gr aft r ej ecti o n   
− 
Occ urr e nc e of all o gr aft dysf u ncti o n t hr o u g h ass ess m e nt of all 
cli nic ally o bt ai n e d s er u m cr e ati ni n e m e as ur es fr o m 2 m o nt hs 
pri or t o a n e pis o d e of  bi o psy -pr ov e n r ej ecti o n a n d u p t o 2 m o nt hs 
aft er r ej ecti o n r es ol uti o n a n d c ess ati o n of t h er a p e utic of 
i m m u n os u p pr essiv e t h er a py.  
•  
All o gr aft f u ncti o n f or e pis o d e(s) of H Z  
− 
Occ urr e nc e of all o gr aft dysf u ncti o n t hr o u g h ass ess m e nt of all 
cli nic ally o bt ai n e d s er u m cr e ati ni n e m e as ur es fr o m 2 m o nt hs 
pri or t o a n e pis o d e of H Z a n d u p t o 2 m o nt hs aft er H Z r es ol uti o n.  
C MI = C ell -M e di at e d I m m u nity;
 E LI S A  = Enzy m e Li nk e d I m m u n os or b e nt Ass ay; 
g E  =  glyc o pr ot ei n E; 
; I C S =  I ntr ac ell ul ar Cyt oki n e St ai ni n g; I L-2  = I nt erl e uki n 2; 
; 
; 
 
T N F α  = T u m or N ecr osis F act or -al p h a; I F N γ = I nt erf er o n -g a m m a ; A E = A dv ers e Ev e nt; S A E  = Seri o us A dv ers e Ev e nt; 
H Z  = H er p es Z ost er;  A E SI   =  A dv ers e Ev e nt of Sp eci al  I nt er est; pI M D s  =  p ot e nti al I m m u n e -M e di at e d Dis e as es  
*T o b e p erf or m e d by a  c e ntr al l a bor at ory  if d e e m e d n ec ess ary. 
( A m e n d e d: 1 5 J u n e 2 0 2 0)  
 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI
C CI
C CI
C CI
C CI

CONFIDENTIAL 
212340 (ZOSTER-073 EXT:041 Y4-10) 
Protocol Amendment 1 Final 
15-JUN-2020 
20 
Overall Design: 
 
HZ/su = Herpes zoster subunit; LTFU = Long term follow-up; Vacc 1-2 = Vaccination dose 1 & 2; re-Vacc 1-2  = Revaccinations dose 1 & 2 
*The second dose of revaccination (Visit 4, Month 25) will be administered 1 to 2 months after the first revaccination dose. 
**Visit 5 (Month 26), Visit 6 (Month 37) and Visit 7 (Month 49) will occur 1, 12 and 24 months after the second revaccination, respectively. 
$Phone contact will occur about 35 days before Visit 3 (Month 24) to remind female subjects of childbearing potential to use adequate contraception. 
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212340 (ZOSTER-073 EXT:041 Y4-10) 
Protocol Amendment 1 Final 
15-JUN-2020 
21 
2. 
SCHEDULE OF ACTIVITIES (SOA) 
Table 3 
Schedule of activities 
Epoch 
Epoch 001  
Epoch 002 
 
Study Phase 
Long-Term Follow-up Phase 
Revaccination Phase 
Follow-up Phase 
 
Type of contact  
Visit 1 
Visit 2 
PC1a 
Visit 3b 
Visit 4c, h 
Visit 5c, h 
Visit 6c 
Visit 7c 
Ad-hoc HZ Visit d 
Timepoints by study Year 
Day 1 
Year 1 
35 days 
prior Year 2 
Year 2 
Year 2 + 1 
month 
Year 2 + 2 
months 
Year 3 + 2 
months 
Year 4 + 2 
months 
 
Timepoints by study Month 
Day 1 
Month 12 
Day 695 
Month 24 
Month 25 
Month 26 
Month 37 
Month 49 
Event driven 
Timepoints associated to Long-Term 
Follow-up Phase (Post-primary 
vaccination in study ZOSTER-041) 
About 4-5 
years post-
last HZ/su 
dose 
About 5-6 
years post-
last HZ/su 
dose 
About 6-7 years post-last 
HZ/su dose 
 
 
 
 
 
Timepoints associated to Revaccination 
Phase in study ZOSTER-073  
 
Pre-Revacc 1 Post-Revacc 1 
Post-Revacc 2 
 
Informed consent 
(section 12.4.3) 
● 
 
 
●* f 
 
 
 
 
 
Collect demographic data 
(section 8.1.2) 
● 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria for 
enrollment (section 6.1.1 and 6.2.1) 
● 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria for 
revaccination (section 6.1.2 and 6.2.2) 
 
 
 
●* 
 
 
 
 
 
Medical history including medications, 
vaccinations, HZ cases, pIMDs and RT 
rejections (section 8.1.3) 
● 
 
 
 
 
 
 
 
 
Interim medical history (section 8.1.4) 
(Amended: 15 June 2020) 
 
O 
 
O 
O 
O 
O 
O 
 
Record transplant specific information, if 
subject received a new transplant since the 
last visit in ZOSTER-041 (section 8.1.5) 
● 
 
 
 
 
 
 
 
 
212340 | Protocol Amendment 1 24 Jun 2020 | TMF-1734453 | 1.0

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
2 2  
E p o c h  
E p o c h 0 0 1  
E p o c h 0 0 2  
 
St u d y P h a s e  
L o n g -T er m F oll o w -u p P h a s e  
R e v a c ci n ati o n P h a s e  
F oll o w -u p P h a s e  
 
T y p e of c o nt a ct   
Vi sit 1  
Vi sit 2  
P C 1 a 
Vi sit 3 b 
Vi sit 4 c , h 
Vi sit 5 c , h 
Vi sit 6 c 
Vi sit 7 c 
A d -h o c  H Z Vi sit d 
Ti m e p oi nt s b y st u d y Y e ar  
D a y 1  
Ye ar 1  
3 5 d a y s 
pri or Y e ar 2  
Ye ar 2  
Ye ar 2 + 1 
m o nt h  
Ye ar 2 + 2 
m o nt h s  
Y e ar 3  + 2  
m o nt h s 
Y e ar 4  + 2  
m o nt h s 
 
Ti m e p oi nt s b y st u d y M o nt h  
D a y 1  
M o nt h 1 2  
D a y 6 9 5  
M o nt h  2 4 
M o nt h 2 5  
M o nt h 2 6  
M o nt h 3 7  
M o nt h 4 9  
E v e nt dri v e n  
P hysic al ex a mi n ati o n (s ecti o n 8. 1. 6 ) 
● 
 
 
●*  
 
 
 
 
 
Hist ory dir ect e d p hysic al ex a mi n ati o n 
(s ecti o n 8. 1. 6 ) 
 
● 
 
 
●* 
● 
● 
● 
● 
R ec or d w ei g ht (s ecti o n 8. 1. 6 ) 
● 
● 
 
● 
● 
● 
● 
● 
● 
R e mi n d  f e m al es of c hil d b e ari n g  p ot e nti al  t o 
us e a d e q u at e c o ntr ac e pti o n . 
 
 
O  
O  
O  
 
 
 
 
C h eck c o ntr ai n dic ati o ns t o  s u bs e q u e nt 
v acci n ati o n (s ecti o n 7. 7 )  
 
 
 
 
O*  
 
 
 
 
C h eck crit eri a f or t e m p o r ary d el ay f or r e-
v acci n ati o n (secti o n 6. 3 )  
 
 
 
O*  
O*  
 
 
 
 
Uri n e p r e g n a ncy t est f or f e m al es of 
c hil d b e ari n g p ot e nti al g 
 
 
 
●*  
●*  
 
 
 
 
R ec or d p r e-r ev acci n ati o n t e m p er at ur e  
 
 
 
●*  
●*  
 
 
 
 
Bi ol o gi c al s a m pli n g   
P hl e b ot o my f or  a : 
Bl o o d s a m pl e f or h u m or al i m m u n e 
r es p o ns e fr o m all s u bj ects (5  m L)  
● 
● 
 
●*  
●*  
● 
● 
● 
 
Bl o o d s a m pl e f or C MI r es p o ns e fr o m C MI 
s u b-c o h ort (3 0  m L)  
● 
● 
 
● * 
●*  
● 
● 
● 
 
 
  
 
 
 
● * 
● * 
● 
● 
● 
 
V a c ci n e  
R ec or d tr e at m e nt n u m b er   
 
 
 
●  
● 
 
 
 
 
V acci n e a d mi nistr ati o n   
 
 
 
●  
● 
 
 
 
 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
2 3  
E p o c h  
E p o c h 0 0 1  
E p o c h 0 0 2  
 
St u d y P h a s e  
L o n g -T er m F oll o w -u p P h a s e  
R e v a c ci n ati o n P h a s e  
F oll o w -u p P h a s e  
 
T y p e of c o nt a ct   
Vi sit 1  
Vi sit 2  
P C 1 a 
Vi sit 3 b 
Vi sit 4 c , h 
Vi sit 5 c , h 
Vi sit 6 c 
Vi sit 7 c 
A d -h o c  H Z Vi sit d 
Ti m e p oi nt s b y st u d y Y e ar  
D a y 1  
Ye ar 1  
3 5 d a y s 
pri or Y e ar 2  
Ye ar 2  
Ye ar 2 + 1 
m o nt h  
Ye ar 2 + 2 
m o nt h s  
Y e ar 3  + 2  
m o nt h s 
Y e ar 4  + 2  
m o nt h s 
 
Ti m e p oi nt s b y st u d y M o nt h  
D a y 1  
M o nt h 1 2  
D a y 6 9 5  
M o nt h  2 4 
M o nt h 2 5  
M o nt h 2 6  
M o nt h 3 7  
M o nt h 4 9  
E v e nt dri v e n  
S af et y a s s e s s m e nt s  
R ec or d cli nic ally a n d l oc ally o bt ai n e d 
s er u m cr e ati ni n e m e as ur es (s ecti o n 8. 1. 9 ) 
● 
● 
 
● 
● 
● 
● 
● 
● 
 
● 
● 
 
● 
● 
● 
● 
● 
 
R ec or d a ny m e dic ati o ns  / v acci n ati o ns 3 0 
d ays b ef or e e ac h st u dy visit  (s ecti o n 7. 5 ) 
● 
● 
 
 
 
 
 
 
 
R ec or d  a ny c o nc o mit a nt m e dic ati o ns/ 
v acci n ati o ns (s ecti o n 7. 5 ) 
 
 
 
● 
● 
● 
● 
● 
● 
Dist ri b uti o n of H Z-s p ecific di ary c ar ds a n d 
Z B PI q u esti o n n air es a n d Tr ai n s u bj ects o n 
c o m pl eti o n of t h e H Z-s p ecific di ary c ar d 
a n d Z B PI q u esti o n n air e (s ecti o n 8. 1. 1 2. 1 ). 
O  
O  
 
O  
 
 
O  
 
O  
Distri b uti o n of di ary c ar ds f or r ec or di n g of 
s olicit e d a n d u ns olicit e d A E ( a n d tr ai n o n 
c o m pl eti o n as n ec ess ary) (s ecti o n 
8. 1. 1 2. 1 )  
 
 
 
O   
O  
 
 
 
 
R et ur n of di ary c ar ds  
 
 
 
 
O  
O  
 
 
 
Tr a nscri pti o n of s olicit e d A Es r e p ort e d 
wit hi n 7 d ays p ost -v acci n ati o n  
 
 
 
 
● 
● 
 
 
 
Tr a nscri pti o n of n o n -s eri o us u ns olicit e d 
A E s r e p ort e d wit hi n 3 0 d ays p ost-
v acci n ati o n 
 
 
 
 
● 
● 
 
 
 
R ec or d A Es/ S A Es l e a di n g t o wit h dr a w al 
fr o m st u dy 
● 
● 
 
● 
● 
● 
● 
● 
 
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Epoch 
Epoch 001  
Epoch 002 
 
Study Phase 
Long-Term Follow-up Phase 
Revaccination Phase 
Follow-up Phase 
 
Type of contact  
Visit 1 
Visit 2 
PC1a 
Visit 3b 
Visit 4c, h 
Visit 5c, h 
Visit 6c 
Visit 7c 
Ad-hoc HZ Visit d 
Timepoints by study Year 
Day 1 
Year 1 
35 days 
prior Year 2 
Year 2 
Year 2 + 1 
month 
Year 2 + 2 
months 
Year 3 + 2 
months 
Year 4 + 2 
months 
 
Timepoints by study Month 
Day 1 
Month 12 
Day 695 
Month 24 
Month 25 
Month 26 
Month 37 
Month 49 
Event driven 
Record SAEs and pIMDs 
post- revaccination (section 12.5.9) 
 
 
 
● 
● 
● 
● 
 
 
Record pregnancies and pregnancy 
outcomes (sections 8.1.13 and 12.5.9.1) 
● 
● 
 
● 
● 
● 
● 
● 
 
Record SAEs related to study participation, 
or to a concurrent GSK medication/vaccine 
● 
● 
 
● 
● 
● 
● 
● 
 
Record SAEs related to study vaccine 
(section 12.5.9) 
● 
● 
 
● 
● 
● 
● 
● 
 
Record intercurrent medical conditions, 
including HZ cases (section 7.6) 
● 
● 
 
● 
● 
● 
● 
● 
 
Record AESI: biopsy-proven allograft 
rejection (section 8.1.14) 
● 
● 
 
● 
● 
● 
● 
● 
 
HZ assessments only in case of a clinically diagnosed suspected HZ 
Return HZ-specific diary cards and ZBPI 
questionnaires to study staff/investigator 
 
 
 
 
 
 
 
 
O 
Transcription of the HZ-specific diary card 
and ZBPI questionnaires by study 
staff/investigator e 
 
● 
 
● 
● 
● 
● 
● 
● 
Take digital photographs of HZ rash and 
upload to e-Clinipix (section 8.1.15) 
 
 
 
 
 
 
 
 
● 
Collect HZ lesion samples (from 3 separate 
lesions) for confirmation by PCR (section 
8.1.15) 
 
 
 
 
 
 
 
 
● 
Record relevant information regarding HZ e 
 
● 
 
● 
● 
● 
● 
● 
● 
Record any medical attention received for 
HZ or any HZ-related complication 
 
 
 
 
 
 
 
 
● 
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Epoch 
Epoch 001  
Epoch 002 
 
Study Phase 
Long-Term Follow-up Phase 
Revaccination Phase 
Follow-up Phase 
 
Type of contact  
Visit 1 
Visit 2 
PC1a 
Visit 3b 
Visit 4c, h 
Visit 5c, h 
Visit 6c 
Visit 7c 
Ad-hoc HZ Visit d 
Timepoints by study Year 
Day 1 
Year 1 
35 days 
prior Year 2 
Year 2 
Year 2 + 1 
month 
Year 2 + 2 
months 
Year 3 + 2 
months 
Year 4 + 2 
months 
 
Timepoints by study Month 
Day 1 
Month 12 
Day 695 
Month 24 
Month 25 
Month 26 
Month 37 
Month 49 
Event driven 
Phone contact follow-up of HZ rash and HZ 
pain resolution (section 8.1.15) e 
 
O 
 
O 
O 
O 
O 
O 
 
Record the resolution date of HZ rash e 
 
● 
 
● 
● 
● 
● 
● 
● 
Primary Study Conclusion 
 
 
 
 
 
● 
 
 
 
Final Study Conclusion 
 
 
 
 
 
 
 
● 
 
Note: The double-line borders indicate analyses that will be performed on all data obtained up to this time point (refer to section 10.4). 
● is used to indicate a study procedure that requires documentation in the individual electronic Case Report Form (eCRF). 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Vacc = Vaccination; PC = Phone Contact; AEs = Adverse Events; CMI = Cell- Mediated Immunity; SAEs = Serious Adverse Events; pIMDs = potential Immune-Mediated Diseases; 
HZ = Herpes Zoster; AESI = Adverse Events of Special Interest; RT = Renal Transplant; ZBPI = Zoster Brief Pain Inventory. 
* Before vaccine administration. 
a  Phone contact 1 (PC1) will occur about 35 days before Visit 3 (Month 24) to remind female subjects of childbearing potential to use adequate contraception. 
b  Visit 3 is the day of the first revaccination. Pre-revaccination and post-revaccination activities at Visit 3 are part of Epoch 001 and Epoch 002, respectively.  
c  Visit 4 is the day of the second revaccination that will be administered 1 to 2 months after the first revaccination. The subsequent visits (Visit 5, Visit 6 and Visit 7) will occur within 1, 
12 and 24 months after the second revaccination, respectively.  
d  An ad-hoc HZ Visit will be planned in case of suspected HZ and will be scheduled preferably within 3 calendar days from appearance of HZ symptom(s). 
e  Study activity to be performed at the next scheduled visit, if this has not been performed during the ad-hoc HZ visit. 
f  A second written informed consent will only be obtained prior to performance of any revaccination procedures, if required by local regulatory authorities or Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC). 
g  Blood sample is substituted for urine sample for pregnancy testing as required by country, local or ethics committee regulations. Pregnancy testing should be completed, and 
results reviewed prior to revaccination. 
h For non-revaccinated subjects (see Glossary of terms for the definition and Section 8.1, for details), Visit 4 and 5 will not occur.  
For non-revaccinated subjects, see Section 8.1. 
Note: 
In times of special circumstances, refer to Section 8.1.16 for study procedures. 
(Amended: 15 June 2020) 
 
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Whenever possible, the investigator should arrange study visits within the intervals 
described in Table 4. 
Table 4 
Intervals between study visits 
Interval 
Optimal length of 
interval a 
Allowed interval 
(days) b 
Visit 1 (Day 1) →Visit 2 (Month 12)  
12 months (360 days) 
330 - 415 
Visit 1 (Day 1) → Visit 3 (Month 24) 
24 months (720 days) 
690 - 775 
PC 1 (Day 695) →Visit 3 (Month 24) 
35 days 
31 - 40 
Visit 3 (Month 24) →Visit 4 (Month 25)  
30c days 
30 - 60 
Visit 4 (Month 25) → Visit 5 (Month 26)  
30 days 
30 - 48  
Visit 4 (Month 25) → Visit 6 * (Month 37) 
12 months (360 days) 
330 - 415  
Visit 4 (Month 25) → Visit 7 * (Month 49)  
24 months (720 days) 
690 - 775 
PC 1 = Phone Contact 1 
a. Whenever possible the investigator should arrange study visits within this interval.  
b. The investigator should endeavour to have the subjects come in for the visits within this interval. However, subjects 
may not necessarily be excluded from the PPS for analysis of immunogenicity if they make the study visit outside this 
interval. 
c. The second dose will be administered 1 to 2 months (30 to 60 days, inclusive) after the first dose.  
* The allowed interval for Visits 6 and 7 should be the same for both the re-vaccinated and non-revaccinated 
subjects.  
In times of special circumstances, refer to Section 8.1.16 for allowed interval between study visits.  
(Amended: 15 June 2020) 
3. 
INTRODUCTION 
3.1. 
Study rationale 
Despite significant medical need, currently no prophylactic vaccine is available for 
prevention of HZ in immunocompromised subjects aged 18-49 YOA, including RT 
subjects taking daily CIS therapy. 
Live attenuated VZV vaccines are contraindicated in immunodeficient or 
immunosuppressed individuals due to underlying disease or IS therapy [Zostavax US 
Prescribing Information, 2013; Zostavax Summary of Product Characteristics, 2013].  
Shingrix (GSK), an adjuvanted recombinant VZV-gE subunit vaccine (gE/AS01B), 
hereafter referred to as HZ/su, is licensed in multiple countries for the prevention of HZ 
and post-herpetic neuralgia (PHN) in older adults (≥ 50 YOA). Since HZ/su vaccine does 
not contain live virus, it is not contraindicated in case of immunosuppression or 
immunodeficiency.  
The HZ/su vaccine is immunogenic and has demonstrated vaccine efficacy of > 90% in 
older subjects (≥ 50 YOA) [Lal, 2015; Cunningham, 2016] and 68% in IC subjects (≥ 18 
YOA) with autologous hematopoietic stem cell transplantation (HSCT) [ZOSTER-002]. 
The safety profile of HZ/su vaccine was clinically acceptable in these populations [Lal, 
2015; Cunningham, 2016; Dagnew, 2018; de la Serna, 2018; Stadtmauer, 2014; Sullivan, 
2018, Cunningham, 2018; López-Fauqued, 2019]. 
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Studies using non-adjuvanted vaccines against common infectious diseases have shown 
variable and often suboptimal humoral and CD4+T-cell responses when administered in 
the presence of daily CIS therapy, regardless of the underlying disease, e.g. SOT, AID or 
other IID. The variable immune response has been suggested to be secondary to direct 
interference by CIS therapies [Mulley, 2012; Salles, 2010; Orcurto, 2012].  
Reports describing alloimmunity in SOT subjects temporally associated with 
administration of AS03-adjuvanted pandemic H1N1 vaccine prompted an in-depth 
investigation of this potential safety signal, including the conduct of a retrospective 
pharmaco-epidemiological study. Based on all accumulated evidence, SOT rejection was 
not considered a potential risk following vaccination with AS03-adjuvanted A/H1N1 
pandemic influenza vaccines [Dos Santos, 2017].  
A placebo-controlled study to ascertain the effect of vaccination with HZ/su on both the 
immune responsiveness of chronically immunosuppressed SOT subjects and on their 
allografts’ safety was conducted [Vink, 2019].  
Study ZOSTER-041 assessed safety and humoral and cell-mediated immunogenicity 
induced by two doses of HZ/su vaccine given 1 to 2-month apart in RT subjects (≥ 18 
YOA) taking daily CIS therapy. This study, in which 132 subjects received the HZ/su 
vaccine, has shown that HZ/su vaccine can induce a strong and persistent immune 
response up to one-year post-vaccination without increasing the risk of allograft rejection 
or allograft dysfunction. No safety concerns, including biopsy-proven allograft rejections, 
were identified in comparison to placebo subjects [Vink, 2019].  
In studies in subjects  50 YOA, a single revaccination dose of HZ/su was shown to 
boost the HZ/su immune responses when given at 10 years after the 2-dose primary 
vaccination series [ZOSTER-060]. In a CIS treated-IC population, a single revaccination 
dose might be insufficient and 2 additional doses may be required to boost and maintain 
the immune response to HZ. 
Study ZOSTER-073 is designed to provide data on the persistence of HZ/su vaccine-
induced immune response at 4 – 7 years after a 2-dose primary HZ/su vaccination in RT 
subjects on CIS therapy. This study will also investigate the immune response after 
revaccination of RT subjects on CIS therapy with HZ/su. 
Eligible RT subjects who participated in the HZ/su treatment group of study 
ZOSTER-041 and who had a complete vaccination course (2 doses of HZ/su vaccine) 
will be offered enrollment into study ZOSTER-073, approximately 5 years after their 
primary vaccination course. Medical history of subjects will be collected to assess HZ 
cases and RT rejections from last visit in study ZOSTER-041 to time of enrollment in 
study ZOSTER-073. Confirmed HZ cases and RT biopsy-proven rejections will be 
collected prospectively throughout study ZOSTER-073. Cell-mediated and humoral 
immunogenicity will be assessed in the long-term follow-up and revaccination phases. 
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Even though an immunologic threshold of protection has not been identified, these data 
will evaluate the potential of HZ/su vaccine in providing long-term immunity against HZ 
in RT subjects (≥18 years) on daily CIS therapy. This study may also provide insight on 
the use of HZ/su vaccine in other populations receiving daily CIS therapy, such as other 
SOT subjects and, potentially, subjects with AID and IID under CIS therapy. 
3.2. 
Background 
VZV causes two distinct diseases. Varicella (chickenpox) occurs shortly after primary 
VZV infection and is characterized by systemic illness and a widely disseminated rash. 
HZ (shingles) occurs when VZV reactivates from latency. Vaccination as a means of 
reducing the risk of HZ has been examined in both ≥50 YOA and IC subjects ≥18 YOA. 
Shingrix (GSK), a licensed vaccine for prevention of HZ in adults ≥50 YOA, is a 
recombinant subunit (su) vaccine (HZ/su) consisting of VZV glycoprotein E (gE) as 
antigen (50 µg) and the adjuvant AS01B [liposomes in combination with 50 µg 3-O-
desacyl-4’-Monophosphoryl Lipid A (MPL) and 50 µg Quillaja saponaria Molina, 
fraction 21 (QS21) per 0.5 mL dose].  
HZ/su vaccine induces strong gE-specific humoral and CD4+ T-cell responses through its 
adjuvant system AS01B, and is efficacious in subjects with weakened immune system, in 
particular subjects ≥ 50YOA and IC population ≥ 18YOA.  
Please refer to the current Investigator Brochure for information regarding the pre-
clinical and clinical studies of GSK’s HZ/su vaccine. 
3.2.1. 
Herpes Zoster 
HZ is characterized by rash, pain, and pruritus. The typical HZ rash, generally blisters in 
a localized, dermatomal band on one side of the body, lasts 2 to 4 weeks and is 
accompanied by severe pain that is often described as burning, shooting, or stabbing. In 
some subjects, even light touching of the affected area may cause pain, a phenomenon 
known as allodynia. Pruritus, which can also be severe, may be as common as pain. Pain 
that persists after the resolution of the HZ rash is called PHN. 
While it is not known what triggers the reactivation of VZV and the subsequent 
development of HZ, it is clear that subjects with impaired cell-mediated immunity (CMI) 
due to advanced age, malignancy, including hematologic malignancy, HIV infection, 
organ transplantation, immunodeficiency, autoimmune disease, and treatment with 
immunosuppressive therapies, are at increased risk for the development of HZ [Cohen, 
2007; Schmipff, 1972; Rusthoven, 1988; Hata, 2011]. 
3.2.2. 
Herpes Zoster in Solid Organ Transplant subjects  
SOT subjects represent a distinct group of subjects with regard to their CMI. Most SOTs 
are allogeneic, that is the transplantation of organs with a different genotype from one 
individual to another. Transplant subjects receive immunosuppressive therapy, 
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chronically, to prevent rejection of these genetically different engrafted organs [EMA, 
2008].  
Secondary to their CIS, SOT subjects are at increased risk of developing HZ. Three large 
SOT studies from North America indicate HZ incidence rates in transplant subjects of 
approximately 8 to 9 times the 3.2 per 1000 person-years estimated for the general US 
population [Insinga, 2005]. A large single center study from the University of Alberta 
Hospital, Edmonton, Canada, which included 869 SOT subjects, reported the percentage 
of subjects with HZ following transplantation of 8.6% for overall SOTs and 7.4% for 
RTs. The mean time of HZ onset post-transplantation was 13.9 months for SOTs and 
15.5 months for RT subjects. The overall HZ incidence rate in SOT subjects was 27.2 per 
1000 person-years [Gourishankar, 2004]. Another single center study, conducted at the 
Mayo Clinic, in Rochester, Minnesota, of 612 RTs, reveals a HZ incidence rate of 28 per 
1000 person-years following transplantation. Furthermore, subjects younger than 60 
years had an incidence rate of 23 per 1000 person-years whereas subjects of 60 years or 
more had an incidence rate of 41 per 1000 person-years [Arness, 2008]. A large 
multicenter study conducted by the US Department of Veterans Affairs of 1077 SOT 
subjects reported the percentage of HZ of 8.3% overall and 9.0% for RTs. The HZ 
incidence rate for SOT was 22.2 per 1000 patient-years and for RT subjects was 24.4 per 
1000 patient-years. Multivariate modelling revealed that African Americans and older 
transplant subjects had increased relative hazards of HZ [Pergam, 2011]. 
The increased incidence rate of HZ within SOT subjects on CIS establishes the basis for 
evaluating GSK’s candidate HZ/su vaccine in this population. 
3.3. 
Benefit/Risk assessment 
The following section outlines the risk assessment and mitigation strategy for this study 
protocol. 
Please refer to the current Investigator Brochure for the summary of potential risks and 
benefits of HZ/su vaccine. 
 
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3.3.1. 
Risk assessment 
Important/Potential/Identified/Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Investigational vaccine 
Hypersensitivity including allergic reaction such as 
anaphylaxis 
Acute allergic reactions such as a rare case of 
anaphylactic event may occur with any vaccine 
administration. These are serious, but rare occurrences 
estimated in the range of 1 to 10 cases per million of 
vaccinations, depending on the vaccine studied 
[Ruggerberg, 2007]. 
History of any reaction or hypersensitivity likely to be 
exacerbated by any component of the vaccine is a 
contraindication to vaccination. The onset of vaccine-related 
allergic symptoms is typically quite prompt. In order to treat 
subjects with a serious allergic reaction to vaccination, all 
subjects will need to remain under observation (i.e. visibly 
followed; no specific procedure) at the vaccination center for 
at least 30 minutes after revaccination where medical 
equipment to treat any serious reactions is available. 
Potential immune-mediated diseases (pIMDs) are a 
theoretical concern with adjuvanted vaccines. 
Based on the theoretical concern that vaccination with 
an adjuvanted vaccine containing potent 
immunostimulants may interfere with immunological 
self-tolerance, pIMDs are adverse events of special 
interest undergoing special safety monitoring for all 
GSK vaccines containing Adjuvant Systems. pIMDs 
are a subset of adverse events that include 
autoimmune diseases and other inflammatory and/or 
neurological disorders of interest which may or may not 
have an autoimmune aetiology. To date, there is no 
evidence of an increased risk of pIMDs following 
vaccination with HZ/su in the populations evaluated (IC 
adults, adults 50 YOA or older) [López-Fauqued, 
2019]. 
During the informed consent process, subjects will be 
informed of this potential risk and the need to attend the clinic 
for change in health status. pIMDs will be collected up to 12 
months after administration of the last dose of study vaccine. 
The occurrence of pIMD cases during the study will be 
described. 
Potential allograft rejection as a theoretical concern with 
adjuvanted vaccines in solid organ transplant subjects 
To date, there is no evidence of an increased risk of 
allograft rejection as demonstrated in ZOSTER-041 
[Vink, 2019]. Refer to section 3.1 for details. 
During the informed consent process for revaccination, the 
subjects will be informed of this potential risk and the need to 
inform the clinic and seek medical attention if unwell after 
revaccination. Clinically management of allograft rejection will 
be per local standard of care and recorded as AE/SAE, as 
appropriate. Any renal biopsy results will be recorded to study 
end. The occurrence of biopsy-proven allograft rejection 
during the study will be described. 
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Important/Potential/Identified/Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Study Procedures 
Intramuscular (IM) injection 
Intramuscular vaccination commonly precipitates a 
transient and self-limiting local inflammatory reaction. 
This may typically include pain at injection site, 
redness, and swelling 
All subjects will remain under observation at the vaccination 
center for at least 30 minutes after revaccination. 
Solicited local adverse events (AE) will be collected and 
reviewed up to Day 7. 
Pain and bruising 
Pain or bruising at the site where blood is drawn. 
A topical analgesic may be applied to the site where blood 
will be taken. 
Syncope 
Syncope (fainting) can occur following or even before 
any vaccination and/or blood draw as a psychogenic 
response to the needle insertion. 
Subject Monitoring  
All subjects will remain under observation at the clinical 
center for at least 30 minutes after revaccination. 
Nerve Injury 
There is a possibility that in the process of collecting 
blood a nerve may be injured. 
Procedure to be performed by qualified personnel. 
Risks from HZ rash lesion sampling 
Discomfort / pain / secondary infection associated with 
swabbing of HZ lesions/crusts 
HZ lesion samples will be obtained by a trained professional 
and anti-bacterial ointment may be applied to minimize the 
potential for secondary infection. 
 
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3.3.2. 
Benefit assessment 
Benefits include: 
• 
Receipt of two additional doses of HZ/su vaccine that may provide a potential 
clinical benefit in reducing the risk of developing HZ at long-term. 
• 
Medical evaluations/assessments associated with study procedures (e.g. physical 
examination). 
3.3.3. 
Overall Benefit: Risk conclusion 
Considering the measures taken to minimise risk to subjects participating in this study, 
the potential or identified risks identified in association with the study HZ/su vaccine are 
justified by the potential benefits (prevention/treatment) that may be afforded to subjects 
receiving two additional doses of HZ/su vaccine. 
4. 
OBJECTIVES AND ENDPOINTS 
The study objectives and endpoints are presented in Table 5. 
Table 5 
Study objectives and endpoints (Amended: 15 June 2020) 
Objectives 
Endpoints 
Primary 
LTFU phase - Immunogenicity assessment  
• 
To evaluate persistence of humoral immunity 
after primary vaccination course. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by ELISA 
at Day 1, Month 12 and Month 24. 
Revaccination active phase - Immunogenicity 
assessment 
• 
To evaluate humoral immunity of HZ/su 
vaccine post-revaccination Doses 1 & 2. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by ELISA 
at pre-revaccination (Month 24) and at 1-month post-
revaccination Dose 1 (Month 25) and Dose 2 (Month 26). 
Secondary 
LTFU phase - Immunogenicity assessment 
• 
To evaluate persistence of cellular immunity 
after primary vaccination course. 
In CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T-cells expressing two 
or more markers such as IFN-γ, IL-2, TNF-α, CD40L as 
determined by ICS at Day 1, Month 12 and Month 24. 
LTFU phase - safety assessment 
• 
To evaluate safety of HZ/su vaccine from the 
study ZOSTER-041 last visit to study ZOSTER-
073 Visit 3. 
In all subjects: 
• 
Related-SAEs 
− 
Occurrence of SAEs related to primary vaccination 
as assessed by the investigator from the study 
ZOSTER-041 last visit (Month 13) to study 
ZOSTER-073 Visit 3 (Month 24). 
• 
HZ episodes 
− 
Occurrence of suspected or confirmed HZ cases 
from the study ZOSTER-041 last visit (Month 13) to 
study ZOSTER-073 Visit 1 (Day 1).  
− 
Occurrence of confirmed HZ cases from Day 1 
through Month 24. 
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Objectives 
Endpoints 
• 
AESIs 
− 
Occurrence of suspected or biopsy-proven allograft 
rejections from the study ZOSTER-041 last visit 
(Month 13) to study ZOSTER-073 Visit 1 (Day 1).  
− 
Occurrence of biopsy-proven allograft rejections 
from Day 1 through Month 24. 
• 
Allograft function for episode(s) of allograft rejection. 
− 
Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of biopsy-proven rejection and up to 2 
months after rejection resolution and cessation of 
therapeutic immunosuppressive therapy for the 
time period from study ZOSTER-041 last visit 
(Month 13) to study ZOSTER-073 Visit 3 (Month 
24).  
• 
Allograft function for episode(s) of HZ 
− 
Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of HZ and up to 2 months after HZ rash 
resolution for the time period from study ZOSTER-
041 last visit (Month 13) to study ZOSTER-073 
Visit 3 (Month 24). 
Revaccination active phase - Immunogenicity 
assessment 
• 
To evaluate cell-mediated immunity 
post- revaccination Doses 1 & 2. 
In revaccinated subjects in CMI sub-cohort: 
 
• 
Frequencies of gE-specific CD4+ T-cells expressing two 
or more markers such as IFN-γ, IL-2, TNF-α, CD40L as 
determined by ICS at pre-vaccination (Month 24) and at 
1-month post-revaccination Dose 1 (Month 25) and Dose 
2 (Month 26). 
Revaccination follow-up phase – Immunogenicity 
assessment 
• 
To evaluate persistence of humoral and cell-
mediated immune responses post-
revaccination Dose 2. 
In all revaccinated subjects: 
• 
Anti-gE antibody concentrations as determined by ELISA 
at 12 months and 24 months post-revaccination Dose 2. 
In revaccinated subjects in CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T- cells expressing two 
or more markers such as IFN-γ, IL-2, TNF-α, CD40L as 
determined by ICS at 12 months and 24 months post-
revaccination Dose 2 in a CMI sub-cohort of subjects. 
Revaccination active and follow-up phases - Safety 
assessment 
• 
To evaluate reactogenicity and safety of the 
HZ/su vaccine after each revaccination. 
In all revaccinated subjects: 
• 
Solicited local and general AEs: 
− 
Occurrence, duration and intensity of solicited local 
AEs within 7 days after each revaccination (i.e., the 
day of revaccination and 6 subsequent days);  
− 
Occurrence, duration and intensity of solicited 
general AEs within 7 days after each revaccination 
dose (i.e., the day of revaccination and 6 
subsequent days) and causal relationship to 
revaccination by investigator assessment.  
• 
Unsolicited AEs  
− 
Occurrence, intensity of unsolicited AEs during 30 
days after each revaccination (i.e., the day of 
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Objectives 
Endpoints 
revaccination and 29 subsequent days) and causal 
relationship to revaccination by investigator 
assessment.  
• 
SAEs  
− 
Occurrence of SAEs (including fatal SAEs) from 
Dose 1 of revaccination (Month 24) until 12 months 
post-last revaccination dose (Month 37).  
− 
Occurrence of related-SAEs (including related-fatal 
SAEs) as per investigator assessment from Dose 1 
of revaccination (Month 24) up to study end (Month 
49).  
• 
AESIs   
− 
Occurrence of all biopsy-proven allograft rejections 
from Dose 1 of revaccination (Month 24) up to 
study end (Month 49) and causal relationship to 
revaccination by investigator assessment.  
− 
Occurrence of pIMDs from Dose 1 of revaccination 
(Month 24) up to 12 months post-last revaccination 
dose (Month 37) and causal relationship by 
investigator assessment. 
• 
HZ episodes  
− 
Occurrence of confirmed HZ cases from Dose 1 of 
revaccination (Month 24) up to study end (Month 
49).  
• 
Allograft function following revaccination  
− 
Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 3 months before the first 
revaccination dose until 3 months after the last 
revaccination dose. 
• 
Allograft function for episode(s) of allograft rejection  
− 
Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of biopsy-proven rejection and up to 2 
months after rejection resolution and cessation of 
therapeutic of immunosuppressive therapy.  
• 
Allograft function for episode(s) of HZ 
− 
Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of HZ and up to 2 months after HZ 
resolution. 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
3 5  
C MI = C ell -M e di at e d I m m u nity; 
; E LI S A  = Enzy m e Li nk e d I m m u n os or b e nt Ass ay; 
g E  = glyc o pr ot ei n E; 
; I C S = I ntr ac ell ul ar Cyt oki n e St ai ni n g; I L-2  = I nt erl e uki n 2; 
; 
; 
 
T N F α  = T u m or N ecr osis F act or -al p h a; I F N γ = I nt erf er o n -g a m m a ; A E = Adv ers e Ev e nt; S A E = Seri o us A dv ers e Ev e nt; 
H Z  = H er p es Z ost er ; A E SI  =  A dv ers e Ev e nt of Sp eci al I nt er est; pI M D s  =  p ot e nti al I m m u n e -M e di at e d Dis e as es.  
* T o b e p erf or m e d by a  c e ntr al l a b or at ory if d e e m e d n ec ess ary. 
( A m e n d e d: 1 5 J u n e 2 0 2 0) 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI
C CI
C CI
C CI
C CI

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5. 
STUDY DESIGN 
5.1. 
Scientific rationale for study design 
This study will evaluate the persistence of gE-specific immunogenicity after the primary 
2-dose HZ/su vaccination in study ZOSTER-041 and the effect on immunogenicity and 
safety of revaccination with two additional doses of HZ/su vaccine after approximately 7 
years in ZOSTER-041 in RT subjects taking daily CIS therapy. Study ZOSTER-073 will 
provide insights into HZ/su-induced immune responses in the RT population and, 
potentially, in other immunocompromised populations including SOT, AID, IID subjects 
receiving CIS.  
Former study ZOSTER-041 subjects who received two doses of HZ/su vaccine will be 
offered enrollment into study ZOSTER-073 at participating centers. 
Study ZOSTER-073 has three distinct phases: 
• 
In the long-term follow-up (LTFU) phase, subjects will be followed for two years* 
(Day 1 to Month 24). Over the same time period, the occurrences of confirmed HZ 
cases and biopsy-proven RT rejections will be prospectively collected. Whereas, the 
occurrences of confirmed/suspected HZ cases; and RT rejections will be 
retrospectively collected back to subjects’ study ZOSTER-041 last visit. (Amended: 
15 June 2020) 
* Subjects who are ineligible for revaccination or unwilling to receive 
revaccination (hereafter referred to as non-revaccinated subjects, see Glossary of 
terms) will be invited to be followed in an extension of the LTFU phase for a total 
of 4 years (Day 1 to Month 49), with safety and immunogenicity assessments at 
Months 37 and 49.  
• 
In the revaccination active phase (Months 24 through 26), subjects will receive two 
additional doses of HZ/su vaccine, administered on a 1 to 2-month apart schedule at 
Months 24 and 25. Safety and immunogenicity assessments will be performed 1 
month post-revaccination Doses 1 and 2 at Months 25 and 26, respectively.  
• 
In the revaccination follow-up phase (Month 26 to study end), safety and 
immunogenicity following revaccination will be prospectively monitored at Months 
37 and 49 (i.e. 12 and 24 months post-revaccination Dose 2). 
In study ZOSTER-073, the occurrence of HZ episodes will be collected and confirmed by 
molecular biology tests (HZ PCR testing) and the HZ Ascertainment Committee (HZAC) 
decision (see section 12.2.2 for details). 
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5.2. 
Scientific rationale for the non-use of control group 
Study ZOSTER-073 has no control group for the following reasons: 
• 
The use of varicella zoster virus live-virus vaccines (ZVLs) is contraindicated in RT 
subjects.  
This is an extension study of the study ZOSTER-041 in which the immunogenicity 
and safety of HZ/su vaccine were tested in 264 RT subjects who either received 
HZ/su vaccine or placebo on a 0, 2-month schedule. The immunogenicity of the 
placebo group showed consistent baseline values up to 1 year of follow-up and in 
both study groups, no safety concerns, including biopsy-proven rejections, were 
identified [Vink, 2019].  
 
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5.3. 
Overall design 
Figure 1 
Study design overview 
 
HZ/su = Herpes zoster subunit; LTFU = Long term follow-up; Vacc 1-2 = Vaccination dose 1 & 2; re-Vacc 1-2  = Revaccinations dose 1 & 2 
*The second dose of revaccination (Visit 4, Month 25) will be administered 1 to 2 months after the first revaccination dose. 
**Visit 5 (Month 26), Visit 6 (Month 37) and Visit 7 (Month 49) will occur 1, 12 and 24 months after the second revaccination, respectively. 
$Phone contact will occur about 35 days before Visit 3 (Month 24) to remind female subjects of childbearing potential to use adequate contraception. 
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Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. Therefore, adherence to the study design requirements, 
including those specified in the schedule of activities (SoA) (see Section 2), are essential 
and required for study conduct. In times of special circumstances, refer to Section 
8.1.16 for study procedures. (Amended: 15 June 2020) 
• 
Type of study: extension of other protocol(s); ZOSTER-041 for the analysis of long 
term immunogenicity and safety. 
• 
Experimental design: Phase IIIB, open-label, uncontrolled, multi-centric, single 
group study.  
• 
Duration of the study: The study duration per subject will be approximately 49 
months.  
− 
Epoch 001: LTFU phase starting at Visit 1 (Day 1) and ending at Visit 3 
(Month 24)  
− 
Epoch 002: Revaccination phase starting at Visit 3 (Month 24) and ending at 
Visit 7 (Month 49) 
• 
Primary completion Date (PCD): Visit 5 (Month 26). 
Refer to glossary of terms for the definition of PCD. 
• 
End of Study (EoS): Release of laboratory results through Visit 7 (Month 49). 
Refer to glossary of terms for the definition of EoS. 
• 
Study group: 
Table 6 
Study group, treatment and epochs foreseen in the study 
Study 
groups* 
Number of subjects 
Age (Min-Max)** 
Treatment 
name 
Epochs 
From ZOSTER-041 primary study 
Epoch 001 (open) 
Epoch 002 (open) 
HZ/su 
86 
20 years - 82 years 
HZ/su 
● 
● 
HZ/su = Herpes Zoster subunit vaccine. 
*HZ/su Group name for subjects who were vaccinated with 2 doses of HZ/su in study ZOSTER 041. 
**Age at the first vaccination in study ZOSTER-041. 
• 
Control: uncontrolled. 
• 
Revaccination schedule: Subjects will receive two additional doses of the HZ/su 
vaccine, at Visit 3 (Month 24) and at Visit 4 (Month 25) in the revaccination phase. 
• 
Treatment allocation: All eligible subjects will be enrolled into HZ/su group.  
• 
Blinding: Open-label 
For a detailed description of treatment allocation, refer to section 7.2. 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
4 0  
•  
S a m pli n g sc he d ule :  
− 
Bl o o d sa m ples t o assess h u m oral i m m u n o ge nicit y will be c ollecte d fr o m all 
s u bjects at Visit 1 ( Da y 1), Visit 2 ( M o nt h 1 2), Visit 3 ( M o nt h 2 4), Visit 4 
( M o nt h 2 5)* , Visit 5 ( M o nt h 2 6)* , Visit 6 ( M o nt h 3 7) a n d Visit 7 ( M o nt h 4 9). 
( A me n de d: 1 5  J u ne  2 0 2 0)  
− 
Bl o o d sa m ples t o assess C MI res p o nses will be c ollecte d i n t he C MI s u b -c o h ort 
at Visit 1 ( Da y 1), Visit 2 ( M o nt h 1 2), Visit 3 ( M o nt h 2 4), Visit 4 ( M o nt h 2 5) * , 
Visit  5 ( M o nt h 2 6 )* , Visit 6 ( M o nt h 3 7) a n d Visit 7 ( M o nt h 4 9). ( A me n de d: 1 5  
J u ne  2 0 2 0)  
* Bl o o d s a m ples will  n ot be c ollecte d at Visit 4 a n d Visit 5 fr o m n o n -rev acci n ate d 
s u bjects. Refer t o Secti o n 7  f or m ore det ails. 
− 
Cli nical s peci me ns of H Z lesi o ns (fr o m 3 se parat e lesi o ns) will be c ollecte d 
fr o m s u bjects cli nicall y dia g n ose d as ha vi n g a s us pecte d case of H Z.  
− 
A uri ne  sa m ple (bl o o d sa m pl e o nl y if re q uire d b y c o u ntr y, l o cal or et hics 
c o m mittee re g ulati o ns) will be c ollecte d fr o m all fe male s u bjects of c hil d beari n g 
p ote ntial bef ore re vacci n ati o n at Visit 3 ( M o nt h 2 4) a n d Visit 4 ( M o nt h 2 5)  f or 
pre g na nc y t esti n g . 
•  
D at a c ollecti o n : electr o nic Case Re p ort F or m ( e C R F).  
− 
S olicite d a n d u ns olicite d A Es  will be c ollecte d usi n g a s u bj ect Diar y ( pa per 
Diar y ) a n d tr a nscri b e d i nt o e C R F. 
− 
I n t he e ve nt of s us p ecte d H Z, t he H Z cli nical c o urse will be c ollecte d usi n g a 
H Z -s pecifi c Diar y a n d Z oster Bri ef Pai n I n ve nt or y ( Z B PI) q uesti o n naire a n d 
tra nscri be d i nt o e C R F.  
•  
S afet y m o nit ori n g : A n i nter nal  safet y re vie w tea m ( S R T, st u d y tea m me m bers) will 
re vie w a v aila ble safet y d ata o n a re g ular b asis t hr o u g h o ut t he st u d y. A n y p ote ntial 
safet y c o n cer n i de ntifi e d will be escalate d t o hi g her g o v er ni n g b o dies as p er i nter nal 
G S K pr ocess.  
5. 4.  
N u m b er of s u bj e ct s  
F or mer st u d y Z O S T E R -0 4 1 s u bjects, w h o ha ve a c o m plete pri mar y vacci nati o n c o urse ( 2 
d oses of H Z/s u  vacci ne ) will be offere d e nr oll me nt  i nt o st u d y Z O S T E R-0 7 3 at 
partici pati n g ce nters. 
U p t o a  ma xi m u m of 8 6 s u bjects  will be tar gete d f or e nr ollme nt . A ss u mi n g f ull 
e nr oll me nt  a n d c o nsi deri n g a 1 5 % dr o p -o ut r ate (i ncl u di n g s u bjects n ot eli gi ble i n t he 
per -pr ot oc ol s et),  a p pr o xi matel y 7 3 e val ua ble s u bj ects are e x pecte d t o c o m plete t he 
st u d y.  
Refer t o Secti o n 1 0. 1  f or f urt her i nf or m ati o n o n sa m ple siz e deter mi nati o n. 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

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Withdrawals will not be replaced. 
Overview of the recruitment plan  
The study will include subjects in multiple centers in countries that previously 
participated in study ZOSTER-041. 
At the time of initiation of study ZOSTER-073, the investigator will contact ONLY those 
subjects who had a complete HZ/su vaccination course (2 doses of HZ/su vaccine) in 
study ZOSTER-041 and who expressed a willingness to participate at a potential follow-
up study when questioned at the conclusion of the primary study. The reason for 
non-participation in study ZOSTER-073 will be documented in the site’s screening log. 
5.5. 
Subject and study completion 
A subject is considered to have completed the study if he/she returns for the concluding 
visit (Visit 7; Month 49) as described in the protocol. 
Global completion of the study is required in order to provide sufficient subjects as 
defined in Section 10.1 Sample Size Determination. 
6. 
STUDY POPULATION 
6.1. 
Inclusion criteria  
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. 
6.1.1. 
Inclusion criteria for enrollment (to be checked at Visit 1) 
All subjects must satisfy ALL the following criteria at study entry: 
• 
Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary cards, return for follow-up 
visits). Or/and subjects’ Legally Acceptable Representative(s) [LAR(s)] who, in the 
opinion of the investigator, can and will comply, with the requirements of the 
protocol (e.g. completion of the diary cards, return for follow-up visits). 
• 
Written informed consent obtained from the subject/LAR(s) of the subject prior to 
performance of any study-specific procedure. 
• 
Subjects who previously participated in study ZOSTER-041 and completed the full 2 
dose HZ/su primary vaccination course. 
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6.1.2. 
Inclusion criteria for revaccination (to be checked at Visit 3) 
All subjects must satisfy ALL enrollment criteria and the following criteria at 
revaccination Visit 3: 
• 
Subjects receiving maintenance CIS therapy for the prevention of allograft rejection 
for a minimum of one month (30 days) prior to the first revaccination. 
• 
Subjects without an episode of allograft rejection within 90 days prior to the first 
revaccination visit. 
• 
Female subjects of non-childbearing potential may be revaccinated. Non-
childbearing potential is defined as pre-menarche, current bilateral tubal ligation or 
occlusion, hysterectomy, bilateral ovariectomy or post-menopause.  
Refer to Glossary of terms for definitions of menarche and menopause. 
• 
Female subjects of childbearing potential may be revaccinated, if the subject: 
− 
has practiced adequate contraception for 30 days prior to revaccination, and 
− 
has a negative pregnancy test on the day of revaccination, and 
− 
has agreed to continue adequate contraception up to 2 months after completion 
of the revaccination series. 
Refer to Glossary of terms for definitions of woman of child bearing potential and 
adequate contraception.  
Note: Subjects not meeting the above inclusion criteria for revaccination may continue to 
participate in the study for long-term immunogenicity and safety evaluations at study 
Visits 6 and 7. 
6.2. 
Exclusion criteria  
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. 
6.2.1. 
Exclusion criteria for enrollment (to be checked at Visit 1) 
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study. 
6.2.1.1. 
Medical conditions 
• 
Vaccination against HZ since completion of study ZOSTER-041. 
• 
Significant underlying illness that, in the opinion of the investigator, is expected to 
prevent completion of the study. 
• 
Any other condition that, in the opinion of the investigator, would interfere with the 
evaluations required by the study. 
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6.2.1.2. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another interventional vaccine or immunosuppressive 
clinical study, in which the subject is exposed to an investigational or a non-
investigational vaccine/product* (drug) at any time during the ZOSTER-073 study. 
(Amended: 15 June 2020)  
*Allowed products: Immunosuppressant(s), which are investigational or non-
registered product(s) at the local/country level, may be used if they are specifically 
prescribed for the prevention of allograft rejection and are: 
− 
available locally through compassionate use programs, 
− 
submitted for and pending local/country registration, 
− 
approved and registered for use in one or more of the other participating 
countries with well-documented Summary of Product Characteristics (SPC) or 
Prescribing Information (PI). 
The name of the active component(s) of these immunosuppressants must be provided 
in the concomitant medication listing. 
6.2.2. 
Exclusion criteria for revaccination (to be checked at Visit 3) 
All enrollment exclusion criteria and the following criteria should be checked at Visit 3. 
If ANY exclusion criterion applies, the subject must not be revaccinated. 
6.2.2.1. 
Medical conditions 
• 
History of confirmed HZ within one year before revaccination visit (Visit 3), i.e. HZ 
between Visit 2 (Month 12) and Visit 3 (Month 24). 
• 
More than one organ transplanted (i.e. kidney-liver, double kidney, or kidney plus 
another organ(s) transplanted). 
• 
Any additional confirmed or suspected immunosuppressive or immunodeficient 
condition (e.g., malignancy, HIV infection, systemic infection). 
• 
History of any reaction or hypersensitivity (e.g. anaphylaxis) likely to be exacerbated 
by any component of the vaccine. 
• 
Any other condition that, in the opinion of the investigator, would interfere with the 
evaluations required by the study or make vaccination unsafe. 
6.2.2.2. 
Prior/Concomitant therapy 
• 
Administration or planned administration of immunoglobulins and/or any blood 
products or plasma derivatives during the period starting 3 months (90 days) before 
the first revaccination dose of study vaccine and ending at Visit 5 (Month 26). 
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• 
Use of anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab, 
ocrelizumab) as maintenance and/or therapeutic immunosuppressive therapy for the 
prevention of allograft rejection within 9 months (274 days) of first revaccination 
dose of study vaccine. 
• 
Evidence or high suspicion, in the opinion of the investigator, of noncompliance or 
nonadherence to use of maintenance immunosuppressive therapies. 
• 
Planned administration/administration of a live vaccine in the period starting 30 days 
before the first dose and ending 30 days after the last dose of study vaccine 
administration.  
• 
Planned administration/administration of a non-replicating or subunit vaccine,* not 
foreseen by the study protocol, in the period starting 8 days before and ending 30 
days after each dose of study vaccine. 
*E.g. inactivated and subunit vaccines, including inactivated and subunit influenza 
vaccines and pneumococcal conjugate vaccines. 
6.2.3. 
Other exclusion criteria for revaccination 
• 
Pregnant or lactating female. 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions up to 2 months post-revaccination Dose 2. 
• 
Any condition which, in the judgment of the investigator, would make intramuscular 
(IM) injection unsafe.  
If any of the above exclusion criteria are met, the subject should be encouraged to remain 
in the study withdrawing only from revaccination, while continuing other study 
procedures (see section 8.4.5). Alternatively, at the discretion of the investigator, the 
subject may be withdrawn from the study (see section 12.5.12). 
6.3. 
Criteria for temporary delay for revaccination  
Revaccination may be postponed within the allowed time interval (see Table 4) until 
transient circumstances cited below have been resolved: 
• 
Acute disease and/or fever at the time of revaccination. Fever is defined as 
temperature 38.0°C. The preferred route for measuring temperature in this study is 
oral. Subjects with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may, be revaccinated at the discretion of the investigator.  
• 
Allograft instability [greater than 20% variability between last two clinically 
obtained creatinine measurements or calculated glomerular Filtration Rates (GFR)]. 
• 
Any condition which, in the judgment of the investigator, would make IM injection 
unsafe. 
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7. 
TREATMENTS 
Study treatment is defined as a set of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject. 
7.1. 
Treatments administered  
All eligible and willing subjects will receive HZ/su vaccine (for details see Table 7). 
(Amended: 15 June 2020) 
Table 7 
Treatments administered 
Study Treatment Name: 
HZ/su 
Vaccine name  
VZV gE 
AS01B 
Presentation 
Lyophilized pellet in a monodose vial 
Liquid in a monodose vial 
Vaccine formulation: 
gE=50µg 
MPL=50µg; QS21=50µg; Liposomes * 
Route of Administration  
IM injection 
Administration site: 
Location 
Deltoid 
Laterality ** 
Non-dominant 
Number of doses to be administered: 
2 
Volume to be administered *** 
0.5 ml 
Packaging and Labelling 
Refer to SPM for more details 
Manufacturer 
GSK 
*QS-21: Quillaja saponaria Molina, fraction 21 (Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation). 
** The non-dominant arm is the preferred site of injection. In case it is not possible to administer the vaccine in the non-
dominant arm, an injection in the dominant arm may be performed. 
*** Refer to the SPM for the volume after reconstitution.  
Refer to the Study Procedures Manual (SPM) for detailed instructions on study vaccine 
reconstitution. 
After completing all prerequisite procedures prior to the first revaccination (including the 
review of inclusion and exclusion criteria [see sections 6.1 and 6.2, respectively]), one 
dose of study vaccine will be administered intramuscularly in the deltoid of preferably 
the non-dominant arm at Visit 3 (Month 24) (refer to Table 7 for details regarding the 
treatment administered).  
After completing all prerequisite procedures prior to the second revaccination (see 
section 7.7 regarding the contraindications to subsequent vaccination), one dose of study 
vaccine will be administered intramuscularly in the deltoid of preferably the 
non- dominant arm at Visit 4 (Month 25) (see Table 7 for details regarding the treatment 
administered).  
If the investigator or delegate determines that the subject’s health on the day of 
administration temporarily precludes vaccine administration, the visit will be rescheduled 
within the allowed interval for this visit (refer to Table 4). 
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The subjects will be observed closely for at least 30 minutes following the administration 
of the vaccine, with appropriate medical treatment readily available in case of 
anaphylaxis and syncope. 
7.2. 
Method of treatment assignment 
7.2.1. 
Subject identification 
Subjects will receive the same subject identification numbers as in primary study 
ZOSTER-041. 
7.2.2. 
Randomization of treatment 
This is a single arm, open-label, non-randomized study. 
7.2.2.1. 
Treatment Allocation to the Subject 
The number of each administered treatment assigned by Source data Base for Internet 
Randomisation (SBIR) must be recorded in the eCRF on the Vaccine Administration 
screen. 
7.2.3. 
Allocation of subjects to CMI sub-cohort 
At participating centers, that have access to Peripheral Blood Mononuclear Cell (PBMC) 
processing facility, up to a maximum of 40 subjects will be targeted for CMI collection 
such that approximately 34 evaluable subjects are available for CMI analyses, 
considering a 15% drop-out rate (including subjects not eligible in the per-protocol set). 
The CMI analyses will be performed at specified timepoints for subjects included in the 
CMI-sub-cohort. CMI subjects from ZOSTER-041 (n = 28) will be targeted for 
enrollment into the ZOSTER-073 CMI sub-cohort. The balance of CMI subjects to be 
enrolled will be selected at random from CMI participating centers to complete the sub-
cohort up to 40 subjects at Visit 1. 
7.3. 
Blinding and unblinding 
This is an open-label study with one treatment group. 
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the subject and study (without any link to the treatment 
attributed to the subject) to each sample. 
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7.4. 
Handling, storage and replacement of study vaccine 
The study vaccine has been developed and manufactured by GSK.  
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 vaccine is labelled and packed according to applicable regulatory requirements. 
For information on dosage and administration of the study vaccine, refer to Table 7. The 
study vaccine will be administered on Visit 3 (Month 24) and Visit 4 (Month 25). 
7.4.1. 
Storage and handling of study vaccine 
The study vaccine must be stored at the respective label storage temperature conditions in 
a safe and locked place. Access to the storage space should be limited to authorised study 
personnel. The storage conditions will be assessed during pre-study activities under the 
responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccine. 
A temperature excursion is any temperature that is not in range of the label storage 
temperature conditions. Temperatures outside the range of label storage temperature 
conditions must be reported and documented. Temperature excursion impacting study 
vaccine must be reported and documented. 
In the frame of the reporting, the lack/absence of temperature monitoring documentation 
from a device meeting GSK requirements has to be considered as a temperature 
excursion. 
Study vaccine(s) that are impacted by a temperature excursion may not be used and must 
be quarantined at label storage conditions until usage approval has been obtained 
from/via the local study contact (e.g. Site Monitor). 
Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on 
the temperature excursion reporting and usage decision process, packaging and 
accountability of the study vaccine. 
7.4.2. 
Replacement of unusable vaccine doses 
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomisation when applicable), at least 20% additional vaccine doses will be 
supplied to replace those that are unusable.  
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7.5. 
Concomitant medication(s)/product(s) and concomitant 
vaccinations 
7.5.1. 
Recording of concomitant medications/products and 
concomitant vaccinations 
At each study visit, the investigator or delegate should question the subject and/or the 
subject’s LAR(s) about any medications/products taken and vaccinations received by the 
subject. 
The following medication(s)/product(s)/vaccine(s) must be recorded in the eCRF. 
• 
All medications/products/vaccines, except vitamins and dietary supplements, 
administered or taken  
− 
at ANY time during the period starting with the administration of revaccination 
Dose 1 (Month 24) and ending 30 days after revaccination Dose 2 (Month 26), 
and 
− 
for 30 days before each study visit. 
• 
Any immunoglobulins and blood or blood products administered at and within for 90 
days before any visit. 
• 
Any long-acting immune-modifying drugs administered at any time during the study 
period (e.g. infliximab). 
• 
Any use of anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab, 
ocrelizumab) administered at any time during the study period. 
• 
Any investigational medication or vaccine administered throughout the study (i.e. 
from Visit 1 up to study conclusion).  
• 
Prophylactic medication is defined as medication administered in the absence of 
ANY symptom and in anticipation of a reaction to the revaccination. 
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 at the time of 
revaccination. 
• 
Medications, administered for the treatment of HZ or any related HZ complications, 
from Visit 1 until study conclusion. 
• 
Following medications for biopsy-proven rejections from Visit 1 until study 
conclusion: 
− 
Maintenance IS therapy in use prior to rejection 
− 
Therapeutic IS therapy 
− 
Maintenance IS therapy resumed post-rejection 
• 
Any concomitant medications/products/vaccines leading to the withdrawal or non-
eligibility of the subject from the study (see section 7.5.2 for further details). 
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• 
Any concomitant medications/products/vaccines relevant to an SAE/Adverse Event 
of Special Interest (AESI) to be reported as per protocol or administered at any time 
during the study period for the treatment of an SAE/AESI’s. In addition, concomitant 
medications relevant to SAEs and AESI’s need to be recorded on the Expedited 
Adverse Event report. 
7.5.2. 
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 10.2 for populations to be analysed. 
• 
Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine used during the study period. 
• 
Long-acting immune-modifying drugs administered at any time during the study 
period (e.g. infliximab). 
• 
Any anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab, 
ocrelizumab) used at any time during the study period. 
• 
A vaccine against HZ (including an investigational or non-registered vaccine) other 
than the study vaccine during the study period. 
• 
A live vaccine administered during the period starting 30 days before the first 
revaccination dose and ending 30 days after the last revaccination dose*. 
• 
An inactivated/subunit vaccine, including influenza vaccine, administered during the 
period starting 8 days before the first revaccination dose and ending 30 days after 
each revaccination*. 
*In case an emergency mass vaccination for an unforeseen public health threat (e.g., 
a pandemic) is organized by the public health authorities, outside the routine 
immunization program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to its Summary of Product 
Characteristics (SmPC) or PI 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 period starting 
90 days before any scheduled visit. 
• 
Drug and/or alcohol abuse. 
A detailed, comprehensive list of reasons for elimination from per-protocol analyses will 
be established prior to data cleaning.  
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7.6. 
Intercurrent medical conditions that may lead to elimination 
of a subject from per-protocol analyses  
At each study visit, it must be recorded if the subject has experienced or is experiencing 
any intercurrent medical condition (IMC) that may lead to elimination from per protocol 
analysis. If it is the case, the condition(s) must be recorded in the eCRF. 
IMCs are clinical events occurring in the course of the study which might alter or 
confound the interpretation of the immunologic (not safety) assessments of the protocol. 
With regards to humoral gE assessments, this includes any clinical event that might 
increase or decrease the level of anti-gE antibodies, such as protein losing conditions in 
which the loss of gamma-globulin or total proteins might underestimate the subject’s gE 
response (e.g. protein loss conditions associated with proteinuria). Additional examples 
would be conditions that would cause the administration of exogenous anti-gE antibodies, 
resulting in an overestimate the subject’s anti-gE response, such as conditions requiring 
the use of immunoglobulin (IV Ig) or blood products. For the CMI assessments, IMCs 
would be active viral infections that may alter CD4+ T cell counts and/or responses. 
Examples, although not exhaustive, of such acute viral infections would include acute 
Hepatitis A, acute Hepatitis B, new onset human immunodeficiency virus (HIV), and 
potentially acute cytomegalovirus (CMV) and/or Epstein Barr virus (EBV) infections. 
The occurrence of an episode of HZ is an IMC, as the anti-gE antibody formed during 
active shingles in response to reactivation of VZV cannot be distinguished from the anti-
gE antibody formed in response to vaccination. At Visit 1, all subjects will be informed 
of the signs and symptoms of typical HZ, provided a HZ-specific diary card and ZBPI 
questionnaire, and instructed to call for an appointment if HZ develops. The reporting 
period for cases of HZ will be from enrollment visit to study end. HZ cases will be 
collected in HZ specific screen in the eCRF. Note that all suspected or confirmed HZ that 
occurred since the primary follow-up study ZOSTER-041 will be collected 
retrospectively as part of the medical history. 
ZOSTER-073 IMCs will be reported either as AE or SAEs (as appropriate) in the eCRF 
from enrollment visit (Visit 1) up to study end (Visit 7). 
7.7. 
Contraindications to subsequent vaccine administration 
Prior to receipt of additional study vaccination, subjects must be evaluated to confirm that 
they are eligible for subsequent vaccination.  
If subjects meet any of the original exclusion criteria for revaccination or the criteria 
listed below, they should not receive additional dose of the HZ/su vaccine. However, the 
subjects should be encouraged to continue other study procedures at the discretion of the 
investigator (see section 8.4.5). 
• 
Subjects who experience any SAE judged to be possibly or probably related to study 
vaccine or non-study vaccines, including hypersensitivity reactions. 
• 
Subjects who develop any new condition which, in the opinion of the investigator, 
may pose additional risk to the subject if he/she continues to participate in the study. 
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• 
Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the 
opinion of the investigator, exposes the subject to unacceptable risk from subsequent 
vaccination. In such cases, the investigator should use his/her clinical judgement 
prior to administering the next dose of the vaccine. Refer to section 12.5.5 for the 
definition of pIMDs and to Table 23 for the pIMD listing. 
• 
Anaphylaxis, following the administration of any previous dose of HZ/su vaccine. 
• 
Pregnancy (see section 12.5.7). 
• 
Allograft rejection, biopsy-proven between Visits 3 and 4. 
• 
An episode of HZ between Visits 3 and 4. 
7.8. 
Treatment after completion of the study 
During the study conclusion visit, the investigator will ask each subject/subject’s LAR(s) 
if they are interested in participating in a long-term study. If a subject/subject’s LAR(s) is 
not interested in participating in the long-term study the reason for refusal will be 
documented, when available, in the subject’s eCRF.  
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (see section 2).  
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns.  
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the subject(s) should discontinue study 
treatment. 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable.  
Procedures conducted as part of the subject’s routine clinical management (e.g. blood 
count) and obtained before signing of ICF may be utilised for screening or baseline 
purposes provided the procedure met the protocol-specified criteria and was performed 
within the time frame defined in the SoA. 
In times of special circumstances, refer to Section 8.1.16 for study procedures. 
(Amended: 15 June 2020) 
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8.1. 
General study aspects 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects. 
The SoA is provided in Table 3 and time intervals between visits are presented in Table 
4.  
Non-revaccinated subjects (see Glossary of terms for the definition) are not required to 
return for Visit 4 and Visit 5.  
For these subjects, the following Visit 3 procedures will not occur: 
• 
Pregnancy testing in participants unwilling to be revaccinated (see Section 8.1.7) 
• 
Temperature measurement  
• 
Revaccination 
• 
Post-revaccination solicited and unsolicited diary cards (see Section 8.1.12.1) 
(Amended: 15 June 2020) 
8.1.1. 
Informed consent 
Before performing any other study procedure, the signed informed consent of the subject 
needs to be obtained. Refer to section 12.4.3 for the requirements on how to obtain 
informed consent.  
Informed consent given at the enrollment visit will be reconfirmed at Visit 3 before 
revaccination if needed as per local requirements. 
8.1.2. 
Collection of demographic data 
Collect each subject’s year of birth and record in the subject’s eCRF at the enrollment 
visit. 
Full demographic data will be utilized from the primary study, ZOSTER-041. 
8.1.3. 
Medical history 
At the enrollment visit, obtain the subject’s medical and vaccination history, since the last 
study ZOSTER-041 visit, by interview and/or review of the subject’s medical records and 
record in the eCRF any pre-existing conditions or signs and/or symptoms present in a 
subject prior to the study start. 
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The following medical conditions, medication(s)/product(s)/vaccine(s) will be collected 
and recorded: 
• 
Chronic disorders (e.g. diabetes mellitus, chronic obstructive pulmonary disease, 
stroke, cardiovascular disorders, gout). 
• 
pIMDs. 
• 
HZ (suspected or confirmed). 
• 
Allograft rejection(s) (suspected or biopsy-proven). 
• 
Medications/products/vaccines (except vitamins and dietary supplements) being 
taken within 1 month (30 days) before the enrollment visit.  
• 
Any immunoglobulins and blood or blood products administered at and within for 90 
days before enrollment visit. 
• 
Any long-acting immune-modifying drugs administered at and within 360 days 
before enrollment visit (e.g. infliximab). 
• 
Any use of anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab, 
ocrelizumab) administered at and within 360 days before enrollment visit.  
8.1.4. 
Interim medical history 
From Visit 2 to Visit 7, obtain the subject’s interim medical history (history since the last 
study visit) by interview and/or review of the subject’s medical records and record new 
findings or exacerbations of previous recorded conditions in source documents. 
8.1.5. 
Record transplant-specific information in case of new transplant 
received since the last visit in ZOSTER-041. 
In the event a subject has received a new allograft since ZOSTER-041, transplant-
specific information on the new transplant must be collected. 
The transplant time points of interest will be: 
• 
Pre-transplantation (from a minimum of at least 6 months prior to transplantation). 
• 
At transplantation (day prior to and day of implantation of allograft, unless otherwise 
specified). 
• 
Post-transplantation (from transplant to time of re-enrollment). 
Record the following transplant information (based on medical history) in the eCRF at 
Visit 1: 
• 
Date of new renal transplant.  
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
5 4  
•  
All o graft fact ors:  
− 
A ge of t he all o graft ( years)  
− 
All o graft s o urce  
N o n -heart beati n g d o nati o ns ( Yes/ N o)  
− 
All o graft’s class I a n d cl ass II H L A a nti ge ns  
•  
Reci pie nt fact ors:  
− 
Pri mar y ki d ne y dise ase as i n dicati o n f or tra ns pla ntati o n  
− 
S m o ki n g hist or y (ci garettes, ci gars a n d/ or pi pes per da y) –  at tra ns pla nt a n d 
p ost -tra ns pla nt 
− 
I n d u cti o n i m m u n os u p pressi ve a ge nts use d wit h st o p dates  
− 
Reci pi e nt’s class I a n d cl ass II H L A a nti ge ns  
− 
Se nsitisati o n:  
1.  P R A/c P R A sc ore –  hist orical ma xi m u m sc ore a n d pre -tra ns pl a nt P R A sc ore 
( hist orical ma xi m u m P R A: ma xi m u m perce nta ge of a nti b o dies pri or t o 
tra ns pla ntati o n; pre-tr a ns pla nt P R A: perce nta ge of a nti b o dies c orres p o n di n g 
t o last ser u m sa m ple a vaila ble) 
•  
Tra ns pla ntati o n fact ors:  
− 
C ol d isc he mic ti me ( h o urs) of t he all o graft  
− 
All o graft f u ncti o n:  
1.  S er u m creati ni ne at a n d p ost -tra ns pla ntati o n (see secti o n 8. 1. 9 ) 
− 
Dela ye d all o graft f u n cti o n –  will be defi ne d as use of dial ysis after first w ee k 
p ost -tra ns pla ntati o n (rec or d t he act ual n u m ber of da ys of dial ysis occ urri n g p ost-
tra ns pla ntati o n, fr o m t he ti me of tra ns pla nt)  
− 
C urre nt all o graft bi o ps y(i es):  
1.  N u m ber a n d d ates of bi o psies  
2.  Reas o n f or bi o ps y(ies): p er s ur veilla nce pr ot oc ol or cli nical i n dicati o n  
3.  Prese nce of bi o ps y c o nfir me d rejecti o n (ac ute, s u b cli nical ac ute, c hr o nic) 
f or eac h bi o ps y 
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8.1.6. 
Physical examinations and history directed physical examination 
• 
At all visits: 
− 
measure and record the subject’s weight. 
− 
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. 
− 
Physical examination/history directed physical examination is to be recorded in 
the source documents and abnormalities/pertinent diagnoses in eCRF. 
• 
At enrollment visit and at Visit 3, perform a physical examination. At Visit 3, if the 
investigator determines that the subject’s health on the day of revaccination 
temporarily precludes revaccination, the visit will be rescheduled. 
• 
At the other visits, perform a history directed physical examination. At Visit 4, if the 
investigator determines that the subject’s health on the day of revaccination 
temporarily precludes revaccination, the visit will be rescheduled.  
8.1.7. 
Pregnancy test 
Female subjects of childbearing potential are to have a urine pregnancy test performed 
and reviewed prior to any study vaccine administration. However, pregnancy testing 
should not be performed if female subjects are unwilling to be revaccinated. 
(Amended: 15 June 2020) 
Note: Pregnancy test must be performed even if the subject is menstruating at the time of 
the study visit. 
A urine pregnancy test is sufficient. A serum pregnancy test should only be performed as 
required by country, local or ethics committee regulations. In case a serum pregnancy test 
is required, a blood sample will be collected at Visits 3 and 4 and testing performed per 
local guidance. The result of serum pregnancy tests will be reviewed prior to any study 
vaccine administration. 
The results of applicable test must be recorded in the eCRF. The study vaccine may only 
be administered if the pregnancy test is negative. 
8.1.8. 
Pre-revaccination body temperature 
The oral (preferred route) body temperature of each subject needs to be measured prior to 
any study vaccine administration and recorded in the eCRF. If the subject has fever [fever 
is defined as temperature 38.0°C (100.4°F) regardless of route of measurement] on the 
day of vaccination, the revaccination visit will be rescheduled within the allowed interval 
for this visit (see Table 4). Pre-revaccination temperature measurements should not be 
performed for non-revaccinated subjects. (Amended: 15 June 2020) 
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8.1.9. 
Record serum creatinine measures 
As the detection of kidney allograft function is paramount to the management of allograft 
health and prevention of allograft rejection, transplant centers have established vigorous 
routine clinical surveillance protocols for the monitoring of the allograft. This study will 
rely on these per site “surveillance protocols” and will not mandate the type or timing of 
tests to participating study sites. 
To follow allograft function, the available serum creatinine measurements, obtained per 
the site’s “surveillance protocol” or for “clinical indication” (locally available), will be 
recorded in the eCRF.  
Record ALL serum creatinine obtained: 
• 
For Allograft rejection 
− 
For 2 months prior to a biopsy-proven allograft rejection, as event baseline. If 
not 2 or more measurements in 2 months, then go back to 3 or 4 months prior to 
biopsy to have a minimum of 2 measurements.  
− 
From onset of allograft rejection through resolution. 
− 
For 2 months after resolution of the biopsy-proven rejection and the cessation of 
therapeutic immunosuppressive therapy, so that 2 or more additional post-
rejection measurements are recorded.  
Post-allograft rejection serum creatinine measurements will be evaluated in 
comparison to the subject’s baseline pre-allograft rejection measurements.  
• 
For revaccination 
− 
For 3 months prior to first revaccination, Visit 3 (Month 24), as pre-vaccination 
baseline. If not 3 or more measurements in 3 months, then go back to 4 or 5 
months prior to revaccination to have a minimum of 3 measurements.  
− 
From Visit 3 (Month 24) through Visit 5 (Month 26). 
− 
For 3 months after last revaccination, Visit 5 (Month 26), so that 3 or more 
additional post-revaccination measurements are recorded.  
Post-revaccination serum creatinine measurements will be evaluated in comparison 
to the subject’s baseline pre-revaccination measurements. 
• 
For episode of HZ cases 
− 
For 2 months prior to a HZ episode, as event baseline. If not 2 or more 
measurements in 2 months, then go back to 3 or 4 months prior to HZ episode to 
have a minimum of 2 measurements.  
− 
From onset of HZ episode until the HZ rash resolution. 
− 
For 2 months after HZ episode rash resolution, so that 2 or more post-HZ 
resolution measurements are recorded.  
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
5 7  
P ost -H Z ser u m creati ni ne meas ure me nts will be e val uate d i n c o m paris o n t o t he 
s u bject’s baseli ne pre-H Z rejecti o n meas ure me nts. 
8. 1. 1 1.  
R e c or d a n y c o n c o mit a nt m e di c ati o n s/ v a c ci n ati o n s a n d a n y 
i nt er c urr e nt m e di c al c o n diti o n s 
C o nc o mita nt me dicati o n/ vacci nati o n m ust be c h ec ke d a n d rec or de d i n t he e C R F as 
descri be d i n secti o n 7. 5 . 
I nterc urre nt me dic al c o n diti o ns m ust be c hec ke d a n d rec or de d i n t he e C R F as des cri be d 
i n Secti o n 7. 6 . 
8. 1. 1 2.  
D at a c oll e cti o n  
8. 1. 1 2. 1.  
Di ar y c ar d s a n d q u e sti o n n air e s  
D iar y car ds a n d t he Z B PI q uesti o n naire will be distri b ute d a n d e x plai ne d  t o s u bject or 
s u bject’s L A R(s) ( or s u bject’s care gi ver) b y t he i n vesti gat or or his/ her dele gat e. A n y 
s u p plie d diar y car ds or q uesti o n naires s h o ul d be c o m plete d b y t he s u bject t he msel ves  or  a 
site trai ne d assista nt.  
If assista nce is n ee de d , a site trai ne d a n d desi g nat e d assista nt (s uc h as L A R, a fa mil y 
me m ber o r a care gi ver ) s h o ul d ai d wit h rea di n g t he q uesti o ns ( ver bati m) a n d/ or 
tra nscri bi n g t he s u bject’s res p o nses o n t he q uesti o n naires a n d/ or diar y car ds. T his 
assista nce s h o ul d be pr o vi de d at t he ti me t he s u bject is re q uire d t o c o m plete t he 
q uesti o n naire or di ar y car d (i.e. i n “real ti me”, n ot retr os pecti vel y).  T he p ossi bilit y of 
assista nce b y a tr ai ne d a n d desi g nat e d pers o n is t o be ta ke n i nt o acc o u nt f or all st u d y 
pr oce d ures rel ate d t o t he c o m pleti o n of diar y car ds a n d q uesti o n naires . Trai ni n g t he 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
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assistant is to be given by the study staff (see Table 3). Study staff will ask the subject (at 
the time of return or at subsequent contact) if he/she received any assistance in 
completing diary cards or questionnaires. If the subject had assistance completing the 
diary card and/or questionnaires, it should be noted in the eCRF. In case questionnaires 
are completed at the study site, study staff can assist in reading the questions (verbatim).  
All revaccinated subjects will receive: 
• 
Diary cards: To be completed by the subject or subject’s trained assistant after each 
revaccination for recording of solicited AEs (from day of revaccination to 
subsequent 6 days), unsolicited AEs (from day of revaccination to subsequent 29 
days), any medically attended visits and all concomitant medications / vaccinations 
taken from day of revaccination to subsequent 29 days or to next study visit.  
Diary cards should not to be provided to non-revaccinated subjects. 
All subjects will receive: 
• 
HZ-specific diary card: To be completed by the subjects or subject’s trained 
assistant beginning immediately (and only) upon development of any symptoms 
suggestive of HZ and prior to visiting the study site for evaluation of suspected HZ. 
• 
ZBPI questionnaire: To be completed by the subject with suspected HZ or subject’s 
trained assistant beginning immediately (and only) upon development of any 
symptoms suggestive of HZ to collect information on the severity and duration of the 
HZ-associated pain and the impact of the HZ-episode on the subject’s quality of life 
(QoL). The study staff/investigator will provide instructions to the subject or 
subject’s trained assistant for completing the ZBPI questionnaires and explain the 
importance of completing and returning the questionnaires to the site in order to 
provide information on HZ episode. 
(Amended: 15 June 2020) 
8.1.13. 
Record pregnancies and pregnancy outcomes 
Pregnancies and pregnancy outcomes in study ZOSTER-073 will be collected and 
recorded from Visit 1 (Day 1) through study conclusion Visit 7 (Month 49). 
Please refer to section 12.5.9.1 for details. 
8.1.14. 
Renal allograft rejection 
At all visits, subjects will be instructed to contact the study site or their private health 
care provider if they develop signs or symptoms perceived as renal allograft dysfunction, 
rejection, or failure, as explained by their transplant physician(s).  
Subjects, after notifying the study site of possible allograft dysfunction, rejection, or 
failure, will undergo the study site’s standard clinical procedures for the diagnosis of 
possible rejection. These allograft diagnostic tests, including any biopsies, will be 
considered “clinically indicated.”  
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In addition to clinically indicated testing and as part of the management of the transplant, 
allograft function testing and biopsies may be routinely performed, per a center defined 
protocol and timetable for surveillance. These tests will be considered as performed per 
“surveillance protocol” and recorded into eCRF screen. 
For study purposes, rejection must be biopsy-proven pathophysiological changes of 
rejection (acute or chronic glomerulitis, tubulitis, intimal arteritis, interstitial infiltration, 
hyaline arteriolar thickening, peritubular capillaritis and/or total interstitial inflammation) 
with or without C4d-staining of biopsy. The rejection will be graded for type and severity 
by means of the Banff criteria [Racusen, 1999; Sis, 2010; Solez, 2008; Solez, 2012; 
Mengel, 2012].  
Biopsy proven rejection will be recorded on the following eCRF screens; Expedited 
Adverse Events Report and Renal Biopsy screens. The reporting period for “biopsy 
proven” rejections will be from Visit 1 (Day 1) to the study end (Month 49). The 
following information on allograft rejection is to be included in eCRF screens: 
• 
Start date as based on: 
− 
Date of first appearance of clinical symptoms indicative of rejection, resulting in 
a “clinically indicated” biopsy or  
− 
Date of “surveillance protocol” biopsy. 
• 
Pertinent medical evaluations with results, including:  
− 
Allograft biopsy - date, histological results, the Banff criteria grading and 
specimen adequacy 
− 
Clinical laboratories, e.g. proteinuria, serum creatinine, estimated GFR, urinary 
creatinine clearance.  
− 
Clinical cultures 
− 
Ultrasounds 
• 
Medical management including but not limited to: 
− 
procedures (plasmapheresis, immunoadsorption, splenectomy, other surgical 
intervention);  
− 
changes in immunosuppressive medications (intravenous immunoglobulin, high-
dose glucocorticoids, antiproliferative agents, anti-B cell agents, anti-plasma cell 
agents, anti-T cell agents, terminal-complement pathway inhibitor);  
− 
initiation of dialysis. 
• 
End date of the rejection event. 
• 
Outcome: not recovered/not resolved (ongoing, stabilised, progressing [e.g. allograft 
rejection progressing to failure]), recovering/resolving/disappearing, 
recovered/resolved. 
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8.1.15. 
Ad-hoc HZ visit and phone call for evaluation of suspected HZ 
Subject or subject’s LAR(s) (or subject’s caregiver) will be instructed to call as soon as 
possible and schedule an ad-hoc HZ visit preferably within 3 calendar days from 
appearance of any symptom suggestive of HZ.  
Subject or subject’s trained assistant will also be instructed to complete HZ-specific diary 
card and ZBPI questionnaire daily, starting within 24 hours from appearance of HZ 
symptom until the day of the ad-hoc HZ Visit. Subject or subject’s LAR(s) (or subject’s 
caregiver) will also be instructed to bring the completed HZ-specific diary card and ZBPI 
questionnaires to the ad-hoc HZ Visit. 
During the ad-hoc HZ Visit, the study staff/investigator will be instructed to: 
• 
Document clinical history of suspected HZ and perform physical exam; 
(Amended: 15 June 2020) 
• 
Transcribe all information from the HZ-specific diary card and ZBPI questionnaire 
completed by the subject or subject’s trained assistant into the eCRF in HZ-specific 
screens; 
• 
Record concomitant medications/vaccinations, including concomitant medication the 
subject has already received and/or will receive for HZ treatment or treatment of any 
HZ-related complications; 
• 
Check if the subject received any medical attention [hospitalisation, emergency room 
visit, or a visit to or from medical personnel (medical doctor)] for HZ or any HZ-
related complication. 
• 
Take digital photographs of HZ rash and upload to e-Clinipix. Please refer to the 
SPM for specific instructions. At the discretion of the investigator, additional ad-hoc 
HZ follow-up visit(s) may be necessary to manage the progression of the rash, 
additional photographs of HZ rash may be appropriate. 
• 
If during clinical evaluation the investigator determines that adequate rash lesion 
samples from at least 3 separate lesions cannot be collected (i.e., <3 lesions present, 
or if only papules are present), ask the subject to return to the study site for collection 
of three additional lesion samples (from at least 3 separate lesions).  
• 
Provide an additional supply of ZBPI questionnaires and HZ-specific diary cards to 
the subjects at ad-hoc HZ visit(s). Concomitant medications section of HZ-specific 
diary cards should be updated as necessary for medication changes, including 
start/stop dates. ZBPI questionnaires should be completed by subjects or subject’s 
trained assistant daily for 30 days from onset of HZ symptoms and then weekly until 
the resolution of the rash. (Amended: 15 June 2020) 
• 
Remind subjects or subject’s LAR(s) (or subject’s caregiver) to return the HZ-
specific diary cards and ZBPI questionnaires completed after the initial ad-hoc HZ 
visit, at the next visit or by mail after resolution of rash. Once the additional 
completed HZ-specific diary cards and ZBPI questionnaires are available, the 
investigator will transcribe the information into the subject’s eCRF.  
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• 
Ask/remind the subjects or subject’s LAR(s) (or subject’s caregiver) to make a 
phone call to study sites to communicate the resolution date of HZ rash and HZ pain.  
• 
In case subjects do not make a phone call to study sites, make a phone contact with 
the subjects within 3 months (90 days) of the last ad-hoc HZ visit for collecting the 
resolution date of HZ rash and confirming whether the HZ pain has resolved or is 
ongoing. 
• 
In the event, the resolution dates for the HZ rash and HZ pain have not otherwise 
been collected, this information is to be captured at next scheduled visit(s). 
8.1.16. 
Study procedures during special circumstances (Amended: 15 
June 2020) 
During special circumstances (e.g., COVID-19 pandemic), specific guidance from local 
public health and other competent authorities regarding the protection of subjects’ 
welfare must be applied. 
The following measures may be implemented, at the discretion of the Sponsor, during 
special circumstances.  
For potential subjects unable to be enrolled due to special circumstances: 
• 
Potential subjects, who were not able to enroll between 09 December 2019 and 18 
March 2020, will be offered enrollment to coincide with the Visit 2 calendar 
period.  
− Enrollment, Visit 1 and Visit 2 study procedures will be scheduled on the same 
day. 
− Visit 2 blood samples will be collected and recorded on Visit 2 eCRF per SoA 
(see Table 3). No Visit 1 blood samples will be collected. 
• 
All subjects will be scheduled together for re-vaccination at Visit 3 (see Table 8 
and SPM, for details). 
For all enrolled subjects: 
• 
For the duration of COVID-19 pandemic, suspected, probable, and confirmed 
cases of COVID-19 will be recorded at the next scheduled visit on the COVID-19 
specific eCRF. 
• 
Individual subject revaccination visits may be delayed, to allow for treatment of, or 
vaccination for, COVID-19 (or other special circumstances). Such delay will allow 
for completion of the therapies and resolution of any therapy-associated AEs and 
immune-modifying effects (see Section 6.2.2) prior to revaccination.  
• 
As necessary and appropriate, safety follow-up may be made by a telephone call, 
other means of virtual contact or home visit. 
• 
Diary cards and ZBPI questionnaire may be transmitted from and to the site by 
conventional mail and/or electronic means. 
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• 
Visits for suspected HZ may take place away from the study site, such as in a 
different location* or at participant’s home. If an in-person visit is not feasible, 
then the medical evaluation of suspected HZ may take place virtually (e.g. video 
call) with documentation of rash and pain by investigator notes, and by subject-
submitted photographs (as possible), diary cards, and ZBPI. 
• 
Biological samples may be collected away from the study site, such as in a different 
medical location* or at subject’s home. Biological samples should not be collected 
if they cannot be processed in a timely manner or appropriately stored until the 
intended use (see SPM, for details). 
* It is the investigator’s responsibility to identify an alternate medical location. The 
investigator should ensure that this alternate location meets ICH GCP 
requirements, such as adequate facilities to perform study procedures, appropriate 
training of the staff and documented delegation of responsibilities in this location. 
This alternate location should be covered by proper insurance for the conduct of 
study on participants by investigator and staff at a site other than the designated 
study site. Refer to EMA Guidance on the Management of Clinical Trials during 
the COVID-19 (Coronavirus) pandemic (version 2, 27 March 2020) for more 
details. 
• 
If despite best efforts, it is not possible to collect blood samples within the interval 
predefined in the protocol (see Table 4), then the interval may be extended as 
defined in Table 8.  
• 
If despite best efforts, it is not possible to administer the second dose of study 
vaccine as defined in the protocol (see Table 4), a maximum dose interval of up to 
6 months after the first revaccination dose may be used. If the maximum dose 
interval length is exceeded, then vaccination should be discontinued. 
Impact on the per protocol set (PPS) for immunogenicity will be determined on a case 
by case basis. 
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Table 8 
Intervals between study visits during special circumstances 
(Amended: 15 June 2020) 
Visits 
At the discretion of Sponsor, during special 
circumstances  
Notes 
Visit(s) may be delayed Allowed interval (days) 
Visit 2   
Up to 6 months 
 
The length of the allowed interval (85 days) 
remains, but the start of the interval may be 
moved by up to 6 months (starting no later 
than 18 months post-Visit 1), e.g. to avoid 
potential seasonal recurrence of COVID-19 
PC 1  
 
30 – 40 days before Visit 3 
 
Visit 3  
Up to 6 months 
 
The length of the allowed interval (85 days) 
remains, but the start of the interval may be 
moved by up to 6 months (starting no later 
than 30 months post-Visit 1), e.g. to avoid 
potential seasonal recurrence of COVID-19 
Visit 4  
 
30 – 182 post-Visit 3 
Optimally 30 - 60 days after Visit 3 (Table 4) 
Visit 5  
 
30 – 90 post-Visit 4 
Optimally 30 – 48 days after Visit 4 (Table 4) 
Visit 6*  
 
330 – 445 post-Visit 4 
 
Visit 7*  
 
690 – 805 post-Visit 4 
Visit 7 may be: 
• 
Scheduled earlier to make up for 
delays incurred during times of special 
circumstance, in order to maintain 
planned duration of the study. 
• 
Delayed or cancelled if special 
circumstances preclude the original 
planned visit. 
Note: Investigator should prioritize conducting the visit as close to the optimal window as possible. 
* The allowed interval for Visits 6 and 7 should be the same for both the re-vaccinated and non-revaccinated 
subjects.  
(Amended: 15 June 2020) 
8.2. 
Efficacy assessments 
Not applicable. 
8.3. 
Immunogenicity assessments 
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment). 
Samples will not be labelled with information that directly identifies the subject but will 
be coded with the subject identification 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 
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maintenance or improvement of these tests, the development of new test methods, as well 
as making sure that new tests are comparable to previous methods and work reliably. 
It is also possible that future findings may make it desirable to use the samples acquired 
in this study for future research, not described in this protocol. Therefore, all subjects will 
be asked to give a specific consent to allow GSK or a contracted partner to use the 
samples for future research. Future research will be subject to the laws and regulations in 
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.  
Any sample testing will be done in line with the consent of the individual 
subject/subject’s LAR(s).  
Refer also to the Amendment 1 Investigator Agreement, where it is noted that the 
investigator cannot perform any other biological assays except those described in the 
protocol or its amendment(s).  
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK.  
8.3.1. 
Use of specified study materials 
When materials are provided by GSK, 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 10.2 for the definition of populations 
for analyses). The investigator must ensure that his/her personnel and the laboratory(ies) 
under his/her supervision comply with this requirement. However, when GSK does not 
provide material for collecting and storing clinical samples, appropriate materials from 
the investigator’s site must be used. Refer to the Module on Clinical Trial Supplies in the 
SPM. 
8.3.2. 
Biological samples 
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples. 
8.3.2.1. 
Blood sampling for immunogenicity response and safety assessments  
Blood samples will be taken at each study visit as specified in section 2. Blood draws 
scheduled on the days of revaccination (Visits 3 and 4) must be done before vaccination. 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
6 5  
•  
A v ol u me of a p pr o xi matel y 5 . 0 m L  of w h o le bl o o d (t o pr o vi de a p pr o xi matel y 
2 .0  m L of s er u m ) s h o ul d be dra w n fr o m eac h s u bj ect f or a nal ysis of h u m or al 
i m m u ne res p o nse at e ac h pre-defi ne d ti me p oi nt. After ce ntrif u gati o n, ser u m sa m ples 
s h o ul d be ke pt at – 2 0° C or bel o w u ntil s hi p me nt. Refer t o t he S P M f or m ore details 
o n sa m ple st ora ge c o n diti o ns.   
•  
A v ol u me of a p pr o xi matel y 3 0  m L  of w h ole bl o o d s h o ul d be dra w n fr o m s u bjects 
i ncl u de d i n t he C MI  s u b-c o h ort f or a n al ysis of cell -me diate d i m m u ne  res p o nse at 
eac h pre-d efi ne d ti me p oi nt. T he bl o o d s h o ul d be st ore d at t he i n vesti gat or’s site at 
r o o m te m perature a n d it m ust n ot  be ce ntrif u ge d. Sa m ples will be s hi p pe d at r o o m 
te m perat ur e (1 5  t o 2 5° C) t o t he desi g nat e d la b orat or y f or cell se parati o n t o be 
perf or me d wit hi n 2 4 h o urs. Refer t o t he S P M f or m ore details o n sa m ple st ora ge 
c o n diti o ns.   
F or eac h s u bject n ot i n t he C MI s u b c o h ort , a n o v erall v ol u me of a p pr o xi matel y 7 5  m L 
will be c ollecte d d uri n g t he e ntire st u d y peri o d  (a p pr o xi matel y 4 9 m o nt hs). 
F or eac h s u bject i n t he t he C MI s u b c o h ort, a n o v erall v ol u me of a p pr o xi matel y 2 8 5  m L 
will be c ollecte d , d uri n g t he  e ntire st u d y peri o d  (a p pr o xi matel y 4 9 m o nt hs). 
B l o o d sa m ples will be c ollecte d  i n t he f oll o wi n g or der : 
1.  A nti -g E a nti b o d y ( 5 m L) 
2.  C MI ( 3 0 m L) 
8. 3. 2. 2.  
H Z l e si o n s s a m pli n g  
I n t he e ve nt t here is a cas e of s us pecte d H Z, s u bjects will ret ur n f or a n a d h oc  H Z Visit 
f or t he c ollecti o n of t hree ( 3) ras h lesi o ns sa m ples. Sa m pli n g will be tar gete d b y t he 
hi g hest pri orit y lesi o n t y pe a vaila ble , as 1) vesicl e fl ui d; 2) cr ust; 3) cr ust s wa b; a n d 4) 
pa p ule s wa b  (s ee secti o n 8. 1. 1 5  f or m ore d etails o n c ollecti n g H Z lesi o n sa m ples). H Z 
lesi o n sa m ples s h o ul d be ke pt at – 2 0° C or bel o w u ntil s hi p me nt.  Refer t o t he S P M f or 
m ore details o n sa m ple st ora ge c o n diti o ns.  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
6 6  
T a bl e 9  
Bi ol o gi c al s a m pl e s  
S a m pl e t y p e  
Q u a ntit y  
U nit  Ti m e p oi nt  
S u b -c o h ort N a m e*  
Bl o o d f or h u m or al r es p o ns e  
a p pr oxi m at ely  5  
m L  
Visit s 1, 2, 3, 4 **, 5**, 6 a n d 7 All s u bj ects  
Bl o o d f or C MI r es p o ns e  
a p pr oxi m at ely  3 0  m L  
Visits 1, 2, 3, 4 **, 5**, 6 a n d 7 C MI s u b -c o h ort  
Cli nic al s p eci m e ns of  r as h l esi o ns 
f or c o nfir m ati o n of H Z by P C R  
3 s a m pl es (fr o m 3 
s e p ar at e l esi o ns) N A  
Ev e nt -driv e n  
Su bj ects cli nic ally 
di a g n os e d as h avi n g a 
s us p ect e d c as e of H Z. 
C MI = C ell -M e di at e d I m m u n o g e nicity; H Z = H er p es Z ost er; P C R = Poly m er as e C h ai n R e acti o n ; N A = N ot A p plic a bl e; 
 
* R ef er t o S ecti o n 1 0. 1  f or s u bs et d escri pti o n.  
** R ef er t o S e cti o n 5. 3  f or n o n -re v a c ci n at e d s u bj e ct s . T h e s e s u bj e ct s will n ot h a v e Vi sit 4 a n d Vi sit 5 bl o o d 
dra w s . ( A m e n d e d: 1 5  J u n e 2 0 20)  
8. 3. 3.  
L a b or at or y a s s a y s  
Please refer t o  A p p e n di x  2  f or a det aile d descri pti o n of t he assa ys perf or m e d i n t he st u d y. 
Please refer t o A p p e n di x 3  f or t he a d dress of t he cli nical la b orat ories us e d f or sa m ple 
a nal ysis .  
8. 3. 3. 1.  
I m m u n ol o gi c al a s s a y s 
g E -s pecific h u m or al i m m u ne res p o nse  
A ssa ys f or t he d eter mi nati o n of g E -s p ecific a nti b o dies will be per f or m e d b y E nz y m e 
Li n ke d I m m u n os or b e nt Assa y ( E LI S A ) at a G S K la b orat or y usi n g sta n dar dize d a n d 
vali date d pr oce d ures (refer  t o Ta ble 1 0 ). 
T a bl e 1 0  
H u m or al I m m u nit y ( A nti b o d y d et er mi n ati o n)  
S y st e m  
C o m p o n e nt  
M et h o d  
Kit/ M a n uf a ct urer  
L a b orat ory * 
S er u m  
V aric ell a Z ost er 
Vir us. Glyc o pr ot ei n E A b.I g G  
ELI S A  
N A  
G S K a n d/ or l a b d esi g n at e d 
by G S K  
A b = A nti b o dy; I g G = I m m u n o gl o b uli n cl ass G; ELI S A = Enzy m e -li nk e d I m m u n os or b e nt Ass ay; 
N A = N ot a p plic a bl e;  
* R ef er t o Ap p e n dix 3  f or t h e l a b or at ory a d dr ess es. 
g E -s pecific C MI res p o nse  
A ssa ys f or t he d eter mi nati o n of g E -s p ecific C D 4 + T -cells e x pressi n g at least 2 acti vati o n 
mar kers (fr o m a m o n g I F N -γ, I L-2, T N F -α a n d C D 4 0 L) will be perf or me d b y i ntracell ular 
c yt o ki ne stai ni n g (I C S) as meas ure d b y c yt o ki ne fl o w c yt o metr y ( C F C) i n a la b orat or y 
desi g nat e d b y G S K usi n g sta n dar dize d a n d vali dat e d pr oce d ures (refer T a ble 1 1 ). 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
6 7  
T a bl e 1 1  
C ell -m e di at e d I m m u nit y ( C MI) u si n g c yt o ki n e fl o w c yt o m etr y 
S y st e m  
C o m p o n e nt F a mil y  
C h all e n g e  M et h o d  
L a b orat ory*  
P B M C  
C D 4. p oly p ositiv es  
C D 4 0 L +I L -2 + T N F α +I F N γ** 
g E  
I C S 
G S K a n d/ or l a b d esi g n at e d by 
G S K   
g E = r ec o m bi n a nt p urifi e d Glyc o pr ot ei n E ; I C S = I ntr ac ell ul ar Cyt oki n e St ai ni n g as m e as ur e d by cyt oki n e fl o w 
cyt o m etry 
* R ef er t o Ap p e n dix 3  f or t h e l a b or at ory a d dr ess es. 
** C D 4. p oly p ositiv es C D 4 0 L +I L-2 + T N F α +I F Nγ = C D 4 + T -c ells ex pr essi n g at l e ast 2 activ ati o n m ark ers (fr o m a m o n g 
I F Nγ, I L-2, T N F α a n d C D 4 0 L).  
V aricell a z ost er vir us ( V Z V ) m olec ul ar bi ol o g y  
F or cli nicall y dia g n os e d s us pecte d H Z cases, t he p ote ntial of H Z i nfecti o n will be 
assesse d b y real-ti me P C R ( P C R) testi n g f or V Z V D N A (see Ta ble 1 2 ). 
T a bl e 1 2  
M ol e c ul ar Bi ol o g y  ( P C R t e st s) 
S y st e m  
C o m p o n e nt  
M et h o d  
L a b orat ory * 
H Z l esi o n s a m pl e  
V aric ell a Z ost er Vir us. D N A  
P C R  
G S K a n d/ or l a b 
d esi g n at e d by G S K  
H Z l esi o n s a m pl e 
β -Acti n G e n e. D N A  
P C R  
G S K  a n d/ or l a b 
d esi g n at e d by G S K   
P C R: P oly m er as e C h ai n R e acti o n  
* R ef er t o Ap p e n dix 3  f or t h e l a b or at ory a d dr ess es. 
A d diti o nal testi n g o n t he vacci ne a n d/ or o n t he dis ease u n der st u d y ma y be perf or me d 
wit hi n t he fra me w or k of t he st u d y if dee me d necessar y f or acc urate i nter pretati o n of t he 
data or s h o ul d s uc h ass a y(s) bec o me a vaila ble at G S K . T hese assa ys ma y n ot be 
re pres e nte d i n t he o bjecti ves/e n d p oi nts of t he st u d y pr ot oc ol. 
T he G S K cli nical la b orat ories ha ve esta blis he d a Q ualit y S yste m s u p p orte d b y 
pr oce d ures. T he acti vities of G S K cli nical la b orat ories are a u dite d re g ularl y f or q ualit y 
assess me nt b y a n i nter nal (s p o ns or -de p e n d e nt) b ut la b orat or y-i n de pe n de nt Q ualit y 
De part me nt.  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol A m e n d m e nt  1  Fi n al  
1 5 -J U N -2 0 2 0  
6 8  
8. 3. 4.  
Bi ol o gi c al s a m pl e s e v al u ati o n  
T he bl o o d sa m ples will be a nal yz e d acc or di n g t o i m m u n ol o gical rea d -o uts pr o vi de d i n 
Ta ble 1 4 . 
T a bl e 1 4  
I m m u n ol o gi c al r e a d-o ut s  
Bl o o d s a m pli n g ti m e p oi nt  
S u b -c o h ort 
n a m e*  
T ar g et e d N o. 
s u bj e ct s (i. e. 
m a xi m u m)  
Sa m pl e t y p e  
C o m p o n e nt s  
T y p e of c o nt a ct a n d 
ti m e p oi nt 
S a m pli n g 
ti m e p oi nt 
Visit 1 ( D ay 1)  
P ost -pri m ary 
V acc 2  
All s u bj ects  
8 6   
Ser u m  
Anti -g E Ab  
C MI s u bj ects**  4 0   
P B M C  
g E -s p ecific C D 4 + 
T -C ells  
Visit 2 ( M o nt h 1 2)  
P ost - pri m ary 
V acc 2  
All s u bj ects  
8 6  
Ser u m  
Anti -g E Ab  
C MI s u bj ects  
4 0   
P B M C  
g E -s p ecific C D 4 + 
T -C ells  
Visit 3 ( M o nt h  2 4)  
pr e -r e V acc 1 
All s u bj ects  
8 6  
Ser u m  
Anti -g E Ab  
C MI s u bj ects  
4 0   
P B M C  
g E -s p ecific C D 4 + 
T -C ells  
All s u bj ects  
8 6  
Ser u m  
 
Visit 4 ( M o nt h 2 5)  *** P ost -r e V acc 1 
All s u bj ects  
8 6  
Ser u m  
Anti -g E Ab  
C MI s u bj ects 
4 0   
P B M C  
g E -s p ecific C D 4 + 
T -C ells  
All s u bj ects  
8 6  
Ser u m  
 
Visit 5 ( M o nt h 2 6)  *** P ost -r e V acc 2 
All s u bj ects  
8 6  
Ser u m  
Anti -g E Ab  
C MI s u bj ects  
4 0   
P B M C  
g E -s p ecific C D 4 + 
T -C ells  
All s u bj ects  
8 6  
Ser u m  
 
Visit 6 ( M o nt h 3 7)  
P ost -r e V acc 2 
All s u bj ects  
8 6  
Ser u m  
Anti -g E  Ab  
C MI s u bj ects  
4 0   
P B M C  
g E -s p ecific C D 4 + 
T -C ells  
All s u bj ects  
8 6  
Ser u m  
 
Visit 7 ( M o nt h 4 9)  
P ost -r e V acc 2 
All s u bj ects  
8 6  
Ser u m  
Anti -g E Ab  
C MI s u bj ects  
4 0   
P B M C  
g E -s p ecific C D 4 + 
T -C ells  
All s u bj ects  
8 6  
Ser u m  
 
reV a c c = r eV acci n ati o n; C MI  =  C ell - M e di at e d I m m u n o g e nicity; A b = Anti b o dy;  g E  = r ec o m bi n a nt p urifi e d Glyc o pr ot ei n 
E;  
 N A  = n ot a p plic a bl e.  
* F or s u bj ects i n C MI s u b-c o h ort a w h ol e bl o o d s a m pl e f or g E-s p ecific C D 4 T -c ell t esti n g will b e t ak e n at  all  st u dy visits.  
 
 
**r ef er t o secti o n 7. 2. 2  f or t h e d efi niti o n of t h e s u bs ets a n d m et h o d of s el ecti o n. 
*** R ef er t o S e cti o n 5. 3  f or n o n-re v a c ci n at e d s u bj e ct s. T h e s e s u bj e ct s will n ot h a v e Vi sit 4 a n d Vi sit 5 bl o o d 
dra w s. ( A m e n d e d: 1 5  J u n e 2 0 20)  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI
C CI
C CI
C CI
C CI
C CI

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8.3.4.1. 
Molecular biology on suspected HZ skin lesions 
Table 15 
Evaluation of suspected HZ cases  
Type of contact and 
timepoint 
Sampling timepoint 
Sub-cohort 
Targeted No. subjects (i.e 
maximum) 
Component 
Event driven   
Suspected HZ skin 
lesions 
Event-driven 
Event-driven 
VZV PCR 
Event driven   
 
Suspected HZ skin 
lesions 
Event-driven 
Event-driven 
Beta-actin PCR 
HZ = Herpes Zoster; VZV = Varicella Zoster Virus; PCR = Polymerase Chain Reaction 
8.3.5. 
Immunological correlates of protection 
No generally accepted immunological CoP has been demonstrated for HZ/su vaccine. 
8.4. 
Safety Assessments 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and any 
designees remain responsible for following up AEs that are serious, considered related to 
the study treatment or the study, or that caused the subject to discontinue the study 
treatment or the study.  
8.4.1. 
Safety definitions 
Please refer to section 12.5 for safety definitions. 
8.4.2. 
Time period and frequency for collecting AE and serious adverse 
event (SAE) information 
An overview of the protocol-required reporting periods for AEs, SAEs, and pregnancies 
is given in Table 16. Refer to the section 12.5.9.1 for details on the time period for 
recording safety information. 
 
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Table 16 
Reporting periods for collecting safety information 
Event 
Visit 1* Visit 2 
Visit 3 
 
 
 
Visit 4 
 
 
 
Visit 5 
Visit 6 
Visit 7 
Timepoint 
Day 1 Month 12 Month 24 
 
 
 Month 25 Post reVacc Post reVacc 
 
Month 26 Month 37 Month 49 
 
 
 
reVacc 1 6 days post 
reVacc 1 
29 days post 
reVacc 1 
 reVacc 2 6 days post 
reVacc 2 
29 days post 
reVacc 2 
 
 
 
Study 
conclusion 
Solicited local and general AEs ** 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Unsolicited AEs ** 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
AEs/SAEs leading to withdrawal 
from the study 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
SAEs and pIMDs 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
SAEs related to the study vaccine $ 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
SAEs related to study participation 
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Intercurrent medical conditions, 
including HZ cases  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
AESI: Biopsy-proven allograft 
rejections 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Pregnancies and pregnancy 
outcomes 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
* i.e. consent obtained. reVacc 1: revaccination Dos 1; reVacc 2: revaccination Dos 2 
** Applicable for revaccinated subjects only (Amended: 15 June 2020) 
$ SAEs related to study vaccine include SAEs occurring before the first revaccination Visit 3 (Month 24) considered as related to primary vaccination in study ZOSTER-041, and SAEs 
related to revaccination course occurring after administration of the first dose from revaccination course in study ZOSTER-073 
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All SAEs will be recorded and reported via Expedited AE Reporting Form to the sponsor 
or designee immediately and under no circumstance should this exceed 24 hours after the 
investigator became aware of it, as indicated in Appendix 5. The investigator will submit 
any updated SAE data to the sponsor within 24 hours of it being available. 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 16. Investigators are not obligated to actively seek AEs 
or SAEs in former study subjects. However, if the investigator learns of any SAE, 
including a death, at any time after a subject has been discharged from the study, and 
he/she considers the event to be reasonably related to the study vaccine, the investigator 
will promptly notify the Study Contact for Reporting SAEs. 
8.4.3. 
Method of detecting AEs and SAEs 
The method of recording, evaluating, and assessing intensity, causality and outcome of 
AEs and SAEs and the procedures for completing and transmitting SAE reports are 
provided in section 12.5.9. 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the subjects/subject’s LAR(s) is the preferred method 
to inquire about AE occurrence.  
8.4.4. 
Reporting of serious adverse events, pregnancies, and other 
events 
Table 17 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK  
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited 
Adverse Events Report 
Pregnancies  
2 weeks* 
electronic pregnancy 
notification report 
2 weeks* 
electronic pregnancy 
follow-up report 
AESIs (pIMDs and 
allograft rejection) 
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 AESI. 
‡ The investigator will be required to confirm review of the SAE/AESI causality by ticking the ‘reviewed’ box in the 
electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/AESI. 
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8.4.4.1. 
Contact information for reporting of serious adverse events (SAEs), 
AESIs and pregnancies 
Table 18 
Contact information for reporting of serious adverse events (SAEs), 
AESIs and pregnancies  
Study contact for questions regarding SAEs, AESIs and pregnancies 
Refer to the local study contact information document 
Back-up Study Contact for Reporting SAEs, AESIs and pregnancies 
24/24 hour and 7/7 day availability: 
 
GSK Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: Rix.CT-safety-vac@gsk.com 
Canadian sites only: 
Fax: 1-866-903-4718 
8.4.4.2. 
Regulatory reporting requirements for SAEs 
Prompt notification of an SAE by the investigator to the sponsor is essential for meeting 
legal obligations and ethical responsibilities for the safety of subjects and the safety of a 
study treatment under clinical investigation.  
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB/IEC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g. summary or listing of SAE) from the sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 
8.4.5. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts. All SAEs and AESIs (serious or non-serious, as 
defined in section 8.4.1), will be followed until the event is resolved, stabilized, otherwise 
explained, or the subject is lost to follow-up. Further information on follow-up 
procedures is given in section 12.5.12. 
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8.4.6. 
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/AESI 
should be recorded in Expedited Adverse Event Report of the subject’s eCRF (refer to 
section 7.5). 
8.4.7. 
Subject card 
Study subjects/subject’s LAR(s) must be provided with the address and telephone 
number of the main contact for information about the clinical study. 
The investigator (or designate) must therefore provide a “subject card” to each 
subject/subject’s LAR(s). In an emergency situation, this card serves to inform the 
responsible attending physician that the subject is in a clinical study and that relevant 
information may be obtained by contacting the investigator. 
Subjects/subject’s LAR(s) must be instructed to keep subject cards in their possession at 
all times during the study duration.  
8.4.8. 
Evaluation and confirmation of suspected HZ cases 
8.4.8.1. 
Suspected Herpes Zoster 
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), or a vesicular rash suggestive of VZV infection regardless of the dermatomal 
distribution and without alternative diagnosis.  
Additionally, sometimes HZ cases do not present with the characteristic HZ or VZV rash, 
but have a clinical presentation and specific laboratory findings* suggestive of VZV 
infection. These cases should also be considered as occurrences of HZ.  
* Specific laboratory findings include VZV-positive polymerase chain reaction (PCR) 
culture, immunohistochemistry, or other tests that strongly suggest VZV-infection, which 
have been performed in the course of a medical evaluation. 
A suspected case of HZ is to be evaluated in the clinic by the investigator, within days of 
onset, ideally while vesicles or ulcerations are present.   
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 and/or HZ complications will constitute an AE/SAE, as 
appropriate. The occurrence of HZ is also an intercurrent medical condition (IMC) (see 
section 7.6).  
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The reporting period for events of HZ will be from Visit 1 (Day 1) to study end 
(Month 49). At Visit 1, all subjects will be informed of the signs and symptoms of typical 
HZ. 
8.4.8.2. 
Confirmed HZ 
A suspected case of HZ can be confirmed in two ways: 
• 
By Polymerase Chain Reaction 
Whenever possible, HZ lesion samples will be collected from subjects clinically 
diagnosed as having a suspected case of HZ (see section 8.1.15). The samples will be 
transferred to GSK or a validated laboratory designated by GSK and tested using 
standardised and validated procedures for laboratory diagnosis of HZ by PCR.  
Refer to section 12.2.1 for details of PCR assay to be performed on HZ lesion samples.  
Refer to section 12.2.2 for details of the PCR testing algorithm to classify suspected cases 
of HZ. 
• 
By the HZ Ascertainment Committee 
All suspected HZ cases not confirmed by PCR will be referred to the HZ Ascertainment 
Committee (HZAC). The HZAC will classify all referred cases as either “HZ” or “not 
HZ”. However, the HZAC classification will serve as the final case definition only when 
the case cannot be confirmed or excluded by PCR results obtained by GSK or a validated 
laboratory designated by GSK, e.g., when all samples from a given subject are inadequate 
(as when both VZV and β-actin PCR results are negative), or when no samples are 
available for a given subject (including when suspected HZ occurs in the absence of a 
characteristic HZ or VZV rash). Therefore, definitive PCR results obtained by GSK or a 
validated laboratory designated by GSK, when available, will determine the final HZ case 
assignment. In such cases, the HZAC classification will not contribute to HZ case 
determination decision. 
The HZAC will consist of physicians with HZ expertise. HZAC members, participating 
as investigator in this study, will not evaluate cases from their own study site. For every 
such case, each reviewing HZAC member will be asked to make a clinical determination 
of whether the case is HZ, based on review of the available clinical and laboratory 
information from the study site (e.g., summary of the rash and pain evaluations, digital 
photographs of the subject's rash, clinical progress notes and site laboratory information). 
A case will be considered as “HZ” if the HZAC members concur unanimously; 
otherwise, it will be classified as “not HZ”. As described above, the HZAC case 
assignment will only be considered as the final case assignment if definitive PCR results 
obtained by GSK or a validated laboratory designated by GSK are not available. Further 
details will be provided in the HZAC charter. 
Please note that PCR test results or HZAC classification as described above will not serve 
as the final case definition if the following applies.  
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Cases of suspected HZ will not be considered a confirmed case of HZ if they potentially 
could constitute a primary VZV infection (varicella).  
8.4.8.3. 
HZ complications 
Any HZ complications, according to the definitions below, will be recorded by the 
investigator. HZ complications will be considered as AEs or SAEs. HZ complications 
associated with confirmed HZ include: 
Ophthalmic disease: 
Defined as HZ affecting any eye structure as per the 
investigator’s judgment. 
PHN: 
Defined by the presence of HZ-associated ‘worst’ pain 
persisting or appearing more than 90 days after onset 
of the HZ rash.  
Others 
HZ vasculitis, disseminated disease, neurologic 
disease, visceral disease 
8.4.8.4. 
Terms related to evaluation of suspected HZ 
• 
Duration of a HZ episode 
In case of suspected HZ, the HZ onset date is the earlier of the following two events: 1) 
the HZ rash start date; or 2) the date on which pain at the site of a subsequent HZ rash is 
first noted. The dates of these two events are recorded in the eCRF. The end date of the 
HZ episode is defined as the first time at which a subject had no rash (papules, vesicles, 
ulcers or crusts) present. This end date will be recorded in the eCRF.  
In case of suspected HZ with absence of the characteristic rash, the HZ onset date is the 
date on which the signs/symptoms related to the clinical diagnosis of suspected HZ were 
first noted. The end date of the HZ episode is defined as the date on which the 
investigator or an attending physician considered the case as resolved. The onset and end 
date will be recorded in the eCRF.  
• 
Severity of HZ-associated pain using the Zoster Brief Pain Inventory 
The ZBPI is an assessment tool in the form of a questionnaire completed by the subject 
that is specifically designed to assess the severity of HZ-associated pain during an HZ 
episode [Coplan, 2004]. The ZBPI also takes into account the effect of HZ treatment on 
subject’s pain and general health status.  
In each case of suspected HZ, the subjects will be asked to assess their HZ-associated 
pain by completing the ZBPI questionnaire, either themselves or or subject’s trained 
assistant, until the rash is resolved. 
HZ occurrence, intensity (severity) and duration will be derived from the data recorded in 
the ZBPI. 
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9. 
DISCONTINUATION CRITERIA 
Refer to the section 7.7 for contraindications to subsequent vaccination. 
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
enrollment visit up to study end (refer to Appendix 5). 
Subjects who participate to study ZOSTER-073 but do not consent to revaccination will 
be encouraged to continue other study procedures for long term immunogenicity and 
safety assessments. 
9.1. 
Discontinuation from the study 
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject who did 
not come back for the concluding visit foreseen in the protocol.  
All data and samples collected until the date of withdrawal/last contact of the subject will 
be used for the analysis. 
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact.  
Investigators will make an attempt to contact those subjects who do not return for 
scheduled visits or follow-up (refer to section 9.3 for details). 
Primary reason for study withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself, by the subject’s LAR(s) or by the investigator, as well as 
which of the following possible reasons was responsible for withdrawal: 
• 
Adverse events requiring expedited reporting, including SAEs, biopsy-proven 
allograft rejections and pIMDs 
• 
HZ episodes 
• 
Unsolicited non-serious adverse event 
• 
Solicited adverse event 
• 
Protocol deviation  
• 
Withdrawal by subject, not due to an adverse event* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
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*In case a subject is withdrawn from the study because he/she/the subject’s LAR(s) has 
withdrawn consent, the investigator will document the reason for withdrawal of consent, 
if specified by the subject/subject’s LAR(s), in the eCRF. 
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see section 12.5.12). 
9.2. 
Discontinuation of study vaccine 
A ‘withdrawal’ from the study vaccine refers to any subject who does not receive the 
complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. 
A subject withdrawn from the study vaccine may continue and should be encouraged to 
continue further study procedures (safety or immunogenicity) if planned in the study 
protocol, as deemed appropriate by the investigator.  
Primary reason relative to premature discontinuation of the study vaccine will be 
documented on the Vaccine Administration screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination was made by the 
subject himself/herself, by the subject’s LAR(s) or by the investigator, as well as which 
of the following possible reasons was responsible for withdrawal: 
• 
Adverse event requiring expedited reporting, including SAEs, biopsy-proven 
rejections and pIMDs 
• 
HZ episodes 
• 
Non-serious adverse event (specify) 
• 
Unsolicited non-serious adverse event 
• 
Solicited adverse event 
• 
Not willing to be revaccinated 
• 
Other (specify). 
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9.3. 
Lost to follow-up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study. 
• 
Before a subject is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• 
Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Sample size determination 
10.1.1. 
Sample size calculation 
Former ZOSTER-041 subjects, who had a complete vaccination course (2 doses of HZ/su 
vaccine) will be offered enrollment into study ZOSTER-073 at participating centers.  
Up to a maximum of 86 subjects meeting the eligibility criteria for enrollment (2 doses of 
HZ/su vaccine in ZOSTER-041) will be targeted for enrollment in participating centers. 
Approximately 15% of the enrolled subjects might withdraw or not be evaluable for 
immunogenicity, therefore the target sample size will be approximately 73 subjects 
evaluable for humoral immunogenicity in per-protocol set (as defined in section 10.2). 
(Amended: 15 June 2020) 
Up to a maximum of 40 subjects will be targeted for the CMI sub-cohort in participating 
centers having CMI capabilities in order to reach 34 evaluable subjects for CMI analyses, 
assuming a 15% of drop-out and non-evaluability rate. CMI subjects from ZOSTER-041 
will be enrolled into the ZOSTER-073 CMI sub-cohort. Also, the balance of CMI 
subjects to be enrolled will be selected at random from CMI participating centers (having 
CMI capabilities) to complete the sub-cohort up to 40 subjects at ZOSTER-073 Visit 1.  
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10.2. 
Populations for analyses 
For purposes of analysis, the following analysis sets are defined [more detailed 
description will be provided in the statistical analysis plan (SAP)]. 
Analysis Set 
Description 
Enrolled Set 
All subjects with a complete vaccination course (2 doses of HZ/su 
vaccine) in study ZOSTER-041 who met the eligibility criteria and 
signed informed consent in the current study.  
PPS for analysis of persistence (LTFU 
phase from Visit 1 to Visit 3) (Amended: 
15 June 2020) 
The PPS for analysis of persistence will include evaluable subjects 
(i.e. those meeting all eligibility criteria, complying with the 
procedures and intervals defined in the protocol, with no elimination 
criteria) from the Enrolled set for whom persistence immunogenicity 
endpoints measures after primary vaccination course are available 
from Visit 1 (Day 1) to Visit 3 (Month 24). (Amended; 15 June 2020) 
ES for revaccination phase 
The ES for analysis of safety will include all subjects with at least one 
HZ/su vaccine dose administered in the study ZOSTER-073. 
PPS for Immunogenicity after 
revaccination course (revaccination 
active phase) 
The PPS for analysis of immunogenicity after revaccination will be 
defined by time-point and will include evaluable subjects (i.e. those 
meeting all eligibility criteria, complying with the procedures and 
intervals defined in the protocol, with no elimination criteria) from the 
ES for revaccination who have received one or two doses of 
revaccination schedule up to the time point considered from Visit 3 
to Visit 5 (Month 26). (Amended: 15 June 2020) 
PPS for persistence after revaccination 
course (revaccination follow-up phase) 
The PPS for persistence for analysis of immunogenicity after 
revaccination will include evaluable subjects (i.e. those meeting all 
eligibility criteria, complying with the procedures and intervals defined 
in the protocol, with no elimination criteria) from the ES for 
revaccination for whom persistence immunogenicity endpoints 
measures after revaccination course are available from Visit 6 
(Month 37) to Visit 7 (Month 49). (Amended: 15 June 2020) 
PPS = per protocol set, ES = exposed set 
For non-revaccinated subjects, the enrolled set will be used for analyses of safety and 
immunogenicity. Details will be described in the statistical analysis plan (SAP). 
(Amended: 15 June 2020) 
10.3. 
Statistical analyses 
All statistical analyses will be descriptive and detailed in the SAP. 
10.3.1. 
Subjects disposition 
Number of enrolled and revaccinated subjects (by dose received) will be tabulated 
overall. 
Number of subjects per protocol and exposed sets will be tabulated, overall. 
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10.3.2. 
Demography and baseline characteristics analyses 
Demographic and baseline characteristics (e.g., in study ZOSTER-041, age in years at the 
time of primary vaccination; in study ZOSTER-073, age in years at the time of 
enrollment and of first revaccination) will be summarized using descriptive statistics:  
• 
Frequency tables will be generated for categorical variables such as center. 
• 
Mean, standard deviation (SD), median, minimum and maximum will be provided 
for continuous data such as age  
Analysis of demographic and baseline characteristics will be performed overall, and by 
age and maintenance immunosuppressive therapy. 
10.3.3. 
Immunogenicity analyses 
LTFU phase  
Analyses will be based on the Per Protocol Set (PPS) for persistence after primary 
vaccination course.  
If, the percentage of subjects with serological results excluded from the PPS for analysis 
of persistence after primary vaccination course is 5% or more, a second analysis based on 
the Enrolled set will be performed to complement the PPS analysis. 
All analyses will be performed overall; additional analyses by age and type of 
maintenance immunosuppressive therapy strata (at the time of primary vaccination in 
study ZOSTER-041) will be performed if deemed necessary and appropriate.  
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Endpoint 
Statistical Analyses for LTFU phase 
Primary 
For persistence of humoral immunity after the primary vaccination course, the following 
parameters will be tabulated: 
• 
GMCs of anti-gE antibody and anti-gE antibody seropositivity rates with 95% CI at Day 1, 
Month 12 and Month 24; 
• 
Descriptive statistics on anti-gE antibody concentrations (mean, SD, min, Q1, median, 
Q3, max) at Day 1, Month 12 and Month 24; 
• 
Vaccine response rates to ZOSTER-041 primary vaccination for anti-gE antibody 
concentrations at ZOSTER-073 Day 1, Month 12 and Month 24; 
• 
Descriptive statistics of the fold increase over ZOSTER-041 pre-vaccination timepoint at 
ZOSTER-073 Day 1, Month 12 and Month 24 (mean, SD, min, Q1, median, Q3, max); 
• 
Distribution of the fold over ZOSTER-041 pre-vaccination timepoint at ZOSTER-073 Day 
1, Month 12 and Month 24; 
• 
MGI, i.e. geometric mean of the ratio post-vaccination timepoint over pre-vaccination 
timepoint in ZOSTER-041 with 95% CI at ZOSTER-073 Day 1, Month 12 and Month 24; 
The distribution of antibody titers at Day 1, Month 12 and Month 24 will be tabulated and 
also presented using reverse cumulative curves. 
Secondary 
For persistence of cellular immunity after the primary vaccination course, the following 
parameters will be tabulated: 
• 
Descriptive statistics (N, mean, SD, min, Q1, median, Q3, max): 
− 
the frequency of gE specific CD4+T-cells secreting at least 2 activation markers 
(among IFN-, IL-2, TNF-, CD40L) at Day 1, Month 12 and Month 24; 
− 
the fold increase over ZOSTER-041 pre-vaccination timepoint for the frequency of gE-
specific CD4(2+) T-cells at ZOSTER-073 Day 1, Month 12 and Month 24; 
Vaccine response rates to ZOSTER-041 primary vaccination for frequency of gE-specific 
CD4(2+) T-cells will be tabulated with 95% CI at ZOSTER-073 Day 1, Month 12 and 
Month 24.  
GMC = Geometric Mean Concentration, MGI = Mean Geometric Increase, N = Number, SD = Standard Deviation, 
Q1 = Quartile 1, Q3 = Quartile 3, Min = Minimum, Max = Maximum, IFN- = Interferon gamma, IL-2 = Interleukine 2, 
TNF- = Tumor Necrosis Factor alpha. 
Revaccination active phase 
Analyses will be based on the PPS for immunogenicity analysis after revaccination 
(revaccination active phase). 
If the percentage of subjects with serological results excluded from the PPS for analysis 
after revaccination is 5% or more, a second analysis based on the Exposed Set (ES) for 
revaccination will be performed to complement the PPS analysis after revaccination. 
All analyses will be performed overall; additional analyses by age stratum (at the time of 
ZOSTER-041 primary vaccination and ZOSTER-073 first revaccination) and by type of 
maintenance immunosuppressive therapy at the time of revaccination (Visit 3, Month 24) 
will be performed if deemed necessary and appropriate. 
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Endpoint 
Statistical Analyses for Revaccination active phase 
Primary 
For humoral immunity after revaccination for the active phase, at Months 24, 25 and 26, 
the following parameters will be tabulated: 
• 
GMCs of anti-gE antibody and anti-gE antibody seropositivity rates with 95% CI at 
Months 24, 25 and 26;  
• 
Vaccine response rates for anti-gE antibody concentrations at Months 25 and 26 
[post- revaccination timepoint over pre-revaccination timepoint] with 95% CI;  
• 
Vaccine response rates to ZOSTER-041 primary vaccination for anti-gE antibody 
concentrations at ZOSTER-073 Months 25 and 26 with 95% CI; 
• 
MGI post-revaccination timepoint over pre-revaccination timepoint at Months 25 and 26 
with 95% CI; 
• 
MGI post-revaccination timepoint over ZOSTER-041 pre-vaccination timepoint at 
Months 24, 25 and 26 with 95% CI; 
• 
Descriptive statistics of the fold increase of anti-gE antibody concentrations at Month 25 
and Month 26 over pre-revaccination timepoint (mean, SD, min, Q1, median, Q3, max). 
• 
Distribution of antibody titers at Months 24, 25 and 26 will be tabulated and also 
presented using reverse cumulative curves. 
Secondary 
For cellular immunity after revaccination for the active phase, the following parameters 
will be tabulated: 
• 
Descriptive statistics (N, mean, SD, min, Q1, median, Q3, max): 
− 
the frequency of gE specific CD4+T-cells secreting at least 2 activation markers 
(among IFN-, IL-2, TNF-, CD40L) at Months 24, 25 and 26; 
− 
the fold increase over pre-revaccination timepoint Month 24 in the frequency of gE 
specific CD4[2+] T-cells at Months 25 and 26. 
− 
the fold increase over ZOSTER-041 pre-vaccination timepoint in the frequency of gE 
specific CD4[2+] T-cells at Months 24, 25 and 26 in the current study. 
• 
Vaccine response rates for frequency of gE-specific CD4(2+) T-cells at Months 25 and 
26 over pre-revaccination timepoint Month 24 will be tabulated with 95% CI. 
• 
Vaccine response rates to ZOSTER-041 primary vaccination for frequency of gE-specific 
CD4(2+) T-cells at ZOSTER-073 Months 24, 25 and 26 will be tabulated with 95% CI. 
GMC = Geometric Mean Concentration, MGI = Mean Geometric Increase, N = Number, SD = Standard Deviation, 
Q1 = Quartile 1, Q3 = Quartile 3, Min = Minimum, Max = Maximum, IFN- = Interferon gamma, IL-2 = Interleukine 2, 
TNF- = Tumor Necrosis Factor alpha.  
Revaccination follow-up phase  
Analyses will be based on the PPS for persistence after revaccination course 
(revaccination follow-up phase). 
If the percentage of subjects with serological results excluded from the PPS for 
persistence analysis after revaccination is 5% or more, a second analysis based on the ES 
for revaccination will be performed to complement the PPS for persistence analysis after 
revaccination. 
All analyses will be performed overall; additional analyses by age stratum (at the time of 
ZOSTER-041 primary vaccination and ZOSTER-073 first revaccination) and by type of 
maintenance immunosuppressive therapy at the time of revaccination (Visit 3, Month 24) 
will be performed if deemed necessary and appropriate. 
212340 | Protocol Amendment 1 24 Jun 2020 | TMF-1734453 | 1.0

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
8 3  
E n d p oi nt  
St ati sti c al A n al y s e s f or R e v a c ci n ati o n f oll o w-u p p h a s e  
Pri m ar y  
N A.  
S e c o n d ar y  
F or h u m oral i m m u nit y aft er re v a c ci n ati o n (re v a c ci n ati o n f oll o w -u p p h a s e), t h e f oll o wi n g 
p ar a m et er s will b e t a b ul at e d:  
•  
G M C of a nti -g E a nti b o dy a n d a nti -g E s er o p ositivity r at es wit h 9 5 % CI at M o nt hs 3 7 a n d 
4 9;  
•  
V acci n e r es p o ns e r at es f or a nti -g E a nti b o dy c o nc e ntr ati o ns at M o nt hs 3 7 a n d 4 9 [ ov er 
pr e -r ev acci n ati o n ti m e p oi nt] wit h 9 5 % CI; 
•  
V acci n e r es p o ns e r at es t o Z O S T E R -0 4 1 pri m ary  v acci n ati o n f or a nti-g E a nti b o dy 
c o nc e ntr ati o ns at Z O S T E R -0 7 3 M o nt hs 3 7 a n d 4 9 wit h 9 5 % CI ; 
•  
M GI p ost -r ev acci n ati o n ov er pr e-r ev acci n ati o n ti m e p oi nt at M o nt hs 3 7 a n d 4 9 wit h 9 5 % 
CI;  
•  
M GI p ost -r ev acci n ati o n ov er Z O S T E R -0 4 1 pr e -v acci n ati o n ti m e p oi nt at M o nt hs  3 7 a n d 4 9 
wit h 9 5 % CI  
•  
D escri ptiv e st atistics of t h e f ol d i ncr e as e of a nti -g E a nti b o dy c o nc e ntr ati o ns at M o nt hs 3 7 
a n d 4 9 ov er pr e -r ev acci n ati o n ti m e p oi nt ( m e a n, st a n d ar d d evi ati o n, mi n, Q 1, m e di a n, Q 3, 
m ax).  
•  
D e scri ptiv e st atistics of t h e f ol d i ncr e as e of a nti-g E a nti b o dy c o nc e ntr ati o ns at M o nt hs 3 7 
a n d 4 9 ov er Z O S T E R -0 4 1 pr e -v acci n ati o n ti m e p oi nt ( m e a n, S D , mi n, Q 1, m e di a n, Q 3, 
m ax).  
•  
Distri b uti o n of a nti b o dy tit ers at M o nt hs 3 7 a n d 4 9 will b e t a b ul at e d a n d als o pr es e nt e d 
usi n g r ev ers e c u m ul ativ e c urv es.  
F or c ell ul ar i m m u nit y aft er re v a c ci n ati o n (re v a c ci n ati o n f oll o w - u p p h a s e), t h e f oll o wi n g 
p ar a m et er s will b e t a b ul at e d:  
•  
D escri ptiv e st atistics ( N, m e a n, S D, mi n, Q 1, m e di a n, Q 3, m ax):  
− 
t h e fr e q u e ncy of g E s p ecific C D 4 + T -c ells s ecr eti n g at l e ast 2 activ ati o n m ark ers 
( a m o n g I F N-, I L-2, T N F -, C D 4 0 L) at M o nt hs 3 7 a n d 4 9; 
− 
t h e f ol d i ncr e as e ov er pr e-r ev acci n ati o n ti m e p oi nt i n t h e fr e q u e ncy of g E s p ecific 
C D 4[ 2 +] T -c ells at M o nt hs 3 7 a n d 4 9. 
•  
V acci n e r es p o ns e r at es f or fr e q u e ncy of g E -s p ecific C D 4( 2 +) T-c ells at M o nt hs 3 7 a n d 4 9 
ov er pr e -r ev acci n ati o n ti m e p oi nt will b e t a b ul at e d wit h 9 5 % CI.  
G M C  = G e o m etric M e a n C o nc e ntr ati o n, M GI  = M e a n G e o m etric I ncr e as e,  N  = N u m b er, S D  = St a n d ar d D evi ati o n, 
Q 1  = Q u artil e 1, Q 3  = Q u artil e 3, Mi n  = Mi ni m u m, M a x = M axi m u m,  I F N- = I nt erf er o n g a m m a, I L-2  = I nt erl e uki n e 2, 
T N F - = T u m or N ecr osis F act or al p h a.  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
8 4  
1 0. 3. 4.  
S af et y a n al y s e s  
A nal ys es will be perf or m e d o n t he E nr olle d  a n d E x p ose d Sets . 
L T F U p h ase  
E n d p oi nt  
St ati sti c al A n al y s e s f or L F T U p h a s e 
Pri m ar y  
N A  
S e c o n d ar y  
•  
P erc e nt a g e of s u bj ects r e p orti n g hist ory of at l e ast o n e S A E r el at e d t o pri m ary v acci n ati o n 
i n st u dy Z O S T E R-0 4 1 cl assifi e d by M e d D R A Pri m ary Syst e m Or g a n Cl ass ( S O C) a n d 
Pr ef err e d T er m ( P T) fr o m Z O S T E R -0 4 1 l ast st u dy visit  ( M o nt h 1 3)  t o Z O S T E R-0 7 3 D ay 1 
will b e t a b ul at e d wit h ex act 9 5 % CI.  
•  
P erc e nt a g e of s u b j ects r e p orti n g at l e ast o n e S A E r el at e d t o pri m ary v acci n ati o n 
cl assifi e d by M e d D R A Pri m ary S O C  a n d P T  fr o m Z O S T E R -0 4 1  D ay  1 t o Z O S T E R -0 7 3 
M o nt h  2 4 will b e t a b ul at e d wit h ex act 9 5 % CI.   
•  
P er c e nt a g e of s u bj e ct s wit h at le a st o n e bi o p s y -pr o v e n all o graft rej e cti o n re p ort e d 
fr o m Z O S T E R -0 7 3 D a y 1  t o Z O S T E R -0 7 3 M o nt h 2 4  will b e t a b ul at e d wit h e x a ct 9 5 % 
CI.  
•  
Listi n g  of s u bj ects wit h hist ory of s us p ect e d all o gr aft r ej ecti o n or hist ory of  bi o psy -pr ov e n 
all o gr aft r ej ecti o ns fr o m Z O S T E R -0 4 1 l ast st u dy visit t o  Z O S T E R -0 7 3  D ay 1 will b e 
pr ovi d e d . 
•  
Listi n g  of s u bj ects wit h bi o psy -pr ov e n all o gr aft r ej ecti o ns fr o m Z O S T E R -0 7 3  D ay 1 t o 
Z O S T E R -0 7 3  M o nt h 2 4 will b e pr o vi d e d . 
•  
Listi n g of s u bj ects wit h hist ory a s us p ect e d H Z e pis o d e fr o m Z O S T E R -0 4 1 l ast st u dy visit 
t o Z O S T E R -0 7 3  D ay 1  will b e pr ovi d e d .  
•  
Listi n g of s u bj ects wit h a c o nfir m e d H Z e pis o d e fr o m  Z O S T E R -0 7 3  D ay 1 t o Z O S T E R-
0 7 3  M o nt h 2 4 will b e  pr ovi d e d . 
•  
N u m b er of s u bj ects wit h d ecli ni n g all o gr aft f u ncti o n , as d et er mi n e d by s er u m cr e ati ni n e 
m e as ur e m e nts will b e d et ail e d i n t h e S A P.  
( A m e n d e d: 1 5  J u n e 2 0 2 0)  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI

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All analyses will be performed overall and by age stratum (based on age at the time of 
primary vaccination in ZOSTER- 041).  
Revaccination phase 
Endpoint 
Statistical Analyses for Revaccination phase  
Primary 
NA 
Secondary 
• 
Percentage of subjects with at least one local AE (solicited and unsolicited), with at least 
one general AE (solicited and unsolicited), and with any AEs during the solicited 7-day 
follow-up period will be tabulated with exact 95% CI after each revaccination dose and 
overall. The same computations will be done for Grade 3 AEs. 
• 
Percentage of subjects reporting each individual solicited local AE (any grade and Grade 
3) and solicited general AE (any grade, Grade 3, any related and Grade 3 related) during 
the 7-day follow-up period (i.e., on the day of revaccination and 6 subsequent days) will 
be tabulated after each revaccination dose and overall.  
• 
Duration of solicited local and general AEs within 7 days and entire duration will be 
tabulated overall. 
• 
Percentage of subjects with any unsolicited AEs during the 30-day follow-up period (i.e., 
on the day of revaccination and 29 subsequent days) with its exact 95% CI will be 
tabulated by Medical Dictionary for Regulatory Activities (MedDRA) preferred term. 
Similar tabulation will be done for Grade 3 unsolicited AEs, for any causally related 
unsolicited AEs, for Grade 3 causally related unsolicited AEs, for Grade 3 non-serious 
unsolicited AEs, for Grade 3 causally related non-serious unsolicited AEs and for 
unsolicited AEs resulting in a medically attended visit. 
• 
Percentage of subjects with at least one report of SAE classified by the MedDRA SOC 
and PTs and reported from revaccination Dose 1 up to 30 days and 12 months post- last 
revaccination dose will be tabulated with exact 95% CI. SAEs will be also described in 
detail. 
• 
Percentage of subjects with at least one report of causally related-SAE classified by the 
MedDRA SOC and Preferred Terms and reported from revaccination Dose 1 up to 30 
days and 12 months post-last revaccination dose, and up to study end (Month 49) will be 
tabulated with exact 95% CI. Related-SAE will be also described in detail. 
• 
Percentage of subjects with at least one pIMD classified by the MedDRA SOC and 
Preferred Terms and percentage of subjects with at least one pIMD with causal 
relationship, reported from Dose 1 up to 30 days and 12 months post- last revaccination 
dose will be tabulated with exact 95% CI. 
• 
Percentage of subjects with at least one biopsy-proven allograft rejection and causal 
relationship reported from Dose 1 up to study end (Month 49) will be tabulated with exact 
95% CI. 
• 
Percentage of subjects reporting unsolicited AEs resulting in a medically attended visit 
from Dose 1 up to 30 days post-last revaccination dose will also be tabulated with exact 
95% CI. 
• 
Fatal SAEs will be described by onset date of SAE and date of death  
• 
SAEs (including fatal SAEs), pIMDs and withdrawal due to AE(s) will be described in 
detail. 
• 
Listing of withdrawals due to AE and SAEs will be provided 
• 
Listing of subjects with confirmed HZ episode will be provided.  
• 
Listing of subjects with biopsy-proven allograft rejection will be provided.  
212340 | Protocol Amendment 1 24 Jun 2020 | TMF-1734453 | 1.0

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
8 6  
E n d p oi nt  
St ati sti c al A n al y s e s f or R e v a c ci n ati o n p h a s e  
•  
N u m b er of s u bj ects wit h d ecli ni n g all o gr aft f u ncti o n (f oll o wi n g r ev acci n ati o n, H Z a n d 
all o gr aft r ej ecti o n), as d et er mi n e d by s er u m cr e ati ni n e m e as ur e m e nts will b e d et ail e d i n 
t h e S A P.  
All a nal ys es will be perf or me d o verall a n d b y a ge strat u m ( base d o n a ge at t he ti me of 
revacci nati o n i n Z O S T E R - 0 7 3).  
1 0. 3. 5.  
I nt eri m a n al y s e s  
All a nal ys es are descri pti ve.  
N o statistical a dj ust me nt will  be ma de f or t he i nteri m a nal ysi s, w hic h is i nte n de d t o 
pr o vi de o ut p uts relate d t o t he differe nt e n d p oi nts a n d  ti me p oi nts i n a p hase d ma n ner. 
1 0. 4.  
S e q u e n c e of a n al y s e s  
T he fi nal st u d y re p ort will c o ntai n at least t he fi nal a nal ys es of all pri mar y a n d sec o n dar y 
e n d p oi nts.  
T he a n al ysis will be perf or me d i n t he f oll o wi n g st e ps:  
•  
A li mite d l o n g-ter m i m m u n o ge ni cit y a nal ysis  will be perf or me d fr o m Z O S T E R -0 4 1 
Visit 3 ( M o nt h 2 ) t o Z O S T E R -0 7 3 Visit 1 ( Da y 1) . N o cli nical st u d y re p ort ( C S R) 
will be writte n at t hat ti me.  
•  
A li mite d l o n g-ter m im m u n o ge ni cit y  a nal ysis will be perf or me d fr o m Z O S T E R-0 4 1 
Visit 3 ( M o nt h 2) t o Z O S T E R -0 7 3 Visit 2 ( M o nt h 1 2) . N o C S R will be writte n at 
t hat ti me. 
•  
I nteri m a nal ysis after t he re vacci nati o n acti ve p h as e will be perf or me d o ne m o nt h 
after t he s ec o n d re vacci n ati o n d ose, M o nt h 2 6 ( Visit 5)  t o assess: 
− 
L o n g -t er m safet y fr o m Z O S T E R -0 4 1 Visit 5 ( M o nt h 1 3 ) t o Z O S T E R -0 7 3 Visit 
3 ( M o nt h 2 4 ). 
− 
P ersiste nce of i m m u n o ge nicit y  fr o m Z O S T E R-0 4 1 Visit 3 ( M o nt h 2) t o 
Z O S T E R -0 7 3 Visit 3 ( M o nt h 2 4).  
− 
S afet y a n d i m m u n o ge nicit y after re v acci nati o n fr o m Z O S T E R-0 7 3 Visit 3 
( M o nt h 2 4) t o Z O S T E R-0 7 3 Visit 5 ( M o nt h 2 6) .  
N o C S R will be writte n at t hat ti me . 
•  
A fi nal a nal ysis o n i m m u n o ge ni cit y a n d safet y will be perf or m e d at st u d y e n d 
( Visit 7), o nce all data are a vaila bl e a n d clea ne d.  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI

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11. 
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Hata A, Kuniyoshi M, Ohkusa Y. Risk of Herpes zoster in patients with underlying 
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Subunit Vaccine in Older Adults. N Engl J Med 2015; 372(22): 2087-96. 
Ledent E., Van-der-Most, R. Vaccine Effect on Cell-Mediated Immunity Accounting for 
Undesired Background Response in Intracellular Cytokine Staining, Poster presented at 
BDS conference October 2009.  
López-Fauqued M, Campora L, Delannois F, et al. Safety profile of the adjuvanted 
recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials. 
Vaccine 2019;37(18):2482-2493.  
Mengel M, et al. Banff 2011 Meeting Report: New Concepts in Antibody-Mediated 
Rejection. Am J Transplant 2012;12:563-570. 
MulleyWR, Visvanathan K, Hurt AC, et al. Mycophenolate and lower graft function 
reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination 
Kidney Int 2012, 82: 212-219 
Orcurto A, Pascual M, Hoschler K, et al. Impact of anti-T-cell therapy in the 
immunogenicity of seasonal influenza vaccine in kidney transplant recipients. 
Transplantation 2012, 94:630-636 
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. 
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Pergam SA, Forsberg CW, Boeckh MJ, Maynard C, Limaye AP, Wald A, et al. Herpes 
zoster incidence in a multicentre cohort of solid organ transplant recipients. Transpl 
Infect Dis 2011;13(1):15-23. 
Racusen, L.C., Solez K., Colvin R.B., et al. The Banff 97 working classification of renal 
allograft pathology. Kidney International, Vol. 55 (1999), pp. 713-723. 
Ruggerberg JU, Gold MS, Bayas JM, et al. Anaphylaxis: case definition and guidelines 
for data collection, analysis, and presentation of immunization safety data. Vaccine 
2007:25(31):5675-84. 
Rusthoven JJ, Ahlgren, P, Elhakiim T, et al. Varicella-Zoster infection in adult cancer 
patients. A population study. Arch Intern Med 1988;148:1561-6. 
Salles MJ, Sens YA, Boas LS, Machado CM. Influenza virus vaccination in kidney 
transplant recipients: serum antibody response to different immunosuppressive drugs. 
Clin Transplant 2010, 24:E17-E23 
Schmipff S, Serpick A, Stoler B, et al. Varicella-zoster infection in patients with cancer. 
Ann Intern Med 1972;76; 241-254. 
Sis B, Mengel M, Haas M, et al. Banff ’09 Meeting Report: antibody mediated graft 
deterioration and implementation of Banff working groups. Am J Transplant 
2010;10:464-471. 
Solez K, Colvin RB, Racusen LC, et al. Banff 07 classification of renal allograft 
pathology; updates and future directions. Am J Transplant 2008;8:753-760. 
Solez K and Racusen LC. The Banff classification revisited. Kidney International. 12 
December 2012 (advance online publication): 1-6. 
Stadtmauer EA, Sullivan KM, Marty FM, et al. A phase 1/2 study of an adjuvanted 
varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant 
recipients. Blood 2014; 124(19): 2921-9. 
Sullivan K, Abhyankar S, Campora L, et al. Immunogenicity and safety of an adjuvanted 
herpes zoster subunit vaccine in adult autologous hematopoietic stem cell transplant 
recipients: phase 3, randomized, placebo-controlled, ZOE-HSCT clinical trial. 44th annual 
meeting of the European Society for Blood Marrow Transplantation 18-21 March, 
Lisbon, Portugal 2018. 
Vink P, RamonTorrell JM, Sanchez Fructuoso A, et al. Immunogenicity and Safety of the 
Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults 
Following Renal Transplant: a Phase III, Randomized Clinical Trial. Clin Infect Dis 2019 
Zostavax (Zoster Vaccine Live) US Prescribing Information, April 2013. 
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2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
9 0  
1 2.  
A P P E N DI C E S  
1 2. 1.  
A p p e n di x 1: A b br e vi ati o n s , gl o s s ar y of t er m s a n d 
tr a d e m ar k s 
1 2. 1. 1.  
Li st  of a b br e vi ati o n s  
A E : 
A d verse E v e nt  
A E SI : 
A d verse E v e nt of S peci al  I nterest 
AI D : 
A ut o -I m m u n e Dis or der 
C F C : 
C yt o ki ne Fl o w C yt o metr y  
CI S : 
C hr o nic I m m u n os u p pressi ve  
C L S : 
Cli nical La b orat or y Scie nces  
C MI : 
Cell -Me diate d I m m u nit y  
C M V : 
C yt o m e gal o vir us  
C o P:  
C orrelate of Pr otecti o n  
C R F : 
Case Re p ort F or m  
 
 
E B V : 
E pstei n Barr vir us  
E LI S A : 
E nz y m e Li n ke d I m m u n os or be nt Assa y  
E o S : 
E n d of St u d y  
F D A:  
F o o d a n d Dr u g A d mi nistrati o n, U nite d States of A merica  
G C P : 
G o o d Cli nical Practice  
G F R : 
Gl o mer ular Filtrati o n Rate  
G S K:  
Gla x o S mit h Kli ne Bi ol o gicals S A  
HI V : 
H u ma n I m m u n o deficie nc y Vir us  
H L A : 
H u ma n Le u k oc yte A nti ge n  
H S C T : 
He mat o p oietic Ste m Cell Tra ns pla ntati o n  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
9 1  
H Z : 
Her pes Z oster, s hi n gl es  
I C F: 
I nf or me d C o nse nt F or m 
I C H: 
I nter nati o nal C o u ncil o n Har m o nisati o n 
I C S: 
I ntr acell ular c yt o ki ne stai ni n g 
I E C: 
I n d e pe n de nt Et hics C o m mittee 
I F Nγ: 
I nterfer o n-ga m ma  
II D: 
I m m u n o-I nfla m mat or y Dis or der 
I L-2 : 
I nterle u ki n 2 
I M C: 
I nterc urre nt Me dical C o n diti o n 
I N D: 
I n v esti gati o nal Ne w Dr u g  
I R B: 
I nstit uti o nal Re vie w B oar d 
L A R:  
Le gall y Acce pta ble Re prese ntati ve  
L S L V:  
Last S u bject Last Visit  
L T F U : 
L o n g -t er m F oll o w-u p  
Me d D R A:  
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
 
 
 
 
P B M C : 
Peri p heral Bl o o d M o n o n uclear Cells  
P C D:  
Pri mar y C o m pleti o n Dat e  
P C R : 
P ol y m eras e C hai n Reacti o n  
P H N : 
P ost -her petic Ne ural gia  
PI : 
Prescri bi n g I nf or m ati o n  
pI M D:  
P ote ntial I m m u ne -Me di ate d Disease  
P P:  
Per pr ot oc ol  
R T : 
Re nal Tra ns pla nt  
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SAE: 
Serious Adverse Event 
SBIR: 
Source data Base for Internet Randomisation  
SmPC: 
Summary of Product Characteristics 
SoA: 
Schedule of Activities 
SOT: 
Solid Organ Transplant 
SPM: 
Study Procedures Manual 
TNFα: 
Tumor Necrosis Factor-alpha 
VE: 
Vaccine Efficacy 
VZV: 
Varicella Zoster Virus 
YOA: 
Years Of Age 
ZBPI: 
Zoster Brief Pain Inventory 
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12.1.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product.  
An adverse event (AE) can therefore be any unfavourable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse. 
Adverse Events of Special 
Interest (AESIs): 
 
AESIs are a subset of AEs/SAEs that include specific 
disorders of interest which may or may not be related to 
vaccination. For this trial, AESIs will be defined as 
potential immune-mediated disorders and renal allograft 
rejection. 
Anamnestic: 
Relating to a rapid increased production of antibodies in 
response to a previously experienced immunogenic 
substance. 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. In an 
open-label study, no blind is used. Both the investigator 
and the subject know the identity of the treatment 
assigned. 
Certified copy: 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e. by a dated 
signature or by generation through a validated process) to 
have the same information, including data that describe 
the context, content, and structure, as the original. 
Donor-specific antibodies: 
Anti-HLA antibodies specifically produced against a 
donor organ’s foreign HLA antigens. Other anti-HLA 
antibodies may be produced against foreign HLA 
antigens from blood transfusion, child birth, or previous 
organ transplant. 
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
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End of Study (EoS)  
(Synonym of End of Trial) 
For studies with collection of human biological samples 
and/or imaging data, the EoS is defined as Last testing 
results released of samples collected up to Visit 7* 
* In this case EoS must be achieved no later than 8 
months after LSLV.  
Epoch: 
Interval of time in the planned conduct of a study. An 
epoch is associated with a purpose (e.g. screening, 
randomisation, treatment, follow-up), which applies 
across all arms of a study. NOTE: Epoch is intended as a 
standardised term to replace: period, cycle, phase, stage.  
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of the 
data produced. 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis (see section 10.2 for 
details on criteria for evaluability). 
Immunological correlate 
of protection: 
The defined immune response above which there is a high 
likelihood of protection in the absence of any host factors 
that might increase susceptibility to the infectious agent. 
Immunosuppressive 
therapy: 
For protocol purposes, there will be four (4) types of 
immunosuppressive (IS) therapy. 
Induction IS therapy: 
For protocol purposes, the “induction” IS therapy will be 
defined as the combination of all IS therapy used pre-
transplant and in the immediate post-transplantation 
period to specifically prevent hyper-acute and acute 
allograft rejection. This is sometimes also referred to as 
initial IS therapy. 
These medications may include varying combinations of 
(listing not exhaustive) basiliximab, thymoglobulin, high-
dose corticosteroids, high-dose mycophenolate mofetil, 
high-dose mycophenolate acid, tacrolimus, cyclosporine, 
and sirolimus. To be considered induction IS therapy for 
protocol purposes, the IS therapy does not need to include 
the use of monoclonal or polyclonal antibodies’.  
Maintenance IS therapy: 
For protocol purposes, the “maintenance” IS therapy will 
refer to the IS therapy used routinely post-transplantation, 
at reduced dosages and/or reduced number of medications 
as compared to the induction IS. Maintenance IS therapy 
is to prevent host-vs.-graft disease while minimizing 
potential medication associated adverse events and 
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1 5 -J U N -2 0 2 0  
9 5  
t o xicities. T his is s o meti mes als o referre d t o as r o uti ne 
me dicati o ns.  
Mai nte na nce m e dicati o ns ma y i ncl u de v ar yi n g 
c o m bi nati o ns of (listi n g n ot c o m pre he nsi ve) l o w -d ose 
c ortic ost er oi ds, l o w -d ose m yc o p h e n olate m ofetil, l o w -
d ose m yc o p he n olate aci d, tacr oli m us, c ycl os p ori n a n d 
sir oli m us. 
T hera p e utic  I S t h era p y: 
F or pr ot oc ol p ur p oses, “t hera pe utic” I S t hera p y will refer 
t o a n y i ncreas e i n n u m ber a n d/ or d osa ge of I S t hera pies 
prescri b e d f or a s u bj ect, pre vi o usl y o n mai nte na n ce I S 
t hera p y, f or t h e p ur p ose of ac utel y tr eati n g all o graft 
rejecti o n. T his is s o meti mes als o referre d t o as 
“ Rejecti o n” t hera p y.  
Ot her  I S t hera p y: 
F or pr ot oc ol p ur p oses, “ ot her” I S t hera p y will refer t o t he 
of a n y I S t hera p y f or p ur p oses ot her t ha n all o graft 
preser vati o n.  E. g. t h e use of pre d nis o n e treat me nt f or a 
g o ut flare.  
I n v esti gati o nal vacci ne: 
( S y n o n y m of 
I n v esti gati o nal Me dici nal 
Pr o d uct)  
A p har mace utical f or m of a n acti ve i n gre die nt bei n g 
teste d i n a cli nical trial, i ncl u di n g a pr o d uct wit h a 
mar keti n g a ut h orisati o n w he n use d i n a wa y differe nt 
fr o m t he a p pr o ve d f or m, or w he n use d f or a n u n a p pr o ve d 
i n dicati o n, or w he n use d t o gai n f urt her i nf or m ati o n a b o ut 
a n a p pr o ve d us e.  
I n v esti gat or 
A  pers o n res p o nsi ble f or t he c o n d uct of t he cli nical trial 
at a trial site. If a trial is c o n d ucte d b y a t ea m of 
i n di vi d uals at a trial site, t he i n vesti gat or is t he 
res p o nsi ble lea der of t he tea m a n d ma y be calle d t he 
pri nci pal i n vesti gat or.   
T he i n vesti ga t or ca n d ele gat e trial-relate d d uties a n d 
f u ncti o ns c o n d ucte d at t he trial site t o q ualifie d i n di vi d ual 
or part y t o perf or m t h ose trial -relate d d uties a n d f u ncti o ns 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI

C O N FI D E N TI A L  
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Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
9 6  
N o n -rev acci n ate d 
s u bjects: 
S u bjects w h o  are  i neli gi ble or u n willi n g t o receive b ot h 
rev acci n ati o n d oses ( A me n de d: 1 5  J u ne 2 0 2 0)  
P ote ntial I m m u ne -
Me diate d Diseas e:  
P ote ntial i m m u ne -me diate d diseases ( pI M Ds) are a s u bset 
of A Es t hat i ncl u de a ut oi m m u ne diseases a n d ot her 
i nfla m mat or y a n d/ or ne ur ol o gic dis or ders of i nterest 
w hic h ma y or ma y n ot ha ve a n a ut oi m m u ne aeti ol o g y.  
Pri mar y c o m pleti o n: date:  
T he date  t hat t he fi n al s u bject was e x a mi ne d or recei ve d 
a n i nter ve nti o n f or t he p ur p ose of fi nal c ollecti o n of data 
f or all pri mar y o utc o m es, w het her t he cli nical trial was 
c o ncl u de d acc or di n g t o t he pre -s p ecifie d pr ot oc ol or was 
ter mi nate d. 
Pr ot oc ol a m e n d m e nt:  
T he I nter n ati o n al C o u ncil o n H ar m o niz ati o n (I C H) 
defi nes a pr ot oc ol a m e n d m e nt as: ‘ A writte n descri pti o n 
of a c h a n ge(s) t o or f or m al cl arific ati o n of a pr ot oc ol.’ 
G S K Bi ol o gic als f urt her det ails t his t o i ncl u de a c h a n ge 
t o a n a p pr ove d pr ot oc ol t h at affects t he s afety of 
s u bjects, sc o pe of t he i nvesti g ati o n, st u dy desi g n, or 
scie ntific i nte grity of t he st u dy. ( A me n de d: 1 5  J u ne 
2 0 2 0)  
Ra n d o misati o n:  
Pr ocess of ra n d o m attri b uti o n of treat me nt t o s u bjects i n 
or der t o re d u ce bias of selecti o n.  
Site M o nit or:  
A n i n di vi d ual assi g ne d b y t he s p o ns or w h o is res p o nsi ble 
f or ass uri n g pr o per c o n d uct of cli nical st u dies at 1 or 
m ore i n vesti gati o nal sites.  
S olicite d a d verse e v e nt:  
Pre -s pecifi e d A Es t o be rec or de d as e n d p oi nts i n t he 
cli nical st u d y. T h e pres e nce/ occ urre n ce /i nte nsit y of t hese 
e ve nts is acti vel y s olicite d fr o m t he s u bject or a n o bser ver 
d uri n g a s p ecifie d p ost -v acci nati o n f oll o w -u p p eri o d.  
S o urce data:  
All i nf or mati o n i n ori gi n al rec or ds a n d certifie d c o pies of 
ori gi nal rec or ds of cli nical fi n di n gs, o bser vat i o ns, or ot her 
acti vities i n a cli nical trial necessar y f or t he 
rec o nstr ucti o n a n d e val u ati o n of t he trial. S o urce data are 
c o ntai ne d i n s o urce d oc u me nts ( ori gi nal rec or ds or 
certifie d c o pies).  
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Source documents: 
Original documents, data, and records (e.g. hospital 
records, clinical and office charts, laboratory notes, 
memoranda, subjects' diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified 
after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-
rays, subject files, and records kept at the pharmacy, at 
the laboratories and at medico-technical departments 
involved in the clinical trial). 
Study vaccine/product: 
Any investigational vaccine/product being tested and/or 
any authorised use of a vaccine/product/placebo as a 
reference or administered concomitantly, in a clinical trial 
that evaluates the use of an investigational 
vaccine/product. 
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 enrollment. 
Subject: 
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the vaccine or as a control. 
Subject number: 
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study. 
Treatment: 
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject. 
Treatment number: 
A number identifying a treatment to a subject, according 
to treatment allocation. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event. 
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12.1.3. 
Trademarks 
In the entire protocol (including the synopsis), the names of the vaccines/products and/or 
medications will be written without the superscript symbol ™ or ® and in italics.  
Trademark Information 
The following trademarks are used in the present protocol: 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Generic description 
Pandemrix 
 
Influenza vaccine (H1N1)v (split virion, 
inactivated, adjuvanted) A/California/7/2009 
(H1N1)v like strain (x-179a) 
Shingrix 
 
Zoster Vaccine Recombinant, Adjuvanted 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
 
Generic description 
Zostavax (Merck & Co., Inc.) 
 
Herpes zoster vaccine consisting of high 
titer live attenuated varicella-zoster virus 
(Oka strain) 
 
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12.2. 
Appendix 2: Clinical laboratory tests 
12.2.1. 
Clinical laboratory tests 
Specific antibody (anti-gE) measurements 
Anti-gE ELISA: Anti-gE Ab concentrations will be measured using an anti-gE ELISA. 
Diluted blood serum samples of study subjects will be added to microtiter wells pre-
coated with VZV gE recombinant antigen. Secondary peroxidase-conjugated anti-human 
antibodies will be added, which bind to the primary human anti-gE antibodies. 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 will be performed on 
human serum at GSK laboratory or another laboratory designated by GSK. 
Intracellular cytokine staining  
CMI responses will be performed by GSK (or designated laboratory) on thawed PBMCs 
by ICS. The assay will be performed on samples collected during the course of the study. 
This assay provides information on the frequency of CD4+ T-cells responding to culture 
medium or antigens (gE peptide pool) by secreting cytokine molecules involved in 
immunity such as IFN-, IL-2, TNF-, and CD40L.  
Briefly, PBMC collected from the subjects are stimulated for two hours using culture 
medium (for evaluation of the non-specific response), a pool of overlapping peptides 
covering the entire sequence of the vaccine antigen gE. Then, an intracellular block 
(brefeldin A) is added to inhibit cytokine secretion for a subsequent overnight incubation. 
Cells are then harvested, stained for surface markers (CD3, CD4 and CD8) and fixed. 
The fixed cells are then permeabilized and stained with anti-cytokine antibodies, washed 
and analyzed by cytofluorometry. 
The results of ICS assays are expressed as the frequency of specific CD4+ T-cells per 
million total CD4+ T-cells. 
PCR Assay for confirmation of suspected cases of HZ  
HZ cases will be confirmed by a PCR based algorithm that assesses the presence of VZV 
DNA in samples, and the adequacy of the samples (by assessing the presence of β-actin 
DNA).  
VZV and β-actin DNA in HZ clinical specimens will be assessed using real-time PCR 
detection by the 5’ nuclease assay based on the Taqman probe technology. If the VZV 
PCR is negative, β-actin PCR will be performed to assess adequacy of the sample and if a 
specimen is found to be VZV–PCR negative and β-actin–PCR negative, it is considered 
to be inadequate. 
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In the Taqman-based PCR experiments, the amplification of a PCR product is monitored 
in real-time by means of fluorogenic probes that bind specifically to the amplified 
product. The reporter fluorophore is at the 5’ end of the Taqman probe and the quencher 
is at the 3’ end. As long as the probe is intact, no fluorescence is produced by the 
fluorophore. During the PCR polymerization step, the 5’ nuclease activity of the DNA 
polymerase separates the fluorophore from the quencher, and a measurable fluorescent 
signal proportional to the DNA copy number is produced. 
As mentioned above, the 5' nuclease-based PCR assay allows the determination of the 
DNA copy number within samples, but in the present study the VZV and β-actin DNA 
PCR data on samples from suspected HZ lesions (swabs of vesicles, papules and crusts, 
and crusts themselves) will be used qualitatively only according to the above mentioned 
approach. 
12.2.2. 
Ascertainment of HZ CASES including PCR testing algorithm to 
classify suspected HZ cases 
A suspected case of HZ will be documented by digital photography of the rash (if rash is 
present) and by collecting any relevant information as described in the clinical protocol. 
To classify the suspected case of HZ, samples from the rash lesions (if available) will be 
collected for laboratory testing by PCR (three samples from separate lesions, collected on 
the same day, per subject).  
If during clinical evaluation at the HZ visit, the investigator determines that adequate rash 
lesion samples cannot be collected (i.e., less than three lesions present, or if only papules 
are present), the subject should be asked to return to the study site for collection of 
additional samples if there is rash progression (i.e., appearance of new/additional lesions 
if originally less than three lesions present, or appearance of vesicles if originally only 
papules present) at an ad-hoc HZ visit. When the subject returns to repeat sample 
collection, three samples from separate lesions should be collected. See the SPM for 
further details on sample collection. 
Each rash lesion will be tested using standardised and validated molecular assays 
according to the PCR testing algorithm described below. 
A hierarchical case definition algorithm, similar to the algorithm used by Merck in their 
Shingle Prevention Study (Zostavax efficacy study) [Oxman, 2005] will be used to 
classify each suspected case of HZ as a confirmed HZ case or not. 
• 
If at least one sample coming from a given subject is “VZV positive” by PCR (as 
defined below), the PCR algorithm will classify the “suspected HZ case” as a 
“confirmed case of HZ”. 
• 
If all the samples coming from a given subject are “VZV negative” (as defined 
below), then β-actin PCR will be performed. If one or more “VZV negative” samples 
are “β-actin positive”, this means that the sampling procedure is valid and that the 
“suspected HZ case” will be classified as “not a case of HZ”.  
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• 
If PCR results for a particular subject do not confirm or exclude a “suspected HZ 
case” (i.e. samples coming from a given subject are considered as “inadequate” as 
both VZV and β-actin PCR results are negative, or no samples are available for the 
subject), only then will the classification by the HZAC be used to confirm or exclude 
the suspected HZ case. The HZAC will consist of physicians with HZ expertise. For 
every suspected HZ case, each HZAC member will be asked to make a clinical 
determination of whether the case is HZ based on review of the available clinical 
information. A “suspected HZ case” will be considered as “HZ” if all HZAC 
members concur (unanimous decision); otherwise, it will be classified as “not HZ”.  
This algorithm includes the following steps (see Figure 2): 
1. DNA extraction from the rash lesion. 
2. VZV PCR assay targeting the orf62 gene is performed to detect VZV in the rash 
lesion: 
a. 
If the VZV PCR signal is ≥ the cut-off level, i.e. the technical limit of detection 
(LOD) of the assay, the sample will be considered as “VZV positive”. 
b. If the VZV PCR signal is above 0 copy/ PCR but below the cut-off level of the 
assay, it will be considered as “VZV borderline” and will be re-tested twice in 
order to obtain three results per sample. The sample will be considered as “VZV 
positive” if at least two results out of the three obtained are ≥ the cut-off level of 
the assay and it will be considered “VZV negative” if fewer than two samples 
are ≥ the cut-off level of the assay.  
c. 
If the VZV PCR signal is equal to 0 copies/ PCR, the sample will be considered 
as “VZV negative”. If every sample is VZV negative, then extracted DNA from 
the samples will be assessed for the presence of β-actin DNA to confirm the 
validity of the rash lesion sampling procedure (see step 3). 
3. As described above, if all the samples are VZV negative for a given subject, then β-
actin PCR will be performed on “VZV negative” samples to confirm the validity of 
the sampling procedure. 
a. 
If the β-actin PCR signal is below the cut-off level of the assay (β-actin 
Negative), the sample will be considered as “inadequate” as no β-actin DNA 
from human cells is detected within the rash lesion sample. If all samples are 
β- actin Negative, then the classification by the HZAC will be used to confirm 
or exclude the HZ case. 
b. If the β-actin PCR signal is ≥ the cut-off level of the assay (β-actin Positive), the 
sample will be considered as “valid” but without any VZV DNA. If at least one 
sample is β-actin Positive, then the HZAC classification of a suspected HZ case 
will not be part of the decision-making process for HZ case confirmation, and 
the HZ rash will be considered “VZV negative”. 
Note: The cut-off level of the VZV PCR and β-actin PCR assays is defined as the 
technical LOD of these assays (i.e. lowest concentration that can be detected by PCR in 
at least 95% of the tests). 
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Figure 2 
Algorithm for HZ case definition by PCR  
 
VZV: Varicella Zoster Virus; PCR: real-time PCR  
DNA: Deoxyribonucleic Acid; ORF: Open Reading Frame. 
* If the VZV PCR signal is above 0 copy/PCR but below the cut-off level of the assay, it will be considered as “VZV 
borderline” and will be re-tested twice in order to obtain three results per sample. The sample will be considered as 
“VZV positive” if at least two results out of the three obtained are ≥ the cut-off level of the assay and it will be 
considered “VZV negative” if fewer than two samples are ≥ the cut-off level of the assay. 
Note: The cut-off level of the VZV PCR assay is defined as the technical limit of detection of the assay (; i.e. lowest 
concentration that can be detected by PCR in at least 95% of the tests) 
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12.3. 
Appendix 3: Clinical laboratories 
Table 19 
GSK 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 
GSK Vaccines GmbH 
Clinical Laboratory Sciences, 
Marburg, Germany 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
Table 20 
Outsourced laboratories 
Laboratory 
Address 
CEVAC-University of Gent 
De Pintelaan, 185 Gent 
Belgium 
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12.4. 
Appendix 4: Study governance considerations 
12.4.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable ICH GCP Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, Informed Consent Form (ICF) or Informed 
Assent Form (IAF), Investigator Brochure, and other relevant documents (e.g. 
advertisements) must be submitted, to an IRB/IEC by the investigator for review and 
approval. These documents will be signed and dated by the investigator before the 
study is initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study subjects.  
• 
GSK will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
12.4.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interest prior 
initiation of the center and at the end of the study. Investigators are responsible for 
providing an update of Financial Disclosure if their financial interest changes at any point 
during their participation in a study and for 1 year after completion of the study.  
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12.4.3. 
Informed consent process 
The investigator or his/her representative will explain the nature of the study to the 
subject or his/her legally authorized representative and answer all questions regarding the 
study.  
Subjects/subjects’ LAR(s) must be informed that their participation is voluntary.  
Freely given and written informed consent must be obtained from each subject and/or 
each subject’s LAR(s), as appropriate, prior to participation in the study at Visit 1 
(Day 1).  
If required by local regulatory authorities or IRB/EC, a second written informed consent 
will be obtained at Visit 3 (Month 24) prior to performance of any revaccination study 
procedures. 
The content of ICF must meet the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
For subjects who become legally emancipated during the course of the study, e.g. become 
of the legal age of consent, re-consent is sought in accordance with local laws and 
regulations. The subject can provide consent by signing an ICF, similar to that provided 
to the parent(s)/LAR(s) at the study start, which summarises the study and includes a 
consent statement and documents that the subject agrees to continue participating in the 
study. 
Subjects/subjects’ LAR(s) must be reconsented to the most current version of the ICF(s) 
or an ICF addendum during their participation in the study.  
A copy of the ICF(s) must be provided to the subject.  
12.4.4. 
Data protection 
Subject will be assigned a unique identifier by the sponsor. Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject’s 
names or any information which would make the subject identifiable will not be 
transferred.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  
The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
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GSK will also ensure the protection of personal data of investigator and the site staff 
which will be collected within the frame and for the purpose of the study.  
12.4.5. 
Committees structure 
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 favorable 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: 
• 
IRB/IEC review and favorable 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 informed consent must be obtained from each subject, as 
appropriate, according to local requirements, prior to participation in the study. 
GSK has prepared a model ICF which embodies the ICH GCP and GSK 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 judgment, 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 and be approved (along with the protocol, and any other necessary documentation) 
by the IRB/IEC. 
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12.4.6. 
Publication policy 
GSK aims to publish the results of this study in searchable, peer reviewed scientific 
literature. GSK will target to submit within 18 months from LSLV for interventional 
studies and from the completion of the analysis for non-interventional studies and follows 
the guidance from the International Committee of Medical Journal Editors. 
12.4.7. 
Dissemination of clinical study data 
The key design elements of this protocol will be posted on the GSK Clinical Study 
Register and on publicly accessible registers including ClinicalTrials.gov. Where 
required, protocol summaries will also be posted on national or regional clinical trial 
registers or databases (e.g. EudraCT database) in compliance with the applicable 
regulations. 
GSK also assures that results will be submitted to ClinicalTrials.gov within the required 
time-frame, in compliance with the current regulations mentioned in the table below.  
At the time of study results posting, the full study protocol and statistical analysis plan 
will also be posted on ClinicalTrials.gov.  
In addition, for studies that are in scope of the EU Clinical Trial Directive, summaries of 
the results of GSK interventional studies (phase I-IV) in adult population will be posted 
within defined timelines on the publicly available EU Clinical Trial Register.  
If it is not possible to submit a summary of the results within the required timelines 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.  
 
Clinicaltrial.gov 
EU 
Protocol summary 
Before enrollment of subjects 
As per CTA submission/Before 
enrollment of subjects 
Results summary 
Within 12 months of PCD (Primary 
and safety endpoint results)/Within 
12 months of LSLV* (for secondary 
endpoint results) 
Within 12 months (for adult 
population studies) of EoS*. 
* As defined in the study protocol. 
Under the framework of the SHARE initiative, anonymized patient-level data from GSK 
sponsored interventional studies that evaluate products will be made available within 6 
months of this publication to independent researchers whose research proposals have 
been approved by an independent panel. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, provided reasonable access to statistical 
tables, figures, and relevant reports. GSK will also provide the investigator with the full 
summary of the study results. The investigator is encouraged to share the summary 
results with the study subjects, as appropriate. 
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12.4.8. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents including source documents (see Glossary of terms for the exact definition of 
essential and source documents). The storage system used during the trial and for 
archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential documents for the trial may be added or reduced where justified (in advance of 
trial initiation) based on the importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, CRF), the copy should fulfil the 
requirements for certified copies (see Glossary of terms for the exact definition of 
certified copies).  
All subject data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g. laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF/eCRF.  
The investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial subjects that supports the 
information entered in the eCRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source.  
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data should be traceable, should not 
obscure the original entry, and should be explained if necessary (e.g. via an audit trail). 
Safety and rights of subjects must be protected and study be conducted in accordance 
with the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Trial records and source documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the investigator for 25 years from the issue of the final 
CSR/equivalent summary unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
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12.4.9. 
Source documents 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Investigator should maintain a record of the location(s) of 
their source documents.  
Data reported on the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available. 
Definition of what constitutes source data and source documents can be found in the 
Glossary of terms. 
12.4.10. 
Study and site closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure will 
be upon study completion. A study site is considered closed when all required 
data/documents and study supplies have been collected and a study-site closure visit has 
been performed.  
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment or retention of subjects by the investigator 
• 
Discontinuation of further study treatment development 
The investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the Study Conclusion screen in the eCRF. 
• 
Answer data clarification queries from GSK. 
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12.5. 
Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting 
12.5.1. 
Definition of AE 
12.5.1.1. 
AE Definition 
An AE is any untoward medical occurrence in a clinical study subject, temporally 
associated with the use of a study treatment, whether or not considered related to the 
study treatment. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment. 
12.5.1.2. 
Events Meeting the AE Definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study vaccine administration even 
though they may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
vaccine or a concurrent medication (overdose per se should not be reported as an 
AE/SAE). 
• 
Signs, symptoms temporally associated with study vaccine administration. 
• 
Significant failure of expected pharmacological or biological action.  
• 
Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen). 
• 
Medically attended visits related to adverse events (e.g. Hospital stays, physician 
visits and emergency room visits). 
AEs to be recorded as endpoints (solicited AEs) are described in section 12.5.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfil the definition of an AE or SAE.  
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12.5.1.3. 
Events NOT Meeting the AE Definition  
• 
Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.  
• 
Pre-existing conditions or signs and/or symptoms present in a subject prior to the 
first study revaccination. These events will be recorded in the medical history section 
of the eCRF. 
12.5.2. 
Definition of SAE 
A SAE is any untoward medical occurrence that: 
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 
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, diarrhea, 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 jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
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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. 
12.5.3. 
Solicited adverse events 
a. Solicited local (injection-site) adverse events 
The following local (injection-site) AEs will be solicited: 
Table 21 
Solicited local adverse events 
Pain at injection site 
Redness at injection site 
Swelling at injection site 
b. Solicited general adverse events 
The following general AEs will be solicited: 
Table 22 
Solicited general adverse events 
Fatigue 
Fever 
Gastrointestinal symptoms † 
Headache 
Myalgia 
Shivering 
†Gastrointestinal symptoms include nausea, vomiting, diarrhea and/or abdominal pain. 
Note: subjects/subjects’ LAR(s) 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/subjects’ LAR(s) will be instructed to record the highest 
temperature in the diary card. 
12.5.4. 
Unsolicited adverse events 
An unsolicited adverse event is an adverse event that was not explicitly solicited using a 
Subject Diary and that was spontaneously communicated or mentioned in the diary under 
adverse events by a subject/LAR who has signed the informed consent. 
Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses 
requiring hospitalization, or emergency room visit, or visit to/by a health care provider), 
or were of concern to the subjects/LAR(s). In case of such events, subjects/LAR(s) will 
be instructed to contact the site as soon as possible to report the event(s). The detailed 
information about the reported unsolicited AEs will be collected by the qualified site 
personnel during the interview and will be documented in the subject’s records. 
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Unsolicited AEs that are not medically attended nor perceived as a concern by 
subjects/LAR(s) will be collected from the subject diary, during interview with the 
subjects/LAR(s) and by review of available medical records at the next visit. 
An unsolicited AE is an AE which includes non-serious and serious AEs unless otherwise 
specified. 
12.5.5. 
Adverse events of special interest  
AESIs for safety monitoring include: 
• 
Allograft rejection, biopsy-proven. 
• 
pIMDs  
12.5.5.1. 
Allograft rejection, biopsy-proven 
Biopsy-proven allograft rejection is defined as an AESI. It will be recorded in Expedited 
Adverse Event Reporting screens, irrespective of the seriousness of the event.  
Refer to section 8.1.14 for guidance on the information to be collected for allograft 
rejections. Refer to section 12.5.10 for reporting details. 
12.5.5.2. 
Potential immune-mediated diseases 
pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory 
and/or neurologic disorders of interest which may or may not have an autoimmune 
etiology. AEs that need to be recorded and reported as pIMDs include those listed in the 
Table 23. Refer to section 12.5.10 for reporting details. 
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 23 
List of potential immune-mediated diseases 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• 
Cranial nerve neuropathy, including paralysis and 
paresis (e.g. Bell’s palsy). 
• 
Optic neuritis. 
• 
Multiple sclerosis. 
• 
Transverse myelitis. 
• 
Guillain-Barré syndrome, including Miller Fisher 
syndrome and other variants. 
• 
Acute disseminated encephalomyelitis, including site 
specific variants e.g.: non-infectious encephalitis, 
encephalomyelitis, myelitis, myeloradiculoneuritis. 
• 
Myasthenia gravis, including Lambert-Eaton 
myasthenic syndrome. 
• 
Demyelinating peripheral neuropathies including: 
• 
Chronic inflammatory demyelinating polyneuropathy,  
• 
Multifocal motor neuropathy  
• 
Polyneuropathies associated with monoclonal 
gammopathy. 
• 
Narcolepsy. 
• 
Systemic lupus erythematosus and associated 
conditions 
• 
Systemic scleroderma (Systemic sclerosis), including: 
• 
Diffuse Scleroderma 
• 
CREST syndrome 
• 
Idiopathic inflammatory myopathies, including: 
• 
Dermatomyositis  
• 
Polymyositis  
• 
Anti-synthetase syndrome. 
• 
Rheumatoid Arthritis and associated conditions 
including:  
• 
Juvenile Idiopathic Arthritis 
• 
Still’s disease. 
• 
Polymyalgia rheumatica. 
• 
Spondyloarthropathies, including:  
• 
Ankylosing Spondylitis,  
• 
Reactive Arthritis (Reiter's Syndrome), 
• 
Undifferentiated Spondyloarthritis, 
• 
Psoriatic Arthritis, 
• 
Enteropathic arthritis. 
• 
Relapsing Polychondritis. 
• 
Mixed Connective Tissue disorder. 
• 
Gout. 
• 
Psoriasis. 
• 
Vitiligo. 
• 
Erythema nodosum. 
• 
Autoimmune bullous skin diseases (including 
pemphigus, pemphigoid and dermatitis 
herpetiformis). 
• 
Lichen planus. 
• 
Sweet’s syndrome. 
• 
Localized Scleroderma (Morphoea). 
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Vasculitis 
Blood disorders 
Others 
• 
Large vessels vasculitis including:  
• 
Giant Cell Arteritis (Temporal Arteritis), 
• 
Takayasu's Arteritis.  
• 
Medium sized and/or small vessels vasculitis including:  
• 
Polyarteritis nodosa, 
• 
Kawasaki's disease,  
• 
Microscopic Polyangiitis,  
• 
Wegener's Granulomatosis (granulomatosis with 
polyangiitis),  
• 
Churg–Strauss syndrome (allergic granulomatous 
angiitis or eosinophilic granulomatosis with 
polyangiitis),  
• 
Buerger’s disease (thromboangiitis obliterans),  
• 
Necrotising vasculitis (cutaneous or systemic),  
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive 
vasculitis (type unspecified), 
• 
Henoch-Schonlein purpura (IgA vasculitis),  
• 
Behcet's syndrome, 
• 
Leukocytoclastic vasculitis. 
• 
Autoimmune hemolytic anemia. 
• 
Autoimmune thrombocytopenia. 
• 
Antiphospholipid syndrome. 
• 
Pernicious anemia. 
• 
Autoimmune aplastic anemia. 
• 
Autoimmune neutropenia. 
• 
Autoimmune pancytopenia. 
• 
Autoimmune glomerulonephritis including: 
• 
IgA nephropathy,  
• 
Glomerulonephritis rapidly progressive,  
• 
Membranous glomerulonephritis,  
• 
Membranoproliferative glomerulonephritis,  
• 
Mesangioproliferative glomerulonephritis.  
• 
Tubulointerstitial nephritis and uveitis syndrome. 
• 
Ocular autoimmune diseases including: 
• 
Autoimmune uveitis  
• 
Autoimmune retinitis. 
• 
Autoimmune myocarditis. 
• 
Sarcoidosis. 
• 
Stevens-Johnson syndrome. 
• 
Sjögren’s syndrome. 
• 
Alopecia areata. 
• 
Idiopathic pulmonary fibrosis. 
• 
Goodpasture syndrome. 
• 
Raynaud’s phenomenon. 
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Liver disorders 
Gastrointestinal disorders 
Endocrine disorders 
• 
Autoimmune hepatitis. 
• 
Primary biliary cirrhosis. 
• 
Primary sclerosing cholangitis. 
• 
Autoimmune cholangitis. 
• 
Inflammatory Bowel disease, including: 
• 
Crohn’s disease,  
• 
Ulcerative colitis,  
• 
Microscopic colitis,  
• 
Ulcerative proctitis. 
• 
Celiac disease. 
• 
Autoimmune pancreatitis. 
• 
Autoimmune thyroiditis (Hashimoto thyroiditis). 
• 
Grave's or Basedow’s disease. 
• 
Diabetes mellitus type I. 
• 
Addison’s disease. 
• 
Polyglandular autoimmune syndrome. 
• 
Autoimmune hypophysitis. 
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When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as AESI. Symptoms, signs or conditions which might (or might not) represent 
the above diagnoses, should be recorded and reported as AEs but not as AESI 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.  
12.5.6. 
COVID-19 (Amended: 15 June 2020) 
COVID-19 is an infectious disease caused by severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2). When reporting an AE (serious or non-serious as 
defined in Section 12.5.2) related to COVID-19 infection, the following verbatim terms 
should be used according to World Health Organisation (WHO) definition (Please 
refer to Appendix 9): 
• 
Suspected COVID-19 infection; or 
• 
Probable COVID-19 infection; or 
• 
Confirmed COVID-19 infection 
Information pertaining to COVID-19 infection should be recorded at the next 
scheduled visit as medical history on the COVID-19 specific eCRF. 
(Amended: 15 June 2020) 
12.5.7. 
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 12.5.1 and 12.5.2). Clinically significant 
abnormal laboratory findings or other abnormal assessments that are present at baseline 
and significantly worsen following the start of the study will also be reported as AEs or 
SAEs. However, clinically significant abnormal laboratory findings or other abnormal 
assessments that are associated with the disease being studied, unless judged by the 
investigator as more severe than expected for the subject’s condition, or that are present 
or detected at the start of the study and do not worsen, will not be reported as AEs or 
SAEs. 
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant. 
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12.5.8. 
Events or outcomes not qualifying as adverse events or serious 
adverse events 
12.5.8.1. 
Pregnancy 
Female subjects who are pregnant or lactating at the time of revaccination must not 
receive additional doses of study vaccine but may continue other study procedures at the 
discretion of the investigator. 
While pregnancy is not considered an AE or SAE, any adverse pregnancy outcome or 
complication or elective termination of a pregnancy for medical reasons will be recorded 
and reported as an AE or a SAE. 
Note: The pregnancy should always be recorded on electronic pregnancy report. 
The following should always be considered as SAE and will be reported as described in 
sections 12.5.10.1 and 12.5.10.4: 
• 
Spontaneous pregnancy loss, including: 
− 
spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation) 
− 
ectopic and molar pregnancy 
− 
stillbirth (intrauterine death of fetus 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).  
• 
Any congenital anomaly or birth defect identified in the offspring of a study subject 
(either during pregnancy, at birth or later) regardless of whether the fetus is delivered 
dead or alive. This includes anomalies identified by prenatal ultrasound, 
amniocentesis or examination of the products of conception after elective or 
spontaneous abortion. 
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the investigator to be reasonably related to the study vaccine will be reported to GSK 
as described in section 12.5.10. While the investigator is not obligated to actively seek 
this information from former subjects, he/she may learn of a pregnancy through 
spontaneous reporting. 
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12.5.9. 
Detecting and recording adverse events, serious adverse events 
and pregnancies 
A Paper Diary (pDiary), hereafter referred to as Subject Diary, will be used in this study 
to capture solicited AEs. The subject should be trained on how and when to complete 
each field of the Subject Diary. 
The subjects/subjects’ LAR(s) be instructed to contact the investigator immediately 
should the subjects manifest any signs or symptoms they perceive as serious.  
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of AEs and who will enter the information into the Subject Diary. This 
individual may not be the subject/subjects’ LAR(s), but if a person other than the 
subject/subjects’ LAR(s) enters information into the Subject Diary, this person’s identity 
must be documented in the subject’s source record. Any individual that makes entries 
into the Subject Diary must receive training on completion of the Subject Diary at the 
time of the visit when Subject Diary is dispensed. This training must be documented in 
the subject’s source record. 
At each revaccination visit, a Subject Diary card will be provided to the subject or 
subjects’ LAR(s). The subject or subjects’ LAR(s) (or subject’s caregiver) will be 
instructed to measure and record the oral body temperature, and any solicited 
local/general AEs (i.e. on the day of revaccination and during the next 6 days) or any 
unsolicited AEs (i.e. on the day of revaccination and during the next 29 days occurring 
after revaccination). The subject or subjects’ LAR(s) (or subject’s caregiver) will be 
instructed to return the completed Subject Diary card to the investigator at the next study 
visit.  
• 
Collect and verify completed Subject Diary cards during discussion with the subject 
on Visit 4 (Month 25) and on Visit 5 (Month 26). 
• 
Any unreturned Subject Diary cards will be sought from the subject through 
telephone call(s) or any other convenient procedure.  
• 
The investigator will transcribe the collected information into the eCRF in English. 
12.5.9.1. 
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies 
All AEs during 30 days following administration of each dose of study vaccine (from day 
of revaccination and 29 subsequent days) 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 at Visit 3 (Month 24) during revaccination phase and will end at Visit 6 (Month 
37) for each subject (See section 12.5.10 for instructions on reporting of SAEs). 
However, any SAEs assessed as related to study participation (e.g. study treatment, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or related to 
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a GSK product will be recorded from the time a subject consents to participate in the 
study until the subject is discharged from the study. 
SAEs that are related to the study vaccine administered during revaccination phase will 
be collected and recorded from the time of the first receipt of study vaccine at Visit 3 
(Month 24) until the subject is discharged from the study or until the end of the study 
(See section 12.5.10 for instructions on reporting of SAEs).  
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the enrollment visit [Visit 1 (Day 1)] up to the last study visit [Visit 7 (Month 49)]. 
After informed consent is obtained, the following events that occurred since the primary 
follow-up study ZOSTER-041 last study visit (Month 13) up to study ZOSTER-073 
Visit 1 (Day 1), will be collected retrospectively and recorded in the medical history:   
• 
all SAEs related to the study vaccine  
• 
all suspected renal allograft rejections 
• 
all biopsy-proven renal allograft rejections  
• 
all suspected episodes of HZ considered as SAEs  
• 
all clinically-confirmed episodes of HZ considered as SAEs  
(Amended: 15 June 2020) 
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 Visit 1 (Day 1) 
and will end at the last study visit [Visit 7 (Month 49)]. See section 12.5.10 for 
instructions on reporting of pregnancies. 
The time period for collecting and recording of pIMDs will begin at the first receipt of 
study vaccine at Visit 3 (Month 24) during revaccination phase and will end at Visit 6 
(Month 37), approximately 12 months following administration of the last revaccination 
dose. See section 12.5.10.5 for instructions on reporting of pIMDs. 
The time period for collecting and recording of biopsy-allograft rejections will begin at 
the enrollment visit [Visit 1 (Day 1)] and will end at the last study visit [Visit 7 (Month 
49)]. See section 12.5.10.5 for instructions on reporting of renal allograft rejection. 
The time period for collecting and recording of IMCs (including HZ) will begin at the 
enrollment visit [Visit 1 (Day 1)] and will end at the last study visit [Visit 7 (Month 49)]. 
See section 12.5.10.5 for instructions on reporting of HZ. 
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Of note, any medical events that occurred since the ZOSTER-041 last study visit 
(Month 13) up to study ZOSTER-073 Visit 1 (Day 1) will be recorded in medical 
history section on the eCRF and should not be reported via expedited reporting. 
(Amended: 15 June 2020) 
Evaluation of adverse events and serious adverse events 
12.5.9.1.1. Active questioning to detect adverse events and serious adverse 
events 
As a consistent method of collecting AEs, the subject or the subject’s LAR(s) should be 
asked a non-leading question such as: 
‘Have you felt different in any way since receiving the vaccine or since the previous 
visit?’ 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers will be blinded on the copies of 
the medical records prior to submission to GSK. 
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms. 
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12.5.9.1.2. Assessment of adverse events 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 24 
Intensity scales for solicited adverse events  
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 
Temperature* 
 
Record temperature in °C/°F [with 1 decimal] 
Headache 
0 
Normal 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
Normal 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Gastrointestinal symptoms 
0 
Normal 
(nausea, vomiting, diarrhea 
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 interfere with normal activity 
 
3 
Severe: Myalgia that prevent normal activity 
Shivering 
0 
Normal 
 
1 
Mild: Shivering that is easily tolerated 
 
2 
Moderate: Shivering that interfere with normal activity 
 
3 
Severe: Shivering that prevent normal activity 
*Fever is defined as temperature 38.0°C. The preferred location for measuring temperature in this study is the oral 
cavity. 
The maximum intensity of local injection site redness/swelling will be scored at GSK as 
follows: 
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 preferred route for recording temperature in this study is oral. When there is no other 
alternative, the temperature may be recorded by another route. If the temperature is taken 
by another route (axillary, rectal or tympanic), the route should be documented. 
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement. 
The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities (In adults, such 
an AE would, for example, prevent attendance at work and would 
necessitate the administration of corrective therapy) 
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets 1 of the pre-defined 
outcomes as described in section 12.5.2. 
Assessment of causality 
The investigator is obligated to assess the relationship between study vaccine and the 
occurrence of each AE/SAE using clinical judgement. In case of concomitant 
administration of multiple vaccines/products, if possible, the investigator should specify 
if the AE could be causally related to a specific vaccine/product administered (i.e. 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine/product cannot be determined, the investigator should indicate the AE 
to be related to all products. 
Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study vaccine will be considered and investigated. The investigator will also consult the 
IB to determine his/her assessment. 
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important that the 
investigator always makes an assessment of causality for every event prior to submission 
of the Expedited Adverse Events Report to GSK. The investigator may change his/her 
opinion of causality in light of follow-up information and update the SAE information 
accordingly. The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
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All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question: 
Is there a reasonable possibility that the AE may have been caused by the study vaccine? 
YES 
: 
There is a reasonable possibility that the study vaccine contributed 
to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to 
the administration of the study vaccine. There are other, more 
likely causes and administration of the study vaccine is not 
suspected to have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see section 12.5.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the vaccine, if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify). 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
12.5.9.1.3. Medically attended visits 
For each solicited and unsolicited AE the subject experiences, the subject/subject’s 
LAR(s) will be asked if he/she received medical attention defined as hospitalization, or 
an otherwise unscheduled visit to or from medical personnel for any reason, 
includingemergency room visits. This information will be recorded in the eCRF. 
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12.5.10. 
Reporting of SAEs, pregnancies, and other events 
12.5.10.1. Prompt reporting of SAEs, pregnancies, and other events to GSK 
SAEs that occur in the time period defined in section 12.5.9 will be reported promptly to 
GSK within the timeframes described in Table 17, once the investigator determines that 
the event meets the protocol definition of a SAE. 
Pregnancies that occur in the time period defined in section 12.5.9 will be reported 
promptly to GSK within the timeframes described in Table 17, once the investigator 
becomes aware of the pregnancy.  
AESIs that occur in the time period defined in section 12.5.9 will be reported promptly to 
GSK within the timeframes described in Table 17, once the investigator determines that 
the event meets the protocol definition of a AESIs. 
12.5.10.2. Expedited reporting of SAEs to GSK 
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event. Even if the investigator does 
not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated 
WITHIN 24 HOURS. 
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE. 
12.5.10.3. Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the Sponsor Information) or to GSK Clinical 
Safety and Pharmacovigilance department within 24 hours.  
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system.  
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12.5.10.4. Completion and transmission of pregnancy reports to GSK  
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 2 WEEKS. 
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the pregnancy 
report. 
12.5.10.5. Reporting of AESI’s to GSK  
Once an AESI is diagnosed (serious or non-serious) in a study subject, the investigator 
(or designate) must complete the information in the electronic Expedited Adverse Events 
Report WITHIN 24 HOURS after he/she becomes aware of the diagnosis. The report 
allows specify that the event is an AESI 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 AESIs standard questionnaire provided. Even if the 
investigator does not have all information regarding an AESI, 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 AESI causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the AESI. 
Refer to section 12.5.10.3 for back-up system in case the electronic reporting system does 
not work. 
12.5.11. 
Updating of SAE, pregnancy, and AESI information after removal 
of write access to the subject’s eCRF 
When additional SAE, pregnancy, or AESI information is received after removal of the 
write access to the subject’s eCRF, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
Sponsor Information) or to GSK Clinical Safety and Pharmacovigilance department 
within the designated reporting time frames specified in Table 17. 
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12.5.12. 
Follow-up of adverse events, serious adverse events, and 
pregnancies 
12.5.12.1. Follow-up of adverse events and serious adverse events 
12.5.12.1.1. 
Follow-up during the study 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide additional relevant information on the subject’s condition to GSK 
(within 24 hours for SAEs; refer to Table 17). 
All SAEs and AESIs (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. 
AESIs of HZ cases 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 resolution of HZ-rash and/or HZ-pain or study conclusion, Visit 7 
(Month 49). 
AESIs of biopsy-proven allograft rejections documented at a previous visit/contact and 
designated as not recovered/not resolved or recovering/resolving will be reviewed at 
subsequent visits until: 
• 
the event has resolved, subsided, stabilized, disappeared, or until the event is 
otherwise explained, or  
• 
study conclusion, Visit 7 (Month 49). 
12.5.12.2. Follow-up after the subject is discharged from the study 
The investigator will follow subjects: 
• with SAEs, AESIs (serious or non-serious), or subjects withdrawn from the study as a 
result of an AE, until the event has resolved, subsided, stabilized, disappeared, or 
until the event is otherwise explained, or the subject is lost to follow-up. 
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK using a paper/electronic Expedited Adverse 
Events Report and/or pregnancy report as applicable. 
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GSK may request that the investigator performs or arranges the conduct of additional 
clinical examinations/tests and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obliged to assist. If a subject dies 
during participation in the study or during a recognized follow-up period, GSK will be 
provided with any available post-mortem findings, including histopathology. 
12.5.12.3. Follow-up of pregnancies 
Pregnant subjects will be followed to determine the outcome of the pregnancy. At the end 
of the pregnancy, whether full-term or premature, information on the status of the mother 
and child will be forwarded to GSK using the electronic pregnancy report and the 
Expedited Adverse Events Report if applicable. Generally, the follow-up period doesn’t 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE. 
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12.6. 
Appendix 6: Contraceptive guidance and collection of 
pregnancy information 
12.6.1. 
Definitions 
12.6.1.1. 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below) 
12.6.1.1.1. Women in the following categories are not considered WOCBP 
• 
Premenarchal 
Menarche is the onset of menses for the first time in a young female and is preceded 
by several changes associated with puberty including breast development and pubic 
hair growth. Menarche usually occurs within 1-2 years of breast development, 
thelarche. However, a young female can become pregnant before her first menses. 
Thus, a conservative definition of non- childbearing potential in a pre-menarcheal 
female is a young female who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue). 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s: review of subject’s medical 
records, medical examination, or medical history interview. 
• 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient.  
• 
Females on HRT and whose menopausal status is in doubt will be required to use 1 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
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12.6.2. 
Contraception guidance 
Female subjects of childbearing potential are eligible to participate if they agree to use an 
adequate contraception consistently and correctly according to the methods listed in GSK 
list of highly effective contraceptive methods provided in Table 25.  
Table 25 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation  
• oral 
• intravaginal  
• transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation  
• injectable  
Highly Effective Methods That Are User Independent  
• Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• bilateral tubal occlusion 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used.)  
Male partner sterilization prior to the female subject’s entry into the study, and this male is 
the sole partner for that subject, 
(The information on the male sterility can come from the site personnel’s review of the 
subject’s medical records; medical examination and/or semen analysis, or medical history 
interview provided by her or her partner). 
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the subject.)  
NOTES:  
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects in clinical studies.  
(Amended: 15 June 2020) 
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12.6.3. 
Collection of pregnancy information 
12.6.3.1. 
Female Subjects who become pregnant 
• 
Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 2 
weeks of learning of a subject's pregnancy.  
• 
Subject will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on subject and neonate, which will be 
forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.  
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in 12.5.10. While the investigator is not obligated to actively seek this 
information in former study subjects, he or she may learn of an SAE through 
spontaneous reporting.  
Refer to sections 12.5.9, 12.5.10 and 12.5.12.3 for further information on detection, 
recording, reporting and follow-up of pregnancies. 
Any female subject who is or becomes pregnant while participating from 1 month before 
Visit 3 to 1 month after Visit 5 will not be revaccinated and will be encouraged to 
continue other study procedures for long term assessments. 
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12.7. 
Appendix 8: Country-specific requirements 
All countries will comply with AE and SAE reporting as described in section 8.4 of the 
protocol. Additionally, countries and sites will follow all applicable local regulations and 
guidelines for AE and SAE reporting as required by their respective healthcare authorities 
and ethics committees.  
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12.8. 
Appendix 9: Case Definition for COVID-19 Coronavirus 
Infection (Amended: 15 June 2020) 
WHO Case Definition (Version: March 20, 2020):  
• 
Suspected case 
− 
A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel 
to or residence in a location reporting community transmission of COVID-19 
disease during the 14 days prior to symptom onset; OR  
− 
A patient with any acute respiratory illness AND having been in contact (see 
definition of “contact” below) with a confirmed or probable COVID-19 case 
(see definition of contact) in the last 14 days prior to symptom onset; OR  
− 
A patient with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation. 
• 
Probable case 
− 
A suspect case for whom testing for the COVID-19 virus is inconclusive 
(inconclusive being the result of the test reported by the laboratory); OR  
− 
A suspect case for whom testing could not be performed for any reason. 
• 
Confirmed case 
− 
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms.  
A contact is a person who experienced any one of the following exposures during 
the 2 days before and the 14 days after the onset of symptoms of a probable or 
confirmed case:  
− 
Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes;  
− 
Direct physical contact with a probable or confirmed case;  
− 
Direct care for a patient with probable or confirmed COVID-19 disease 
without using proper personal protective equipment; OR  
− 
Other situations as indicated by local risk assessments.  
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 
days before through the 14 days after the date on which the sample was taken 
which led to confirmation. 
(Amended: 15 June 2020) 
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12.9. 
Appendix 10: Amendments and Administrative Changes to 
the Protocol 
The Protocol Amendment Summary of Changes Table for the current amendment 
is located directly before the Table of Contents (TOC). 
Document history 
Document 
Date 
Amendment 1 
15-Jun-2020 
Protocol Version 1 
07-Jun-2019 
Overall rationale for the Amendment 1: 
The purpose of the amendment is to: 
• 
Outline measures to be applied during special circumstances (e.g., COVID-19 
pandemic), to protect participant’s welfare and safety, and, as far as possible, to 
ensure the potential benefit to the participant and promote study integrity.  
• 
Define study procedures / assessments to allow participation of non-revaccinated 
subjects in an extended long-term follow-up phase. 
• 
Minor corrections and clarifications 
List of main changes in the protocol and their rationale: 
Section # and Name 
Description of Change 
Brief rationale 
Section 8.1.16 Study 
procedures during special 
circumstances  
Added new 
To provide guidance on adapting study 
procedures during special 
circumstances, such as COVID-19 
pandemic 
Across the document, including 
objectives and endpoints 
sections 
Revised text or added new text for 
non-revaccinated subjects 
To nuance differences in study 
procedures / assessments for non-
revaccinated subjects 
Detailed description of Protocol Amendment 1: 
In the following sections, deleted text is indicated in strikethrough and changed text in 
bold italics: 
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Section 1. SYNOPSIS 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
LTFU phase - Immunogenicity assessment  
• 
To evaluate persistence of humoral immunity after 
primary vaccination course. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by 
ELISA at Day 1, Month 12 and Month 24. 
Revaccination active phase - Immunogenicity 
assessment 
• 
To evaluate humoral immunity of HZ/su vaccine 
post-revaccination Doses 1 & 2. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by 
ELISA at pre-revaccination (Month 24) and at 1-
month post-revaccination Dose 1 (Month 25) and 
Dose 2 (Month 26). 
Secondary 
LTFU phase - Immunogenicity assessment 
• 
To evaluate persistence of cellular immunity after 
primary vaccination course. 
In CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T-cells expressing 
two or more markers such as IFN-γ, IL-2, TNF-α, 
CD40L as determined by ICS at Day 1, Month 12 
and Month 24in a CMI sub-cohort of subjects. 
LTFU phase - safety assessment 
• 
To evaluate safety of HZ/su vaccine from the study 
ZOSTER-041 last visit to study ZOSTER-073 
Visit 3. 
In all subjects: 
• 
Related-SAEs 
− Occurrence of SAEs related to primary 
vaccination as assessed by the investigator from 
the study ZOSTER-041 last visit (Month 13) to 
study ZOSTER-073 Visit 3 (Month 24). 
• 
HZ episodes 
− Occurrence of suspected or confirmed HZ cases 
from the study ZOSTER-041 last visit 
(Month 13) to study ZOSTER-073 Visit 1 (Day 
1).  
− Occurrence of confirmed HZ cases from Day 1 
through Month 24. 
• 
AESIs 
− Occurrence of suspected or biopsy-proven 
allograft rejections from the study ZOSTER-041 
last visit (Month 13) to study ZOSTER-073 Visit 
1 (Day 1).  
− Occurrence of biopsy-proven allograft rejections 
from Day 1 through Month 24. 
• 
Allograft function for episode(s) of allograft 
rejection. 
− Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of biopsy-proven rejection and up to 2 
months after rejection resolution and cessation 
of therapeutic immunosuppressive therapy for 
the time period from study ZOSTER-041 last 
visit (Month 13) to study ZOSTER-073 Visit 3 
(Month 24).  
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Objectives 
Endpoints 
• 
Allograft function for episode(s) of HZ 
− Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of HZ and up to 2 months after HZ rash 
resolution for the time period from study 
ZOSTER-041 last visit (Month 13) to study 
ZOSTER-073 Visit 3 (Month 24). 
Revaccination active phase - Immunogenicity 
assessment 
• 
To evaluate cell-mediated immunity 
post- revaccination Doses 1 & 2. 
In revaccinated subjects in CMI sub-cohort: 
 
• 
Frequencies of gE-specific CD4+ T-cells expressing 
two or more markers such as IFN-γ, IL-2, TNF-α, 
CD40L as determined by ICS at pre-vaccination 
(Month 24) and at 1-month post-revaccination Dose 
1 (Month 25) and Dose 2 (Month 26)in a CMI sub-
cohort of subjects. 
Revaccination follow-up phase – Immunogenicity 
assessment 
• 
To evaluate persistence of humoral and cell-
mediated immune responses post-revaccination 
Dose 2. 
In all revaccinated subjects: 
• 
Anti-gE antibody concentrations as determined by 
ELISA at 12 months and 24 months post-
revaccination Dose 2. 
In revaccinated subjects in CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T- cells 
expressing two or more markers such as IFN-γ, IL-
2, TNF-α, CD40L as determined by ICS at 12 
months and 24 months post-revaccination Dose 2 
in a CMI sub-cohort of subjects. 
Revaccination active and follow-up phases - Safety 
assessment 
• 
To evaluate reactogenicity and safety of the HZ/su 
vaccine after each revaccination. 
In all revaccinated subjects: 
• 
Solicited local and general AEs: 
− Occurrence, duration and intensity of solicited 
local AEs within 7 days after each revaccination 
(i.e., the day of revaccination and 6 subsequent 
days);  
− Occurrence, duration and intensity of solicited 
general AEs within 7 days after each 
revaccination dose (i.e., the day of revaccination 
and 6 subsequent days) and causal relationship 
to revaccination by investigator assessment.  
• 
Unsolicited AEs  
− Occurrence, intensity of unsolicited AEs during 
30 days after each revaccination (i.e., the day of 
revaccination and 29 subsequent days) and 
causal relationship to revaccination by 
investigator assessment.  
• 
SAEs  
− Occurrence of SAEs (including fatal SAEs) from 
Dose 1 of revaccination (Month 24) until 12 
months post-last revaccination dose (Month 37).  
− Occurrence of related-SAEs (including related-
fatal SAEs) as per investigator assessment from 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
1 3 7  
O bj e cti v e s  
E n d p oi nt s  
D os e 1 of r ev acci n ati o n ( M o nt h  2 4) u p t o st u dy 
e n d ( M o nt h 4 9).  
•  
A E SIs  
− .  
− O cc urr e nc e of all bi o psy-pr ov e n all o gr aft 
r ej ecti o ns fr o m D os e 1 of r ev acci n ati o n ( M o nt h 
2 4) u p t o st u dy e n d ( M o nt h 4 9) a n d c a us al 
r el ati o ns hi p t o r ev acci n ati o n by i nv esti g at or 
ass ess m e nt.  
− Occ urr e nc e of pI M Ds fr o m D os e 1 of 
r ev acci n ati o n ( M o nt h 2 4) u p t o 12 m o nt hs p ost -
l ast r ev acci n ati o n d os e ( M o nt h 3 7) a n d c a us al 
r el ati o ns hi p by i nv esti g at or ass ess m e nt. 
•  
H Z e pis o d es  
− Occ urr e nc e of c o nfir m e d H Z c as es fr o m D os e 1 
of r ev acci n ati o n ( M o nt h 2 4) u p t o st u dy e n d 
( M o nt h 4 9).  
•  
All o gr aft f u ncti o n f oll o wi n g r ev acci n ati o n  
− Occ urr e nc e of all o gr aft dysf u ncti o n t hr o u g h 
ass ess m e nt of all cli nic ally o bt ai n e d s er u m 
cr e ati ni n e m e as ur es fr o m 3 m o nt hs b ef or e t h e 
first r ev acci n ati o n d os e u ntil 3 m o nt hs aft er t h e 
l ast r ev acci n ati o n d os e. 
•  
All o gr aft f u ncti o n f or e pis o d e(s) of all o gr aft r ej ecti o n  
− Occ urr e nc e of all o gr aft dysf u ncti o n t hr o u g h 
ass ess m e nt of all cli nic ally o bt ai n e d s er u m 
cr e ati ni n e m e as ur es fr o m 2 m o nt hs pri or t o a n 
e pis o d e of  bi o psy -pr ov e n r ej ecti o n a n d u p t o 2 
m o nt hs aft er r ej e cti o n r es ol uti o n a n d c ess ati o n 
of t h er a p e utic of i m m u n os u p pr essiv e t h er a py.   
•  
All o gr aft f u ncti o n f or e pis o d e(s) of H Z  
− Occ urr e nc e of all o gr aft dysf u ncti o n t hr o u g h 
ass ess m e nt of all cli nic ally o bt ai n e d s er u m 
cr e ati ni n e m e as ur es fr o m 2 m o nt hs pri or t o a n 
e pis o d e of H Z a n d u p t o 2 m o nt hs aft er H Z 
r es ol uti o n. 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
1 3 8  
C MI = C ell -M e di at e d I m m u nity; 
; E LI S A  = Enzy m e Li nk e d I m m u n os or b e nt Ass ay; 
g E  = glyc o pr ot ei n E; 
 I C S = I ntr ac ell ul ar Cyt oki n e St ai ni n g; I L-2  = I nt erl e uki n 2; 
; 
; 
 
T N F α  = T u m or N ecr osis F act or -al p h a; I F N γ = I nt erf er o n -g a m m a; A E = A dv ers e Ev e nt; S A E  = Seri o us A dv ers e Ev e nt; 
H Z  = H er p es Z ost er;  A E SI   =  A dv ers e Ev e nt of Sp eci al I nt er est; pI M D s  =  p ot e nti al I m m u n e -M e di at e d Dis e as es  
* T o b e p erf or m e d by a t h e c e ntr al l a b or at ory if d e e m e d n ec ess ary.  
T he f o ot n ote s of t he o v erall desi g n fi g ure hav e  bee n u p date d as f oll o ws : 
H Z/ s u  = H er p es z ost er s u b u nit; L T F U  = L o n g t er m f oll o w -u p; Va c c 1 -2  = Vacci n ati o n d os e 1 & 2; re-Va c c  1 -2  = 
R ev acci n ati o ns d os e 1 & 2  
* T h e s ec o n d d os e of r ev acci n ati o n ( Visit 4, M o nt h 2 5) will b e a d mi nist er e d 1 t o 2 m o nt hs aft er t h e first r ev acci n ati o n 
d os e.  
** Visit 5 ( M o nt h 2 6), Visit 6 ( M o nt h 3 7) a n d Visit 7 ( M o nt h 4 9) will occ ur 1, 1 2 a n d 2 4 m o nt hs aft er t h e s ec o n d 
r ev acci n ati o n, r es p ectiv ely. 
$P h o n e c o nt act will occ ur a b o ut 3 5 d ays b ef or e Visit 3 ( M o nt h 2 4) t o r e mi n d f e m al e s u bj ects of c hil d b e ari n g p ot e nti al t o 
us e a d e q u at e c o ntr ac e pti o n.  
I n ti m e s of s p e ci al circ u m st a n ce s, ref er t o Se cti o n  8. 1. 1 6 . 
Secti o n 2.  S C H E D U L E O F A C TI VI TI E S ( S O A)  
T he f o ot n ote s of Ta bl e 3  ha ve  bee n u p date d as f oll o ws:  
I nt eri m m e dic al hist ory 
(s ecti o n 8. 1. 4)  
 
O  
 
O  
O  
O  
O  
O  
O  
N ot e: T h e d o u bl e -li n e b or d ers i n dic at e a n alys es t h at will b e p erf or m e d o n all d at a o bt ai n e d u p t o t his ti m e p oi nt (r ef er 
t o s ecti o n 1 0. 4 ). 
● is us e d t o i n dic at e a st u dy pr oc e d ur e t h at r e q uir es d oc u m e nt ati o n i n t h e i n divi d u al el ectr o nic C as e R e p ort F or m 
( e C R F). 
O is us e d t o i n dic at e a st u dy pr oc e d ur e t h at d o es n ot r e q uir e d oc u m e nt ati o n i n t h e i n divi d u al e C R F.  
V a c c  = V acci n ati o n; P C  = P h o n e C o nt act; A Es  = Adv ers e Ev e nts; C MI  = C ell - M e di at e d I m m u nity; S A Es  = Seri o us 
A dv ers e Ev e nts; pI M D s  = p ot e nti al I m m u n e -M e di at e d Dis e as es; H Z  = H er p es Z ost er; A E SI  = Adv ers e Ev e nts of 
S p eci al I nt er est; R T  = R e n al Tr a ns pl a nt; Z B PI  = Z ost er Bri ef Pai n I nv e nt ory.  
* B ef or e v acci n e a d mi nistr ati o n. 
a  P h o n e c o nt act 1 ( P C 1) will occ ur a b o ut 3 5 d ays b ef or e Visit 3 ( M o nt h 2 4) t o r e mi n d f e m al e s u bj ects of c hil d b e ari n g 
p ot e nti al t o us e a d e q u at e c o ntr ac e pti o n.  
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI
C CI
C CI
C CI
C CI

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b  Visit 3 is the day of the first revaccination. Pre-revaccination and post-revaccination activities at Visit 3 are part of 
Epoch 001 and Epoch 002, respectively.  
c  Visit 4 is the day of the second revaccination that will be administered 1 to 2 months after the first revaccination. The 
subsequent visits (Visit 5, Visit 6 and Visit 7) will occur within 1, 12 and 24 months after the second revaccination, 
respectively.  
d  An ad-hoc HZ Visit will be planned in case of suspected HZ and will be scheduled preferably within 3 calendar days 
from appearance of HZ symptom(s). 
e  Study activity to be performed at the next scheduled visit, if this has not been performed during the ad-hoc HZ visit. 
f  A second written informed consent will only be obtained prior to performance of any revaccination procedures, if 
required by local regulatory authorities or Institutional Review Boards (IRB)/Independent Ethics Committees (IEC). 
g  Blood sample is substituted for urine sample for pregnancy testing only ifas required by country, local or ethics 
committee regulations. Pregnancy testing should be completed, and results reviewed prior to revaccination. 
h For non-revaccinated subjects (see Glossary of terms for the definition and Section 8.1, for details), Visit 4 
and 5 will not occur.  
For non-revaccinated subjects, see Section 8.1. 
Note: 
In times of special circumstances, refer to Section 8.1.16 for study procedures. 
The footnotes of Table 4 have been updated as follows: 
PC 1 = Phone Contact 1 
a. Whenever possible the investigator should arrange study visits within this interval.  
b. The investigator should endeavour to have the subjects come in for the visits within this interval. However, subjects 
may not necessarily be excluded from the PPS for analysis of immunogenicity if they make the study visit outside this 
interval. 
c. The second dose will be administered 1 to 2 months (30 to 60 days, inclusive) after the first dose.  
* The allowed interval for Visits 6 and 7 should be the same for both the re-vaccinated and non-revaccinated 
subjects.  
In times of special circumstances, refer to Section 8.1.16 for allowed interval between study visits.  
Section 4 
OBJECTIVES AND ENDPOINTS 
Table 5 
Study objectives and endpoints: 
Objectives 
Endpoints 
Primary 
LTFU phase - Immunogenicity assessment  
• 
To evaluate persistence of humoral immunity after 
primary vaccination course. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by 
ELISA at Day 1, Month 12 and Month 24. 
Revaccination active phase - Immunogenicity 
assessment 
• 
To evaluate humoral immunity of HZ/su vaccine 
post-revaccination Doses 1 & 2. 
In all subjects: 
• 
Anti-gE antibody concentrations as determined by 
ELISA at pre-revaccination (Month 24) and at 1-
month post-revaccination Dose 1 (Month 25) and 
Dose 2 (Month 26). 
Secondary 
LTFU phase - Immunogenicity assessment 
• 
To evaluate persistence of cellular immunity after 
primary vaccination course. 
In CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T-cells expressing 
two or more markers such as IFN-γ, IL-2, TNF-α, 
CD40L as determined by ICS at Day 1, Month 12 
and Month 24. 
LTFU phase - safety assessment 
• 
To evaluate safety of HZ/su vaccine from the study 
ZOSTER-041 last visit to study ZOSTER-073 
Visit 3. 
In all subjects: 
• 
Related-SAEs 
− Occurrence of SAEs related to primary 
vaccination as assessed by the investigator from 
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Objectives 
Endpoints 
the study ZOSTER-041 last visit (Month 13) to 
study ZOSTER-073 Visit 3 (Month 24). 
• 
HZ episodes 
− Occurrence of suspected or confirmed HZ cases 
from the study ZOSTER-041 last visit 
(Month 13) to study ZOSTER-073 Visit 1 (Day 
1).  
− Occurrence of confirmed HZ cases from Day 1 
through Month 24. 
• 
AESIs 
− Occurrence of suspected or biopsy-proven 
allograft rejections from the study ZOSTER-041 
last visit (Month 13) to study ZOSTER-073 Visit 
1 (Day 1).  
− Occurrence of biopsy-proven allograft rejections 
from Day 1 through Month 24. 
• 
Allograft function for episode(s) of allograft 
rejection. 
− Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of biopsy-proven rejection and up to 2 
months after rejection resolution and cessation 
of therapeutic immunosuppressive therapy for 
the time period from study ZOSTER-041 last 
visit (Month 13) to study ZOSTER-073 Visit 3 
(Month 24).  
• 
Allograft function for episode(s) of HZ 
− Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 2 months prior to an 
episode of HZ and up to 2 months after HZ rash 
resolution for the time period from study 
ZOSTER-041 last visit (Month 13) to study 
ZOSTER-073 Visit 3 (Month 24). 
Revaccination active phase - Immunogenicity 
assessment 
• 
To evaluate cell-mediated immunity 
post- revaccination Doses 1 & 2. 
In revaccinated subjects in CMI sub-cohort: 
 
• 
Frequencies of gE-specific CD4+ T-cells expressing 
two or more markers such as IFN-γ, IL-2, TNF-α, 
CD40L as determined by ICS at pre-vaccination 
(Month 24) and at 1-month post-revaccination Dose 
1 (Month 25) and Dose 2 (Month 26). 
Revaccination follow-up phase – Immunogenicity 
assessment 
• 
To evaluate persistence of humoral and cell-
mediated immune responses post-revaccination 
Dose 2. 
In all revaccinated subjects: 
• 
Anti-gE antibody concentrations as determined by 
ELISA at 12 months and 24 months post-
revaccination Dose 2. 
In revaccinated subjects in CMI sub-cohort: 
• 
Frequencies of gE-specific CD4+ T- cells 
expressing two or more markers such as IFN-γ, IL-
2, TNF-α, CD40L as determined by ICS at 12 
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Objectives 
Endpoints 
months and 24 months post-revaccination Dose 2 
in a CMI sub-cohort of subjects. 
Revaccination active and follow-up phases - Safety 
assessment 
• 
To evaluate reactogenicity and safety of the HZ/su 
vaccine after each revaccination. 
In all revaccinated subjects: 
• 
Solicited local and general AEs: 
− Occurrence, duration and intensity of solicited 
local AEs within 7 days after each revaccination 
(i.e., the day of revaccination and 6 subsequent 
days);  
− Occurrence, duration and intensity of solicited 
general AEs within 7 days after each 
revaccination dose (i.e., the day of revaccination 
and 6 subsequent days) and causal relationship 
to revaccination by investigator assessment.  
• 
Unsolicited AEs  
− Occurrence, intensity of unsolicited AEs during 
30 days after each revaccination (i.e., the day of 
revaccination and 29 subsequent days) and 
causal relationship to revaccination by 
investigator assessment.  
• 
SAEs  
− Occurrence of SAEs (including fatal SAEs) from 
Dose 1 of revaccination (Month 24) until 12 
months post-last revaccination dose (Month 37).  
− Occurrence of related-SAEs (including related-
fatal SAEs) as per investigator assessment from 
Dose 1 of revaccination (Month 24) up to study 
end (Month 49).  
• 
AESIs  
− Occurrence of all biopsy-proven allograft 
rejections from Dose 1 of revaccination (Month 
24) up to study end (Month 49) and causal 
relationship to revaccination by investigator 
assessment.  
− Occurrence of pIMDs from Dose 1 of 
revaccination (Month 24) up to 12 months post-
last revaccination dose (Month 37) and causal 
relationship by investigator assessment. 
• 
HZ episodes  
− Occurrence of confirmed HZ cases from Dose 1 
of revaccination (Month 24) up to study end 
(Month 49).  
• 
Allograft function following revaccination  
− Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
creatinine measures from 3 months before the 
first revaccination dose until 3 months after the 
last revaccination dose. 
• 
Allograft function for episode(s) of allograft rejection  
− Occurrence of allograft dysfunction through 
assessment of all clinically obtained serum 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
1 4 2  
O bj e cti v e s  
E n d p oi nt s  
cr e ati ni n e m e as ur es fr o m 2 m o nt hs pri or t o a n 
e pis o d e of  bi o psy -pr ov e n r ej ecti o n a n d u p t o 2 
m o nt hs aft er r ej ecti o n r es ol uti o n a n d c ess ati o n 
of t h er a p e utic of i m m u n os u p pr essiv e t h er a py.   
•  
All o gr aft f u ncti o n f or e pis o d e(s) of H Z  
− Occ urr e nc e of all o gr aft dysf u ncti o n t hr o u g h 
ass ess m e nt of all cli nic ally o bt ai n e d s er u m 
cr e ati ni n e m e as ur es fr o m 2 m o nt hs pri or t o a n 
e pis o d e of H Z a n d u p t o 2 m o nt hs aft er H Z 
r es ol uti o n. 
C MI = C ell -M e di at e d I m m u nity;
; E LI S A  = Enzy m e Li nk e d I m m u n os or b e nt Ass ay; 
g E  = glyc o pr ot ei n E;
; I C S = I ntr ac ell ul ar Cyt oki n e St ai ni n g; I L-2  = I nt erl e uki n 2; 
; 
; 
; 
T N F α  = T u m or N ecr osis F act or -al p h a; I F N γ = I nt erf er o n -g a m m a; A E = A dv ers e Ev e nt; S A E  = Seri o us A dv ers e Ev e nt; 
H Z  = H er p es Z ost er;  A E SI   =  A dv ers e Ev e nt of Sp eci al I nt er est; pI M D s  =  p ot e nti al I m m u n e -M e di at e d Dis e as es  
* T o b e p erf or m e d a by  t h e c e ntr al l a b or at ory if d e e m e d n ec ess ary. 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C
C
I
C CI
C CI
C CI
C CI
C CI
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
1 4 3  
Secti o n 5. 1  Scie ntific r ati o n ale f or st u d y desi g n  
St u d y Z O S T E R -0 7 3 has t hree disti nct p hases:  
•  
In t he l o n g -ter m f oll o w-u p ( L T F U) p hase, s u bjects will be f oll o we d f or t w o years * 
( Da y 1 t o M o nt h 2 4). O ver t he sa me ti me p eri o d, t he occ urre n ces of c o nfir me d H Z 
cases a n d bi o ps y-pr o ve n R T rejecti o ns will be pr os pecti vel y c ollecte d. W h ereas, t h e 
occ urre nces  of c o nfir me d/s us pecte d H Z cases; a n d R T rejecti o ns will be 
retr os pecti vel y c ollecte d bac k t o s u bjects’ st u d y Z O S T E R-0 4 1 last visit s. 
* S u bjects w h o are i neli gi ble f or rev acci n ati o n or u n willi n g t o receive 
rev acci n ati o n ( here after referre d t o as n o n-rev a cci n ate d s u bjects, see Gl oss ary of 
ter ms) will be i nvite d t o be f oll o we d i n a n e xte nsi o n of t he L T F U p h ase f or a t ot al 
of 4 ye ars ( D a y 1 t o M o nt h 4 9), wit h s afety a n d i m m u n o ge nicity assess me nts at 
M o nt hs 3 7 a n d 4 9.  
Secti o n 5. 3  O ver all desi g n  
T he f o ot n ote s of Fi g ure 1 ha ve  bee n u p date d as f oll o ws:  
H Z/ s u  = H er p es z ost er s u b u nit; L T F U  = L o n g t er m f oll o w -u p; Va c c 1 -2  = Vacci n ati o n d os e 1 & 2; re-Va c c  1 -2  = 
R ev acci n ati o ns d os e 1 & 2  
* T h e s ec o n d d os e of r ev acci n ati o n ( Visit 4, M o nt h 2 5) will b e a d mi nist er e d 1 t o 2 m o nt hs aft er t h e first r ev acci n ati o n 
d os e.  
** Visit 5 ( M o nt h 2 6), Visit 6 ( M o nt h 3 7) a n d Visit 7 ( M o nt h 4 9) will occ ur 1, 1 2 a n d 2 4 m o nt hs aft er t h e s ec o n d 
r ev acci n ati o n, r es p ectiv ely. 
$P h o n e c o nt act will occ ur a b o ut 3 5 d ays b ef or e Visit 3 ( M o nt h 2 4) t o r e mi n d f e m al e s u bj ects of c hil d b e ari n g p ot e nti al t o 
us e a d e q u at e c o ntr ac e pti o n.  
I n ti m e s of s p e ci al circ u m st a n ce s, r ef er t o S e cti o n 8. 1. 1 6. 
Secti o n 5. 3  O ver all desi g n  
Pr ot oc ol wai vers or e x e m pti o ns are n ot all o we d u nless necessar y f or t h e ma na ge me nt of 
i m me diate safet y c o n cer ns. T heref ore, a d h ere nce t o t he st u d y desi g n re q uire me nts, 
i ncl u di n g t h ose s pecifie d i n t he sc he d ule of acti vities ( S o A) (see Secti o n 2 ), are ess e ntial 
a n d re q uir e d f or st u d y c o n d uct. I n ti m es of s peci al circ u mst a nces, refer t o Secti o n 
8. 1. 1 6  f or st u dy pr oce d ures.  
•  
S a m pli n g sc he d ule :  
− 
Bl o o d sa m ples t o assess h u m oral i m m u n o ge nicit y will be c ollecte d i nfr o m all 
s u bjects at Visit 1 ( Da y 1), Visit 2 ( M o nt h 1 2), Visit 3 ( M o nt h 2 4), Visit 4 
( M o nt h 2 5) *, Visit 5 ( M o nt h 2 6) *, Visit 6 ( M o nt h 3 7) a n d Visit 7 ( M o nt h 4 9).  
− 
Bl o o d sa m ples t o assess C MI res p o nses will be c ollecte d i n at he C MI s u b-c o h ort 
at Visit 1 ( Da y 1), Visit 2 ( M o nt h 1 2), Visit 3 ( M o nt h 2 4), Visi t 4 ( M o nt h 2 5) *, 
Visit  5 ( M o nt h 2 6) *, Visit 6 ( M o nt h 3 7) a n d Visit 7 ( M o nt h 4 9).  
* Bl o o d s a m ples will n ot be c ollecte d at Visit 4 a n d Visit 5 fr o m n o n -rev acci n ate d 
s u bjects. Refer t o Secti o n 7  f or m ore det ails. 
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Section 6.2.1.2 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another interventional vaccine or immunosuppressive 
clinical study, at any time during the study period, in which the subjecthas been or 
will be is exposed to an investigational or a non-investigational vaccine/product* 
(drug) at any time during the ZOSTER-073 study. 
Section 7.1 Treatments administered 
All eligible and willing subjects will receive HZ/su vaccine (for details see Table 7).  
Section 8 
STUDY ASSESSMENTS AND PROCEDURES 
In times of special circumstances, refer to Section 8.1.16 for study procedures. 
Section 8.1 General study aspects 
Non-revaccinated subjects (see Glossary of terms for the definition) are not required to 
return for Visit 4 and Visit 5.  
For these subjects, the following Visit 3 procedures will not occur: 
• 
Pregnancy testing in participants unwilling to be revaccinated (see Section 8.1.7) 
• 
Temperature measurement  
• 
Revaccination 
Post-revaccination solicited and unsolicited diary cards (see Section 8.1.12.1) 
Section 8.1.7 
Pregnancy test 
Female subjects of childbearing potential are to have a urine pregnancy test performed 
and reviewed prior to any study vaccine administration. However, pregnancy testing 
should not be performed if female subjects are unwilling to be revaccinated. 
Section 8.1.8 
Pre-revaccination body temperature 
The oral (preferred route) body temperature of each subject needs to be measured prior to 
any study vaccine administration and recorded in the eCRF. If the subject has fever [fever 
is defined as temperature 38.0°C (100.4°F) regardless of route of measurement] on the 
day of vaccination, the revaccination visit will be rescheduled within the allowed interval 
for this visit (see Table 4). Pre-revaccination temperature measurements should not be 
performed for non-revaccinated subjects. 
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Section 8.1.12.1 
Diary cards and questionnaires 
All revaccinated subjects will receive: 
• 
Diary cards: To be completed by the subject or subject’s trained assistant after each 
revaccination for recording of solicited AEs (from day of revaccination to 
subsequent 6 days), unsolicited AEs (from day of revaccination to subsequent 29 
days), any medically attended visits and all concomitant medications / vaccinations 
taken from day of revaccination to subsequent 29 days or to next study visit.  
Diary cards should not to be provided to non-revaccinated subjects. 
All subjects will receive: 
• 
HZ-specific diary card: To be completed by the subjects or subject’s trained assistant 
beginning immediately (and only) upon development of any symptoms suggestive of 
HZ and prior to visiting the study site for evaluation of suspected HZ. 
Section 8.1.15 
Ad-hoc HZ visit and phone call for evaluation of 
suspected HZ 
During the ad-hoc HZ Visit, the study staff/investigator will be instructed to: 
• 
Document clinical history of suspected HZ and perform physical exam;  
• 
Transcribe all information from the HZ-specific diary card and ZBPI questionnaire 
completed by the subject or subject’s trained assistant into the eCRF in HZ-specific 
screens; 
• 
Record concomitant medications/vaccinations, including concomitant medication the 
subject has already received and/or will receive for HZ treatment or treatment of any 
HZ-related complications; 
• 
Check if the subject received any medical attention [hospitalisation, emergency room 
visit, or a visit to or from medical personnel (medical doctor)] for HZ or any HZ-
related complication. 
• 
Take digital photographs of HZ rash and upload to e-Clinipix. Please refer to the 
SPM for specific instructions. At the discretion of the investigator, additional ad-hoc 
HZ follow-up visit(s) may be necessary to manage the progression of the rash, 
additional photographs of HZ rash may be appropriate. 
• 
If during clinical evaluation the investigator determines that adequate rash lesion 
samples from at least 3 separate lesions cannot be collected (i.e., <3 lesions present, 
or if only papules are present), ask the subject to return to the study site for collection 
of three additional lesion samples (from at least 3 separate lesions).  
• 
Provide an additional supply of ZBPI questionnaires and HZ-specific diary cards to 
the subjects at ad-hoc HZ visit(s). Concomitant medications section of HZ-specific 
diary cards , specifically the concomitant medications section should be updated as 
necessary for medication changes, andincluding start/stop dates. ZBPI 
questionnaires should be completed by subjects or subject’s trained assistant daily 
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for 30 days from onset of HZ symptoms and then weekly until the resolution of the 
rash. 
Section 8.1.16 
Study procedures during special circumstances 
During special circumstances (e.g., COVID-19 pandemic), specific guidance from local 
public health and other competent authorities regarding the protection of subjects’ 
welfare must be applied.  
The following measures may be implemented, at the discretion of the Sponsor, during  
special circumstances.  
For potential subjects unable to be enrolled due to special circumstances: 
• 
Potential subjects, who were not able to enroll between 09 December 2019 and 18 
March 2020, will be offered enrollment to coincide with the Visit 2 calendar 
period.  
− Enrollment, Visit 1 and Visit 2 study procedures will be scheduled on the same 
day. 
− Visit 2 blood samples will be collected and recorded on Visit 2 eCRF per SoA 
(see Table 3).  No Visit 1 blood samples will be collected. 
• 
All subjects will be scheduled together for re-vaccination at Visit 3 (see Table 8 
and SPM, for details). 
For all enrolled subjects: 
• 
For the duration of COVID-19 pandemic, suspected, probable, and confirmed 
cases of COVID-19 will be recorded at the next scheduled visit on the COVID-19 
specific eCRF. 
• 
Individual subject revaccination visits may be delayed, to allow for treatment of, or 
vaccination for, COVID-19 (or other special circumstances). Such delay will allow 
for completion of the therapies and resolution of any therapy-associated AEs and 
immune-modifying effects (see Section 6.2.2) prior to revaccination.  
• 
As necessary and appropriate, safety follow-up may be made by a telephone call, 
other means of virtual contact or home visit. 
• 
Diary cards and ZBPI questionnaire may be transmitted from and to the site by 
conventional mail and/or electronic means. 
• 
Visits for suspected HZ may take place away from the study site, such as in a 
different location* or at participant’s home. If an in-person visit is not feasible, 
then the medical evaluation of suspected HZ may take place virtually (e.g. video 
call) with documentation of rash and pain by investigator notes, and by subject-
submitted photographs (as possible), diary cards, and ZBPI. 
• 
Biological samples may be collected away from the study site, such as in a different 
medical location* or at subject’s home. Biological samples should not be collected 
if they cannot be processed in a timely manner or appropriately stored until the 
intended use (see SPM, for details). 
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* It is the investigator’s responsibility to identify an alternate medical location. The 
investigator should ensure that this alternate location meets ICH GCP 
requirements, such as adequate facilities to perform study procedures, appropriate 
training of the staff and documented delegation of responsibilities in this location. 
This alternate location should be covered by proper insurance for the conduct of 
study on participants by investigator and staff at a site other than the designated 
study site. Refer to EMA Guidance on the Management of Clinical Trials during 
the COVID-19 (Coronavirus) pandemic (version 2, 27 March 2020) for more 
details. 
• 
If despite best efforts, it is not possible to collect blood samples within the interval 
predefined in the protocol (see Table 4), then the interval may be extended as 
defined in Table 8.  
• 
If despite best efforts, it is not possible to administer the second dose of study 
vaccine as defined in the protocol (see Table 4), a maximum dose interval of up to 
6 months after the first revaccination dose may be used. If the maximum dose 
interval length is exceeded, then vaccination should be discontinued. 
Impact on the per protocol set (PPS) for immunogenicity will be determined on a case 
by case basis. 
Table 8 
Intervals between study visits during special circumstances  
Visits 
At the discretion of Sponsor, during special 
circumstances 
Notes 
Visit(s) may be delayed Allowed interval (days) 
Visit 2   
Up to 6 months 
 
The length of the allowed interval (85 days) 
remains, but the start of the interval 
may be moved by up to 6 months 
(starting no later than 18 months post-
Visit 1), e.g. to avoid potential seasonal 
recurrence of COVID-19 
PC 1  
 
30 – 40 days before Visit 3 
 
Visit 3*  
Up to 6 months 
 
The length of the allowed interval (85 days) 
remains, but the start of the interval 
may be moved by up to 6 months 
(starting no later than 30 months post-
Visit 1), e.g. to avoid potential seasonal 
recurrence of COVID-19 
Visit 4  
 
30 – 182 post-Visit 3 
Optimally 30 - 60 days after Visit 3 (Table 4) 
Visit 5  
 
30 – 90 post-Visit 4 
Optimally 30 – 48 days after Visit 4 (Table 4) 
Visit 6*  
 
330 – 445 post-Visit 4 
 
Visit 7*  
 
690 – 805 post-Visit 4 
Visit 7 may be: 
Scheduled earlier to make up for delays 
incurred during times of special 
circumstance, in order to maintain 
planned duration of the study. 
Delayed or cancelled if special 
circumstances preclude the original 
planned visit. 
Note: Investigator should prioritize conducting the visit as close to the optimal window as possible. 
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C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0
1 4 8  
* T h e all o w e d i nt er v al f or Vi sit s 6 a n d 7 s h o uld b e t h e s a m e f or b ot h t h e r e -v a c ci n at e d a n d n o n -re v a c ci n at e d
s u bj e ct s. 
Secti o n 8. 3. 2. 2  
H Z lesi o ns s a m pli n g  
T he f o ot n ote s of Ta bl e 9 ha ve  bee n u p date d as f oll o ws:  
C MI = C ell -M e di at e d I m m u n o g e nicity; H Z = H er p es Z ost er; P C R = Poly m er as e C h ai n R e acti o n; N A = N ot A p plic a bl e; 
 
* R ef er t o S ecti o n 1 0. 1  f or s u bs et d escri pti o n.
** R ef er t o S e cti o n  5. 3  f or n o n-re v a c ci n at e d s u bj e ct s. T h e s e s u bj e ct s will n ot h a v e Vi sit 4 a n d Vi sit 5 bl o o d
dra w s.
Secti o n 8. 3. 4  
Bi ol o gic al s a m ples e v al u ati o n 
T he f o ot n ote s of Ta bl e 1 4 ha ve  bee n u p date d as f oll o ws:  
re V a c c = r e V acci n ati o n; C MI  =  C ell - M e di at e d I m m u n o g e nicity; A b = Anti b o dy;  g E  = r ec o m bi n a nt p urifi e d Glyc o pr ot ei n 
E;
; N A  = n ot a p plic a bl e.  
* F or s u bj ects i n C MI s u b-c o h ort a w h ol e bl o o d s a m pl e f or g E-s p ecific C D 4 T-c ell t esti n g will b e t ak e n at all st u dy visits.
**r ef er t o s ecti o n 7. 2. 2  f or t h e d efi niti o n of t h e s u bs ets a n d m et h o d of s el ecti o n.
*** R ef er t o S e cti o n 5. 3 f or n o n -re v a c ci n at e d s u bj e ct s. T h e s e s u bj e ct s will n ot h a v e Vi sit 4 a n d Vi sit 5 bl o o d
dra w s.
Secti o n 8. 4. 2  Ti me peri o d a n d fre q ue nc y f or c ollecti n g A E a n d seri o us 
a d verse e ve nt ( S A E) i nf or m ati o n  
T he f o ot n ote s of Ta bl e 1 6 ha ve  bee n u p date d as f oll o ws:  
*i. e. c o ns e nt o bt ai n e d. r e V acc 1: r ev acci n ati o n D os 1; r e Vacc 2: r ev acci n ati o n D os 2
** A p pli c a bl e f or r e v a c ci n at e d s u bj e ct s o nl y
$ S A Es r el at e d t o st u dy v acci n e i ncl u d e S A Es occ urri n g b ef or e t h e first r ev acci n ati o n Visit 3 ( M o nt h 2 4) c o nsi d er e d as
r el at e d t o pri m ary v acci n ati o n i n st u dy Z O S T E R-0 4 1, a n d S A Es r el at e d t o r ev acci n ati o n c o urs e occ urri n g aft er
a d mi nistr ati o n of t h e first d os e fr o m r ev acci n ati o n c o urs e i n st u dy Z O S T E R -0 7 3
Secti o n 1 0. 1. 1  
S a m ple size c alc ul ati o n  
U p t o a ma xi m u m of 8 6 s u bjects meeti n g t h e eli gi bilit y criteria f or e nr oll me nt ( 2 d oses of 
H Z/s u va cci ne i n Z O S T E R-0 4 1 ) will be tar gete d f or e nr oll me nt i n partici p ati n g ce nters. 
A p pr o xi matel y 1 5 % of t he e nr olle d s u bjects mi g ht wit h dra w or n ot be e v al ua ble f or 
i m m u n o ge nicit y, t heref ore t he tar get s a m ple siz e will be a p pr o xi matel y 7 3 s u bjects 
e val ua ble f or h u m oral i m m u n o ge nicit y i n per -pr ot oc ol set (as defi ne d  i n se cti o n 1 0. 2). 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI
C CI
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
1 4 9  
Secti o n 1 0. 2  
P o p ul ati o ns f or a n al yses  
A n al y si s S et  
D e s cri pti o n  
E nr oll e d S et  
All s u bj ects wit h a c o m pl et e v acci n ati o n c o urs e ( 2 d os es of H Z/s u 
v acci n e) i n st u dy Z O S T E R-0 4 1 w h o m et t h e eli gi bility crit eri a a n d 
si g n e d i nf or m e d c o ns e nt i n t h e c urr e nt st u dy.  
P P S f or a n alysis of p ersist e nc e ( L T F U 
p h as e fr o m Visit 1 t o Visit 3)  
T h e P P S f or a n alysis of p ersist e nc e will i ncl u d e ev al u a bl e s u bj ects 
(i. e. t h os e m e eti n g all eli gi bility crit eri a, c o m plyi n g wit h t h e 
pr oc e d ur es a n d i nt erv als d efi n e d i n t h e pr ot oc ol, wit h n o eli mi n ati o n 
crit eri a) fr o m t h e E nr oll e d s et f or w h o m p ersist e nc e i m m u n o g e nicity 
e n d p oi nts m e as ur es af t er pri m ary v acci n ati o n c o urs e ar e av ail a bl e 
fr o m Visit 1 ( D ay 1)  , Visit 2 ( M o nt h 1 2) a n dt o Visit 3 ( M o nt h 2 4).  
E S f or r ev acci n ati o n p h as e  
T h e E S f or a n alysis of s af ety will i ncl u d e all s u bj ects wit h at l e ast o n e 
H Z/s u v acci n e d os e a d mi nist er e d i n t h e st u dy Z O S T E R -0 7 3.  
P P S f or I m m u n o g e nicity aft er r ev acci n ati o n 
c o urs e (r ev acci n ati o n activ e p h as e)  
T h e  P P S f or a n alysis of i m m u n o g e nicity aft er r ev acci n ati o n will b e 
d efi n e d by ti m e -p oi nt a n d will i ncl u d e ev al u a bl e s u bj ects (i. e.  t h os e 
m e eti n g all eli gi bility  crit eri a, c o m plyi n g wit h t h e pr oc e d ur es a n d 
i nt erv als d efi n e d i n t h e pr ot oc ol, wit h n o eli mi n ati o n crit eri a) fr o m t h e 
E S f or r ev acci n ati o n w h o h av e r ec eiv e d o n e or t w o d os es of 
r ev acci n ati o n sc h e d ul e u p t o t h e ti m e p oi nt c o nsi d er e d fr o m Visit 3 
( M o nt h 2 4, Visit 4 ( M o nt h 2 5) a n d t o Visit 5 ( M o nt h 2 6) .  
P P S f or p ersist e nc e aft er r ev acci n ati o n 
c o urs e (r ev acci n ati o n f oll o w-u p p h as e)  
T h e P P S f or p ersist e nc e f or a n alysis of i m m u n o g e nicity aft er 
r ev acci n ati o n will i ncl u d e ev al u a bl e s u bj ects (i. e. t h os e m e eti n g all 
eli gi bility crit eri a, c o m plyi n g wit h t h e pr oc e d ur es a n d i nt erv als d efi n e d 
i n t h e pr ot oc ol, wit h n o eli mi n ati o n crit eri a) fr o m t h e E S f or 
r ev acci n ati o n f or w h o m p ersist e nc e i m m u n o g e nicity e n d p oi nts 
m e as ur es aft er r ev acci n ati o n c o urs e ar e av ail a bl e fr o m Visit 6 ( M o nt h 
3 7)  a n d t o Visit 7 ( M o nt h 4 9).  
P P S = p er pr ot oc ol s et, E S = ex p os e d s et  
F or n o n -rev acci n ate d s u bjects, t he e nr olled set will be use d f or a n alyses of s afety a n d 
i m m u n o ge nicity. Det ails will be descri be d i n t he st atistic al a n alysis pl a n ( S A P). 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

C O N FI D E N TI A L  
2 1 2 3 4 0  (Z O S T E R -0 7 3 E X T: 0 4 1 Y 4 -1 0 ) 
Pr ot o c ol  A m e n d m e nt 1  Fi n al  
1 5 -J U N -2 0 2 0  
1 5 0  
Secti o n 1 0. 3. 4  
S afet y a n al yses  
L T F U p h ase  
E n d p oi nt  
St ati sti c al A n al y s e s f or L F T U p h a s e  
Pri m ar y  
N A  
S e c o n d ar y  
•  
P erc e nt a g e of s u bj ects r e p orti n g hist ory of at l e ast o n e S A E r el at e d t o pri m ary v acci n ati o n 
i n st u dy Z O S T E R-0 4 1 cl assifi e d by M e d D R A Pri m ary Syst e m Or g a n Cl ass ( S O C) a n d 
Pr ef err e d T er m ( P T) fr o m Z O S T E R -0 4 1 l ast st u dy visit ( M o nt h 1 3) t o Z O S T E R-0 7 3 D ay 1 
wi ll b e t a b ul at e d wit h ex act 9 5 % CI.  
•  
P erc e nt a g e of s u bj ects r e p orti n g at l e ast o n e S A E r el at e d t o pri m ary v acci n ati o n 
cl assifi e d by M e d D R A Pri m ary S O C a n d P T fr o m Z O S T E R -0 4 1  D ay  1 t o Z O S T E R -0 7 3 
M o nt h  2 4 will b e t a b ul at e d wit h ex act 9 5 % CI.  
•  
P er c e nt a g e of s u bj e ct s wit h at le a st o n e bi o p s y -pr o v e n all o graft rej e cti o n re p ort e d 
fr o m Z O S T E R-0 7 3 D a y 1 t o Z O S T E R -0 7 3 M o nt h 2 4 will b e t a b ul at e d wit h e x a ct 9 5 % 
CI.  
•  
Listi n g of s u bj ects wit h hist ory of s us p ect e d all o gr aft r ej ecti o n or hist ory of bi o psy -pr ov e n 
all o gr aft r ej ecti o ns fr o m Z O S T E R-0 4 1 l ast st u dy visit t o Z O S T E R -0 7 3  D ay 1 will b e 
pr ovi d e d.  
•  
Listi n g of s u bj ects wit h bi o psy -pr ov e n all o gr aft r ej ecti o ns fr o m Z O S T E R -0 4 1 0 7 3  D ay 1 t o 
Z O S T E R -0 7 3 M o nt h 2 4 will b e  pr o vi d e d t a b ul at e d wit h ex act 9 5 % CI. 
•  
Listi n g of s u bj ects wit h hist ory a s us p ect e d H Z e pis o d e fr o m Z O S T E R -0 4 1 l ast st u dy visit 
t o Z O S T E R-0 7 3 D ay 1 will b e pr ovi d e d.  
•  
Listi n g of s u bj ects wit h a c o nfir m e d H Z e pis o d e fr o m Z O S T E R -0 7 3 D ay 1 t o Z O S T E R -
0 7 3 M o nt h 2 4 will b e pr ovi d e d.  
•  
N u m b er of s u bj ect s wit h d ecli ni n g all o gr aft f u ncti o n, as d et er mi n e d by s er u m cr e ati ni n e 
m e as ur e m e nts will b e d et ail e d i n t h e S A P.  
Secti o n 1 2. 1. 2  
Gl oss ar y o f ter ms 
N o n -rev acci n ate d 
s u bjects: 
S u bjects w h o are i neli gi ble or u n willi n g t o receive b ot h 
rev acci n ati o n d oses 
Pr ot oc ol a m e n d m e nt:  
T he I nter n ati o n al C o u ncil o n H ar m o niz ati o n (I C H) 
defi nes a pr ot oc ol a m e n d m e nt as: ‘ A writte n descri pti o n of 
a c h a n ge(s) t o or f or m a l cl arific ati o n of a pr ot oc ol.’ G S K 
Bi ol o gic als f urt her det ails t his t o i ncl u de a c h a n ge t o a n 
a p pr ove d pr ot oc ol t h at affects t he s afet y of s u bjects, sc o pe 
of t he i nvesti g ati o n, st u dy desi g n, or scie ntific i nte grity of 
t he st u dy. 
2 1 2 3 4 0 | Pr ot oc ol A me n d me nt 1 2 4 J u n 2 0 2 0 | T M F- 1 7 3 4 4 5 3 | 1. 0
C CI

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Section 12.5.6 
COVID-19 
COVID-19 is an infectious disease caused by severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2). When reporting an AE (serious or non-serious as 
defined in Section 12.5.2) related to COVID-19 infection, the following verbatim terms 
should be used according to World Health Organisation (WHO) definition (Please 
refer to Appendix 9): 
• 
Suspected COVID-19 infection; or 
• 
Probable COVID-19 infection; or 
• 
Confirmed COVID-19 infection 
Information pertaining to COVID-19 infection should be recorded at the next 
scheduled visit as medical history on the COVID-19 specific eCRF. 
Section 12.5.9.1 Time period for detecting and recording adverse 
events, serious adverse events and pregnancies 
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the enrollment visit [Visit 1 (Day 1)] up to the last study visit [Visit 7 (Month 49)]. 
All SAEs related to the study vaccine After informed consent is obtained, the following 
events that occurred since the primary follow-up study ZOSTER-041 last study visit 
(Month 13) up to study ZOSTER-073 Visit 1 (Day 1), will be collected retrospectively 
after informed consent is obtained.and recorded in the medical history:  
• 
all SAEs related to the study vaccine  
• 
all suspected orrenal allograft rejections 
• 
all biopsy-proven renal allograft rejections considered as SAEs that occurred since 
the primary follow-up study ZOSTER-041 will be collected retrospectively, after 
informed consent is obtained. 
• 
all suspected or episodes of HZ considered as SAEs  
• 
all clinically-confirmed episodes of HZ considered as SAEs that occurred since the 
primary follow-up study ZOSTER-041 will be collected retrospectively, after 
informed consent is obtained. 
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 Visit 1 (Day 1) 
and will end at the last study visit [Visit 7 (Month 49)]. See section 12.5.10 for 
instructions on reporting of pregnancies. 
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The time period for collecting and recording of pIMDs will begin at the first receipt of 
study vaccine at Visit 3 (Month 24) during revaccination phase and will end at Visit 6 
(Month 37), approximately 12 months following administration of the last revaccination 
dose. See section 12.5.10.5 for instructions on reporting of pIMDs. 
The time period for collecting and recording of biopsy-allograft rejections will begin at 
the enrollment visit [Visit 1 (Day 1)] and will end at the last study visit [Visit 7 (Month 
49)]. See section 12.5.10.5 for instructions on reporting of renal allograft rejection. 
The time period for collecting and recording of IMCs (including HZ) will begin at the 
enrollment visit [Visit 1 (Day 1)] and will end at the last study visit [Visit 7 (Month 49)]. 
See section 12.5.10.5 for instructions on reporting of HZ. 
Of note, any medical events that occurred since the ZOSTER-041 last study visit 
(Month 13) up to study ZOSTER-073 Visit 1 (Day 1) will be recorded in medical 
history section on the eCRF and should not be reported via expedited reporting. 
Section 12.6.2 
Contraception guidance 
The following footnote has been removed from Table 25: 
b Hormonal contraception may be susceptible to interaction with the study drug, which 
may reduce the efficacy of the contraceptive method. In this case 2 highly effective 
methods of contraception should be utilised during the treatment period and for at least 2 
months after the last dose of study treatment  
Section 12.8 
Appendix 9: Case Definition for COVID-19 
Coronavirus Infection  
WHO Case Definition (Version: March 20, 2020 ):  
• 
Suspected case 
− 
A patient with acute respiratory illness (fever and at least one sign/symptom of 
respiratory disease, e.g., cough, shortness of breath), AND a history of travel 
to or residence in a location reporting community transmission of COVID-19 
disease during the 14 days prior to symptom onset; OR  
− 
A patient with any acute respiratory illness AND having been in contact (see 
definition of “contact” below) with a confirmed or probable COVID-19 case 
(see definition of contact) in the last 14 days prior to symptom onset; OR  
− 
A patient with severe acute respiratory illness (fever and at least one 
sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND 
requiring hospitalization) AND in the absence of an alternative diagnosis that 
fully explains the clinical presentation. 
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• 
Probable case 
− 
A suspect case for whom testing for the COVID-19 virus is inconclusive 
(inconclusive being the result of the test reported by the laboratory); OR  
− 
A suspect case for whom testing could not be performed for any reason. 
• 
Confirmed case 
− 
A person with laboratory confirmation of COVID-19 infection, irrespective of 
clinical signs and symptoms.  
A contact is a person who experienced any one of the following exposures during 
the 2 days before and the 14 days after the onset of symptoms of a probable or 
confirmed case:  
− 
Face-to-face contact with a probable or confirmed case within 1 meter and for 
more than 15 minutes;  
− 
Direct physical contact with a probable or confirmed case;  
− 
Direct care for a patient with probable or confirmed COVID-19 disease 
without using proper personal protective equipment; OR  
− 
Other situations as indicated by local risk assessments.  
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 
days before through the 14 days after the date on which the sample was taken 
which led to confirmation. 
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