A first-time-in Human (FTIH), Phase I/II, Randomized, Multi-centric, Single-blind, Controlled Dose-escalation Study to Evaluate the Reactogenicity, Safety, Immunogenicity and Efficacy of GSK Biologicals' HBV Viral Vector Vaccines Given in a Prime-boost Schedule With Sequential or Co-administration of Adjuvanted Proteins Therapeutic Vaccine (GSK3528869A) in Chronic Hepatitis B Patients (18-65 Years Old) Well Controlled Under Nucleo(s)Tide Analogue (NA) Therapy
Phase: PHASE1
Conditions: Hepatitis B, Chronic
Sponsor: GlaxoSmithKline

Protocol Amendment 11
Study ID:  204852
Official Title of Study: A first-time-in human (FTIH), Phase I/II, randomized, 
multicentric, single-blind, controlled dose-escalation study to evaluate the 
reactogenicity, safety, immunogenicity and efficacy of GSK Biologicals’ HBV viral 
vector vaccines given in a prime-boost schedule with sequential or coadministration 
of adjuvanted proteins therapeutic vaccine (GSK3528869A) in chronic Hepatitis B 
patients (18-65 years old) well controlled under nucleo(s)tide analogue (NA) 
therapy
NCT number: NCT03866187
Date of Document: 23-Jun-2023

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204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
22 June 2023 
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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut 89 
1330 Rixensart, Belgium 
Primary Study vaccines 
and numbers 
• GlaxoSmithKline (GSK) Biologicals’ Hepatitis B Virus 
(HBV) viral vectored vaccines and adjuvanted proteins 
vaccine (GSK3528869A) including: 
− 
Chimpanzee adenovirus HBV vaccine (ChAd155-
hIi-HBV) 
− 
Modified Vaccinia Ankara HBV vaccine (MVA-
HBV) 
− 
HBc-HBs/AS01B-4 
Other Study product 
• Placebo 
eTrack study number 
and Abbreviated Title 
204852 (TH HBV VV-001) 
EudraCT number 
2017-001452-55 
Date of protocol 
Final Version 1: 15 November 2017 
Date of protocol 
amendment 
Amendment 1 Final: 22 May 2018 
Amendment 2 Final: 17 December 2018 
Amendment 3 Final: 6 August 2019 
Amendment 4 Final: 29 April 2020 
Amendment 5 Final: 20 May 2020 
Amendment 6 Final: 16 March 2021 
Amendment 7 Final: 30 July 2021 
Amendment 8 Final: 8 November 2021 
Amendment 9 Final: 16 June 2022 
Amendment 10 Final: 23 September 2022 
Amendment 11 Final: 22 June 2023 
Title 
Safety, efficacy, immunogenicity study of GSK 
Biologicals’ HBV viral vector and adjuvanted proteins 
vaccine (GSK3528869A) in adult patients with chronic 
Hepatitis B infection. 
Detailed Title  
A first-time-in human (FTIH), Phase I/II, randomized, 
multi-centric, single-blind, controlled dose-escalation study 
to evaluate the reactogenicity, safety, immunogenicity and 
efficacy of GSK Biologicals’ HBV viral vector vaccines 
given in a prime-boost schedule with sequential or co-
administration of adjuvanted proteins therapeutic vaccine 
(GSK3528869A) in chronic Hepatitis B patients (18-65 
years old) well controlled under nucleo(s)tide analogue 
(NA) therapy. 

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204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
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eTrack study number 
and Abbreviated Title 
204852 (TH HBV VV-001) 
EudraCT number 
2017-01452-55 
Detailed Title 
A first-time-in human (FTIH), Phase I/II, randomized, 
multi-centric, single-blind, controlled dose-escalation study 
to evaluate the reactogenicity, safety, immunogenicity and 
efficacy of GSK Biologicals’ HBV viral vector vaccines 
given in a prime-boost schedule with sequential or co-
administration of adjuvanted proteins therapeutic vaccine 
(GSK3528869A) in chronic Hepatitis B patients (18-65 
years old) well controlled under nucleo(s)tide analogue 
(NA) therapy. 
Co-ordinating authors 
(Amended: 22 June 
2023) 
 and 
 
, Scientific Writers, Modis for GSK Biologicals  
, Scientific Writer 
Contributing authors 
(Amended: 22 June 
2023) 
• 
 and 
, Clinical 
Science Leads 
• 
, 
 and 
, Study 
Delivery Leads 
• 
 and 
, Lead Statistician 
• 
 and 
, Study 
Statistician 
• 
 
 and 
, Clinical Laboratory 
Science Representatives, Clinical Readout Team 
Leaders 
• 
 
and 
, Laboratory Science 
Representatives, Laboratory Study Managers 
• 
 
 and 
, 
Clinical Safety Representatives 
• 
 
 and 
, Clinical Trial Supply 
Managers 
• 
 
 and 
, 
Study Data Managers 
• 
 and 
, Oversight 
Data Managers 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
P
P
D
PPD
PPD
PPD

CONFIDENTIAL 
204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
22 June 2023 
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eTrack study number 
and Abbreviated Title 
204852 (TH HBV VV-001) 
EudraCT number 
2017-01452-55 
Detailed Title 
A first-time-in human (FTIH), Phase I/II, randomized, 
multi-centric, single-blind, controlled dose-escalation study 
to evaluate the reactogenicity, safety, immunogenicity and 
efficacy of GSK Biologicals’ HBV viral vector vaccines 
given in a prime-boost schedule with sequential or co-
administration of adjuvanted proteins therapeutic vaccine 
(GSK3528869A) in chronic Hepatitis B patients (18-65 
years old) well controlled under nucleo(s)tide analogue 
(NA) therapy. 
Contributing authors 
(Contd.) (Amended: 22 
June 2023) 
• 
 
 and 
, Global Regulatory Leads 
• 
 and 
 
Global Patent Representatives  
• 
 
 and 
 Public Disclosure 
Representatives 
• 
 
Clinical and R&D Project Leads (CPLs) 
GSK Biologicals’ Protocol DS v 15.0 
©2017-2023 GSK group of companies or its licensor 
PPD
PPD
PPD
PPD
PPD
PPD
PPD

CONFIDENTIAL 
204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
22 June 2023 
4 
Protocol Amendment 11 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001)  
EudraCT number 
2017-001452-55  
Date of protocol amendment  Amendment 11 Final: 22 June 2023 
Detailed Title 
A first-time-in human (FTIH), Phase I/II, 
randomized, multi-centric, single-blind, controlled 
dose-escalation study to evaluate the reactogenicity, 
safety, immunogenicity and efficacy of GSK 
Biologicals’ HBV viral vector vaccines given in a 
prime-boost schedule with sequential or co-
administration of adjuvanted proteins therapeutic 
vaccine (GSK3528869A) in chronic Hepatitis B 
patients (18-65 years old) well controlled under 
nucleo(s)tide analogue (NA) therapy. 
Sponsor signatory 
(Amended: 22 June 2023) 
Dietrich Bosse, MD 
Clinical and R&D Project Lead 
Therapeutic Hepatitis B (CHB-TI) vaccines, 
GlaxoSmithKline Biologicals, SA 
 
 
Signature 
 
 
 
Date 
 
 
 
Note: Not applicable if an alternative signature process (e.g. electronic signature or 
email approval) is used to get the sponsor approval. 

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204852 (TH HBV VV-001) 
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Protocol Amendment 11 Rationale 
Amendment number: 
Amendment 11 
CCI

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Protocol Amendment 11 Investigator Agreement 
I agree: 
• To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals. 
• To assume responsibility for the proper conduct of the study at this site. 
• That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.  
• To ensure that all persons assisting me with the study are adequately informed about 
the GSK Biologicals’ study vaccines and other study-related duties and functions as 
described in the protocol. 
• To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality Assurance 
procedure manual. 
• To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK Biologicals and the express written informed 
consent of the patient and/or the patient’s legally acceptable representative.  
• To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).  
• To co-operate with a representative of GSK Biologicals in the monitoring process of 
the study and in resolution of queries about the data. 
• That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccines, and more generally about his/her financial 
ties with the sponsor. GSK Biologicals will use and disclose the information solely 
for the purpose of complying with regulatory requirements. 
Hence I: 
• Agree to supply GSK Biologicals with any necessary information regarding 
ownership interest and financial ties (including those of my spouse and dependent 
children). 
• Agree to promptly update this information if any relevant changes occur during the 
course of the study and for one year following completion of the study.  
• Agree that GSK Biologicals may disclose any information it has about such 
ownership interests and financial ties to regulatory authorities. 
• Agree to provide GSK Biologicals with an updated Curriculum Vitae and other 
documents required by regulatory agencies for this study. 

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204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001)  
EudraCT number 
2017-001452-55  
Date of protocol amendment 
Amendment 11 Final: 22 June 2023 
Detailed Title 
A first-time-in human (FTIH), Phase I/II, 
randomized, multi-centric, single-blind, controlled 
dose-escalation study to evaluate the reactogenicity, 
safety, immunogenicity and efficacy of GSK 
Biologicals’ HBV viral vector vaccines given in a 
prime-boost schedule with sequential or co-
administration of adjuvanted proteins therapeutic 
vaccine (GSK3528869A) in chronic Hepatitis B 
patients (18-65 years old) well controlled under 
nucleo(s)tide analogue (NA) therapy.  
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
For Germany only: 
Leiter der klinischen 
Prüfung name, function and 
title 
 
 
 
Signature 
 
 
 
Date 
 
 
 

CONFIDENTIAL 
204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
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SPONSOR INFORMATION 
Sponsor 
GlaxoSmithKline Biologicals 
Rue de l’Institut 89 
1330 Rixensart, Belgium 
Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
Sponsor Study Monitor 
Refer to the local study contact information document. 
Sponsor Study Contact for Reporting of a Serious Adverse Event 
GSK Biologicals Central Back-up Study Contact for Reporting SAEs: refer to protocol 
Section 8.4.2. 
GSK Biologicals’ Central Safety Physician On-Call Contact information for 
Emergency Unblinding  
GSK Biologicals Central Safety Physician Phone contact: refer to protocol Section 
5.3.1. 

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204852 (TH HBV VV-001) 
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SYNOPSIS 
Detailed Title 
A first-time-in human (FTIH), Phase I/II, randomized, multi-
centric, single-blind, controlled dose-escalation study to 
evaluate the reactogenicity, safety, immunogenicity and 
efficacy of GSK Biologicals’ HBV viral vector vaccines given 
in a prime-boost schedule with sequential or co-administration 
of adjuvanted proteins therapeutic vaccine (GSK3528869A) 
in chronic Hepatitis B patients (18-65 years old) well 
controlled under nucleo(s)tide analogue (NA) therapy. 
Indication 
Chronic hepatitis B (CHB) infection 
Rationale for the 
study and study 
design 
• Rationale for the study: Treatment with GSK Biologicals’ 
HBV therapeutic vaccines aims to restore immunity to 
HBV, leading to clearance of HBsAg or reduction of 
HBsAg concentration, in order to allow patients to safely 
discontinue NA therapy without virological or clinical 
relapse. 
• Rationale for the study design: This clinical dose-finding 
study will be conducted in one segment of the CHB 
patients that is at low risk of severe hepatitis exacerbation. 
The choice of the intramuscular route for each of the 
vaccines is based on clinical data obtained with similar 
type of vaccines when given intramuscularly in human 
and for which the safety, reactogenicity and 
immunogenicity profile was established. Two different 
doses of ChAd155-hIi-HBV (5x109 and 5x1010 vp) and 
MVA-HBV (2x107 and 2x108 pfu]) will be assessed and 
were selected based on available clinical data with 
ChAd3- and MVA-based vectored vaccines using other 
antigens. Two different doses of HBc-HBs antigens will 
be assessed, containing 20-20, and 80-80 µg of HBc and 
HBs, respectively. The existing HBV vaccines containing 
20 µg of HBsAg and up to 100 µg of HBs without or with 
HBcAg have been administered safely in clinical trials in 
CHB patients.  
• Rationale for the use of placebo: A PBS solution is 
included as a negative control (placebo) in a low number 
of patients in the study. The use of the placebo control and 
the single-blind, randomized study design will allow 
controlling for potential biases in the conduct of the study. 
Importantly, each patient including those in the control 
group will remain under NA treatment throughout the 
duration of the study. 

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Objectives 
Primary 
• To assess the safety of escalating doses of the HBV viral 
vector vaccines (prime-boost) and/or adjuvanted proteins 
vaccines in patients with chronic HBV infection who are 
virally suppressed on NA therapy. 
 
Secondary 
• To assess the immunogenicity of the HBV viral vector 
vaccines (prime-boost) and/or adjuvanted proteins 
vaccines in patients with chronic HBV infection who are 
virally suppressed on NA therapy.  
• To assess the efficacy of the HBV viral vector vaccines 
(prime-boost) and/or adjuvanted proteins vaccines in 
patients with chronic HBV infection who are virally 
suppressed on NA therapy.  
Proof-of-principle (PoP) will be achieved if  
− 
At least
% of patients (i.e. a lower limit of the 80% 
CI of at least 15%) in one vaccine group show a at 
least 10-fold decrease (i.e. 1-log difference) in 
qHBsAg or show HBsAg loss at Day 337 versus Day 
1, or  
− 
There is a 10-fold difference in mean HBsAg 
concentration between a vaccine group at Day 337 
and the respective control group (i.e. the criterion is 
to observe a point estimate of at least 10-fold 
decrease between the groups with statistical 
significance, i.e., 80% CI on the ratio not including 
1). 
• To assess the long-term safety of escalating doses of the 
HBV viral vector vaccines (prime-boost) and/or 
adjuvanted proteins vaccines in patients with chronic 
HBV infection who are virally suppressed on NA therapy. 
 
CCI
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Study design  
• Experimental design: FTIH, Phase I/II, single-blind, 
randomized, controlled, multi-centric, multi-country study 
with a staggered design and limited enrolment at the 
beginning of each step. 
• Duration of the study: 
− 
Epoch 001: The Screening Visit will take place 
approximately 30 days before the planned first 
vaccine administration (Day -29). 
− 
Epoch 002: The primary phase will start on the day 
of the first vaccine administration until 6 months 
after the last vaccine dose (Day 337). 
− 
Epoch 003: The follow-up phase will start at the end 
of the primary phase (Day 337) and will last 18 
months (up to Day 841). 
• Primary completion Date (PCD): Visit 22 (Day 337) 
• End of Study (EoS): Last testing results released of 
samples collected at Visit 26. 
• Study groups: 
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Synopsis Table 1 Study groups, treatments and epochs foreseen in the 
study 
Study 
group 
Study treatment 
Approximate 
Number of 
patients 
Age 
(Min/Max) 
Epoch 
001 
Epoch 
002 
Epoch 
003 
Screening 
phase 
Primary 
phase 
Follow-
up phase 
A1 
D1: ChAd155-hIi-HBV 5x109 vp  
D57: MVA-HBV 2x107 pfu 
D113:HBc-HBs/AS01B-4 20-20 µg 
D169: HBc-HBs/AS01B-4 20-20 µg 
18 years – 
65 years 
● 
● 
● 
A2 
D1: HBc-HBs/AS01B-4 20-20 µg 
D57: HBc-HBs/AS01B-4 20-20 µg 
D113: HBc-HBs/AS01B-4 20-20 µg 
D169: HBc-HBs/AS01B-4 20-20 µg 
18 years – 
65 years 
● 
● 
● 
A3* 
D1: PBS 
D57: PBS 
D113:PBS 
D169: PBS 
18 years – 
65 years 
● 
● 
●* 
B1 
D1: ChAd155-hIi-HBV 5x1010 vp  
D57: MVA-HBV 2x108 pfu 
D113: HBc-HBs/AS01B-4 80-80 µg 
D169: HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
B2 
D1: HBc-HBs/AS01B-4 80-80 µg 
D57: HBc-HBs/AS01B-4 80-80 µg 
D113: HBc-HBs/AS01B-4 80-80 µg 
D169: HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
B3 
D1: PBS 
D57: PBS 
D113: ChAd155-hIi-HBV 5x1010 vp  
D169: MVA-HBV 2x108 pfu 
18 years – 
65 years 
● 
● 
● 
C1 
D1: ChAd155-hIi-HBV 5x1010 vp & 
HBc-HBs/AS01B-4 80-80 µg 
D57: MVA-HBV 2x108 pfu &  
HBc- HBc-HBs/AS01B-4  80-80 µg 
D113: MVA-HBV 2x108 pfu &  
HBc- HBc-HBs/AS01B-4 80-80 µg  
D169: MVA-HBV 2x108 pfu &  
HBc- HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
C2 
D1: PBS 
D57: PBS 
D113: ChAd155-hIi-HBV 5x1010 vp 
& HBc-HBs/AS01B-4 80-80 µg 
D169: MVA-HBV 2x108 pfu  
& HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
* Patients of Group A3 will be unblinded at the end of primary phase and will be given the option to continue in follow-
up phase in Step A or to participate in Step B or C provided that all eligibility criteria are met. 
 
• Control: 
− 
Safety assessment: Group A3 (placebo control) will 
be used for Step A. For Step B and Step C, Group B3 
and C2 data obtained up to Day 113 (placebo control 
up to Day 113) will be used respectively. 
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− 
For PoP efficacy objective: For Step B and Step C, 
Group B3 and C2 data obtained up to Day 113 
(placebo control up to Day 113) will be used as 
placebo control, respectively. 
• Vaccination schedules: Heterogeneous prime-boost-boost-
boost on Day 1, 57, 113, 169. 
• Treatment allocation: Following the assessment of 
eligibility (i.e., after Screening conclusion), patients will 
be randomized using a centralized randomization system 
on internet (SBIR) before the first study vaccine 
administration. The randomization ratio in each step are: 
Step A: 1:1:1; Step B: 2:1:1; Step C: 2:1. Study products 
administration must take place as soon as possible after 
randomization.  
• Blinding: 
Synopsis Table 2 Blinding of study epochs 
Study Epochs 
Blinding 
Epoch 001 
Not applicable 
Epoch 002 
Single-blind* 
Epoch 003 
Single-blind 
* Patients of Group A3 will be unblinded at the end of primary phase (Epoch 002) and will be given the option to 
continue in follow-up phase (Epoch 003) in Step A or to participate in Step B or C provided that all eligibility criteria are 
met.  
 
• Sampling schedule: 
− 
Blood samples for serological markers of HBV, HCV, 
HDV and HIV, and autoimmune antibodies will be 
collected at the Screening Visit. 
− 
Blood samples for hematology and biochemistry will 
be collected at all time points throughout the study, 
except for Days 3, 31, 87, 143, 199, 253 * and 309 * 
that are not mandatory and can be collected at the 
discretion of the Investigator. In case of abnormal 
parameters, blood samples may be collected at 
additional unscheduled visits.  
* For patients in Step B and Step C, blood collection is 
cancelled for Days 253 and 309. 
− 
Blood samples for markers of hepatic fibrosis 
(FibroTest) and HCC (α-fetoprotein) will be collected 
at the Screening Visit and on Day 337, 505 and 841. 
− 
Blood samples for HBsAg, HBV-DNA (and, if 
deemed necessary, new HBV markers) will be 
collected at the Screening Visit and every month since 

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204852 (TH HBV VV-001) 
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the vaccination during the primary phase and all time 
points during the follow-up phase, except for Days 3 *, 
31 *, 87, 143, 199, 253 †and 309 † that are not 
mandatory and can be collected at the discretion of the 
Investigator.  
* For patients participating in TH HBV VV-031 
HBS:001 study, blood collection specific to that study 
remains mandatory for Days 3 and 31. 
† For patients in Step B and Step C, blood collection 
will be cancelled for Days 253 and 309. 
 
− 
Blood samples for humoral response to HBV antigens 
will be collected on Day 1, 15, 71, 113, 127, 183, 337, 
505 and 841. 
− 
Blood samples for cell-mediated immune response to 
HBV antigens will be collected on Day 1, 15, 57, 64, 
71, 113, 127, 169, 183, 337, 505 and 841. 
− 
− 
Blood samples for serum repository will be collected 
on Day 1, 71, 113, 127, 183, 337, 505 and 841. 
− 
Blood samples in case of a TTS event should be 
collected within 2 weeks of the diagnosis of the TTS 
for exploratory testing. This blood sample can be 
collected at the next study visit or at an unscheduled 
visit in case the next study visit is >2 weeks from the 
TTS diagnosis. The blood sample collection for TTS 
event reported during the follow-up phase is optional. 
− 
Urine samples for urinalysis will be collected at all 
time points during the primary phase of the study, 
except for Days 3 *, 31 *, 87, 143, 199, 253 † and 309 † 
that are not mandatory and can be collected at the 
discretion of the Investigator.  
* For patients participating in TH HBV VV-031 
HBS:001 study, urine collection specific to that study 
remains mandatory for Days 3 and 31. 
† For patients in Step B and Step C, urine collection is 
cancelled for Days 253 and 309. 
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• Type of study: self-contained. 
• Data collection: Electronic Case Report Form (eCRF). 
• Safety monitoring: Internal Safety Review Committee 
(iSRC). An external expert with clinical expertise in 
hepatology will work together with the iSRC to review the 
safety data and contribute to the decision-making process to 
hold or continue the study.  
Number of patients 
A total of approximately
patients are planned to be 
recruited in this study. 
Endpoints  
Primary 
• Occurrence of adverse events (AEs) from vaccination up to 
Day 337: 
− 
Occurrence of each solicited local and general 
symptoms within 7 days after each vaccination (from 
day of vaccination to six days after vaccination). 
− 
Occurrence of unsolicited AEs within 30 days after 
each vaccination (from day of vaccination to 29 days 
after vaccination). 
CCI
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204852 (TH HBV VV-001) 
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− 
Occurrence of hematological, biochemical or 
urinalysis laboratory abnormalities within 30 days after 
each vaccination (from day of vaccination to 29 days 
after vaccination). 
− 
Occurrence of serious adverse events (SAEs) up to six 
months after the last dose (Day 337, Visit 22). 
− 
Occurrence of potential immune-mediated diseases 
(pIMDs) up to six months after the last dose (Day 337, 
Visit 22). 
− 
Occurrence of liver-disease related AEs up to six 
months after the last dose (Day 337, Visit 22). 
− 
Occurrence of hematological adverse events of special 
interest (AESIs) up to six months after the last dose 
(Day 337, Visit 22). 
− 
Occurrence of medically attended events (MAEs) up to 
six months after the last dose (Day 337, Visit 22). 
 
Secondary 
Immunogenicity 
• Immunogenicity with respect to HBV components of the 
viral vectored vaccines and adjuvanted proteins vaccines, at 
predefined time points. 
− 
Anti-HBc antibodies: seropositivity and concentration. 
− 
Anti-HBs antibodies: seroconversion and 
concentration; anti-HBs ≥10 mIU/ml and ≥100 
mIU/ml. 
− 
Frequency of HBc- and HBs- specific CD4+ T-cells 
and CD8+ T-cells; CD4+ T-cells responder, CD8+ T-
cells responder. 
Efficacy 
• qHBsAg: number of patients with ≥ 0.5 log decrease, ≥ 1-
log decrease, HbsAg loss and log-changes since pre-
vaccination.  
• Number of patients with HbsAg loss and anti-HBs 
seroconversion. 
• Mean qHBsAg in each group. 

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204852 (TH HBV VV-001) 
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Safety 
• Occurrence of AEs from vaccination up to Day 841  
− 
Occurrence of any SAEs throughout the study period. 
− 
Occurrence of SAEs causally related to an 
investigational vaccine throughout the study period. 
− 
Occurrence of MAEs throughout the study period. 
− 
Occurrence of pIMDs throughout the study period. 
− 
Occurrence of liver disease-related AEs throughout the 
study period. 
− 
Occurrence of spontaneous local or general bleeding 
with thrombocytopenia (< 50,000 platelets/mm3). 
− 
Occurrence of anemia with Hb < 9.5 g/dl. 
− 
Occurrence of AEs and SAEs leading to study 
withdrawal. 
• Pregnancy and pregnancy outcome throughout the study 
period. 
 
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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 8 
SYNOPSIS ...................................................................................................................... 9 
LIST OF ABBREVIATIONS ........................................................................................... 28 
GLOSSARY OF TERMS ............................................................................................... 31 
1. 
INTRODUCTION .................................................................................................... 35 
1.1. 
Background ................................................................................................ 35 
1.1.1. 
Medical Need ............................................................................... 35 
1.1.2. 
Need for a new vaccination strategy ............................................ 35 
1.2. 
Rationale for the study and study design .................................................... 37 
1.2.1. 
Rationale for the study ................................................................. 37 
1.2.2. 
Rationale for the study design ...................................................... 38 
1.2.3. 
Rationale for the use of placebo .................................................. 41 
1.3. 
Benefit : Risk Assessment .......................................................................... 41 
1.3.1. 
Risk Assessment ......................................................................... 42 
1.3.1.1. 
Vaccination ................................................................. 42 
1.3.1.2. 
ChAd155-hIi-HBV and MVA-HBV ............................... 42 
1.3.1.3. 
HBc-HBs/AS01B-4 ....................................................... 44 
1.3.1.4. 
Risks linked to the study population (i.e. 
chronically infected HBV patients) .............................. 44 
1.3.1.5. 
Risks linked to the collection of biospecimens 
in the study ................................................................. 45 
1.3.2. 
Benefit Assessment ..................................................................... 45 
1.3.3. 
Overall Benefit: Risk Conclusion .................................................. 45 
2. 
OBJECTIVES ......................................................................................................... 46 
2.1. 
Primary objective ........................................................................................ 46 
2.2. 
Secondary objectives .................................................................................. 46 
2.3. 
Tertiary objectives ....................................................................................... 46 
3. 
STUDY DESIGN OVERVIEW ................................................................................ 47 
4. 
STUDY COHORT ................................................................................................... 53 
4.1. 
Number of patients/centers ......................................................................... 53 
4.2. 
Inclusion criteria for enrolment .................................................................... 54 
4.3. 
Exclusion criteria for enrolment ................................................................... 55 
5. 
CONDUCT OF THE STUDY .................................................................................. 58 
5.1. 
Regulatory and ethical considerations, including the informed 
consent process.......................................................................................... 58 
5.2. 
Patient identification and randomization ...................................................... 59 
5.2.1. 
Patient identification ..................................................................... 59 
5.2.2. 
Randomization of treatment ......................................................... 59 
5.2.2.1. 
Treatment allocation to the patient .............................. 59 
5.2.2.1.1. 
Study group and treatment 
number allocation ................................... 59 

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5.2.2.1.2. 
Treatment number allocation for 
subsequent doses .................................. 60 
5.3. 
Method of blinding ...................................................................................... 60 
5.3.1. 
Emergency unblinding ................................................................. 60 
5.4. 
General study aspects ................................................................................ 61 
5.5. 
Outline of study procedures (Amended: 22 June 2023) .............................. 62 
5.6. 
Detailed description of study procedures .................................................... 70 
5.6.1. 
Informed consent ......................................................................... 70 
5.6.2. 
Check inclusion and exclusion criteria ......................................... 71 
5.6.3. 
Collect demographic data ............................................................ 71 
5.6.4. 
Medical history ............................................................................. 71 
5.6.5. 
HBV disease history .................................................................... 71 
5.6.6. 
Measure/record height and weight ............................................... 72 
5.6.7. 
Physical examination ................................................................... 72 
5.6.8. 
Pregnancy test ............................................................................. 73 
5.6.9. 
Check contraindications to vaccination ........................................ 73 
5.6.10. 
Assess pre-vaccination body temperature ................................... 73 
5.6.11. 
Study group and treatment number allocation .............................. 73 
5.6.12. 
Biospecimen sampling ................................................................. 73 
5.6.13. 
Study Vaccines administration ..................................................... 75 
5.6.14. 
Check and record concomitant medication/vaccination and 
intercurrent medical conditions .................................................... 75 
5.6.15. 
Recording of AEs, SAEs, AESIs and pregnancies ....................... 75 
5.6.16. 
Home nursing procedures ............................................................ 76 
5.6.17. 
Screening conclusion, primary phase conclusion and 
study conclusion .......................................................................... 76 
5.6.18. 
Study procedures during special circumstances .......................... 76 
5.7. 
Biological sample handling and analysis ..................................................... 80 
5.7.1. 
Use of specified study materials .................................................. 81 
5.7.2. 
Biological samples ....................................................................... 82 
5.7.3. 
Laboratory assays ....................................................................... 83 
5.7.4. 
Biological samples evaluation ...................................................... 87 
5.7.4.1. 
Evaluation of hematology, biochemistry and 
urinalysis .................................................................... 87 
5.7.4.2. 
Evaluation of serum HBV antigens ............................. 88 
5.7.4.3. 
Evaluation of molecular biology .................................. 89 
5.7.4.4. 
Evaluation of immunogenicity ..................................... 89 
6. 
STUDY VACCINES AND ADMINISTRATION ........................................................ 90 
6.1. 
Description of study vaccines ...................................................................... 90 
6.2. 
Storage and handling of study vaccines ...................................................... 92 
6.3. 
Dosage and administration of study vaccines ............................................. 92 
6.4. 
Minimizing environmental contamination with genetically modified 
organisms ................................................................................................... 93 
6.5. 
Replacement of unusable vaccine doses .................................................... 93 
6.6. 
Contraindications to subsequent vaccination .............................................. 93 
6.7. 
Concomitant medications/products and concomitant vaccinations .............. 95 
6.7.1. 
Recording of concomitant medications/products and 
concomitant vaccinations ............................................................. 95 
6.7.2. 
Concomitant medications/products/vaccines that may lead 
to the elimination of a patient from per-protocol analyses ............ 95 

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6.8. 
Intercurrent medical conditions that may lead to elimination of a 
patient from per-protocol analyses .............................................................. 96 
7. 
HEALTH ECONOMICS .......................................................................................... 96 
8. 
SAFETY ................................................................................................................. 96 
8.1. 
Safety definitions ........................................................................................ 97 
8.1.1. 
Definition of an adverse event ...................................................... 97 
8.1.2. 
Definition of a serious adverse event ........................................... 98 
8.1.3. 
Solicited adverse events .............................................................. 99 
8.1.3.1. 
Solicited local (injection-site) adverse events .............. 99 
8.1.3.2. 
Solicited general adverse events ................................ 99 
8.1.4. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................ 99 
8.1.5. 
Adverse events of special interest (AESIs) ................................ 100 
8.1.5.1. 
Liver disease-related adverse events ....................... 100 
8.1.5.2. 
Hematological adverse events of special 
interest ..................................................................... 100 
8.1.5.2.1. 
Thrombosis with 
Thrombocytopenia Syndrome 
(Amended: 22 June 2023) .................... 101 
8.1.5.3. 
Potential immune-mediated diseases ....................... 101 
8.1.6. 
COVID-19 .................................................................................. 103 
8.2. 
Events or outcomes not qualifying as adverse events or serious 
adverse events ......................................................................................... 103 
8.2.1. 
Pregnancy ................................................................................. 103 
8.3. 
Detecting and recording adverse events, serious adverse events 
and pregnancies ....................................................................................... 104 
8.3.1. 
Time period for detecting and recording adverse events, 
serious adverse events and pregnancies ................................... 104 
8.3.2. 
Post-Study adverse events and serious adverse events ............ 108 
8.3.3. 
Evaluation of adverse events and serious adverse events ......... 108 
8.3.3.1. 
Active questioning to detect adverse events 
and serious adverse events ...................................... 108 
8.3.3.2. 
Assessment of adverse events ................................. 108 
8.3.3.2.1. 
Assessment of intensity ........................ 108 
8.3.3.2.2. 
Assessment of causality ....................... 110 
8.3.3.3. 
Assessment of outcomes.......................................... 111 
8.3.3.4. 
Medically attended visits ........................................... 111 
8.4. 
Reporting of serious adverse events, pregnancies, and other events ....... 112 
8.4.1. 
Prompt reporting of serious adverse events, pregnancies, 
and other events to GSK Biologicals .......................................... 112 
8.4.2. 
Contact information for reporting serious adverse events, 
pregnancies and AESIs (liver disease-related AEs, 
hematological AESIs and pIMDs) .............................................. 112 
8.4.3. 
Completion and transmission of SAE reports to GSK 
Biologicals ................................................................................. 113 
8.4.3.1. 
Back-up system in case the electronic 
reporting system does not work ................................ 113 
8.4.4. 
Completion and transmission of pregnancy reports to GSK 
Biologicals ................................................................................. 113 

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8.4.5. 
Reporting of AESIs to GSK Biologicals ...................................... 113 
8.4.6. 
Updating of SAE, pregnancy, and AESI information after 
removal of write access to the patient’s eCRF ........................... 114 
8.4.7. 
Regulatory reporting requirements for serious adverse 
events ........................................................................................ 114 
8.5. 
Follow-up of adverse events, serious adverse events, pregnancies, 
AESIs and handling of abnormal parameters ............................................ 115 
8.5.1. 
Follow-up of adverse events and serious adverse events .......... 115 
8.5.1.1. 
Follow-up during the study ........................................ 115 
8.5.1.2. 
Follow-up after the patient is discharged from 
the study ................................................................... 115 
8.5.2. 
Follow-up of pregnancies ........................................................... 115 
8.5.3. 
Handling of abnormal biochemistry and hematology 
parameters ................................................................................ 116 
8.6. 
Treatment of adverse events .................................................................... 117 
8.7. 
Subject card .............................................................................................. 117 
8.8. 
Holding rules and safety monitoring .......................................................... 117 
8.8.1. 
Internal Safety Review Committee (iSRC) ................................. 117 
8.8.2. 
Details on the staggered vaccination and dose escalation ......... 118 
8.8.3. 
Holding rules .............................................................................. 120 
8.8.3.1. 
Holding rules definitions and monitoring ................... 120 
8.8.3.2. 
Risk assessment for the holding rules ...................... 121 
9. 
PATIENT COMPLETION AND WITHDRAWAL .................................................... 126 
9.1. 
Patient completion .................................................................................... 126 
9.2. 
Patient withdrawal ..................................................................................... 126 
9.2.1. 
Patient withdrawal from the study .............................................. 126 
9.2.2. 
Patient withdrawal from study vaccines ..................................... 127 
9.3. 
Screening and baseline failures ................................................................ 128 
10. STATISTICAL METHODS .................................................................................... 128 
10.1. 
Primary endpoints ..................................................................................... 128 
10.2. 
Secondary endpoints ................................................................................ 129 
10.3. 
Tertiary endpoints ..................................................................................... 130 
10.4. 
Determination of sample size .................................................................... 131 
10.4.1. 
Sample size considerations at final analysis linked to PoP 
objective .................................................................................... 131 
10.4.2. 
Sample size considerations for interim analyses linked to 
CMI response 14 days post-vaccination Dose 2 ........................ 133 
10.5. 
Cohorts for Analyses ................................................................................ 134 
10.5.1. 
Exposed Set .............................................................................. 134 
10.5.2. 
Per-protocol cohort for analysis of immunogenicity/efficacy ....... 134 
10.6. 
Derived and transformed data ................................................................... 134 
10.7. 
Analysis of demographics ......................................................................... 135 
10.8. 
Analysis of immunogenicity/efficacy .......................................................... 136 
10.8.1. 
Within groups assessment ......................................................... 136 
10.9. 
Analysis of safety ...................................................................................... 138 
10.9.1. 
Within groups assessment ......................................................... 138 
10.9.2. 
iSRC safety evaluations ............................................................. 139 
10.10. Interpretation of analyses .......................................................................... 139 
10.11. Conduct of analyses ................................................................................. 139 
10.11.1. Sequence of analyses................................................................ 140 

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10.11.2. Statistical considerations for interim analyses ............................ 141 
11. ADMINISTRATIVE MATTERS ............................................................................. 141 
11.1. 
electronic Case Report Form instructions ................................................. 141 
11.2. 
Study Monitoring by GSK Biologicals ........................................................ 142 
11.3. 
Record retention ....................................................................................... 142 
11.4. 
Quality assurance ..................................................................................... 143 
11.5. 
Posting of information on publicly available clinical trial registers and 
publication policy ...................................................................................... 143 
11.6. 
Provision of study results to investigators ................................................. 144 
11.7. 
Data Sharing ............................................................................................. 144 
11.8. 
Pharmacogenomics .................................................................................. 144 
12. COUNTRY SPECIFIC REQUIREMENTS ............................................................. 144 
12.1. 
Germany ................................................................................................... 144 
12.2. 
France ...................................................................................................... 147 
13. REFERENCES ..................................................................................................... 152 
 

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LIST OF TABLES 
PAGE 
Table 1 
Study groups, treatments and epochs foreseen in the study .................. 50 
Table 2 
Blinding of study epochs ........................................................................ 51 
Table 3 
Contact information for emergency unblinding ....................................... 61 
Table 4 
List of study procedures: Screening and primary phase 
(Screening Visit to Visit 17) (Amended: 22 June 2023)........................... 63 
Table 5 
List of study procedures: primary phase (Visit 18 to Visit 22), 
follow-up phase (Visit 23 to Visit 26) and unscheduled visits 
(Amended: 22 June 2023) ...................................................................... 67 
Table 6 
Intervals between study visits ................................................................. 70 
Table 7 
Study visits of Epoch 002 to be performed if subsequent 
vaccination cannot take place within allowed interval of 53 - 63 
days from previous vaccination .............................................................. 79 
Table 8 
Recommendations on spacing between COVID-19 vaccine and 
study vaccination by type of COVID-19 vaccine ..................................... 80 
Table 9 
Biological samples ................................................................................. 82 
Table 10 
Hematology, biochemistry, autoimmune antibody and urine tests .......... 84 
Table 11 
HBV, HCV, HDV and HIV serology and HBV virology assays ................ 85 
Table 12 
Humoral Immunity (Antibody determination) ........................................... 85 
Table 13 
Cell-mediated Immunity .......................................................................... 86 
Table 14 
HLA and host genome polymorphism ..................................................... 87 
Table 15 
Evaluation of hematology, biochemistry and urinalysis ........................... 87 
Table 16 
Evaluation of serum HBV antigens ......................................................... 88 
Table 17 
Evaluation of molecular biology .............................................................. 89 
Table 18 
Evaluation of humoral immunogenicity ................................................... 89 
Table 19 
Evaluation of cell-mediated immunogenicity ........................................... 90 
Table 20 
Study vaccines ....................................................................................... 91 
Table 21 
Dosage and administration ..................................................................... 92 
Table 22 
Solicited local adverse events ................................................................ 99 

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Table 23 
Solicited general adverse events ............................................................ 99 
Table 24 
List of potential immune-mediated diseases ......................................... 102 
Table 25 
Reporting periods for collecting safety information ............................... 106 
Table 26 
Intensity scales for solicited symptoms ................................................. 109 
Table 27 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK Biologicals ............................................... 112 
Table 28 
Holding rules ........................................................................................ 121 
Table 29 
Probability of meeting holding rule with 4 or 5 patients ......................... 123 
Table 30 
Power to demonstrate at least a 1-log decrease (i.e. 10-fold 
decrease) in qHBsAg or shows HBsAg loss at Day 337 versus 
Day 1 ................................................................................................... 131 
Table 31 
Exact 80% CI around observed percentage of responders, 
considering 30 evaluable patients ........................................................ 132 
Table 32 
Power to demonstrate a defined fold-decrease (i.e. log-
difference) between two groups with 30 and 15 evaluable 
patients per group respectively, SD varying from 0.5 to 0.9 – 
one-sided alpha = 10% ........................................................................ 132 
Table 33 
Exact 80% CI around observed percentage of CMI responders, 
considering a range of evaluable patients ............................................ 133 
Table 34 
GSK Biologicals’ laboratories ............................................................... 162 
Table 35 
Outsourced laboratories ....................................................................... 162 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design .......................................................................................... 48 
Figure 2 
Study step-wise recruitment and study groups ....................................... 48 
Figure 3 
Staggered enrolment within each step ................................................. 118 
Figure 4 
Staggered vaccination and dose escalation between steps .................. 119 
Figure 5 
Safety holding rules with associated probabilities ................................. 122 
Figure 6 
Safety holding rules with associated probabilities after 19 
patients ................................................................................................ 124 
Figure 7 
Safety holding rules with associated probabilities after 38 
patients ................................................................................................ 125 
 

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LIST OF APPENDICES 
PAGE 
APPENDIX A LABORATORY ASSAYS ..................................................................... 159 
APPENDIX B CLINICAL LABORATORIES ................................................................ 162 
APPENDIX C TOXICITY GRADING FOR HEMATOLOGY, BIOCHEMISTRY 
AND URINALYSIS PARAMETERS ...................................................... 163 
APPENDIX D CASE DEFINITION FOR COVID-19 CORONAVIRUS 
INFECTION .......................................................................................... 164 
APPENDIX E UPDATED BRIGHTON COLLABORATION CASE DEFINITION 
FOR THROMBOSIS WITH THROMBOCYTOPENIA 
SYNDROME (TTS) .............................................................................. 165 
APPENDIX F AMENDMENTS AND ADMINISTRATIVE CHANGES TO THE 
PROTOCOL ......................................................................................... 168 
 

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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AFP 
α-Fetoprotein 
ALEH 
Asociación Latinoamericana para el Estudio del Hígado 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Transaminase 
APRI 
Aspartate Transaminase to Platelets Ratio Index 
AS 
Adjuvant System 
BMI 
Body Mass Index 
CBC 
Complete Blood Count 
cccDNA 
Covalently Closed Circular Deoxyribonucleic Acid 
CCLIA 
Competitive Chemiluminescent Immunoassay 
CDC 
Centers for Disease Control 
CFC 
Cytokine Flow Cytometry 
ChAd 
Chimpanzee Adenovirus 
CHB 
Chronic Hepatitis B 
CKD-EPI 
Chronic Kidney Disease Epidemiologic Collaboration 
CLIA 
Chemiluminescent Immunoassay 
CLS 
Clinical Laboratory Sciences 
CMI 
Cell-Mediated Immunity 
CMIA 
Chemiluminescent Microparticle Immunoassay 
COVID-19 
Coronavirus Disease 2019 
CRA 
Clinical Research Associate 
CRDL 
Clinical Research and Development Lead 
CyTOF 
Cytometry by Time of Flight 
DNA 
Deoxyribonucleic Acid 
EASL 
European Association for the Study of the Liver 
eCRF 
electronic Case Report Form 
ELISA 
Enzyme Linked Immunosorbent Assay 
EoS 
End of Study 
ES 
Exposed Set 
ETV 
Entecavir 
FDA 
Food and Drug Administration, United States of America 
FTIH 
First-Time-In Human 
GCP 
Good Clinical Practice 

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GFR 
Glomerular Filtration Rate 
GMC 
Geometric Mean Concentration 
GMT 
Geometric Mean Titre 
GSK 
GlaxoSmithKline 
HBc 
Hepatitis B core protein 
HBcrAg 
Hepatitis B Core-Related Antigen 
HBIg 
Hepatitis B Immunoglobulin 
HBpol 
Hepatitis B Polymerase 
HBs 
Hepatitis B surface protein 
HBsAb 
Anti-HBs Antibody 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B Virus 
HCC 
Hepatocellular Carcinoma 
hCG 
Human Chorionic Gonadotrophin 
HCV 
Hepatitis C Virus 
HDV 
Hepatitis D Virus 
hIi 
Human Invariant Chain 
HIV 
Human Immunodeficiency Virus 
HLA 
Human Leukocyte Antigen 
HSV 
Herpes Simplex Virus 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
ICS 
Intracellular Cytokine Staining 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
IM 
Intramuscular 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
iSRC 
Internal Safety Review Committee 
IU 
International Unit 
kPa 
KiloPascal 
LLOQ 
Lower Limit Of Quantification  
LSLV 
Last Subject Last Visit 
MACDP 
Metropolitan Atlanta Congenital Defects Program 
MAE 
Medically Attended Event 
MedDRA 
Medical Dictionary for Regulatory Activities 

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METAVIR 
Meta-Analysis of Histological Data in Viral Hepatitis 
MHC 
Major Histocompatibility Complex 
mRNA 
messenger Ribonucleic Acid 
MVA 
Modified Vaccinia Ankara 
NA 
Nucleo(s)tides Analogues 
NHP 
Non-Human Primates 
PBMC 
Peripheral Blood Mononuclear Cell 
PCD 
Primary Completion Date 
PCR 
Polymerase Chain Reaction 
PegIFN 
Pegylated Interferon 
Pfu 
Plaque Forming Unit 
PID 
Patient Identification Number 
pIMD 
Potential Immune-Mediated Disease 
Pol 
Polymerase 
PoP 
Proof of Principle 
PP 
Per protocol 
PT 
Preferred Term 
qHBsAg 
Quantitative Hepatitis B Surface Antigen 
RNA 
Ribonucleic Acid 
SAE 
Serious Adverse Event 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SBIR 
Randomisation System on Internet 
SD 
Standard Deviation 
SDV 
Source Document Verification 
SmPC 
Summary of Product Characteristics 
SOC 
System Organ Class 
SpA 
Spondyloarthritis 
SPM 
Study Procedures Manual 
SRT 
Safety Review Team 
TAF 
Tenofovir alafenamide 
TDF 
Tenofovir Disoproxil Fumarate 
TE 
Transient Elastography 
TTS 
Thrombosis with Thrombocytopenia Syndrome 
ULN 
Upper Limit of Normal 
vp 
Virus Particle 
VSMB 
Vaccines Safety Monitoring Board 
WHO 
World Health Organisation 

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GLOSSARY OF TERMS 
Adequate contraception: 
Adequate contraception is defined as a contraceptive 
method with failure rate of less than 1% per year when 
used consistently and correctly and when applicable, in 
accordance with the product label for example:  
• abstinence from penile-vaginal intercourse, when this 
is their preferred and usual lifestyle, 
• current bilateral tubal ligation or occlusion, 
• Combined estrogen and progesterone oral 
contraceptives, 
• injectable progestogen, 
• implants of etenogestrel or levonorgestrel, 
• Contraceptive vaginal ring, 
• percutaneous contraceptive patches, 
• intrauterine device or intrauterine system, 
• male partner sterilisation prior to the female patient’s 
entry into the study, and this male is the sole partner 
for that patient, 
The information on the male sterility can come from 
the site personnel’s review of the patient’s medical 
records; or interview with the patient on her medical 
history. 
• male condom combined with a vaginal spermicide 
(foam, gel, film, cream or suppository), and/or 
progesterone alone oral contraceptive. 
Adequate contraception does not apply to patients of 
child bearing potential with same sex partners, or for 
patients who are and will continue to be abstinent from 
penile-vaginal intercourse on a long term and persistent 
basis, when this is their preferred and usual lifestyle. 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product.  
An adverse event (AE) can therefore be any unfavourable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), 
abuse or misuse. 

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Blinding: 
A procedure in which one or more parties to the trial are 
kept unaware of the treatment assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level 
of quality will appropriate personnel be unblinded or 
when required in case of a serious adverse event. In a 
single-blind study, the investigator and/or his staff are 
aware of the treatment assignment but the patient is not. 
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
End of Study: 
(Synonym of End of 
Trial) 
For studies without collection of human biologicals 
samples or imaging data EoS is the Last Subject Last 
Visit (LSLV).  
For studies with collection of Human Biologicals 
Samples or imaging data, EoS is defined as the date of 
the last testing/reading released of the Human Biological 
Samples or imaging data, related to primary and 
secondary endpoints. EoS must be achieved no later than 
8 months after LSLV 
Epoch: 
An epoch is a set of consecutive time points or a single 
time point from a single protocol. Epochs are defined to 
support a main purpose which is either to draw 
conclusions on patient participation or to draw a 
complete conclusion to define or precise the targeted 
label of the product. Supporting means that data collected 
at the time points included in an epoch must be sufficient 
to fulfil the purpose of the epoch. 
Typical examples of epochs are screening, primary 
vaccinations, boosters, yearly immunogenicity follow-
ups, and surveillance periods for efficacy or safety. 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis (see Sections 6.7.2 
and 10.5 for details on criteria for evaluability). 
Investigational vaccine: 
(Synonym of 
Investigational Medicinal 
Product) 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorisation when used in a way different 
from the approved form, or when used for an unapproved 
indication, or when used to gain further information about 
an approved use.  

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Menarche: 
Menarche is the onset of menses for the first time in a 
young female and is preceded by several changes 
associated with puberty including breast development and 
pubic hair growth. Menarche usually occurs within 1-2 
years of breast development, thelarche. However, a young 
female can become pregnant before her first menses. 
Thus, a conservative definition of non-childbearing 
potential in a pre-menarcheal female is a young female 
who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue). 
Menopause / Post-
menopause: 
Menopause is the age associated with complete cessation 
of menstrual cycles, menses, and implies the loss of 
reproductive potential by ovarian failure. 
A postmenopausal state is defined as no menses for 12 
months without an alternative medical cause. A blood 
sample for simultaneous follicle-stimulating hormone and 
estradiol levels may be collected at the discretion of the 
investigator to confirm non-reproductive potential. 
Patient: 
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the vaccine(s) or as a control. 
Patient number: 
A unique number identifying a patient, assigned to each 
patient consenting to participate in the study. 
Pharmacogenomics: 
The International Conference on Harmonization (ICH) 
E15 Guidance for Industry defines pharmacogenomics as 
Study of variation of DNA and RNA characteristics as 
related to drug or treatment response. Pharmacogenetics, 
which is a subset of pharmacogenomics, is “the study of 
variations in DNA sequence as related to drug response.” 
Pharmacogenomic biomarkers include germline (host) 
DNA and RNA as well as somatic changes (e.g., 
mutations) that occur in cells or tissues. 
Pharmacogenomic biomarkers are not limited to human 
samples but include samples from viruses and infectious 
agents as well as animal samples. The term 
pharmacogenomic experiment includes both the 
generation of new genetic or genomic (DNA and/or 
RNA) data with subsequent analysis as well as the 
analysis of existing genetic or genomic data to understand 
drug or treatment response (pharmacokinetics, safety, 
efficacy or effectiveness, mode of action). Proteomic and 
metabolomic biomarker research are not 
pharmacogenomics. 

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Potential Immune-
Mediated Disease: 
Potential immune-mediated diseases (pIMDs) are a subset 
of AEs that include autoimmune diseases and other 
inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology. 
Primary completion 
date: 
The date that the final patient was examined or received 
an intervention for the purpose of final collection of data 
for all primary outcomes, whether the clinical trial was 
concluded according to the pre-specified protocol or was 
terminated. 
Protocol amendment: 
The International Conference on Harmonisation (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK Biologicals further details this to include a change 
to an approved protocol that affects the safety of patients, 
scope of the investigation, study design, or scientific 
integrity of the study. 
Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  
Randomization: 
Process of random attribution of treatment to patients in 
order to reduce bias of selection. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Site Monitor: 
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at one or 
more investigational sites. 
Solicited adverse event: 
AEs to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively 
solicited from the patient or an observer during a 
specified post-vaccination follow-up period. 
Study vaccine/product: 
Any investigational vaccine/product being tested and/or 
any authorized use of a vaccine/ product /placebo as a 
reference or administered concomitantly, in a clinical trial 
that evaluates the use of an investigational 
vaccine/product. 
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 patient. 
Treatment number: 
A number identifying a treatment to a patient, 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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1. 
INTRODUCTION 
1.1. 
Background 
1.1.1. 
Medical Need 
The burden of chronic Hepatitis B virus (HBV) infection constitutes a public health threat 
in many areas of the world. According to the WHO global hepatitis report [WHO, 2017], 
more than 250 million people are chronically infected with HBV. The prevalence of HBV 
infection varies in different parts of the world: more than 6% of the general population in 
Africa and Western Pacific regions but less than 1% of the general population in 
America. If left untreated, chronic HBV infection can lead to cirrhosis, hepatic 
decompensation and hepatocellular carcinoma. These long-term complications are life-
threatening and accounted for 887 000 deaths.  
Currently, there are two main treatment options for chronic hepatitis B (CHB) patients: 
either by pegylated interferon alpha (PegIFNα) or by nucleo(s)tide analogues (NA) 
[EASL, 2017]. PegIFNα aiming at induction of a long-term immune control with a finite 
duration treatment may achieve sustained off-treatment control, but durable virological 
response and hepatitis B surface antigen (HBsAg) loss is limited to a small proportion of 
patients. In addition, owing to its poor tolerability and long-term safety concerns, a 
significant number of patients are ineligible for this type of treatment.  
NAs target HBV virion synthesis. The NAs approved in Europe for HBV treatment 
include entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide 
(TAF) that are associated with high barrier against HBV resistance as well as lamivudine 
(LAM), adefovir dipivoxil (ADV) and telbivudine (TBV) that are associated with low 
barrier to HBV resistance. The main advantage of treatment with a potent NA with high 
barrier to resistance (i.e., ETV, TDF, TAF) is its predictable high long-term antiviral 
efficacy leading to HBV DNA suppression in the vast majority of compliant patients as 
well as its favourable safety profile. The disadvantage of NA treatment is its long-term 
therapeutic regimen, because a NA does not usually achieve HBV eradication and NA 
discontinuation may lead to the HBV relapse [Kranidioti, 2015]. HBsAg loss 
representing a functional cure is now the gold standard treatment endpoint in CHB 
[Block, 2017; Cornberg, 2017], which however, is rarely achieved with NA treatment 
[Zoutendijk, 2011].  
Despite the potent suppression of HBV replication in livers by a NA, the dysfunction of 
HBV-specific antiviral immunity persists in patients. Combinations of direct antivirals 
and restoration of immune responses may be needed for the sustainability of the 
functional cure. 
1.1.2. 
Need for a new vaccination strategy 
Previous therapeutic vaccines have induced very low levels of HBV-specific T cell 
response with minimal effects on viral suppression or HBV seroconversion events. Early 
effort on recombinant vaccines based on HBV surface and/or PreS antigens preliminarily 
induced antibody response but no HBV-specific CD8+ T-cell response, with no clinical 
or virological benefit [Jung, 2002; Vandepapelière, 2007]. A DNA vaccine expressing 

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HBV envelope failed to restore T cell response specific to HBsAg and HBcAg thus did 
not decrease the risk of relapse in patients after NA discontinuation [Fontaine, 2015]. 
With new delivery systems, a DNA vaccine (prime vaccine) and MVA viral vector 
vaccine (boost vaccine) encoding S, preS1/S2 showed no T cell induction or reduction in 
viremia suggesting HBV PreS and surface antigens alone are not sufficient to cure 
patients [Cavenaugh, 2011]. A lipopeptide vaccine targeting a CTL epitope derived from 
HBcAg was shown to initiate CTL activity but at a very low magnitude that failed in viral 
clearance [Heathcote, 1999]. More recently, vaccine strategies targeting multiple HBV 
antigens and new delivery systems have been investigated. A recombinant 
HBsAg/HBcAg vaccine led to a viral load decrease to a very low level (i.e. ~50 IU/ml) in 
only half of the patients [Al-Mahtab, 2013]. A DNA vaccine encoding S, preS1/S2, core, 
polymerase and X proteins with genetically adjuvanted IL-12 together with lamivudine 
induced a multi-specific T cell response and a >2 log10 decrease in viral load in half of 
the patients. However, changes in quantitative detection of HBsAg, loss of HBsAg or 
HBsAg seroconversion were not observed in any patients [Yang, 2012]. The GS-4774 
vaccine, a yeast-based T cell vaccine expressing large S, core and X proteins of HBV did 
not provide significant reduction in HBsAg in virally-suppressed CHB patients. The 
vaccine was shown to elicit HBV-specific T cell response preliminarily to X- and core 
antigens but much weaker response to the S antigen [Lok, 2016]. 
GSK Biologicals’ new vaccination strategy relies on a heterologous prime-boost 
approach with HBV viral vector vaccines (ChAd155-hIi-HBV followed by MVA-HBV) 
with sequential or co-administration of AS01B-4-adjuvanted HBc-HBs proteins. The 
vaccines will be administered in patients with chronic HBV infection who are virally 
suppressed on NA therapy but not functionally cured. This strategy is based on the 
following observations: 
• Adenovirus and MVA vectors are potent and technologically advanced CD8+ T-cell-
inducing viral vectors [Folgori, 2006; Zaiss, 2010; Barnes, 2012; Sheehy, 2012; 
Cottingham, 2013]. Specifically, when a MVA vector is administered after 
adenovirus immunization, it has been shown to significantly boost the adenovirus-
induced CD8+ T-cell responses [Swadling, 2014].  
• Enhanced and sustained CD8+ T-cell responses were demonstrated in mice and 
non-human primates using an adenoviral vector-based vaccine encoding fusion of 
target antigen with the major histocompatibility complex (MHC) Class II CD74 
invariant chain (hIi, genetic adjuvant) [Mikkelsen, 2011; Capone, 2014]. 
• Combining an adjuvant system such as AS01 to Malaria RTS, S antigen, HBsAg or 
Zoster glycoprotein E antigen was shown to dramatically enhance the antibody and 
CD4+ T-cell adaptive response to the targeted antigen, as the ability of AS01 to 
improve adaptive immune responses is linked to a transient stimulation of the innate 
immune system leading to the generation of high number of efficient Ag-presenting 
dendritic cells [Chlibek, 2013; Chlibek, 2014; Didierlaurent, 2014; Leroux-Roels, 
2014; Leroux-Roels, 2016].  
• Administration of viral vectored vaccines together with adjuvanted proteins may 
therefore induce a strong, multifunctional and complementary antigen-specific 
immune response [Omosa-Manyonyi, 2015]. 

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A decrease in HBV-DNA load precedes the detection of HBV specific T-cell responses, 
both in patients resolving natural infections and in those displaying flare-ups of hepatitis 
associated with HBeAg seroconversion during chronic infection [Webster, 2004]. 
Reducing HBV DNA load by antiviral chemotherapy prior to starting therapeutic 
vaccination may, therefore, increase the responsiveness of HBV-specific T-cells to the 
vaccines [Michel, 2011; Boni, 2012]. 
Please refer to the current Investigator Brochure for information regarding the pre-
clinical information of ChAd155-hIi-HBV, MVA-HBV and HBc-HBs/AS01B-4. 
1.2. 
Rationale for the study and study design 
1.2.1. 
Rationale for the study 
Treatment with GSK Biologicals’ HBV therapeutic vaccines aims to restore immunity to 
HBV, as evidenced by clearance of HBsAg or reduction of HBsAg concentration, in 
order to allow patients to safely discontinue NA therapy without virological or clinical 
relapse [Chong, 2017; Lampertico, 2014]. 
Considering the current knowledge on HBV immunity, GSK Biologicals’ vaccination 
strategy relies on the administration of three vaccines in heterologous prime-boost 
regimens: primed with ChAd155-hIi-HBV followed by a boost with MVA-HBV, with 
subsequent or co-administration of HBc-HBs/AS01B-4.  
The two viral vectored vaccines aim to induce an immune response (CD8+ T-cells and, to 
a lesser extent, CD4+ T-cells) to the core and surface antigens; the adjuvanted proteins 
aim to induce a robust CD4+ T-cell and antibody response to the same core and surface 
antigens.  
The aims of the study are as follows:  
• Phase I Dose-escalation safety lead-in (Step A and Step B) aims to assess safety of 
a low dose (Step A) and a target dose (Step B) of the vaccine, both in a sequential 
regimen; 
• Phase II Regimen-finding that assesses the target doses of the vaccines given in 
different regimens in Step B and Step C, aims: 
− 
To evaluate the safety profile of sequential regimen in Step B (with or without 
adjuvanted proteins i.e. group B1 and B3 respectively), adjuvanted proteins 
given alone (group B2) and co-administration regimens in Step C, 
− 
To evaluate whether one or more vaccine regimens tested will induce a decrease 
in serum HBsAg concentration (proof-of-principle [PoP]), 
− 
To evaluate the added value of the adjuvanted proteins on top of viral vector 
vaccines, 

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− 
To evaluate the best vaccination regimen for the administration of the 
adjuvanted proteins (i.e. either sequentially to or co-administered with the viral 
vectored vaccines), 
− 
To evaluate the added value of 3 boost doses versus one boost dose of MVA-
HBV co-administered with adjuvanted proteins (group C1 and C2), 
− 
To assess the induction of HBV-specific CD8+ and CD4+ T-cell responses and 
antibody responses by different vaccine regimens. 
1.2.2. 
Rationale for the study design 
Study population: This first-time-in human (FTIH) study will be conducted in one 
segment of the CHB patients that is at low risk of severe hepatitis exacerbation: adult 
patients between 18 and 65 years of age, HBeAg-negative chronic HBV infection, with 
no cirrhosis or no advanced fibrosis, with HBV viral suppression and normal ALT on 
entecavir (ETV) or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) 
treatment for at least 24 months. 
It has shown that patients under long-term effective therapy with NA have a restored 
function of HBV-specific T-cells [Boni, 2012]. ETV, TDF and TAF are highly effective 
NAs with no or minimal resistance reported to date. Selecting patients well-controlled 
under these NA therapy may therefore optimize their response to the vaccines while 
minimizing the risk for viral reactivation due to appearance of drug-resistant mutant. 
At Screening, liver fibrosis stage assessment (aiming to exclude patients with advanced 
fibrosis/cirrhosis) will rely on two different non-invasive approaches: a ‘‘biological’’ 
approach based on the quantification of biomarkers in serum samples and a ‘‘physical’’ 
approach based on the measurement of liver stiffness. 
As per European Association for the Study of the Liver (EASL) and Asociación 
Latinoamericana para el Estudio del Hígado (ALEH) clinical practice guidelines for non-
invasive tests for evaluation of liver disease severity and prognosis, FibroTest is one of 
the most widely used and validated patented tests in clinical practice due to its high 
applicability and good inter-laboratory reproducibility [EASL, 2015]. It is less accurate in 
detecting intermediate stages of fibrosis than cirrhosis. The performance is better for 
detecting cirrhosis than significant fibrosis. Serum biomarkers of fibrosis are well 
validated in patients with chronic viral hepatitis with more evidence for HCV than for 
HBV and HIV/HCV coinfection. Transient elastography (TE) FibroScan can be 
considered the non-invasive standard for the measurement of liver stiffness. It is well 
validated in viral hepatitis with performance equivalent in hepatitis B, hepatitis C and in 
HIV-HCV coinfection. It performs better for detection of cirrhosis than for detection of 
significant fibrosis and is a reliable method for the diagnosis of cirrhosis in patients with 
chronic liver diseases, that generally performs better at ruling out than ruling in cirrhosis 
(with negative predictive value higher than 90%). 
Among the different available strategies, algorithms combining TE and serum biomarkers 
appear to be the most attractive and validated one [Leroy, 2016; Castéra, 2005]. In 
patients with viral hepatitis C, when TE and serum biomarkers results are in accordance, 

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the diagnostic accuracy is increased for detecting significant fibrosis but not for cirrhosis. 
In cases of unexplained discordance, a liver biopsy should be performed if the results 
would change the patient management. In a prospective study of chronic hepatitis C 
(CHC), a significant positive correlation was observed between liver stiffness as 
measured by FibroScan and fibrosis stages as determined by on biopsy [Ziol, 2005]. The 
distinctive cut-off values of 9.6 kiloPascal (kPa) and 14.5 kPa were considered in 
diagnosis of extensive fibrosis (METAVIR F3) and cirrhosis (METAVIR F4), 
respectively. In another prospective study in CHC patients, the performance of FibroScan 
was compared with FibroTest, aspartate transaminase to platelets ratio index (APRI) and 
liver biopsy [Castéra, 2005]. FibroScan and FibroTest have shown similar accuracy in 
estimating the liver fibrosis staging. The best performance was obtained by combining 
the FibroScan and FibroTest, The most discriminant cut-off value for advanced fibrosis 
(METAVIR F3) was determined as 9.5 kPa and 12.5 kPa for cirrhosis (METAVIR F4). 
In a meta-analysis of the FibroTest diagnostic value, it was found that FibroTest had a 
higher or similar prognostic value compared with biopsy in patients with CHB, CHC and 
alcoholic liver disease (ALD) [Halfon, 2008]. In another prospective study in patients 
with alcoholic liver disease, FibroTest has been shown to identify advanced liver fibrosis 
with high diagnostic accuracy [Thiele, 2018]. The cutoff score 0.58 ruled out advanced 
fibrosis with a negative predictive value (NPV) of 97%. In a Phase III study on the 
combination of several direct antiviral agents (DAAs) in treating genotype 3 chronic 
HCV infection with advanced liver disease, liver biopsy, Fibroscan and FibroTest plus 
APRI were used to define the liver fibrosis stage of the study population [Leroy, 2016]. 
Advanced fibrosis was defined as a METAVIR score of F3 or an Ishak score of 4 on liver 
biopsy, or a FibroScan ≥ 9.6 kPa but < 14.6 kPa, or a FibroTest score of 0.58-0.74 plus an 
APRI score above 1 but below 2. Cirrhosis was defined as a METAVIR score of F4 or an 
Ishak score > 4 on liver biopsy, a liver stiffness value ≥ 14.6 kPa, or a FibroTest result ≥ 
0.75 plus APRI ≥ 2. Where different testing methods yielded conflicting results, biopsy 
data took precedence. If biopsy data were not available, a FibroScan result took 
precedence over the FibroTest/APRI result. In this study, we adopt both Fibroscan and 
FibroTest to rule out patients with advanced liver fibrosis or cirrhosis. Only patients with 
FibroScan < 9.6 kPa or FibroTest score < 0.59, will be included in this FTIH study. 
Route of administration: The choice of the intramuscular route for ChAd155-hIi-HBV 
is based on the assumption that no co-infection of natural human Adenovirus could occur 
at this site. Furthermore, there is a large body of data from clinical trials in humans using 
replication defective Ad5- and Ad6-based HIV vaccines injected intramuscularly 
showing an excellent safety profile, no viral shedding, and high levels of 
immunogenicity. MVA-HBV will also be given by the intramuscular route following 
several studies on other MVA vector vaccines demonstrating similar immunogenicity but 
less local reactivity when MVA vectors were administered by the intramuscular 
compared to the subcutaneous route. Intramuscular vaccination with AS01B-containing 
vaccines has been largely studied in the Company’s Zoster program [Lal, 2015; 
Cunningham, 2016], Malaria program [Agnandji, 2011; Asante, 2011; Lusingu, 2010] 
and Tuberculosis program [Penn-Nicholson, 2015] with an acceptable safety profile. 
Dose of each of the vaccines: Two different doses of ChAd155-hIi-HBV (5x109 and 
5x1010 vp) and MVA-HBV (2x107 and 2x108 pfu) will be assessed and were selected 
based on available clinical data with ChAd3- and MVA-based vectored vaccines using 

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other antigens. ChAd3 vector is closely related to ChAd155. In HCV clinical trials where 
ChAd3-NSmut was assessed at doses of 5x108, 5x109, 2.5x1010, 7.5x1010 vp in healthy 
adults and in patients with chronic HCV, each vaccine dose was well tolerated while a 
dose response was observed up to the 2.5x1010 dose [Barnes, 2012; Kelly, 2016]. Booster 
doses of HCV MVA-NSmut were administered at doses of 2x106, 2x107 or 2x108 pfu in 
subjects primed with 2.5x1010 vp of ChAd3 NSmut: the 2x107 and 2x108 pfu doses were 
equally well tolerated and immunogenic [Swadling, 2016]. The clinical development of 
an Ebola vaccine candidate has used ChAd3 as a vector (ChAd3-EBO-Z). In this 
program, doses of 1x1010, 2.5x1010, 5x1010 and 1x1011 vp were evaluated in healthy 
adults [Tapia, 2016]. The vaccines were well tolerated and higher immune responses 
were associated with the highest dose. 
Two different doses of HBc-HBs antigens will be assessed, containing 20-20, and 80-80 
µg of HBc and HBs, respectively. The existing HBV vaccines containing 20 µg of 
HBsAg and up to 100 µg of HBs without or with HBcAg have been administered safely 
in clinical trials in CHB patients [Vandepapelière, 2007; Al-Mahtab, 2013]. Clinical data 
with other AS01B-adjuvanted vaccines suggest vaccine containing lower antigen doses 
may perform as good as or better than those containing higher doses [Van Braeckel, 
2011]. 
 
 
 
 
 
 Such interference observed in mice may however not be deemed relevant to 
the administration of the vaccine in CHB patients [Al-Mahtab, 2013]. A vaccine 
containing equal concentrations of HBcAg and HBsAg was able to induce an immune 
response to both antigens. 
Vaccine regimen: The two lead vaccine regimens tested in our study will be 1) a prime 
with ChAd155-hIi-HBV and boost with MVA-HBV, followed by two booster doses of 
adjuvanted proteins, and 2) a prime with ChAd155-hIi-HBV co-administered with 
adjuvanted proteins followed with three booster doses of MVA-HBV co-administered 
with adjuvanted proteins. The clinical study design includes also three active control 
groups consisting of 1) patients vaccinated with adjuvanted proteins only, and 2) patients 
primed with ChAd155-hIi-HBV and boosted with MVA-HBV only, and 3) patients 
primed with ChAd155-hIi-HBV co-administered with adjuvanted protein followed with 
one booster dose of MVA-HBV co-administered with adjuvanted protein. The interval of 
8 weeks between doses is based on existing clinical data with other related vaccines. 
Previous data generated at GSK showed that AS01B-adjuvanted proteins induce strong 
antibody and antigen-specific CD4+ T-cell responses but CD8+ T-cell response after 
AS01B-adjuvanted proteins is however weak [Leroux-Roels, 2010; Van Braeckel, 2011]. 
Therefore the co-administration or sequential administration of AS01B-adjuvanted protein 
vaccine with the heterologous prime-boost with viral vector vaccines aims to complement 
the breadth of the immune response to the targeted antigens. 
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 Please refer to the Investigator Brochure 
for more information. 
In a recent study on human immunodeficiency virus (HIV) vaccine, GSK has evaluated 
the prime-boost or co-administration of adenoviral vector (Ad35-GRIN) with adjuvanted 
proteins (F4co/AS01B). The co-administration of the adjuvanted protein and the 
adenovirus vector was shown to be well tolerated and resulted in a strong, polyfunctional 
and complementary HIV-specific immune response in HIV-uninfected volunteers after 
two doses that was maintained up to one year post third dose. The regimen “priming with 
adjuvanted proteins followed by boosting with the viral vector” appeared to induce CD4+ 
T-cells that were less polyfunctional than when the adenovectored vaccine was given as 
priming vaccine [Omosa-Manyonyi, 2015]. Based on these data, the FTIH study with 
therapeutic HBV vaccine will evaluate different vaccination schedules where HBc-
HBs/AS01B-4 is given either sequentially to or co-administered with the heterologous 
prime-boost with ChAd155-hIi-HBV and MVA-HBV. 
1.2.3. 
Rationale for the use of placebo 
A PBS solution is included as a negative control (placebo) in a low number of patients in 
the study. The use of the placebo control and the single-blind, randomized study design 
will allow controlling for potential biases in the conduct of the study. 
Importantly, each patient including those in the control group will remain under NA 
treatment throughout the duration of the study. 
1.3. 
Benefit : Risk Assessment 
Approximately 
patients in this study will receive the investigational HBV viral 
vector and/or adjuvanted protein vaccines, whereas the other approximately
patients 
will receive the placebo only. 
Although clinical data on similar type of vaccines are available that are supportive to the 
use of each vaccine in the proposed vaccine regimen (see Sections 1.2.2 and 1.3.1), none 
of the investigational vaccines to be used in this study have been administered in humans 
yet prior the study start. Therefore, safety and efficacy of the proposed vaccine regimen 
are unknown until the data are generated. 
Please refer to the current Investigator Brochure for the summary of potential risks and 
benefits of the ChAd155-hIi-HBV, MVA-HBV and HBc-HBs/AS01B-4 and for the data 
generated during the study. 
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The following section outlines the risk assessment and mitigation strategy for this study 
protocol. 
1.3.1. 
Risk Assessment 
1.3.1.1. 
Vaccination 
Vaccination in general may lead to local reactions at injection site, such as pain, redness 
and swelling. 
As with all injectable vaccines, immediate systemic allergic reactions to vaccination can 
occur. These are however very rare and are estimated to occur once per 450,000 
vaccinations to once per 1,000,000 for vaccines which do not contain allergens such as 
gelatin or egg protein [Zent, 2002]. In order to be able to treat patients with an immediate 
systemic allergic reaction to vaccination, all patients will need to remain under 
observation at the study site for at least 60 minutes after vaccination. For the management 
of anaphylactic reactions, access to an emergency room or to a first aid kit will be 
available at the sites. 
1.3.1.2. 
ChAd155-hIi-HBV and MVA-HBV 
ChAd155-hIi-HBV has not previously been tested in humans. Adenoviral gene transfer 
vectors are known to induce thrombocytopenia when administered systemically (i.v.).
 
 In clinical development programs of other adenoviral 
vectors within the Company, a transient drop in thrombocyte counts and hemoglobin 
were noted following intramuscular administration, without clinical signs and restored 
over time. Given these observations, the risks of spontaneous bleeding due to 
thrombocytopenia and anemia were considered as potential risks for the ChAd155-hIi-
HBV vaccine. With accumulation of safety data in clinical development programs of 
other adenoviral vectors within the Company, this risk has been redefined as “transient 
(non-clinically significant) decreases in hematologic parameters”. Safety provisions will 
be included in this FTIH study such as enrolling patients with normal hematology 
parameters and a broad safety hematology and biochemistry evaluation at each study 
visit. 
 
 
 
 
 
MVA is widely considered as the vaccinia virus strain of choice for clinical investigation 
because of its acceptable safety profile. Over 120,000 humans have been inoculated and 
successfully vaccinated against smallpox with MVA during the campaign for the 
eradication of smallpox in Germany in the 1970s, including elderly and 
immunocompromised persons. More recently, the use of MVA in recombinant vaccines 
have been tested in a number of clinical studies, including those for vaccines against HIV 
and HCV [Guerra, 2010; Currier, 2010; Earl, 2009; Habersetzer, 2009; Bain, 2009; 
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Fournillier, 2007]. The safety data obtained from previous trials using other MVA based 
vaccines have shown that they are generally well tolerated. 
The heterologous prime-boost regimen with Chimpanzee adenoviral vector vaccine and 
MVA vector vaccines showed that the MVA vector vaccine was more reactogenic than 
the Chimpanzee adenoviral vector vaccine but was still well tolerated with the majority 
of AEs being mild in intensity [Swadling, 2014; Mensah, 2016; Green, 2015; Ewer, 
2016]. 
 
 
 
 
Two recent publications have shown that autoantibodies targeting the CLIP peptide (a 
region of the hIi) could be a biomarker for the early diagnosis of the autoimmune disease 
inflammatory spondyloarthritis (SpA) [Baerlecken, 2014; Baraliakos, 2014].  
However, several arguments suggest the risk for vaccine-induced SpA or other potential 
immune mediated diseases (pIMDs) is minimal: 
• A humanized anti-CD74 monoclonal antibody (milatuzumab) targeting cell surface 
expressed epitope of the molecule CD74 which is expressed on monocytes, 
macrophages, and B cells but not T-cells was assessed in patients with multiple 
myeloma or B-cell lymphoma. No spondyloarthritis cases were reported in these 
patients [Christian, 2015; Martin, 2015]. The anemia, lymphopenia, neutropenia, 
thrombocytopenia reported in these patients could be due to the patient’s underlying 
disease as similar AE have been observed with other monoclonal antibody therapies. 
Single dose studies of milatuzumab in monkeys showed no adverse effects but did 
transiently decrease circulating B and T lymphocytes and natural killer cells 
[Kaufman, 2013; Christian, 2015; Martin, 2015; Stein, 2007]. 
• SpA therapy relies on non- steroidal anti-inflammatory drugs and anti-TNFα therapy, 
the latter being effective in approximately half of patients. TNFα is mostly produced 
by dendritic cells and monocytes. A B-cell-directed therapy (rituximab) was safely 
tested but ineffective in patients with SpA failing to respond to TNFα blockers. 
Altogether these data support that the mechanism for SpA pathogenesis involves 
MHC class I cells and not B-cells nor antibodies [Song, 2010; Bowness, 2015]. 
• 
 
 (Please refer to IB 
for more information). 
Nevertheless, the risk that the ChAd155-hIi-HBV vaccine induces an immune response 
against the hIi and a pIMD cannot be entirely ruled out. 
 
 
 
 
 
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1.3.1.3. 
HBc-HBs/AS01B-4 
The formulation with the AS01B-4 adjuvant and the HBV antigens was selected for the 
HBV therapeutic program as it demonstrated the highest process robustness. To date, the 
AS01-containing vaccines have been largely studied in the Company’s Zoster program 
[Lal, 2015; Cunningham, 2016; Leroux-Roels, 2012], Malaria program [Agnandji, 2011; 
Asante, 2011; Lusingu, 2010] and Tuberculosis program [Penn-Nicholson, 2015] with an 
acceptable safety profile.  
The general concern that Adjuvant Systems could induce events of possible autoimmune 
etiology is considered a potential risk. In order to ensure adequate detection and follow-
up of pIMDs, the occurrence of pIMDs will be duly monitored and reported for the entire 
study period.  
1.3.1.4. 
Risks linked to the study population (i.e. chronically infected HBV 
patients) 
During the natural course of the disease, viral clearance of HBV occurs through 
immunological mechanism that may be associated with hepatitis flares, and in some rare 
instances, it can lead to fulminant hepatic failure. Hepatic damage is possibly triggered 
by inefficient T-cell control and recruitment of inflammatory cells (macrophages) during 
the disease progress. When the HBV-specific CD8+ T-cell response is unable to control 
virus replication, it may contribute to liver pathology, not only directly but also by 
causing the recruitment of non-virus-specific T-cells while, in the presence of an 
effective HBV-specific CD8+ T-cell response, inhibition of virus replication can be 
independent of liver damage [Maini, 2000]. Importantly, cytokines can mediate viral 
clearance without direct hepatocyte killing [Phillips, 2010]. Also, several mechanisms are 
in place to control “exuberant” T-cell activation and protect from liver failure (IL-10, 
arginase, PD1 and other co-inhibitory pathways). 
The proposed vaccination strategy aims to induce a robust response in terms of 
antibodies, CD4+ and CD8+ T-cells to the selected antigens: robust antibody response and 
CD4+ T-cell response (but no CD8+ T-cell response) have already been observed in 
previous studies in CHB patients and no life-threatening hepatitis flares were reported 
[Vandepapelière, 2007]. 
Several types of vaccines have been tested in CHB patients. These vaccines consisted of 
recombinant protein vaccines (with or without adjuvants), immuno-complexes HBs-anti-
HBs, DNA/MVA prime-boost vaccination and yeast-based vaccine expressing 
recombinant proteins. To the Company’s knowledge, no significant safety issues were 
reported in these trials but the vaccines were generally ineffective in controlling the virus. 
None of these vaccines was able to mount a de-novo robust and broad immune response 
targeting both the HBc and HBs antigens as well as the different segments of the immune 
system (CD4+ T-cells, CD8+ T-cells and antibodies) [Michel, 2015]. 
However, when similar viral vectored-based vaccines using HCV immunogens were 
tested in chronic HCV-infected patients, the safety profile was acceptable but the vaccine 
failed to induced virus-specific T-cell responses [Swadling, 2016]. 
Considering the risk of hepatic failure that may be triggered by vaccine-induced immune 
response, this FTIH will be conducted in CHB adult (18-65 years of age) patients at low 

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risk of hepatitis flares, i.e. in those patients under NA therapy since at least 24 months, 
well-controlled (HBV DNA suppressed and alanine transaminase [ALT] normalized 
within the past 24 months) and with no advanced liver fibrosis or cirrhosis of any stage.  
In order to detect any potential safety issue, patients will be closely monitored for safety 
and testing will include liver chemistry and coagulation. 
1.3.1.5. 
Risks linked to the collection of biospecimens in the study 
Biospecimens to be collected in this study are blood samples, buccal swabs and urine 
samples, which are commonly used in clinical diagnosis with generally few procedural 
complications. The volume of blood being taken during the course of the study is not 
expected to compromise patients’ health. It is less than the safe limit in a clinical trial 
recommended by the WHO [Howie, 2011]. Therefore we do not anticipate adverse events 
as a consequence of blood sampling. 
1.3.2. 
Benefit Assessment 
Although vaccination strategy aims to induce an immune response that has been 
suggested to play an important role in the clearance of the HBV virus as evidenced by 
HBsAg loss, the patients receiving the investigational HBV therapeutic vaccines may not 
directly benefit from vaccination as the investigational vaccines have not been assessed 
yet and it is hence not known whether it will be truly effective against chronic HBV 
infection. 
The patient’s participation will benefit other patients in the future since information 
collected during this study will help in the evaluation of HBV therapeutic vaccines and 
other vaccines based on similar technology. 
The vaccines and study tests will be provided free of costs to the patient. 
1.3.3. 
Overall Benefit: Risk Conclusion 
The investigational vaccine regimen aims to achieve functional cure of HBV infection as 
evidenced by HBsAg loss. This trial is a first-time-in-human study: the investigational 
HBV viral vector vaccines and adjuvanted protein vaccines have not been tested in 
human to date so information on vaccine safety and efficacy is not available. Clinical 
data with similar type of technology (ChAd and/or MVA prime-boost) but other 
immunogens (Malaria, Ebola, HCV, HIV) are available and did not raise major safety 
concerns. Clinical data with other AS01B adjuvanted vaccines, including with HBsAg are 
available and did not raise major safety concerns. Immune-mediated liver toxicity cannot 
be ruled out. Measures to minimize risk to patients participating in this study are included 
in the study protocol and holding rules are built in case of safety signals. In addition, the 
study will be followed up by an internal Safety Review Committee (iSRC) including also 
a hepatologist. The potential risks associated with the HBV viral vector and adjuvanted 
proteins vaccines are justified by the potential benefits to patients. 

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2. 
OBJECTIVES 
2.1. 
Primary objective 
• To assess the safety of escalating doses of the HBV viral vector vaccines (prime-
boost) and/or adjuvanted proteins vaccines in patients with chronic HBV infection 
who are virally suppressed on NA therapy.  
Refer to Section 10.1 for the definition of the primary endpoints. 
2.2. 
Secondary objectives 
• To assess the immunogenicity of the HBV viral vector vaccines (prime-boost) and/or 
adjuvanted proteins vaccines in patients with chronic HBV infection who are virally 
suppressed on NA therapy. 
• To assess the efficacy of the HBV viral vector vaccines (prime-boost) and/or 
adjuvanted proteins vaccines in patients with chronic HBV infection who are virally 
suppressed on NA therapy. 
Proof-of-principle (PoP) will be achieved if  
− 
At least
% of patients (i.e. a lower limit of the 80% CI of at least 15%) in one 
vaccine group show at least 10-fold decrease (i.e. 1-log difference) in qHBsAg 
or show HBsAg loss at Day 337 versus Day 1, or  
− 
If there is at least a 10-fold difference in mean HBsAg concentration between a 
vaccine group at Day 337 and the respective control group (i.e. the criterion is to 
observe a point estimate of at least 10-fold decrease between the groups with 
statistical significance, i.e., 80% CI on the ratio not including 1). 
• To assess the long-term safety of escalating doses of the HBV viral vector vaccines 
(prime-boost) and/or adjuvanted proteins vaccines in patients with chronic HBV 
infection who are virally suppressed on NA therapy. 
Refer to Section 10.2 for the definition of the secondary endpoints. 
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3. 
STUDY DESIGN OVERVIEW 
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. Therefore, adherence to the study design requirements, 
including those specified in the outline of study procedures (Section 5.5), are essential 
and required for study conduct. 
During special circumstances (e.g., Coronavirus disease 2019 [COVID-19] pandemic), 
certain study procedures should be adapted to protect patient’s welfare, and as far as 
possible ensure the potential benefit to the patient and promote data integrity (Section 
5.6.18). 
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Figure 1 
Study design 
 
D: Day; N: Total number; NA: Nucleo(s)tides analogues; PoP: Proof-of-principle; S: Screening. 
For information on the dose escalation, refer to Figure 4. 
Refer to Section 5.6.18 for study procedures to be adapted during special circumstances. 
D: Day; N: Approximate number of patients to be enrolled and vaccinated. 
* Step A, B and C will be performed in a staggered manner. Note that prior moving to Step B, safety assessment of at 
least
patients who completed Visit 8 in Step A, may be considered sufficient, if approved by local authorities. 
Please, see Section 8.8.2 for more information. 
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• Experimental design: FTIH, Phase I/II, single-blind, randomized, controlled, multi-
centric, multi-country study with a staggered design. 
• Duration of the study: 
− 
Epoch 001: The Screening Visit will take place approximately 30 days before 
the planned first vaccine administration (Day -29). 
− 
Epoch 002: The primary phase will start on the day of the first vaccine 
administration until 6 months after the last vaccine dose (Day 337). 
− 
Epoch 003: The follow-up phase will start at the end of the primary phase (Day 
337) and will last 18 months (up to Day 841). 
• Primary completion Date (PCD): Visit 22 (Day 337) 
Refer to glossary of terms for the definition of PCD. 
• End of Study (EoS): Last testing results released of samples collected at Visit 26. 
Refer to glossary of terms for the definition of EoS. 

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• Study groups: 
Table 1 
Study groups, treatments and epochs foreseen in the study 
Study 
group 
Study treatment 
Approximate 
Number of 
patients 
Age 
(Min/Max) 
Epoch 
001 
Epoch 
002 
Epoch 
003 
Screening 
phase 
Primary 
phase 
Follow-
up phase 
A1 
D1: ChAd155-hIi-HBV 5x109 vp  
D57: MVA-HBV 2x107 pfu 
D113:HBc-HBs/AS01B-4 20-20 µg 
D169: HBc-HBs/AS01B-4 20-20 µg 
18 years – 
65 years 
● 
● 
● 
A2 
D1: HBc-HBs/AS01B-4 20-20 µg 
D57: HBc-HBs/AS01B-4 20-20 µg 
D113: HBc-HBs/AS01B-4 20-20 µg 
D169: HBc-HBs/AS01B-4 20-20 µg 
18 years – 
65 years 
● 
● 
● 
A3 * 
D1: PBS 
D57: PBS 
D113:PBS 
D169: PBS 
18 years – 
65 years 
● 
● 
● * 
B1 
D1: ChAd155-hIi-HBV 5x1010 vp  
D57: MVA-HBV 2x108 pfu 
D113: HBc-HBs/AS01B-4 80-80 µg 
D169: HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
B2 
D1: HBc-HBs/AS01B-4 80-80 µg 
D57: HBc-HBs/AS01B-4 80-80 µg 
D113: HBc-HBs/AS01B-4 80-80 µg 
D169: HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
B3 
D1: PBS 
D57: PBS 
D113: ChAd155-hIi-HBV 5x1010 vp  
D169: MVA-HBV 2x108 pfu 
18 years – 
65 years 
● 
● 
● 
C1 
D1: ChAd155-hIi-HBV 5x1010 vp & 
HBc-HBs/AS01B-4 80-80 µg 
D57: MVA-HBV 2x108 pfu &  
HBc- HBc-HBs/AS01B-4  80-80 µg 
D113: MVA-HBV 2x108 pfu &  
HBc- HBc-HBs/AS01B-4 80-80 µg  
D169: MVA-HBV 2x108 pfu &  
HBc- HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
C2 
D1: PBS 
D57: PBS 
D113: ChAd155-hIi-HBV 5x1010 vp 
& HBc-HBs/AS01B-4 80-80 µg 
D169: MVA-HBV 2x108 pfu  
& HBc-HBs/AS01B-4 80-80 µg 
18 years – 
65 years 
● 
● 
● 
For information on vaccines administered to each group, please refer to Table 20 and Table 21. 
* Patients of Group A3 will be unblinded at the end of primary phase (Epoch 002) and will be given the option to 
continue in follow-up phase (Epoch 003) in Step A or to participate in Step B or C provided that all eligibility criteria are 
met.  
• Control: 
− 
Safety assessment: Group A3 (placebo control) will be used for Step A. For Step 
B and Step C, Group B3 and C2 data obtained up to Day 113 (placebo control 
up to Day 113) will be used respectively. 
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− 
For PoP efficacy objective: For Step B and Step C, Group B3 and C2 data 
obtained up to Day 113 (placebo control up to Day 113) will be used as placebo 
control, respectively. 
• Vaccination schedules: Heterogeneous prime-boost-boost-boost on Day 1, 57, 113, 
169. 
• Treatment allocation: Following the assessment of eligibility (i.e., after Screening 
conclusion), patients will be randomized using a centralized randomization system on 
internet (SBIR) before the first study vaccine administration. The randomization ratio 
in each step are: Step A: 1:1:1; Step B: 2:1:1; Step C: 2:1. Study products 
administration must take place as soon as possible after randomization.  
• Step-wise approach: The study will be conducted in three consecutive steps as 
described in Figure 2. 
For details on the staggered enrolment on, please see Section 8.8.2. 
• Blinding: 
Table 2 
Blinding of study epochs 
Study Epochs 
Blinding 
Epoch 001 
Not applicable 
Epoch 002 
Single-blind * 
Epoch 003 
Single-blind 
* Patients of Group A3 will be unblinded at the end of primary phase (Epoch 002) and will be given the option to 
continue in follow-up phase (Epoch 003) in Step A or to participate in Step B or C provided that all eligibility criteria are 
met. 
• Sampling schedule: 
− 
Blood samples for serological markers of HBV, HCV, HDV and HIV, and 
autoimmune antibodies will be collected at the Screening Visit. 
− 
Blood samples for hematology and biochemistry will be collected at all time 
points throughout the study, except on Days 3, 31, 87, 143, 199, 253 * and 309 * 
that are not mandatory and can be collected at the discretion of the Investigator 
(see Table 4 and Table 5). In case of abnormal parameters, blood samples may 
be collected at additional unscheduled visits. For more information, see Section 
8.5.3. 
* For patients in Step B and Step C, blood collection is cancelled for Days 253 
and 309. 
− 
Blood samples for markers of hepatic fibrosis (FibroTest) and HCC (AFP) will 
be collected at the Screening Visit and on Day 337, 505 and 841. 
− 
Blood samples for HBsAg, HBV-DNA (and, if deemed necessary, new HBV 
markers) will be collected at the Screening Visit and every month since the 
vaccination during the primary phase and all time points during the follow-up 
phase, except on Days 3 *, 31 *, 87, 143, 199, 253 † and 309 † that are not 
mandatory and can be collected at the discretion of the Investigator. 

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* For patients participating to TH HBV VV-031 HBS:001 study, blood collection 
specific to that study remains mandatory for Days 3 and 31. 
† For patients in Step B and Step C, blood collection is cancelled for Days 253 
and 309. 
− 
Blood samples for humoral response to HBV antigens will be collected on Day 
1, 15, 71, 113, 127, 183, 337, 505 and 841. 
− 
Blood samples for cell-mediated immune response to HBV antigens will be 
collected on Day 1, 15, 57, 64, 71, 113, 127, 169, 183, 337, 505 and 841. 
− 
 
 
 
 
− 
Blood samples for serum repository will be collected on Day 1, 71, 113, 127, 
183, 337, 505 and 841. 
− 
Blood samples in case of a TTS event should be collected within 2 weeks of the 
diagnosis of the TTS for exploratory testing. This blood sample can be collected 
at the next study visit or at an unscheduled visit in case the next study visit is >2 
weeks from the TTS diagnosis. The blood sample collection for TTS event 
reported during the follow-up phase is optional. 
− 
Urine samples for urinalysis will be collected at all time points during the 
primary phase of the study, except on Days 3 *, 31 *, 87, 143, 199, 253 † and 
309 † that are not mandatory and can be collected at the discretion of the 
Investigator.  
* For patients participating in TH HBV VV-031 HBS:001 study, urine collection 
specific to that study remains mandatory for Days 3 and 31. 
† For patients in Step B and Step C, urine collection is cancelled for Days 253 
and 309. 
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• Patient input into study design: Due to the feedback from patients that the number of 
visits may be challenging, the study team is working with countries/sites to provide 
an option where patients may be offered home nursing visits according to local 
regulations. The home nursing providers will go to the patient’s home, decreasing the 
number of times the patient must travel to the research site. Only selected visits will 
have the option to be performed as a home visit, these may include biological samples 
collection, patient’s assessments and data collection. The full specifications of the 
home nursing services will be outlined in the SPM. 
• Type of study: self-contained. 
• Data collection: Electronic Case Report Form (eCRF). 
• Safety monitoring: Internal Safety Review Committee (iSRC). An external expert 
with a clinical expertise in hepatology will work together with the iSRC to review the 
safety data and contribute to the decision-making process to hold or continue the 
study. Refer to Section 8.8 for detailed description of holding rules and safety 
monitoring.  
• 
 
 
 
• Provision for patients in placebo group of Step A (Group A3): Patients randomized in 
the Group A3 that have received placebo in Step A will be informed about the 
treatment assignment after completing their Day 337 visit in Step A and will be given 
the option to continue in the follow-up phase (Epoch 003) in Step A or to participate 
in Step B or Step C.  
• Ancillary study: To evaluate the shedding potential of the replication incompetent 
ChAd155-hIi-HBV vaccine, an ancillary study has been set-up and described in a 
separate study protocol TH HBV VV-031 HBS:001. This ancillary study will be 
performed on a subset of patients recruited in Step B. Biological samples (throat swab 
and urine samples) from these subjects will be collected at Visits 1, 2, 3, 4 and 5. 
4. 
STUDY COHORT 
4.1. 
Number of patients/centers 
This will be a multi-centric, multi-country study. 
The target is to enroll approximately
eligible patients. Refer to Section 10.4 for the 
estimation of the sample size. 
When target enrolment is reached, any additional eligible patient who has provided 
informed consent before the target was reached will be allowed to be enrolled into the 
study. 
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4.2. 
Inclusion criteria for enrolment 
Deviations from inclusion criteria are not allowed because they can potentially jeopardize 
the scientific integrity, regulatory acceptability of the study or patient safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
All patients must satisfy ALL the following criteria at study entry: 
• Patients 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 patient prior to performing any study 
specific procedure.  
• A male or female between, and including, 18 and 65 years of age at the time of the 
first vaccination.  
• Female patients of non-childbearing potential may be enrolled in the study. Non-
childbearing potential is defined as hysterectomy, bilateral ovariectomy or post-
menopause.  
Please, refer to the glossary of terms for the definition of menopause. 
• Female patients of childbearing potential may be enrolled in the study if the patient: 
− 
has practiced adequate contraception for 30 days prior to vaccination, and 
− 
has a negative pregnancy test at Screening, and 
− 
has agreed to continue adequate contraception from Screening until 12 weeks 
after completion of the vaccination series. 
Please refer to the glossary of terms for the definition of adequate contraception. 
• Male patients 
− 
with documented bilateral vasectomy and resultant azoospermia, bilateral 
orchiectomy or azoospermia, or  
− 
who agree to practice abstinence from penile-vaginal intercourse (when this is 
their preferred and usual lifestyle) or use condoms from Screening until 12 
weeks after completion of the vaccination series. 
• CHB patient, under and adherent to treatment with a nucleos(t)ide analogue with high 
barrier to resistance (e.g. ETV, TDF, TAF) given as per approved label/dosage for at 
least 24 months.  
• Documented medical history of HBeAg-negative CHB prior to onset of NA therapy 
(applicable to all patients in Step A and Step B and to some patients in Step C) or 
documented medical history of HBeAg-negative CHB over a period of at least 24 
months prior screening (applicable to some patients in Step C only). 
• Documented HBV viral suppression as per local clinical diagnosis within the 
previous 24 months AND at Screening test HBV DNA < 10 IU/mL. If no results are 
available, two Screening tests need to be performed at least 2 weeks apart. Small 

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fluctuations of HBV DNA (≤ 10 x lower limit of quantification (LLOQ); LLOQ 
defined by laboratory that performed testing) are allowed provided HBV DNA is < 10 
IU/mL at Screening and was clearly not rising during the previous 24 months.  
• Documented normal level of ALT as per local clinical diagnosis within the previous 
24 months AND at Screening test ALT ≤ 48 U/L. Small fluctuations of ALT (≤ 1.5 X 
ULN) are allowed provided ALT ≤ 48 U/L at Screening. If no results are available, 
two Screening tests need to be performed at least 2 weeks apart. ULN are to be 
defined according to local laboratory reference range.  
• No clinical diagnosis of cirrhosis (e.g. F4 by METAVIR scoring system or ≥ 6 by 
Ishak scoring system or FibroScan TE score > 12.5 kPa) within the previous 24 
months.  
• FibroScan TE score < 9.6 kPa and FibroTest score < 0.59 at Screening. A patient with 
one of these parameters out of range, but having the liver biopsy within 12 months 
before screening that showed F0-2 by METAVIR scoring system or stage 0-4 by 
Ishak scoring system, can be included. 
• HBsAg concentration > 50 IU/ml and anti-HBs negative at Screening.  
• Anti-HBc positive at Screening.  
• HBeAg-negative at Screening.  
4.3. 
Exclusion criteria for enrolment 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study or patient safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 
The following criteria should be checked at the time of study entry. If ANY 
exclusion criterion applies, the patient must not be included in the study: 
• Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccines during the period starting 30 days before the first dose of study 
vaccines (Day -29 to Day 1), or planned use during the study period.  
• Any medical condition that in the judgment of the investigator would make 
intramuscular (IM) injection unsafe.  
• Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs (including but not limited to 
IFN) during the period starting six months prior to the first vaccine dose. For 
corticosteroids, this will mean prednisone ≥ 10 mg/day or equivalent. Inhaled and 
topical steroids are allowed. 
• Administration of immunoglobulins and/or any blood products during the period 
starting 3 months before the first dose of study vaccines or planned administration 
during the study period.  
• Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal 
medicines which, in the opinion of the investigator, may have activity against HBV 

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within the previous 6 months prior to randomization into this study. Antiviral 
treatment/prevention for influenza or herpes simplex virus (HSV) is allowed.  
• Administration of adenovirus/adenovector-based or MVA-based vaccine within the 
last 12 months except for adenovirus/adenovector-based COVID-19 vaccines that 
could be administered up to 30 days prior to the first study vaccine dose (applicable 
for all patients except for the patients in France) OR Administration of 
adenovirus/adenovector-based or MVA-based vaccine within the last 12 months 
(applicable for the patients in France only).  
• Planned administration/administration of a vaccine not foreseen by the study protocol 
in the period starting 14 days before each dose and ending 30 days after each dose of 
vaccines, with the exception of influenza vaccine that may be given at any time 
except within a 7-day period before or after each vaccine dose and COVID-19 
vaccine that may be given at any time except within a 30-day period before or after 
each vaccine dose apart from COVID-19 mRNA based-vaccines that may be 
administered any time except for the period of 14 days before and 30 days after each 
study vaccine dose.  
Note: If the type of COVID-19 vaccine is unknown, the allowed interval of 30 days 
before or after each study vaccine dose should be followed. 
• Treatment with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, 
vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine, etc.) or competitors of 
renal excretion (e.g. probenecid) within 2 months prior to Screening or the 
expectation that patient will receive any of these during the course of the study. 
TAF/TDF given as NA therapy is allowed.  
• Concurrently participating in another clinical study, at any time during the study 
period, in which the patient has been or will be exposed to an investigational or a 
non-investigational vaccine/product (pharmaceutical product or device).  
• Medical history of cirrhosis.  
• Medical history of hepatic decompensation (e.g. ascites, spontaneous bacterial 
peritonitis, hepatorenal syndrome, variceal bleeding, or hepatic encephalopathy).  
• Planned for liver transplantation or previous liver transplantation.  
• Personal or family (first degree) history of autoimmune disease.  
• Family history of congenital or hereditary immunodeficiency.  
• History of any reaction or hypersensitivity likely to be exacerbated by any component 
of the vaccines.  
• Evidence of HCV and hepatitis D Virus (HDV) infection. History of acute hepatitis A 
and acute hepatitis E is not an exclusion criterion.  
• Suspicion of or confirmed HCC or any other liver cancer in medical history or at 
Screening: 
• Suspicious foci at liver imaging exam. 
• Elevated α-fetoprotein > 50 ng/ml. 

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• Documented evidence of other currently active cause of hepatitis (e.g. auto-immune 
hepatitis, primary biliary cirrhosis; primary sclerosing cholangitis, hemochromatosis, 
alpha-1 antitrypsin deficiency, Wilson's disease). 
• Hematology and biochemistry parameters outside normal clinical range at Screening: 
Biochemistry: 
− 
Glomerular filtration rate (GFR) < 60 mL/min 
− 
Bilirubin > 27.5 µmol/L unless it is considered as clinically not significant by 
the Investigator or the diagnosis of Gilbert Syndrome has been established and 
confirmed by the Investigator  
− 
GGT > 65 U/L for males or GGT > 45 U/L for females unless it is considered as 
clinically not significant by the Investigator  
− 
ALT > 48 U/L 
− 
AST > 42 U/L unless it is considered as clinically not significant by the 
Investigator  
− 
ALP > 125 U/L unless it is considered as clinically not significant by the 
Investigator  
Hematology: 
− 
Hemoglobin < 12.0 g/dl (for females) or < 13.5 g/dl (for males) unless it is 
considered as clinically not significant by the Investigator  
− 
Red blood cell (RBC) count < 3.9 x 106 cells/mm3 (females) or < 4.4 x 106 
cells/mm3 (males) unless it is considered as clinically not significant by the 
Investigator  
− 
White blood cell count (WBC) < 3,500 cells/mm3 or > 12,000 cells/mm3 unless 
it is considered as clinically not significant by the Investigator  
− 
Platelets < 140,000 cells/mm3 
− 
International Normalized Ratio (INR) > 1.32 (i.e. 1.1 x ULN)  
• Known diabetes Type I.  
• Body Mass Index (BMI) > 35 kg/m² at Screening.  
• Any serious or active medical or psychiatric illnesses other than chronic hepatitis B 
which, in the opinion of the investigator, would interfere with patient treatment, 
assessment or compliance with the protocol. This would include any uncontrolled 
clinically significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, 
metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders 
or cancer.  
• History of or current drug abuse and/or excess of alcohol consumption as defined per 
local guidelines.  
• HIV-positive patient.  
• Pregnant or lactating female.  

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• Female planning to become pregnant or planning to discontinue contraceptive 
precautions in the period starting from the Screening Visit up to 12 weeks post-last 
vaccination visit. 
• Fever and or acute minor illness (such as mild diarrhea, mild upper respiratory 
infection) may, be enrolled for Screening at the discretion of the investigator, 
provided that the condition is resolved at the time of vaccination.  
5. 
CONDUCT OF THE STUDY 
5.1. 
Regulatory and ethical considerations, including the 
informed consent process 
The study will be conducted in accordance with all applicable regulatory requirements. 
The study will be conducted in accordance with the ICH Guideline for GCP, all 
applicable patient privacy requirements and the guiding principles of the Declaration of 
Helsinki.  
GSK will obtain favourable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country. 
Conduct of the study includes, but is not limited to, the following: 
• Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments. 
• Patient informed consent. 
• Investigator reporting requirements as stated in the protocol. 
GSK will provide full details of the above procedures to the investigator, either verbally, 
in writing, or both. 
Freely given and written or witnessed/ thumb printed informed consent must be obtained 
from each patient prior to participation in the study.  
GSK Biologicals will prepare a model Informed Consent Form (ICF) which will embody 
the ICH GCP and GSK Biologicals required elements. While it is strongly recommended 
that this model ICF is to be followed as closely as possible, the informed consent 
requirements given in this document are not intended to pre-empt any local regulations 
which require additional information to be disclosed for informed consent to be legally 
effective. Clinical judgement, local regulations and requirements should guide the final 
structure and content of the local version of the ICF.  
The investigator has the final responsibility for the final presentation of the ICF, 
respecting the mandatory requirements of local regulations. The ICF generated by the 
investigator with the assistance of the sponsor’s representative must be acceptable to 
GSK Biologicals and be approved (along with the protocol, and any other necessary 
documentation) by the IRB/IEC. 

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5.2. 
Patient identification and randomization 
5.2.1. 
Patient identification 
Patient identification numbers (PIDs) will be assigned sequentially to the patients who 
have consented to participate in the study, according to the range of PIDs allocated to 
each study center. 
5.2.2. 
Randomization of treatment 
Allocation ratio: 
Step A: 1:1:1; Step B: 2:1:1; Step C: 2:1 
Over-randomization: 
 
No 
 
X Yes, description: At least 20% over-randomization 
 
Subset: 
X No 
 
 
 
Yes, description: 
 
SBIR: 
 
No 
 
X Yes: HBsAg concentration at Screening will be used as a 
minimization factor (<1000 IU/ml and ≥ 1000 IU/ml) for 
Step B and Step C randomization except for the patients 
needed for the first iSRC review in Step C. 
 
Replacement randomized: X No 
 
 
Yes 
 
5.2.2.1. 
Treatment allocation to the patient 
The treatment numbers will be allocated by component. 
5.2.2.1.1. Study group and treatment number allocation 
The target will be to enrol approximately 
eligible patients, with possible 20% over-
randomization. Randomization will be performed within each sequential step with the 
following randomization ratio: Step A: 1:1:1; Step B: 2:1:1; Step C: 2:1 (See Section 3 
for more information on the groups). 
Allocation of the patient to a study group at the investigator site will be performed using 
a randomization system on internet (SBIR). The randomization algorithm will use a 
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minimization procedure [White, 1978] accounting for HBsAg concentration 
(<1000 IU/ml and ≥ 1000 IU/ml) measured at Screening. The minimization procedure 
will be applied for patients enrolled in the steps B and C except for the patients needed 
for the first iSRC review in Step C to ensure to have not more than
patients in a 
treatment group as required for the iSRC evaluations. 
After obtaining the signed and dated ICF from the patient and having Investigator 
checked the eligibility of the patient after screening procedures have been all completed, 
the site staff in charge of the vaccine administration will access SBIR. Upon receiving the 
patient identification number and HBsAg concentration, the randomization system will 
determine the study group and will provide the treatment number to be used for the first 
dose.  
The first dose of the study vaccine can be administered only after the eligibility has been 
confirmed at Visit 1 (Please refer to Section 5.6.2). The number of each administered 
treatment must be recorded in the eCRF on the Vaccine Administration screen.  
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions. 
5.2.2.1.2. Treatment number allocation for subsequent doses  
For each dose subsequent to the first dose, the study staff in charge of the vaccine 
administration will access SBIR, provide the patient identification number, and the 
system will provide a treatment number consistent with the allocated study group. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
5.3. 
Method of blinding  
For this FTIH study, single-blinding will be used because there is a difference in the 
volume to be administered to patients in the different groups (0.1 ml or 0.5 ml) of Step A 
and because the products are to be stored at different temperature. 
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the patient and study (without any link to the treatment 
attributed to the patient) to each sample. 
5.3.1. 
Emergency unblinding  
Unblinding a participant’s individual intervention number should occur ONLY in case of 
a medical emergency when knowledge of the intervention is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention via SBIR, 
an automated Internet-based system. 
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As back up process, the investigator has the option of contacting a GSK Biologicals’ 
Helpdesk (refer to the Table 3) if he/she needs help performing the unblinding (i.e. he/she 
cannot access the automated Internet-based system). 
A non-investigator physician (e.g. physician from emergency room) or participant/care 
giver/family member may also request emergency unblinding either via the investigator 
(preferred option) or via the GSK Biologicals’ Helpdesk (back up process).  
Where applicable, the patient/participant card lists contact information for both the 
investigator and GSK Biologicals’ Helpdesk. 
Table 3 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Phone (for countries where the toll-free number is not available): +32 2 656 68 04 
Country 
Toll-free number 
Belgium, France, Germany, Spain, Taiwan 
00 800 4344 1111 
Hongkong 
006 800 4344 1111 
Thailand 
001 800 4344 1111 
United Kingdom 
0800 056 7221 
Fax: +32 2 401 25 75 
E-mail: rix.ugrdehelpdesk@gsk.com 
5.4. 
General study aspects 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the patients. 
The burden of the study for the subject will be minimised as much as possible. For taking 
blood samples, three attempts at most should be performed. If the physician is not 
successful after the third attempt, he/she will make no further attempts. A local numbing 
cream or patch will also be offered at the discretion of the investigator prior to blood 
sampling, in order to minimise pain when blood samples are drawn. 
Patients enrolled in this study will remain under NA therapy throughout the study. 
However, if a patient has experienced a drug-induced toxicity, the NA drug may be 
switched to another NA drug at the discretion of the Investigator.  
For information on the holding rules applicable to this study, refer to Section 8.8.3. For 
information on safety evaluation by the iSRC, refer to Section 8.8.1. 

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5.5. 
Outline of study procedures (Amended: 22 June 2023) 
For a detailed list of study procedures to be performed for all steps (A, B and C) during 
the primary phase and the follow-up phase, refer to Table 4 (Screening to Visit 17) and 
Table 5 (Visit 18 to Visit 26 and unscheduled visits). Intervals authorized between study 
visits are provided in Table 6. 
For study procedures to be adapted during special circumstances, refer to Section 5.6.18. 
 

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Table 4 
List of study procedures: Screening and primary phase (Screening Visit to Visit 17) (Amended: 22 June 2023) 
Epoch 
Epoch 001 
Epoch 002  
Study Phase 
Screening 
Primary Phase 
Type of contact 
Screening 
Visit t 
Visit 1 
 
Visit 2 
q, s 
Visit 3 
s 
Visit 4 
s 
Visit 5 
q, s 
Visit 6 
^ 
Visit 7 
s 
Visit 
8 s 
Visit  
9 q, s 
Visit 
10 ^ 
Visit 
11 s 
Visit 
12 s 
Visit 
13 q, s 
Visit 
14 ^ 
Visit 
15 s 
Visit 
16 s 
Visit 
17 q, s 
Time points 
Day -29  Day 1 Day 3  Day 8  Day 15 Day 31 Day 57 Day 
64  
Day 
71  
Day 
87  
Day 
113  
Day 
120  
Day 
127  
Day 
143  
Day 
169  
Day 
176  
Day 
183  
Day 
199  
Sampling time point(s) 
Screening Pre 
Post-Vacc 1 
Post-Vacc 2 
Post-Vacc 3 
Post-Vacc 4 
Informed consent  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check inclusion/exclusion criteria  
● 
O 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect demographic data  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure/record height and weight  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B history  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead electrocardiogram n  
● 
● 
 
 
 
 
● n 
 
 
 
● n 
 
 
 
● n 
 
 
 
Liver ultrasound j 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Transient elastography (FibroScan)  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination/vital signs m;  n  
● 
● 
O 
O 
O 
O 
● n 
O 
O 
O 
● n 
O 
O 
O 
● n 
O 
O 
O 
Urine pregnancy test a, n  
● 
● 
 
 
 
 
● n 
 
 
 
● n 
 
 
 
● n 
 
 
 
Screening conclusion  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
eCRF investigator’s signature  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biospecimen sampling 
 
Blood sampling for biochemistry (~3.5 ml) b,g,k  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for biochemistry (AFP) (~3.5 
ml) k  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for FibroTest (~8.5 ml) k 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for hematological tests/CBC 
(~2.0 ml) c, g,  
●  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for hematological tests/INR 
(~4.5 ml) c,g 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for autoimmune antibodies 
(~13.5 ml)  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for HBV, HCV, HDV and HIV 
serology (~18.5 ml) 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for qHBsAg (~3.5 ml) 
● 
● 
 
 
 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
● 

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204852 (TH HBV VV-001) 
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Epoch 
Epoch 001 
Epoch 002  
Study Phase 
Screening 
Primary Phase 
Type of contact 
Screening 
Visit t 
Visit 1 
 
Visit 2 
q, s 
Visit 3 
s 
Visit 4 
s 
Visit 5 
q, s 
Visit 6 
^ 
Visit 7 
s 
Visit 
8 s 
Visit  
9 q, s 
Visit 
10 ^ 
Visit 
11 s 
Visit 
12 s 
Visit 
13 q, s 
Visit 
14 ^ 
Visit 
15 s 
Visit 
16 s 
Visit 
17 q, s 
Time points 
Day -29  Day 1 Day 3  Day 8  Day 15 Day 31 Day 57 Day 
64  
Day 
71  
Day 
87  
Day 
113  
Day 
120  
Day 
127  
Day 
143  
Day 
169  
Day 
176  
Day 
183  
Day 
199  
Sampling time point(s) 
Screening Pre 
Post-Vacc 1 
Post-Vacc 2 
Post-Vacc 3 
Post-Vacc 4 
Blood sampling for HBV-DNA and new viral 
markers (~10 ml) 
● 
 
 
 
 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
● 
Blood sampling for CMI response (~20 ml) d  
 
● 
 
 
● 
 
● 
● 
● 
 
● 
 
● 
 
● 
 
● 
 
Blood sampling for humoral response to HBV 
antigens (~3.5 ml) e 
 
● 
 
 
● 
 
 
 
● 
 
● 
 
● 
 
 
 
● 
 
Blood sampling for serum repository (~3.5 ml)  
 
● 
 
 
 
 
 
 
● 
 
● 
 
● 
 
 
 
● 
 
Urine sampling for urine chemistry (dipstick) f 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Vaccines 
Study group randomization r  
O r 
O r 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment number allocation n  
 
O 
 
 
 
 
O n 
 
 
 
O n 
 
 
 
O n 
 
 
 
Pre-vaccination body temperature n  
 
● 
 
 
 
 
● n 
 
 
 
● n 
 
 
 
● n 
 
 
 
Check contraindications to vaccination n 
 
O 
 
 
 
 
O n 
 
 
 
O n 
 
 
 
O n 
 
 
 
Vaccine administration n  
 
● 
 
 
 
 
● n 
 
 
 
● n 
 
 
 
● n 
 
 
 
Recording of administered treatment number n 
 
● 
 
 
 
 
● n 
 
 
 
● n 
 
 
 
● n 
 
 
 
Safety assessment 
Recording of concomitant 
medications/vaccinations h 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record intercurrent medical conditions leading 
to elimination from per-protocol i 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Distribution of diary cards n  
 
O 
 
 
 
 
O n 
 
 
 
O n 
 
 
 
O n 
 
 
 
Return of diary cards  
 
 
O 
O 
 
 
 
O 
 
 
 
O 
 
 
 
O 
 
 
Diary card transcription by investigator (or 
delegate)  
 
 
● 
● 
 
 
 
● 
 
 
 
● 
 
 
 
● 
 
 
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Epoch 
Epoch 001 
Epoch 002  
Study Phase 
Screening 
Primary Phase 
Type of contact 
Screening 
Visit t 
Visit 1 
 
Visit 2 
q, s 
Visit 3 
s 
Visit 4 
s 
Visit 5 
q, s 
Visit 6 
^ 
Visit 7 
s 
Visit 
8 s 
Visit  
9 q, s 
Visit 
10 ^ 
Visit 
11 s 
Visit 
12 s 
Visit 
13 q, s 
Visit 
14 ^ 
Visit 
15 s 
Visit 
16 s 
Visit 
17 q, s 
Time points 
Day -29  Day 1 Day 3  Day 8  Day 15 Day 31 Day 57 Day 
64  
Day 
71  
Day 
87  
Day 
113  
Day 
120  
Day 
127  
Day 
143  
Day 
169  
Day 
176  
Day 
183  
Day 
199  
Sampling time point(s) 
Screening Pre 
Post-Vacc 1 
Post-Vacc 2 
Post-Vacc 3 
Post-Vacc 4 
Recording of solicited AEs (Days 1–7 post-
vaccination) self-reported by the patient n  
 
● 
● 
●  
 
 
● n 
●  
 
 
● n 
●  
 
 
● n 
●  
 
 
Recording of unsolicited AEs within 30 days 
post-vaccination (Day 1-30) n, o  
 
● 
● 
● 
● 
● 
● n 
● 
● 
● o 
● 
● 
● o 
● o 
● 
● 
● 
● o  
Recording of SAEs  
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of MAEs  
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of AESIs v  
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of AEs/SAEs leading to study 
withdrawal  
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of pregnancy and pregnancy 
outcome  
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
AE: Adverse events; AESI: Adverse event of special interest; AFP: alpha-fetoprotein; CBC: complete blood count; CMI: cell-mediated immunity; DNA: Deoxyribonucleic acid; eCRF: 
electronic Case Report Form GSK: GlaxoSmithKline; HBV: hepatitis B virus; HCV: hepatitis C virus; HDV: hepatitis D virus; HIV: human immunodeficiency virus; HLA: human leukocyte 
antigen; hIi: human invariant chain; INR: international normalized ratio; MAE: medically attended event; ml: milliliter; pIMDs: potential immune-mediated diseases; qHBsAg: quantitative 
hepatitis B surface antigen; SAE: serious adverse event; Vacc: vaccination. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
^ If subsequent vaccination cannot be administered within an interval of 53 - 63 days due to special circumstances or any other reasons, please refer to Section 5.6.18.  
Refer to Section 5.6.18 for study procedures to be adapted during special circumstances.  
a Women of childbearing potential are to have a pregnancy test prior to study vaccination (either a blood or urine test, depending on local clinical requirement). For women of non-
childbearing potential, the specific reason for not performing a pregnancy test needs to be documented in the eCRF (current tubal ligation, hysterectomy, ovariectomy, post-menopause 
or other). 
b For biochemical tests to be performed, please refer to Table 10 and Table 15. 
c For information about hematological tests to be performed, please refer to Table 10 and Table 15. 
d Blood sampling for CMI response will be collected from patients in centres with access to the PBMC processing facilities. For information about CMI response assays to be 
performed, please refer to Table 13 and Table 19.  
e For information about humoral response assays to be performed, please refer to Table 12 and Table 18 

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204852 (TH HBV VV-001) 
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f For information about urinalysis tests to be performed, please refer to Table 10 and Table 15.  
Routine urinalysis is done by dipstick. A microscopic examination and albumin to creatinine ratio (ACR) should be done (locally) if there is blood or protein reported from 
urine dipstick. If urine albumin and/or creatinine values are <LLOQ due to which the ACR cannot be calculated, it should be documented in the eCRF. 
g Additional blood sampling for biochemical/hematological testing may need to be performed in case of abnormal lab parameters. For more information, please refer to Section 8.5.3. 
h For more information please refer to Section 6.7. 
i For more information, please refer to Section 6.8. 
j If liver ultrasound is not possible, alternative liver imaging examination (e.g. magnetic resonance or computerized tomography) may be performed at the discretion on the investigator. 
If it is not possible to perform a liver ultrasound at screening, a routine ultrasound performed within 180 days prior to the vaccination visit 1, can be used for eligibility assessment. For 
Germany, please see the country-specific requirements in Section 12. 
k Blood samples for creatinine, FibroTest and Liver kidney microsomal type 1 (LKM-1) autoantibody tests should be collected after a minimum 8 hour fast. 
l 
 
. 
m At Screening, a physical examination should be performed based on the clinical history of the patient. Physical examination at each subsequent study visit will be performed only if 
the patient indicates during questioning and test result review that there might be some underlying pathology(ies) or if deemed necessary by the Investigator or delegate. At Screening 
and at each vaccination, vital signs (including systolic/diastolic blood pressure, heart rate and respiratory rate after at least 10 minutes of rest) should be collected. Collected 
information needs to be recorded in the eCRF. 
n Procedure not applicable if vaccination could not be administered at that vaccination visit.  
o Procedure not applicable if vaccination was not administered at preceding vaccination visit.  
q The minimum requirements at Visits 2, 5, 9, 13 and 17 are safety assessment including, but not limited to, recording of solicited symptoms, unsolicited AEs within 30 days post-
vaccination, SAEs, MAEs, AESIs, SAEs related to study participation, or to a concurrent GSK medication/vaccine, AEs/SAEs leading to study withdrawal, pregnancy and pregnancy 
outcome, intercurrent medical conditions leading to elimination from per-protocol analyses and concomitant medications/vaccinations. The collection of data for safety assessment can 
be performed remotely (e.g. via phone contact). Other study procedures including biological samples collection and physical examination are optional at the discretion of the 
Investigator. However, efforts should be made for the patients needed for the first iSRC review in Step C to perform Visit 2 at the site to allow collection of biological samples for safety 
evaluation by iSRC. For patients participating to TH HBV VV-031 HBS:001 study, biological samples collection specific to that study remains mandatory for Visits 2 and 5. 
r The randomization is performed after screening and prior Visit 1. All eligibility criteria should be confirmed before vaccination at Day 1 visit (i.e. Visit 1).  
s In the sites/countries where a home nursing is possible according to local regulations, the patients may be offered the option to have a home visit. Only selected visits will have the 
option to be performed as a home visit, these may include biological samples collection, patients’ assessments and data collection. The full specifications of the home nursing services 
will be outlined in the SPM. 
t The screening window is extended from 90 days to 180 days except for CBC, INR, liver chemistry and HBV-DNA for which testing should be repeated if the interval between blood 
sampling at screening visit and the first dose vaccination at Visit 1 exceeds 90 days. 
v In case of a TTS event, an additional blood sample should be collected within 2 weeks of the diagnosis of the TTS for exploratory testing. This blood sample can be collected at the 
next study visit or at an unscheduled visit in case the next study visit is >2 weeks from the TTS diagnosis. For more information, please refer to Section 5.7.2. 
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*
 
).  
Table 5 
List of study procedures: primary phase (Visit 18 to Visit 22), follow-up phase (Visit 23 to Visit 26) and 
unscheduled visits (Amended: 22 June 2023) 
Epoch 
Epoch 002 
Epoch 003 
 
Study Phase 
Primary Phase 
Follow-up Phase 
 
Type of contact 
Visit 18 m Visit 19 l, m Visit 20 m Visit 21 l, m Visit 22 
m 
Visit 23 m Visit 24 m Visit 25 m Visit 26 m Unscheduled 
visit  
Time points 
Day 225  Day 253  Day 281  
Day 309  Day 337 Day 421  Day 505  Day 673  Day 841  
 
Sampling time point(s) 
Post-Vacc 4 
 
Physical examination  
O 
O 
O 
O 
O 
O 
O 
O 
O 
O 
Liver ultrasound j, k 
 
 
 
 
● 
 
● 
 
● 
 
Transient elastography (FibroScan) k 
 
 
 
 
● 
 
● 
 
● 
 
Biospecimen sampling 
 
 
Blood sampling for biochemistry (~3.5 ml) a, h,i 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for biochemistry (AFP) (~3.5 ml) i 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for FibroTest (~8.5 ml) i 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for hematological tests/CBC (~2.0 ml) b, h 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for hematological tests/INR (~4.5 ml) b,h 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for qHBsAg (~3.5 ml)  
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
Blood sampling for HBV-DNA n and new viral markers (~10 ml)  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● n 
Blood sampling for CMI response (~20 ml) c 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for humoral response to HBV antigens (~3.5 
ml) d 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for serum repository (~3.5 ml)  
 
 
 
 
● 
 
● 
 
● 
 
Urine sampling for urine chemistry (dipstick) e 
● 
● 
● 
● 
● 
 
 
 
 
 
Safety assessments 
 
 
Recording of concomitant medications/vaccinations f 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Record intercurrent medical conditions leading to elimination 
from per-protocol g 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of SAEs  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of MAEs  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of AESIso  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
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Epoch 
Epoch 002 
Epoch 003 
 
Study Phase 
Primary Phase 
Follow-up Phase 
 
Type of contact 
Visit 18 m Visit 19 l, m Visit 20 m Visit 21 l, m Visit 22 
m 
Visit 23 m Visit 24 m Visit 25 m Visit 26 m Unscheduled 
visit  
Time points 
Day 225  Day 253  Day 281  
Day 309  Day 337 Day 421  Day 505  Day 673  Day 841  
 
Sampling time point(s) 
Post-Vacc 4 
 
Recording of SAEs related to study participation, or to a 
concurrent GSK medication/vaccine  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of AEs/SAEs leading to study withdrawal  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of pregnancy and pregnancy outcome  
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Conclusion 
 
 
eCRF investigator’s signature  
 
 
 
 
● 
 
 
 
● 
 
Primary phase conclusion  
 
 
 
 
● 
 
 
 
 
 
Study Conclusion 
 
 
 
 
 
 
 
 
● 
 
AE: Adverse events; AESI: Adverse event of special interest; AFP: alpha-fetoprotein; CBC: complete blood count; CMI: cell-mediated immunity; DNA: Deoxyribonucleic acid; eCRF: 
electronic Case Report Form; GSK: GlaxoSmithKline; HBV: hepatitis B virus; INR: international normalized ratio; MAE: medically attended event; ml: milliliter; pIMDs: potential immune-
mediated diseases; qHBsAg: quantitative hepatitis B surface antigen; SAE: serious adverse event; Vacc: vaccination. 
Note: The double-line border following Visit 22 indicates the analyses which will be performed on all data (i.e. data that are as clean as possible) obtained up to Visit 22. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Refer to Section 5.6.18 for study procedures to be adapted during special circumstances. 
a For information about biochemical and biomarkers tests to be performed, please refer to Table 10 and Table 15. For information about virological tests to be performed, please refer 
to Table 11. 
b For information about hematological tests to be performed, please refer to Table 10 and Table 15. 
c For information about CMI response assays to be performed, please refer to Table 13 and Table 19. 
d For information about humoral response assays to be performed, please refer to Table 12 and Table 18. 
e For information about urinalysis tests to be performed, please refer to Table 10 and Table 15. Routine urinalysis is done by dipstick. A microscopic examination and albumin to 
creatinine ratio (ACR) should be done (locally) if there is blood or protein reported from urine dipstick. If urine albumin and/or creatinine values are <LLOQ due to which 
the ACR cannot be calculated, it should be documented in the eCRF. 
f For detailed information, please refer to Section 6.7. 
g For detailed information, please refer to Section 6.8. 
h Additional blood sampling for biochemical/hematological testing may need to be performed in case of abnormal lab parameters. For more information, please refer to Section 8.5.3. 
i Blood samples for creatinine and FibroTest tests should be collected after a minimum 8 hour fast.  
j If liver ultrasound is not possible, alternative liver imaging examination (e.g. magnetic resonance or computerized tomography) may be performed at the discretion on the investigator. 
If it is not possible to perform a liver ultrasound at screening, a routine ultrasound performed within 180 days prior to the vaccination visit 1, can be used for eligibility assessment. For 
Germany, please see the country-specific requirements in Section 12. 
k If procedure has not been performed at the respective timepoints, it should be done at earliest convenience.  

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l For patients in Step A: the minimum requirements of Visits 19 and 21 are safety assessment including recording of solicited symptoms, unsolicited AEs within 30 days post-
vaccination, SAEs, MAEs, AESIs, SAEs related to study participation, or to a concurrent GSK medication/vaccine, AEs/SAEs leading to study withdrawal, pregnancy and pregnancy 
outcome, intercurrent medical conditions leading to elimination from per-protocol analyses and concomitant medications/vaccinations. The safety assessment can be performed via 
telephone contact. Other study procedures including biological samples collection and physical examination are optional at the discretion of the Investigator. For patients in Step B and 
Step C, Visits 19 and 21 are cancelled. 
m In the sites/countries where a home nursing is possible according to local regulations, the patients may be offered the option to have a home visit. Only selected visits will have the 
option to be performed as a home visit, these may include biological samples collection, patients’ assessments and data collection. The full specifications of the home nursing services 
will be outlined in the SPM. 
n Procedure to be performed in addition to the other procedures only if Unscheduled visit is planned in order to check for contraindication to the subsequent vaccination in case no 
biological samples have been collected since the previous vaccination visit due to special circumstances. Please refer to Section 5.6.18. 
o In case of a TTS event, collection of an additional blood sample within 2 weeks of the diagnosis of the TTS for exploratory testing is optional. This blood sample can be collected at 
the next study visit or at an unscheduled visit in case the next study visit is >2 weeks from the TTS diagnosis. For more information, please refer to Section 5.7.2. 

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Whenever possible, the investigator should arrange study visits within the interval 
described in Table 6. 
Table 6 
Intervals between study visits 
Interval 
Optimal length of interval a 
Allowed interval c 
Screening Phase 
 
 
Screening Visit (Day -29) → Visit 1 (Day 1) 
30 days  
15 – 180 days e  
Primary Phase 
 
 
Visit 1 (Day 1) → Visit 2 (Day 3) 
2 days  
1 - 3 days  
Visit 1 (Day 1) → Visit 3 (Day 8) 
7 days  
7 - 9 days  
Visit 1 (Day 1) → Visit 4 (Day 15) 
14 days  
12 - 18 days  
Visit 1 (Day 1) → Visit 5 (Day 31) 
30 days  
30 - 42 days  
Visit 1 (Day 1) → Visit 6 (Day 57) 
56 days  
53 - 63 days b, c, d 
Visit 6 (Day 57) → Visit 7 (Day 64) 
7 days  
7 - 9 days  
Visit 6 (Day 57) → Visit 8 (Day 71) 
14 days  
12 - 18 days 
Visit 6 (Day 57) → Visit 9 (Day 87) 
30 days  
30 - 42 days  
Visit 6 (Day 57) → Visit 10 (Day 113) 
56 days  
53 - 63 days b, c, d 
Visit 10 (Day 113) → Visit 11 (Day 120) 
7 days  
7 - 9 days  
Visit 10 (Day 113) → Visit 12 (Day 127) 
14 days  
12 - 18 days  
Visit 10 (Day 113) → Visit 13 (Day 143) 
30 days  
30 - 42 days  
Visit 10 (Day 113) → Visit 14 (Day 169) 
56 days  
53 - 63 days b, c, d 
Visit 14 (Day 169) → Visit 15 (Day 176) 
7 days  
7 - 9 days  
Visit 14 (Day 169) → Visit 16 (Day 183) 
14 days  
12 - 18 days  
Visit 14 (Day 169) → Visit 17 (Day 199) 
30 days  
30 - 42 days  
Visit 14 (Day 169) → Visit 18 (Day 225) 
56 days  
56 - 60 days  
Visit 14 (Day 169) → Visit 19 (Day 253) 
84 days  
77 - 90 days  
Visit 14 (Day 169) → Visit 20 (Day 281) 
112 days  
105 - 118 days  
Visit 14 (Day 169) → Visit 21 (Day 309) 
140 days  
133 - 146 days  
Visit 14 (Day 169) → Visit 22 (Day 337) 
168 days  
147 - 188 days  
Follow-up Phase 
 
 
Visit 14 (Day 169) → Visit 23 (Day 421) 
252 days (36 weeks)  
232 - 270 days 
Visit 14 (Day 169) → Visit 24 (Day 505) 
336 days (48 weeks) 
312 - 360 days  
Visit 14 (Day 169) → Visit 25 (Day 673) 
504 days (72 weeks) 
468 - 540 days  
Visit 14 (Day 169) → Visit 26 (Day 841) 
672 days (96 weeks) 
620 - 720 days  
a. Whenever possible the investigator should arrange study visits within this interval. 
b. In case abnormal biochemistry or hematology parameter(s) are detected but do not fulfil the contraindication for 
subsequent vaccination, the interval can be extended to 84 days. 
c  In case of special circumstances, this interval between two subsequent doses can be extended up to 84 days. 
d For all subjects: If a subject did not receive a study dose within allowed interval from administration of the previous 
vaccine dose, study vaccination should continue provided that maximum interval of 111 days between doses is 
respected (Please refer to section 5.6.18 and section 9.2.2). 
e The screening window is extended from 90 days to 180 days except for CBC, INR, liver chemistry and HBV-DNA for 
which testing should be repeated if the interval between blood sampling at screening visit and the first dose vaccination 
at Visit 1 exceeds 90 days.  
5.6. 
Detailed description of study procedures 
5.6.1. 
Informed consent 
The signed informed consent of the patient must be obtained before study participation. 
Refer to Section 5.1 for the requirements on how to obtain informed consent. 

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5.6.2. 
Check inclusion and exclusion criteria 
Check all inclusion and exclusion criteria as described in Sections 4.2 and 4.3 at 
enrolment. 
Eligibility criteria (Please refer to Sections 4.2 and 4.3) must be carefully assessed at the 
Screening visit and at the Visit 1. 
Medical and medication history will be assessed as related to the inclusion/exclusion 
criteria listed in Sections 4.2 and 4.3. 
At Screening, if a patient has hematological/biochemical parameters out of normal range 
which are expected to be temporary, a re-Screening visit may be scheduled during which 
blood sample collection for hematology/biochemistry will be repeated. Other screening 
procedures may be repeated if the investigator believes there is a reason to do so.  
Eligible patients who fall out of the 180-day Screening window, a re-Screening should be 
performed to confirm eligibility, except for CBC, INR, liver chemistry and HBV-DNA 
for which testing should be repeated if the interval between blood sampling at screening 
visit and the first dose vaccination at Visit 1 exceeds 90 days. 
Patients who failed to meet eligibility criteria under previous versions of the protocol 
may be re-screened to enter the study.  
Upon completion of all Screening procedures (refer to Table 4), the investigator will 
review the inclusion/exclusion criteria for each patient. Patients meeting all eligibility 
criteria will be randomized in the study. Their Screening information will be recorded on 
the appropriate screen of eCRF. 
5.6.3. 
Collect demographic data 
Record demographic data such as year of birth, sex, race and ethnicity in the patient’s 
eCRF. 
5.6.4. 
Medical history 
Obtain the patient’s medical history by interview and/or review of the patient’s medical 
records and record any pre-existing conditions or signs and/or symptoms present in a 
patient prior to the first study vaccination in the eCRF. 
5.6.5. 
HBV disease history 
• 
The following details on HBV disease history will be collected and recorded in the 
eCRF. 
• Year of HBV detection, 
• Suspected mode of infection (parenteral, perinatal, sexual, unknown), 
• Previous history of acute Hepatitis B (Yes/ No/ Unknown. If yes, precise year), 

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• Previous clinical monitoring of Hepatitis B, if available,  
HBV DNA (concentration and date), 
ALT (serum ALT level and date), 
Liver fibrosis staging (method, date, result), 
• Previous treatment of chronic Hepatitis B other than ETV, TDF or TAF (Yes/ No/ 
Unknown. If yes, drug name, route, start and end dates), 
• History and ongoing treatment with high barrier to resistance NAs, e.g. ETV, TDF or 
TAF (drug name, route, start date and end date, if applicable), 
• Genotype, if available. 
5.6.6. 
Measure/record height and weight 
Measure patient’s height and weight and record in the patient’s eCRF. 
5.6.7. 
Physical examination 
At Screening, perform a targeted physical examination based on the clinical history of the 
patient. Physical examination at each subsequent study visit will be performed only if the 
patient indicates during questioning and test result review that there might be some 
underlying pathology(ies) or if deemed necessary by the Investigator or delegate. 
Collected information needs to be recorded in the eCRF. 
At Screening and at each vaccination, vital signs (including systolic/diastolic blood 
pressure, heart rate and respiratory rate after at least 10 minutes of rest) will be collected 
and 12-lead electrocardiogram (ECG) will be performed. Collected information needs to 
be recorded in the eCRF. 
Routine clinical management of chronic HBV infection and if deemed necessary, a 
further targeted workup will be performed according to local medical practice. 
Liver ultrasound and transient elastography (FibroScan) will be performed according to 
local medical practice. Collected information will be recorded in the eCRF. If liver 
ultrasound is not possible, alternative liver imaging examination (e.g. magnetic resonance 
or computerized tomography) may be performed at the discretion on the investigator. If it 
is not possible to perform a liver ultrasound at screening, a routine ultrasound performed 
within 180 days prior to the vaccination visit 1, can be used for eligibility assessment. For 
Germany, please see the country-specific requirements in Section 12. 
Treatment of any abnormality observed during physical examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider.  

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5.6.8. 
Pregnancy test 
Female patients of childbearing potential are to have a urine pregnancy test or a serum 
human chorionic gonadotrophin (hCG) test at Screening and prior to any study vaccine 
administration. The study vaccines may only be administered if the pregnancy test is 
negative.  
Note: Pregnancy test must be performed even if the patient is menstruating at the time of 
the study visit. 
5.6.9. 
Check contraindications to vaccination 
Contraindications to vaccination must be checked at the beginning of each vaccination 
visit. Refer to Section 6.6 for more details. 
5.6.10. 
Assess pre-vaccination body temperature 
The oral body temperature of each patient needs to be measured prior to any study 
vaccine administration. If the patient has fever (fever is defined as temperature 
≥38.0°C/100.4°F) on the day of vaccination, the vaccination visit will be rescheduled 
within the allowed interval for this visit (see Table 6).  
5.6.11. 
Study group and treatment number allocation 
Study group and treatment number allocation will be performed as described in Section 
5.2.2. The number of each administered treatment must be recorded in the eCRF. 
5.6.12. 
Biospecimen sampling 
During the study, blood sampling will be performed on all patients, regardless of the 
study groups, for: 
• Biochemistry (ALT, AST, ALP, GGT, Bilirubin and Creatinine): ~3.5 ml  
• Biochemistry (AFP): ~3.5 ml, 
• Biochemistry (FibroTest): ~8.5 ml, 
• Complete blood count: ~2.0 ml, 
• INR: ~4.5 ml, 
• Autoimmune antibodies: ~13.5 ml, 
• Viral serology (HBV, HCV, HDV and HIV): ~18.5 ml, 
• qHBsAg: ~3.5 ml, 
• HBV-DNA and new viral markers: ~10.0 ml, 
• CMI response (only in patients from sites with access to PBMC processing facilities): 
~20.0 ml, 

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• humoral response to HBV antigens: ~3.5 ml, 
• 
 
• Serum repository: ~3.5 ml. 
Blood samples for creatinine, FibroTest and Liver kidney microsomal type 1 (LKM-1) 
autoantibody tests should be collected after a minimum 8 hour fast.  
A maximum volume of blood to be drawn during the 2.5 year study period (from 
Screening to Day 841) from each patient from centres with access to PBMC processing 
facilities is approximately 883.5 mL and from each patient from centres with no access to 
PBMC processing facilities is approximately 643.5 mL. Among all visits, the highest 
volume of blood on a single visit will be approximately 64 mL (on Day -29) and the 
highest volume of blood over 8-week will be approximately 186 mL for patients from 
centres with access to PBMC processing facilities or 106 mL for patients from centres 
with no access to PBMC processing facilities (from Day 57 to Day 113), which are below 
the safe limits as recommended by the WHO [Howie, 2011]. 
• Urine samples (dipstick) will be collected for urine chemistry. 
For more information on the biological sampling to be performed at each study visit, 
please refer to Table 4 and Table 5.  
Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples. 
Refer to Section 8.5.3 for the handling of abnormal hematology/biochemistry parameters. 
CCI
CCI

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5.6.13. 
Study Vaccines administration 
• After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine will be administered intramuscularly (IM) in the deltoid of the non-dominant 
arm. For patients receiving co-administrations of HBc-HBs/AS01B-4 with either 
MVA-HBV or ChAd155-hIi-HBV (patients randomized in the C1 or C2 group), one 
vaccine will be administered in the non-dominant deltoid, while the other vaccine will 
be administered in the dominant deltoid (refer to Section 6.3 for detailed description 
of the vaccines administration procedure). 
• If the investigator or delegate determines that the patient’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 6). 
• The patients will be observed closely for at least 60 minutes following the 
administration of the vaccines, with appropriate medical treatment readily available in 
case of anaphylaxis. 
5.6.14. 
Check and record concomitant medication/vaccination and 
intercurrent medical conditions 
Concomitant medication/vaccination must be checked and recorded in the eCRF as 
described in Section 6.7. 
Intercurrent medical conditions that may lead to elimination of a patient from per-
protocol analyses must be checked and recorded in the eCRF as described in Section 6.8. 
5.6.15. 
Recording of AEs, SAEs, AESIs and pregnancies 
• Refer to Section 8.3 for procedures for the investigator to record AEs, SAEs, AESI 
and pregnancies. Refer to Section 8.4 for guidelines and how to report SAEs, AESIs 
and pregnancies to GSK Biologicals. 
• The patient will be instructed to contact the investigator immediately should they 
manifest any signs or symptoms they perceive as serious.  
• At each vaccination visit, diary cards will be provided to the patient. The patient will 
be instructed to measure and record body temperature, and any solicited local/general 
AEs on the day of vaccination and during the next 6 days. The patient will be 
instructed to return the completed diary card to the investigator at the next study 
visits. 
• Collect and verify completed diary cards during discussion with the patient on Visit 2, 
Visit 3, Visit 7, Visit 11 and Visit 15.  
• Any unreturned diary cards will be sought from the patient through telephone call(s) 
or any other convenient procedure.  
• The investigator or delegate will transcribe the collected information into the eCRF in 
English. 

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5.6.16. 
Home nursing procedures 
In the sites/countries where a home nursing is possible according to local regulations, the 
patients may be offered the option to have a home visit. Only selected visits will have the 
option to be performed as a home visit, these may include biological samples collection, 
patient assessments and data collection. The full specifications of the home nursing 
services will be outlined in the SPM. 
5.6.17. 
Screening conclusion, primary phase conclusion and study 
conclusion 
At the end of the Screening phase (Screening visit), at the end of the primary phase (Visit 
22) and at the end of the study (Visit 26), the investigator will: 
• Review data collected to ensure accuracy and completeness; 
• Complete the Screening Conclusion/Primary Phase Conclusion/Study Conclusion 
screen, as applicable, in the eCRF. 
5.6.18. 
Study procedures during special circumstances  
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, the 
following measures may be implemented for enrolled patients of the impacted countries 
or sites:  
• Study visits may be replaced by a telephone call, other means of virtual contact or 
home visit, if appropriate to collect the safety information (AEs and concomitant 
medications/vaccinations), unless a patient presents symptoms or reports AEs that 
necessitate a site visit in Investigator’s judgement. 
• Diary cards may be transmitted from and to the site by electronic means and/or 
conventional mail. 
• The screening activities and vaccine administration may be put on hold in line with 
specific local guidance or when deemed necessary by the Investigator or by Sponsor. 
Notification to Ethical Committees / Independent Review Boards and Competent 
Authorities should be made as appropriate. When it deems appropriate to resume the 
screening activities and vaccine administration, this can be done following 
notification to the Ethical Committees / Independent Review Boards and Competent 
Authorities and approvals as needed.  
• Maximum interval between study vaccinations: If despite best efforts it is not possible 
to administer subsequent dose of study vaccine as defined in the protocol (see Table 
6), a maximum dose interval of 111 days between two subsequent doses should be 
used. The maximum interval has been determined based on experience with Ebola 
ChAd-MVA prime-boost in Phase I study [Tapia, 2016]. In this study, MVA-BN-Filo 
booster vaccine given 11 – 16 weeks (79 - 111 days) after priming with ChAd3-EBO-

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Z was well tolerated and immunogenic eliciting both anamnestic antibody responses 
and robust multifunctional CD4 and CD8 memory T-cell responses. 
• Discontinuation from study vaccination: If a maximum interval of 111 days since 
previous vaccination is exceeded, vaccination should be discontinued. 
• Adaptation of study visits when subsequent vaccination cannot be administered as 
defined in the protocol i.e. at interval of 53 – 63 days: 
• If subsequent vaccination cannot be administered within an interval of 53 - 63 days, 
only the visits specified in Table 7 should be performed at least every 4 weeks after 
the previous vaccination to follow up on safety and laboratory parameters. For 
management of those visits, refer to Table 7. Data collected at those visits should be 
encoded using unscheduled visit form in eCRF until the vaccination is resumed 
within a maximum of 111 days interval from the previous vaccination.  
• If subsequent vaccination can be administered within maximum interval of 111 days 
from the date of previous dose administration, the visit related to this vaccination 
should be performed and further visits should follow as defined in Table 4, Table 5 
and Table 6. If no biological samples have been collected since the previous 
vaccination visit,  an unscheduled should be performed, as defined in Table 5 to 
check for contraindications to the subsequent vaccination. Vaccination visit and 
subsequent visits should be encoded as regular visits in eCRF.  
• If subsequent vaccination cannot be administered within maximum interval of 111 
days from the date of previous dose administration, patient should discontinue study 
vaccination and management of follow up visits in the primary phase (Epoch 002) 
should be performed as indicated in Table 7 and described below: 
− 
For patients who discontinued vaccination after vaccination Dose 1, Visits 10, 
12, 13, 14 and 17-22 should be performed, as defined in Table 4 and Table 5, for 
follow up on safety and laboratory parameters. 
− 
For patients who discontinued vaccination after vaccination Dose 2, Visits 14 
and 17-22 should be performed, as defined in Table 4 and Table 5, for follow up 
on safety and laboratory parameters.  
− 
For patients who discontinued vaccination after vaccination Dose 3, Visits 18-22 
should be performed, as defined in Table 5, for follow up on safety and 
laboratory parameters. 
Data collected at the above mentioned visits should be encoded as regular visits in 
eCRF.  
For all patients who discontinued study vaccination, the planned visits in the follow 
up phase (Epoch 003) should be performed as defined by protocol. 
Biological samples may be collected at a different location* other than the study site or at 
patient’s home, in line with applicable local guidance. Biological samples should not be 
collected if they cannot be processed in a timely manner or appropriately stored until the 
intended use. In case of anticipated delay or urgency in obtaining the biological sample 
result to follow safety parameters post-vaccination, the investigator is recommended to 

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collect an additional biological sample for local testing. If such sample is required, it is 
important that the sample for central testing is obtained at the same time. 
• In case a Grade 3 laboratory parameter abnormality is detected, an unscheduled visit 
should be performed, per protocol planned as a site visit. However, Investigator 
should practice his/her medical judgement on the clinical relevance of any 
abnormality and manage this according to the local clinical practice and local 
guideline concerning the COVID-19. If the site visit restriction is in place, the 
Investigator should contact the concerned patient in a remote manner (e.g. phone 
contact or home visit, if appropriate) to collect the safety information. Whenever 
possible and in line with applicable local guidance, the Investigator should arrange 
the clinical and laboratory examination at a different location* other than the study 
site that is accessible for the concerned patient. 
* It is the investigator’s responsibility to identify an alternate 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 European Medicines Agency Guidance on the Management of Clinical 
Trials during the COVID-19 (Coronavirus) pandemic (version 2, 27 March, 2020) 
for more details. 
Impact on the per protocol set for immunogenicity and efficacy will be determined on a 
case by case basis. Due to potential increase of the drop-out rate and potential 
administration of COVID-19 vaccines during study participation (outside of study 
procedures), to ensure sufficient number of evaluable patients: 
• Allowed intervals between two subsequent vaccinations, that constitute criterion for 
per protocol set, has been extended from 53 - 63 days to 84 days;  
• An increase of maximum 15% in sample size in Step B and in Step C can be 
anticipated.  

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Table 7 
Study visits of Epoch 002 to be performed if subsequent vaccination cannot take place within allowed interval of 
53 - 63 days from previous vaccination 
Epoch 
Epoch 002 
Study Phase 
Primary Phase 
Type of contact 
Visit 1  Visits 
2-5 
Visit 6 Visit 7 Visit 8 Visit 9 Visit 
10 
Visit 
11 
Visit 
12 
Visit 
13 
Visit 
14  
Visit 
15 
Visit 
16 
Visit 
17 
Visit 
18 
Visit 
19 ^ 
Visit 
20 
Visit 
21 ^ 
Visit 
22 
Time points 
Day 1  Day 3 - 
Day 31 
Day 57 Day 64 Day 71 Day 87 Day 
113  
Day 
120  
Day 
127  
Day 
143  
Day 
169  
Day 
176  
Day 
183  
Day 
199  
Day 
225  
Day 
253  
Day 
281  
Day 
309  
Day 
337  
Previous vaccination Dose  
 
Dose 1 
Dose 1 
N 
Un 
C 
C 
Un 
MV* 
C 
N 
N 
MV 
C 
C 
N 
N 
N 
N 
N 
N 
Dose 2 
 
 
Dose 2 
N 
N 
N 
Un 
C 
Un 
Un 
MV* 
C 
C 
N 
N 
N 
N 
N 
N 
Dose 3 
 
 
 
 
 
 
Dose 3 
N 
N 
N 
Un 
C 
C 
Un 
N* 
N 
N 
N 
N 
Dose 4 
 
 
 
 
 
 
 
 
 
 
Dose 4 
N 
N 
N 
N 
N 
N 
N 
N 
N: Visit including procedures as defined for this visit in Table 4 and Table 5. Visit should be encoded as regular visit in eCRF. 
Un: Visit performed in special circumstances (e.g. remotely, home visit) including as many procedures as possible as defined for this visit in Table 4. Visit should be encoded using 
Unscheduled visit form in eCRF. 
C: Visit cancelled if subsequent vaccination was not yet administered  
MV: Modified Visit applicable for patient who discontinued from study vaccination. This visit excludes vaccination-related procedures while maintaining all non vaccination-related 
procedures. For details, refer to Table 4. Visit should be encoded using vaccination visit form in eCRF. 
* Discontinuation of study vaccination may apply, if interval of 111 days from the date of previous dose administration is exceeded. This should be determined based on the actual date 
of the previous dose administration. 
^ For patients in Step B and Step C, Visits 19 and 21 are cancelled. 
Note: 
1. If the above visits are performed in special circumstances (e.g. remotely, home visit), as many procedures as possible should be done (refer to Table 4 and Table 5). 
2. If subsequent vaccination can be administered within maximum interval of 111 days from the date of previous dose administration, the visit related to this vaccination should be 
performed and further visits should follow as defined in Table 4, Table 5 and Table 6. Vaccination and subsequent visits should be encoded as regular visits in eCRF. 
3. If subsequent vaccination cannot be administered within a maximum interval of 111 days from the date of previous dose administration, patient should discontinue study vaccination 
and follow up visits should be performed as indicated above. The timepoints from vaccination Dose 1, Dose 2 and Dose 3 at which patient should be considered as discontinued from 
study vaccination are marked with * in the above table and should be determined based on the actual date of the previous dose administration. 
4. Management of visits for patient who completed Dose 4 vaccination is shown for completeness 
 

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In view of the current medical need for COVID-19 vaccination, 
guidance/recommendations from National Authorities should apply first and foremost 
if/when existing. 
Recommendations on spacing between COVID-19 vaccine and study vaccination based 
on type of COVID-19 vaccine are outlined in Table 8. Note that the interval between two 
subsequent study vaccine doses can be extended up to 84 days to accommodate COVID-
19 vaccinations. 
Table 8 
Recommendations on spacing between COVID-19 vaccine and study 
vaccination by type of COVID-19 vaccine 
COVID-19 vaccine 
Prior study vaccination 
During study vaccination 
After study vaccination 
mRNA based 
14 days before first study 
vaccine dose 
At least 14 days before or 30 
days after study vaccination 
30 days after last 
vaccine dose 
Adenovector-
based 
30 days before first study 
vaccine dose (applicable for 
all patients except for the 
patients in France) OR 12 
months before first study 
vaccine dose (applicable for 
the patients in France only). 
At least 30 days before or 
after study vaccination 
30 days after last 
vaccine dose 
Protein-based 
adjuvanted 
30 days before first study 
vaccine dose 
At least 30 days before or 
after study vaccination 
30 days after last 
vaccine dose 
Other 
technologies 
30 days before first study 
vaccine dose 
At least 30 days before or 
after study vaccination 
30 days after last 
vaccine dose 
Whenever multiple types of COVID-19 vaccine are offered, a COVID-19 vaccine that is 
not adenovector-based may be considered as a better choice. 
5.7. 
Biological sample handling and analysis 
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment). 
Samples will not be labelled with information that directly identifies the patient but will 
be coded with the patient identification number (PID). 
• Collected samples will be used for protocol mandated research and purposes related 
to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. This may include the management of the quality of these 
tests, the maintenance or improvement of these tests, the development of new test 
methods, as well as making sure that new tests are comparable to previous methods 
and work reliably. 
• It is also possible that future findings may make it desirable to use the samples 
acquired in this study for future research, not described in this protocol. Therefore, all 
patients 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. 

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Information on further investigations and their rationale can be obtained from GSK 
Biologicals. 
Any sample testing will be done in line with the consent of the individual patient.  
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s).  
If additional testing is performed, the marker priority ranking given in Section 5.7.4 may 
be changed. 
Collected samples will be stored for a maximum of 20 years (counting from when the last 
patient 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 patient 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK Biologicals. 
5.7.1. 
Use of specified study materials 
When materials are provided by GSK Biologicals, it is MANDATORY that all clinical 
samples (including serum samples) be collected and stored exclusively using those 
materials in the appropriate manner. The use of other materials could result in the 
exclusion of the patient from the per-protocol analysis (See Section 10.5 for the definition 
of cohorts to be analyzed). The investigator must ensure that his/her personnel and the 
laboratory(ies) under his/her supervision comply with this requirement. However, when 
GSK Biologicals does not provide material for collecting and storing clinical samples, 
appropriate materials from the investigator’s site must be used. Refer to the Module on 
Clinical Trial Supplies in the SPM. 

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5.7.2. 
Biological samples 
Table 9 
Biological samples 
Sample type 
Component 
Time point *** 
Quantity 
Unit 
Cohort/subset 
Blood 
HBV, HCV, HDV and HIV 
serology  
Screening 
~18.5 
ml 
All patients 
Autoimmune antibodies * 
Screening 
~13.5 
ml 
Biochemistry (FibroTest) * 
Screening, Visit 22, Visit 24 
and Visit 26 
~8.5 
ml 
Biochemistry (AFP) * 
Screening, Visit 22, Visit 24 
and Visit 26 
~3.5 
ml 
Biochemistry (ALT, AST, 
ALP, GGT, Bilirubin and 
Creatinine) * 
All visits 
~3.5 
ml 
Hematology (CBC) ** 
All visits 
~2.0 
ml 
Hematology (INR) 
All visits 
~4.5 
ml 
HBV-DNA and new viral 
markers  
Screening, Visit 5, Visit 6, Visit 
9, Visit 10, Visit 13, Visit 14 
Visit 17, Visit 18, Visit 19, Visit 
20, Visit 21, Visit 22, Visit 23, 
Visit 24, Visit 25 and Visit 26 
~10 
ml 
qHBsAg 
Screening, Visit 1, Visit 5, Visit 
6, Visit 9, Visit 10, Visit 13, 
Visit 14, Visit 17, Visit 18, Visit 
19, Visit 20, Visit 21, Visit 22, 
Visit 23, Visit 24, Visit 25 and 
Visit 26 
~3.5 
ml 
CMI response 
Visit 1, Visit 4, Visit 6, Visit 7, 
Visit 8, Visit 10, Visit 12, Visit 
14, Visit 16, Visit 22, Visit 24 
and Visit 26 
~20 
ml 
All patients 
from sites with 
access to 
PBMC 
processing 
facilities 
Humoral response to HBV 
antigens 
Visit 1, Visit 4, Visit 8, Visit 10, 
Visit 12, Visit 16, Visit 22, Visit 
24 and Visit 26 
~3.5 
ml 
All patients 
Serum repository 
Visit 1, Visit 8, Visit 10, Visit 
12, Visit 16, Visit 22, Visit 24 
and Visit 26 
~3.5 
ml 
Urine  
Urine chemistry 
All visits up to Visit 22 
included. 
NA 
NA 
* Blood samples for creatinine, FibroTest and LKM-1 autoantibodies tests should be collected after a minimum 8 hour 
fast. 
** CBC includes erythrocytes, leukocytes, neutrophils, lymphocytes, eosinophils, basophils, monocytes, platelets, 
hemoglobin and hematocrit. 
*** For all patients, biological samples collection at Visits 2, 5, 9, 13 and 17 are not mandatory and can be collected at 
the discretion of the Investigator.  
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    For patients in Step B and Step C, biological samples collection is cancelled for Visits 19 and 21.  
   For patients participating in TH HBV VV-031 HBS:001 study, biological samples collection specific to that study 
remains mandatory for Visits 2 and 5. 
† This buccal swab sampling is optional and will only be performed for patients who consented to have 
pharmacogenomics tests done on their samples. 
A serum or plasma sample collected before the NA treatment, if the sample is available 
and if the patient consents, will be used for HBV genotyping. 
In case of a TTS event, an additional blood sample (~3.5ml) should be collected within 2 
weeks of the diagnosis of the TTS. This blood sample can be collected at the next study 
visit or at an unscheduled visit in case the next study visit is >2 weeks from the TTS 
diagnosis. Additional blood sample collection for TTS event reported during the follow-
up phase is optional. This serum sample (if available) as well as the samples collected for 
repository, as already specified in the protocol, will be used for exploratory testing and 
better understanding of the pathogenesis of TTS event. Since scientific knowledge on 
TTS pathology and biomarkers for TTS risks in relation to adenovector-based vaccines is 
evolving, this exploratory testing is not to guide TTS management and no assay details 
are specified in the protocol. This testing will be performed at a laboratory designated by 
GSK Biologicals. 
5.7.3. 
Laboratory assays 
Please refer to APPENDIX A for a detailed description of the assays performed in the 
study. Please refer to APPENDIX B for the address of the clinical laboratories used for 
sample analysis. 
Hematology, biochemistry, autoimmune antibodies and urine chemistry assessments will 
be performed at GSK Biologicals or at a laboratory designated by GSK Biologicals using 
commercial tests (see Table 10). 
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Table 10 
Hematology, biochemistry, autoimmune antibody and urine tests 
System 
Discipline 
Component 
Method 
Scale 
Laboratory 
Whole 
blood 
Hematology 
Erythrocytes (Red Blood Cells) 
As per Q2 
Solutions 
practice 
Quantitative 
Q2 Solutions 
Leukocytes (White Blood Cells) 
Quantitative 
Neutrophils 
Quantitative 
Lymphocytes 
Quantitative 
Eosinophils 
Quantitative 
Basophils 
Quantitative 
Monocytes 
Quantitative 
Platelets 
Quantitative 
Hemoglobin 
Quantitative 
Hematocrit 
Quantitative 
Prothrombin Time International 
Normalised Ratio (INR) 
Quantitative 
Serum 
Biochemistry 
Alanine Aminotransferase (ALT) 
Quantitative 
Aspartate Aminotransferase (AST) 
Quantitative 
Alkaline Phosphatase (ALP) 
Quantitative 
Gamma Glutamyl Transferase (GGT) 
Quantitative 
Total Bilirubin 
Quantitative 
Creatinine 
Quantitative 
Alpha-fetoprotein 
Quantitative 
FibroTest 
Quantitative 
Autoimmune 
antibodies 
Antinuclear antibodies (ANAs) 
Qualitative 
Smooth muscle antibodies (SMAs) 
Qualitative 
Liver kidney microsomal 1 Ab.IgG 
(LKM-1) 
Qualitative 
Anti-liver cytosol 1 (anti LC1) antibodies 
Quantitative 
Urine 
Urine 
chemistry 
Leukocytes, Blood, Proteins, Glucose, 
Ketones, Bilirubin, Urobilinogen, Nitrite, 
Specific gravity, pH 
As per 
local 
practice 
Semi-
quantitative 
On site 
Serology and virology assays will be performed at laboratories designated by GSK 
Biologicals using commercial tests or tests to be developed at the lab (see Table 10). 

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Table 11 
HBV, HCV, HDV and HIV serology and HBV virology assays 
System 
Discipline 
Component 
Method 
Scale 
Laboratory 
Serum 
HBV serology 
Hepatitis B 
Virus.Surface Ab (Anti-
HBs)a 
CMIA  
Qualitative 
GSK 
Biologicals’ 
laboratory or 
laboratory 
designated by 
GSK 
Hepatitis B 
Virus.Surface Ag 
(HBsAg) 
CMIA  
Quantitative  
Hepatitis B Virus.e Ag  
(HBeAg)a 
CLIA  
Qualitative 
Q2 Solutions 
Hepatitis B Virus.Core 
Ab (Anti-HBc) a 
CMIA  
Qualitative 
Hepatitis B Virus.e Ab  
(Anti-HBe)a 
CCLIA  
Qualitative 
HCV 
serology 
Hepatitis Virus C Ab 
(anti-HCV) a 
CMIA  
Qualitative 
Q2 Solutions 
HDV 
serology 
Hepatitis Virus D Ab 
(Anti-HDV) a 
ELISA  
Qualitative 
Q2 Solutions 
HIV serology 
Human 
Immunodeficiency 
Virus Ab (Anti-HIV) a 
CMIA  
Qualitative 
Q2 Solutions 
HBV virology 
Hepatitis B Virus DNA  
(HBV DNA) 
qPCR  
Quantitative  
DDL 
Diagnostic 
Laboratory 
HBV DNA whole 
sequencingb 
Sequencing 
N/A 
a This test will be performed at Screening only. 
b This test will be performed in case of virological breakthrough. 
The cut-off for HBV DNA measured by qPCR will be 10 IU/mL. 
Antibody concentrations will be measured by immune-chemistry assays at GSK 
Biologicals’ laboratory or designated laboratory using standardized procedures (see Table 
12). 
Table 12 
Humoral Immunity (Antibody determination) 
System 
Component 
Method 
Components 
priority rank 
Laboratory a 
Serum 
Hepatitis B Virus.Surface Ab  
CLIA  
1 
GSK Biologicals’ 
laboratory or 
laboratory 
designated by GSK 
Hepatitis B Virus Core Ab 
ELISA 
2 
a GSK Biologicals laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium. 
Refer to APPENDIX B for the laboratory addresses. 
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CMI assays will be performed in GSK Biologicals’ laboratory or designated laboratory 
using standardized procedures (see Table 13). 
Table 13 
Cell-mediated Immunity 
System 
Component 
Challenge 
Method 
Component 
priority rank 
Laboratorya 
PBMC 
HBc-specific 
(CD4+/CD8+) T-cells 
HBc peptide pool 
CFC 
1 
GSK Biologicals’ 
laboratory or 
laboratory designated 
by GSK 
HBs-specific 
(CD4+/CD8+) T-cells 
HBs peptide pool 
CFC 
2 
a GSK Biologicals laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium. 
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The GSK Biologicals’ clinical laboratories have established a Quality System supported 
by procedures. The activities of GSK Biologicals’ clinical laboratories are audited 
regularly for quality assessment by an internal (sponsor-dependent) but laboratory-
independent Quality Department. 
5.7.4. 
Biological samples evaluation 
5.7.4.1. 
Evaluation of hematology, biochemistry and urinalysis 
Table 15 
Evaluation of hematology, biochemistry and urinalysis 
Sample 
type 
Type of contact 
and time point ** 
Study 
group 
Approximate 
No Patients 
Component 
Components 
priority rank 
Hematology 
Blood 
At Screening 
All study 
groups 
INR 
NA 
CBC* 
NA 
All time points 
All study 
groups 
INR 
1 
CBC* 
2 
Biochemistry 
Serum 
At Screening 
All study 
groups 
ALT, AST, GGT, ALP, 
Bilirubin, Creatinine 
NA 
AFP 
FibroTest 
Visit 1 ~ Visit 26 
All study 
groups 
ALT, AST, GGT, ALP, 
Bilirubin, Creatinine 
NA 
Visit 22, Visit 24 
and Visit 26 
All study 
groups 
ALT, AST, GGT, ALP, 
Bilirubin, Creatinine 
1 
FibroTest 
2 
AFP 
3 
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Sample 
type 
Type of contact 
and time point ** 
Study 
group 
Approximate 
No Patients 
Component 
Components 
priority rank 
Urinalysis 
Urine 
All time points up 
to Visit 22 
included. 
All study 
groups 
Leucocytes, Blood, 
Proteins, Glucose, 
Ketones, Bilirubin, 
Urobilinogen, Nitrite, 
Specific gravity, pH 
NA 
NA: not applicable 
* CBC includes erythrocytes, leukocytes, neutrophils, lymphocytes, eosinophils, basophils, monocytes, platelets, 
hemoglobin and hematocrit. 
** For all patients, biological samples collection at Visits 2, 5, 9, 13 and 17 are not mandatory and can be collected at 
the discretion of the Investigator.  
   For patients in Step B and Step C, biological samples collection is cancelled for Visits 19 and 21.  
   For patients participating in TH HBV VV-031 HBS:001 study, biological samples collection specific to that study 
remains mandatory for Visits 2 and 5. 
5.7.4.2. 
Evaluation of serum HBV antigens 
Table 16 
Evaluation of serum HBV antigens 
Sample 
type 
Type of contact and 
time point * 
Study 
group 
No 
Patients 
Component 
Components 
priority rank 
Serum 
Screening, Visit 1, Visit 
5, Visit 6, Visit 9, Visit 
10, Visit 13, Visit 14, 
Visit 17, Visit 18, Visit 
19, Visit 20, Visit 21, 
Visit 22, Visit 23, Visit 
24, Visit 25 and Visit 26 
All study 
groups 
HBsAg 
NA 
* For all patients, biological samples collection at Visits 5, 9, 13 and 17 are not mandatory and can be collected at the 
discretion of the Investigator.  
  For patients in Step B and Step C, biological samples collection is cancelled for Visits 19 and 21.  
  For patients participating in TH HBV VV-031 HBS:001 study, biological samples collection specific to that study 
remains mandatory for Visit 5. 
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5.7.4.3. 
Evaluation of molecular biology 
Table 17 
Evaluation of molecular biology 
Sample 
type 
Type of contact and time 
point * 
Study 
group 
No 
Patients 
Component 
Components 
priority rank 
Serum 
Screening, Visit 5, Visit 6, 
Visit 9, Visit 10, Visit 13, 
Visit 14, Visit 17, Visit 18, 
Visit 19, Visit 20, Visit 21, 
Visit 22, Visit 23, Visit 24, 
Visit 25 and Visit 26 
All study 
groups 
HBV DNA 
1 
* For all patients, biological samples collection at Visits 5, 9, 13 and 17 are not mandatory and can be collected at the 
discretion of the Investigator.  
  For patients in Step B and Step C, biological samples collection is cancelled for Visits 19 and 21.  
  For patients participating in TH HBV VV-031 HBS:001 study, biological samples collection specific to that study 
remains mandatory for Visit 5. 
5.7.4.4. 
Evaluation of immunogenicity 
Table 18 
Evaluation of humoral immunogenicity 
Sample 
type 
Type of contact and time point 
Sub 
groups 
No. 
patients 
Component 
Components 
priority rank 
Blood for 
humoral 
response 
Visit 1, Visit 4, Visit 8, Visit 10, Visit 12, 
Visit 16, Visit 22, Visit 24 and Visit 26 
All study 
groups 
Anti-HBc 
2 
Anti-HBs Ig total 
1 
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Table 19 
Evaluation of cell-mediated immunogenicity 
Sample 
type 
Type of contact and time point 
Sub 
groups 
No. patients b 
Component 
Components 
priority rank 
Blood for 
CMI 
response 
Visit 1, Visit 4, Visit 6, Visit 7, Visit 8, 
Visit 10, Visit 12, Visit 14, Visit 16, 
Visit 22, Visit 24 and Visit 26 
All 
study 
groups 
HBc-specific 
(CD4+/CD8+) T-cells 
1 
HBs-specific 
(CD4+/CD8+) T-cells 
2 
a 
 
b Patients from the sites with access to PBMC processing facilities  
 
. 
In case of insufficient blood sample volume to perform all assays, the samples will be 
analyzed according to priority ranking provided in Table 18 and Table 19. 
6. 
STUDY VACCINES AND ADMINISTRATION 
6.1. 
Description of study vaccines 
All candidate vaccines/products to be used have been developed and manufactured by 
GSK Biologicals.  
The Quality Control Standards and Requirements for the candidate vaccines are 
described in separate Quality Assurance documents (e.g. release protocols, certificate of 
analysis) and the required approvals have been obtained.  
The vaccines are labelled and packed according to applicable regulatory requirements. 
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Table 20 
Study vaccines 
Treatment 
name 
Product 
Formulation 
Presentation 
Volume of 
product to be 
administered 
Total 
treatment 
volume to be 
administered 
Number of 
doses 
ChAd155-hIi-HBV 
5x109 vp a 
ChAd155-hIi-
HBV  
0.05 ml 
0.1 ml 
1 (Step A: 
Group A1) 
NaCl  
0.05 ml 
ChAd155-hIi-HBV 
5x1010 vp 
ChAd155-hIi-
HBV  
0.5 ml 
0.5 ml 
1 (Step B: 
Groups B1 
and B3; Step 
C: all groups) 
MVA-HBV 2x107 
pfu b 
MVA-HBV  
0.05 ml 
0.1 ml 
1 (Step A, 
Group A1) 
NaCl  
0.05 ml 
MVA-HBV 2x108 
pfu 
MVA-HBV  
0.5 ml 
0.5 ml 
1 (Step B: 
Groups B1 
and B3. Step 
C: Group C2) 
3 (Step C: 
Group C1) 
HBc-HBs/AS01B-
4 20-20 
HBc-HBs  
NA 
0.5 ml 
2 (Step A: 
Group A1) 
AS01B-4  
0.5 ml 
4 (Step A: 
Group A2) 
HBc-HBs/AS01B-
4 80-80 
HBc-HBs  
NA 
0.5 ml 
2 (Step 
B:Group B1) 
3 (Step 
C:Group C2) 
AS01B-4  
0.5 ml 
4 (Step B: 
Group B2. 
Step C: 
Group C1) 
Placebo 
(Formulation 
buffer S9B 
(PBS)) 
Formulation 
buffer S9b  
0.5 ml 
0.5 ml 
4 (Step A: 
Group A3. 
Step C: 
Group C2) 
2 (Step B: 
Group B3) 
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6.2. 
Storage and handling of study vaccines 
The study vaccines must be stored at the respective label storage temperature conditions 
in a safe and locked place. Access to the storage space should be limited to authorized 
study personnel. The storage conditions will be assessed during pre-study activities under 
the responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccines. 
Temperature excursions must be reported in degree Celsius. 
Any temperature excursion impacting investigational medicinal products (IMPs) must be 
reported in the appropriate (electronic) temperature excursion decision form ([e]TDF). 
The impacted IMPs must not be used and must be stored in quarantine at label 
temperature conditions until usage approval has been obtained from the sponsor. Refer to 
the Module on Clinical Trial Supplies in the SPM for more details on temperature 
excursion ranges of the study vaccines. 
6.3. 
Dosage and administration of study vaccines 
Table 21 
Dosage and administration 
Type of contact 
and time point 
Study 
group 
Treatment name 
Volume to be 
administered Route 
Site 
Sidea 
Step A 
Visit 1 (D1) 
A1 
ChAd155-hIi-HBV 5x109 vp  
0.1 ml 
IM 
Deltoid Non-dominant 
A2 
HBc-HBs/AS01B-4 20-20  
0.5 ml 
A3 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Visit 6 (D57) 
A1 
MVA-HBV 2x107 pfu  
0.1 ml 
IM 
Deltoid Non-dominant 
A2 
HBc-HBs/AS01B-4 20-20  
0.5 ml 
A3 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Visit 10 (D113) 
and Visit 14 
(D169) 
A1 
HBc-HBs/AS01B-4 20-20  
0.5 ml 
IM 
Deltoid Non-dominant 
A2 
HBc-HBs/AS01B-4 20-20  
0.5 ml 
A3 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Step B 
Visit 1 (D1) 
B1 
ChAd155-hIi-HBV 5x1010 vp  
0.5 ml 
IM 
Deltoid Non-dominant 
B2 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
B3 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Visit 6 (D57) 
B1 
MVA-HBV 2x108 pfu  
0.5 ml 
IM 
Deltoid Non-dominant 
B2 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
B3 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Visit 10 (D113) 
B1 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
IM 
Deltoid Non-dominant 
B2 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
B3 
ChAd155-hIi-HBV 5x1010 vp  
0.5 ml 
Visit 14 (D169) 
B1 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
IM 
Deltoid Non-dominant 
B2 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
B3 
MVA-HBV 2x108 pfu  
0.5 ml 
Step C 
Visit 1 (D1)  
C1 
ChAd155-hIi-HBV 5x1010 vp  
0.5 ml 
IM 
Deltoid 
Dominant 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
Non Dominant 
C2 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
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Type of contact 
and time point 
Study 
group 
Treatment name 
Volume to be 
administered Route 
Site 
Sidea 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Non Dominant 
Visit 6 (D57) 
C1 
MVA-HBV 2x108 pfu  
0.5 ml 
IM 
Deltoid 
Dominant 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
Non Dominant 
C2 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Dominant 
Placebo (Formulation buffer S9B (PBS))  
0.5 ml 
Non Dominant 
Visit 10 (D113) 
C1 
MVA-HBV 2x108 pfu  
0.5 ml 
IM 
Deltoid 
Dominant 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
Non-
Dominant 
C2 
ChAd155-hIi-HBV 5x1010 vp  
0.5 ml 
Dominant 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
Non-
Dominant 
Visit 14 (D169) 
C1 
MVA-HBV 2x108 pfu  
0.5 ml 
IM 
Deltoid 
Dominant 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
Non-
Dominant 
C2 
MVA-HBV 2x108 pfu  
0.5 ml 
Dominant 
HBc-HBs/AS01B-4 80-80  
0.5 ml 
Non-
Dominant 
6.4. 
Minimizing environmental contamination with genetically 
modified organisms 
Each product will be used in accordance with the applicable genetically modified 
organism (GMO) regulations. 
To minimize release of the recombinant vectored vaccine virus into the environment, 
each vaccine is produced under good manufacturing practice (GMP) conditions with the 
handling of live material in appropriate laboratory facilities. This is to ensure that any 
release of modified organism is contained, inactivated and incinerated, using single use 
equipment as much as possible, to avoid release of modified genetic material into the 
environment. 
After each vaccination, the injection site will be covered with a dressing in order to 
absorb any virus that may leak out through the needle track. The dressing will be 
removed only after 30 minutes and will be disposed as GMO waste in accordance with 
the applicable guidelines/standard operating procedures at the investigator’s site. 
6.5. 
Replacement of unusable vaccine doses 
In addition to the vaccine doses provided for the planned number of patients (including 
over-randomization when applicable), at least 30% additional vaccine doses will be 
supplied to replace those that are unusable.  
6.6. 
Contraindications to subsequent vaccination 
The following events constitute absolute contraindications to further administration of the 
study vaccine. If any of these events occur during the study, the patient must not receive 
additional doses of vaccine but may continue other study procedures at the discretion of 
the investigator (see Section 8.5).  

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• Anaphylaxis following the administration of vaccines, 
• Pregnancy (see Section 8.2.1), 
• Confirmed ALT flares (ALT > 8 x ULN), 
• Confirmed ALT flares (ALT > 5 x ULN) for more than 2 weeks, 
• Confirmed ALT flares (ALT > 3 x ULN) and liver-related substantial biochemical 
changes (i.e. INR > 1.5 or bilirubin > 2 x ULN), 
• Confirmed ALT flares (ALT > 3 x ULN) with the appearance of clinical symptoms of 
hepatitis (fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, 
rash, and/or eosinophilia. 
Note: At Laboratory Q2 Solutions, The ULN for ALT is 48 U/L, ULN for bilirubin is 
22 µmol/L. In case the test is performed locally, the reference range of the local 
laboratory should be used. 
• Hepatic decompensation.  
• HBV-DNA breakthrough. 
• Spontaneous local or general bleeding AND thrombocytes < 50000/mm3. 
• Any confirmed or suspected immunosuppressive or immunodeficient condition, 
including HIV infection. 
• Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
• Any other significant condition which, in the opinion of the investigator, would 
preclude further administration of the study vaccine. 
• Occurrence of a pIMD that, in the opinion of the investigator, exposes the patient to 
unacceptable risk from subsequent vaccination. In such cases, the investigator should 
use his/her clinical judgement prior to administering the next dose of the vaccine(s). 
Refer to Section 8.1.5.3 for the definition of pIMDs. 
• Discontinuation of NA therapy 
The following events constitute contraindications to administration of the study vaccines 
at that point in time; if any of these events occur at the time scheduled for vaccination, 
the patient may be vaccinated at a later date, within the time window specified in the 
protocol (see Section 5.5), or the patient may be withdrawn at the discretion of the 
investigator (see Section 8.5).  
• Acute disease and/or fever at the time of vaccination.  
− 
Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for 
measuring temperature in this study will be the oral cavity. 
− 
Patients with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) can be administered all vaccines/products. 

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6.7. 
Concomitant medications/products and concomitant 
vaccinations 
At each study visit, the investigator or delegate should question the patient about any 
medications/products taken and vaccinations received by the patient. 
6.7.1. 
Recording of concomitant medications/products and 
concomitant vaccinations 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in 
the eCRF. 
• All concomitant medications/products, except vitamins and dietary supplements, 
administered during a 30-day follow-up (i.e. day of vaccination and 29 subsequent 
days). 
• Any concomitant vaccination administered in the period starting 30 days before the 
first dose of study vaccines and ending at the last study visit (Day -29 to Day 841). 
• Any COVID-19 vaccine administered in the period starting 12 months prior to the 
vaccination visit 1 and ending at the last study visit. 
• Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination). 
E.g. an anti-pyretic is considered to be prophylactic when it is given in the absence 
of fever and any other symptom, to prevent fever from occurring [fever is defined as 
temperature ≥38.0°C/100.4°F]. The preferred location for measuring temperature in 
this study will be the oral cavity. 
• Any concomitant medications/products/vaccines listed in Section 6.7.2. 
• Any concomitant medications/products/vaccines relevant to a SAE/AESI to be 
reported as per protocol or administered at any time during the study period for the 
treatment of a SAE/AESI. In addition, concomitant medications relevant to SAEs and 
AESIs need to be recorded on the expedited Adverse Event report. 
• Nucleos(t)ide analogues with high barrier to resistance (e.g. ETV, TDF, TAF). that 
the patient takes to control chronic hepatitis B. 
6.7.2. 
Concomitant medications/products/vaccines that may lead to the 
elimination of a patient from per-protocol analyses 
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the patient from the study but may determine a patient’s evaluability in the 
per-protocol analysis. See Section 10.5 for cohorts to be analyzed. 
• Any investigational or non-registered product (drug or vaccine) other than the study 
vaccines used during the study period.  

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• Immunosuppressants or other immune-modifying drugs administered chronically (i.e. 
more than 14 days in total) during the study period. For corticosteroids, this will mean 
prednisone ≥ 10 mg/day or equivalent. Inhaled and topical steroids are allowed.  
• A vaccine not foreseen by the study protocol administered during the period starting 
14 days before each dose and ending 30 days after administration of the last 
vaccine(s) dose*, with the exception of annual influenza vaccine or pandemic 
influenza vaccine and COVID-19 vaccine (COVID-19 vaccines may be given at any 
time except within a 30-day period before or after each vaccine dose apart from 
COVID-19 mRNA based-vaccines that may be administered any time except for the 
period of 14 days before and 30 days after each study vaccine dose).  
Note: If the type of COVID-19 vaccine is unknown, the allowed interval of 30 days 
before or after each study vaccine dose should be followed. 
*In case an emergency mass vaccination for an unforeseen public health threat (e.g.: 
a pandemic) is organised by the public health authorities, outside the routine 
immunisation program, the time period described above can be reduced if, necessary 
for that vaccine provided it is licensed and used according to its Product Information. 
• Immunoglobulins and/or any blood products administered within 30 days before the 
blood sampling.  
6.8. 
Intercurrent medical conditions that may lead to elimination 
of a patient from per-protocol analyses 
At each study visit subsequent the vaccination visit, it must be verified if the patient has 
experienced or is experiencing any intercurrent medical condition. If it is the case, the 
condition(s) must be recorded in the eCRF. 
Patients may be eliminated from the per-protocol cohort for efficacy/immunogenicity if, 
during the study, they incur a condition that has the capability of altering their immune 
response or are confirmed to have an alteration of their initial immune status.  
Patients may be eliminated from the per-protocol cohort for efficacy/immunogenicity if 
they develop a concurrent infection with HDV and/or HIV or an immunodeficiency 
disorder.  
7. 
HEALTH ECONOMICS 
Not applicable. 
8. 
SAFETY 
The investigator or site staff is/are responsible for the detection, documentation and 
reporting of events meeting the criteria and definition of an adverse event (AE) or serious 
adverse event (SAE) as provided in this protocol.  
Each patient will be instructed to contact the investigator immediately should they/the 
patient manifest any signs or symptoms they perceive as serious. 

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8.1. 
Safety definitions 
8.1.1. 
Definition of an adverse event 
An AE is any untoward medical occurrence in a clinical investigation subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. 
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal products, this also includes 
failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse.  
Examples of an AE include: 
• 
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 vaccines 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 
vaccines or a concurrent medication (overdose per se should not be reported as an 
AE/SAE). 
• Signs, symptoms temporally associated with study vaccine(s)/product(s) 
administration. 
• Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of patient’s previous therapeutic regimen). 
AEs to be recorded as endpoints (solicited AEs) are described in Section 8.1.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
Examples of an AE DO NOT include: 
• Medical or surgical procedures (e.g. endoscopy, appendectomy); the condition that 
leads to the procedure is an AE/SAE. 
• Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.  
• The disease/disorder being studied, or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the patient’s 
condition. 

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• Pre-existing conditions or signs and/or symptoms present in a patient prior to the first 
study vaccination. These events will be recorded in the medical history section of the 
eCRF. 
8.1.2. 
Definition of a serious adverse event  
A SAE is any untoward medical occurrence that: 
• Results in death, 
• Is life-threatening, 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the patient was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe. 
• Requires hospitalisation or prolongation of existing hospitalisation, 
Note: In general, hospitalisation signifies that the patient has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or in an out-patient setting. Complications 
that occur during hospitalisation are also considered AEs. If a complication prolongs 
hospitalisation or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalisation’ occurred or was necessary, the 
AE should be considered serious. 
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline is 
NOT considered an AE. 
• Results in disability/incapacity, OR 
Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhoea, influenza like illness, and accidental trauma (e.g. sprained 
ankle) which may interfere or prevent everyday life functions but do not constitute a 
substantial disruption. 
• Is a congenital anomaly/birth defect in the offspring of a study patient. 
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise the 
patient or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalisation. 

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8.1.3. 
Solicited adverse events 
8.1.3.1. 
Solicited local (injection-site) adverse events 
The following local (injection-site) AEs will be solicited: 
Table 22 
Solicited local adverse events 
Pain at injection site 
Redness at injection site 
Swelling at injection site 
8.1.3.2. 
Solicited general adverse events 
The following general AEs will be solicited: 
Table 23 
Solicited general adverse events 
Fatigue 
Fever 
Gastrointestinal symptoms † 
Headache 
Myalgia 
Chills 
†Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain. 
Note: Patients will be instructed to measure and record the body temperature in the 
evening. Should additional temperature measurements be performed at other times of 
day, patients will be instructed to record the highest temperature in the diary card. The 
preferred location for measuring temperature in this study is the oral cavity. 
8.1.4. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events  
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
hematology, urinalysis) or other abnormal assessments (e.g. physical examination) that 
are judged by the investigator to be clinically significant will be recorded as AE or SAE 
if they meet the definition of an AE or SAE (refer to Sections 8.1.1 and 8.1.2). Clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen following the start of the study will also be reported as 
AEs or SAEs. However, clinically significant abnormal laboratory findings or other 
abnormal assessments that are associated with the disease being studied, unless judged by 
the investigator as more severe than expected for the patient’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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8.1.5. 
Adverse events of special interest (AESIs) 
8.1.5.1. 
Liver disease-related adverse events 
Liver-disease-related (LDR) adverse events are defined as adverse events related to the 
underlying chronic HBV infection and characterized by one or more of the following 
[Lok, 2003]:  
ALT flares 
• Elevation of ALT > 3 X ULN: 
− 
Mild: > 3-5 X ULN 
− 
Moderate: > 5-10 X ULN 
− 
Severe: > 10 X ULN 
ALT flares with other substantial biochemical changes 
• Bilirubin ≥ 2 X ULN 
• And/or INR > 1.5 
Note: At Laboratory Q2 Solutions, the ULN for ALT is 48 U/L, ULN for bilirubin is 22 
µmol/L. In case the test is performed locally, the reference range of the local laboratory 
should be used. 
Hepatic decompensation 
• Occurrence of one or more of the following events: ascites, spontaneous bacterial 
peritonitis, hepatorenal syndrome, variceal bleeding, or hepatic encephalopathy. 
HBV-DNA breakthrough 
• Any increase in serum HBV DNA by >1 log10 from nadir or redetection of serum 
HBV DNA at levels 10-fold the LLOQ of the viral load after HBV DNA was 
undetectable. 
In case of liver disease-related AE (as defined above), patient will be queried for possible 
medication/herbal substance that may have altered these parameters, as well as for the 
followings signs/symptoms: appearance or worsening of fatigue, nausea, vomiting, 
abdominal pain, jaundice, fever. 
8.1.5.2. 
Hematological adverse events of special interest 
• Spontaneous local or general bleeding with thrombocytes < 50,000 platelets/mm3, 
• Anemia with hemoglobin < 9.5 g/dl. 

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8.1.5.2.1. Thrombosis with Thrombocytopenia Syndrome (Amended: 22 June 
2023) 
Recently, following COVID-19 vaccines, thrombosis with thrombocytopenia syndrome 
(TTS), in some cases accompanied by bleeding, has been observed very rarely following 
vaccination with adenovector-based COVID-19 vaccines. This includes severe cases 
presenting as venous thrombosis, including unusual sites such as cerebral venous sinus 
thrombosis, splanchnic vein thrombosis, as well as arterial thrombosis, concomitant with 
thrombocytopenia. Some cases had a fatal outcome. The majority of these cases 
occurred within the first two weeks following adenovector-based COVID-19 
vaccination and mostly in women under 60 years of age (applicable for all patients 
except for the patients in Belgium). OR The majority of these cases occurred within the 
first three weeks following adenovector-based COVID-19 vaccination and mostly in 
individuals under 60 years of age (applicable for the patients in Belgium only). 
Currently available data are insufficient to either disprove or confirm that TTS is a class 
effect for adenovector-based vaccines. As of May 2021, no TTS event has been reported 
in any GSK studies using adenovector-based vaccines. However, as a precautionary 
measure, safety information related to occurrence of TTS will be collected in this study 
and additional blood sample will be asked from a patient reporting TTS. 
Individuals diagnosed with thrombocytopenia during the entire vaccination phase (from 
dose 1 till 1 month post-last dose) and follow-up phase should be actively investigated for 
signs of thrombosis. Similarly, individuals who present with thrombosis during the entire 
vaccination phase (from dose 1 till 1 month post-last dose) and follow-up phase should be 
evaluated for thrombocytopenia. For diagnostic algorithm and clinical management of 
TTS, clinical guidelines and local recommendations should be followed. For case 
definition of TTS, please refer to the Brighton Collaboration Case Definition provided in 
APPENDIX E. 
In case a confirmed TTS event is reported during this study, patients will be queried for 
additional information which will be documented in the eCRF by the investigator and an 
additional blood sample should be collected within 2 weeks of the diagnosis of the TTS 
for exploratory testing and better understanding of the pathogenesis. Additional blood 
sample collection for TTS event reported during the follow-up phase is optional. Since 
scientific knowledge on TTS pathology and biomarkers for TTS risks in relation to 
adenovector-based vaccines is evolving, this exploratory testing is not to guide TTS 
management and no assay details are specified in the protocol. 
8.1.5.3. 
Potential immune-mediated diseases 
Potential immune-mediated diseases (pIMDs) are a subset of AEs that include 
autoimmune diseases and other inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology. AEs that need to be recorded and 
reported as pIMDs include those listed in Table 24. 
However, the investigator will exercise his/her medical and scientific judgement in 
deciding whether other diseases have an autoimmune origin (i.e. pathophysiology 

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involving systemic or organ-specific pathogenic autoantibodies) and should also be 
recorded as a pIMD. 
Table 24 
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. 
Localised Scleroderma 
(Morphoea). 
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),  
Necrotizing vasculitis (cutaneous or 
systemic),  
anti-neutrophil cytoplasmic antibody 
(ANCA) positive vasculitis (type 
unspecified), 
Henoch-Schonlein purpura (IgA 
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. 

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Vasculitis 
Blood disorders 
Others 
Behcet's syndrome, 
Leukocytoclastic vasculitis. 
 
Idiopathic pulmonary 
fibrosis. 
Goodpasture syndrome. 
Raynaud’s phenomenon. 
Liver disorders 
Gastrointestinal disorders 
Endocrine disorders 
Autoimmune hepatitis. 
Primary biliary cirrhosis. 
Primary sclerosing cholangitis. 
Autoimmune cholangitis. 
Inflammatory Bowel disease, including: 
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. 
When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as a pIMD. Symptoms, signs or conditions which might (or might not) represent 
the above diagnoses, should be recorded and reported as AEs but not as pIMDs until the 
final or definitive diagnosis has been determined, and alternative diagnoses have been 
eliminated or shown to be less likely. 
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire and a list of preferred terms (PTs) and PT codes corresponding to the above 
diagnoses will be available to investigators at study start. 
8.1.6. 
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 8.1.2) related to COVID-19 infection, the following verbatim terms should be 
used according to World Health Organisation (WHO) definition (Please refer to 
APPENDIX D): 
• Suspected COVID-19 infection; or 
• Probable COVID-19 infection; or 
• Confirmed COVID-19 infection 
Information pertaining to COVID-19 infection should be entered in the dedicated eCRF 
page. 
8.2. 
Events or outcomes not qualifying as adverse events or 
serious adverse events  
8.2.1. 
Pregnancy 
Female patients who are pregnant or lactating at the time of vaccination must not receive 
additional doses of study vaccines but may continue other study procedures at the 
discretion of the investigator. 

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While pregnancy itself is not considered an AE or SAE, any adverse pregnancy outcome 
or complication or elective termination of a pregnancy for medical reasons will be 
recorded and reported as an AE or a SAE. 
Note: The pregnancy itself should always be recorded on an electronic pregnancy report. 
The following should always be considered as SAE and will be reported as described in 
Sections 8.4.1 and 8.4.3: 
• Spontaneous pregnancy loss, including: 
− 
spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation) 
− 
ectopic and molar pregnancy 
− 
stillbirth (intrauterine death of foetus after 22 weeks of gestation). 
Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure [EMA, 2006]. It is recognized that national 
regulations might be different. 
• Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life).  
• Any congenital anomaly or birth defect (as per CDC MACDP guidelines) identified 
in the offspring of a study patient (either during pregnancy, at birth or later) 
regardless of whether the foetus is delivered dead or alive. This includes anomalies 
identified by prenatal ultrasound, amniocentesis or examination of the products of 
conception after elective or spontaneous abortion. 
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the investigator to be reasonably related to the study vaccines will be reported to GSK 
Biologicals as described in Section 8.4.3. While the investigator is not obligated to 
actively seek this information from former study participants, he/she may learn of a 
pregnancy through spontaneous reporting. 
8.3. 
Detecting and recording adverse events, serious adverse 
events and pregnancies 
8.3.1. 
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies 
All AEs starting within 30 days following administration of each dose of study vaccine(s) 
(i.e. day of vaccination 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 
vaccines and will end at study conclusion. See Section 8.4 for instructions on reporting of 
SAEs. 

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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 patient consents to participate in the study until she/he is discharged from the 
study. 
The time period for collecting and recording pregnancies will begin at the first receipt of 
study vaccines and will end at study conclusion. See section 8.4 for instructions on 
reporting of pregnancies. 
The time period for collecting and recording of AESIs (liver disease-related AEs, 
hematological AESIs and pIMDs) will begin at the first receipt of study vaccines and will 
end at study conclusion. See section 8.4 for instructions on reporting of pIMDs. 
An overview of the protocol-required reporting periods for AEs, SAEs, pIMDs, liver 
disease-related AEs, hematological AESIs and pregnancies is given in Table 25. 

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Table 25 
Reporting periods for collecting safety information 
Event 
Screening 
 
V1 
 
 
 
V6 
 
 
 
V10 
 
 
 
V14 
 
 
 
V24 
V25 
V26 
 
D1 
Vacc1 
D7 
End of 
7-day 
FU 
D30 
End of 
30-day 
FU 
D57 
Vacc2 
D63 
End of 
7-day 
FU 
D86 
End of 
30-day 
FU 
D113 
Vacc3 
D119 
End of 
7-day 
FU 
D142 
End of 
30-day 
FU 
D169 
Vacc4 
D175 
End of 
7-day 
FU 
D198 
End of 
30-day 
FU 
 
D505 
D673 
D841 
Solicited local 
and general AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
study 
participation  
or concurrent 
GSK medication/ 
vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MAE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Event 
Screening 
 
V1 
 
 
 
V6 
 
 
 
V10 
 
 
 
V14 
 
 
 
V24 
V25 
V26 
 
D1 
Vacc1 
D7 
End of 
7-day 
FU 
D30 
End of 
30-day 
FU 
D57 
Vacc2 
D63 
End of 
7-day 
FU 
D86 
End of 
30-day 
FU 
D113 
Vacc3 
D119 
End of 
7-day 
FU 
D142 
End of 
30-day 
FU 
D169 
Vacc4 
D175 
End of 
7-day 
FU 
D198 
End of 
30-day 
FU 
 
D505 
D673 
D841 
Liver disease-
related adverse 
event* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematological 
AESI* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs 
leading to study 
withdrawal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs: adverse events; AESI: adverse events of special interest; D: Day; FU: follow-up; GSK: GlaxoSmithKline; MAE: medically attended event; pIMDs: potential immune-mediated 
diseases; SAEs: serious adverse events; SC: study conclusion; V: visit; Vacc: vaccination. 
The double-bordered lines indicate timings of vaccine administration 
*For information on AESIs (i.e. pIMDs, liver disease-related adverse event and hematological AESIs), please refer to Section 8.1.5. 
 

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8.3.2. 
Post-Study adverse events and serious adverse events 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 25. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE at 
any time after a patient has been discharged from the study, and he/she considers the 
event reasonably related to the study vaccines, the investigator will promptly notify the 
Study Contact for Reporting SAEs. 
8.3.3. 
Evaluation of adverse events and serious adverse events 
8.3.3.1. 
Active questioning to detect adverse events and serious adverse 
events 
As a consistent method of collecting AEs, the patient should be asked a non-leading 
question such as: 
‘Have you felt different in any way since receiving the vaccine(s) or since the previous 
visit?’ 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the patient’s 
medical records to GSK Biologicals instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK Biologicals. In this instance, all patient identifiers will be blinded on 
the copies of the medical records prior to submission to GSK Biologicals. 
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms. 
8.3.3.2. 
Assessment of adverse events 
8.3.3.2.1. Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 

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Table 26 
Intensity scales for solicited symptoms 
Adverse Event 
Intensity grade 
Parameter 
Pain at injection site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal every day activities. 
 
2 
Moderate: Painful when limb is moved and interferes with 
every day activities. 
 
3 
Severe: Significant pain at rest. Prevents normal every 
day activities. 
Redness at injection site 
Record greatest surface diameter in mm 
Swelling at injection site 
Record greatest surface diameter in mm 
Fever* 
 
Record temperature in °C/°F 
Headache 
0 
Normal 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
Normal 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Gastrointestinal symptoms 
0 
Normal 
(nausea, vomiting, diarrhoea and/or 
abdominal pain) 
1 
Mild: Gastrointestinal symptoms that are easily tolerated 
 
2 
Moderate: Gastrointestinal symptoms that interfere with 
normal activity 
 
3 
Severe: Gastrointestinal symptoms that prevent normal 
activity 
Chills 
0 
Normal 
 
1 
Mild: Chills that is easily tolerated 
 
2 
Moderate: Chills that interferes with normal activity 
 
3 
Severe: Chills that prevents normal activity 
Myalgia 
0 
Normal 
 
1 
Mild: Myalgia that is easily tolerated 
 
2 
Moderate: Myalgia that interferes with normal activity 
 
3 
Severe: Myalgia that prevents normal activity 
*Fever is defined as temperature ≥38.0°C / 100.4°F. The preferred location for measuring temperature in this study will 
be the oral cavity. 
The maximum intensity of local injection site redness/swelling will be scored at GSK 
Biologicals as follows: 
Grade 0 
≤ 20 mm 
Grade 1 
> 20 mm to ≤ 50 mm 
Grade 2 
> 50 mm to ≤ 100 mm 
Grade 3 
> 100 mm 
Fever will be scored as follows: 
 
Celsius 
Fahrenheit 
Grade 1 
38.0 to 38.4°C 
100.4 to 101.1°F 
Grade 2 
38.5 to 38.9°C 
101.2 to 102.0°F 
Grade 3 
≥ 39°C 
≥ 102.1°F 

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The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement. 
The intensity should be assigned to one of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the patient, causing minimal 
discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities. Such an AE 
would, for example, prevent attendance at work and would 
necessitate the administration of corrective therapy. 
An AE that is assessed as Grade 3 (severe) should not be confused with a SAE. Grade 
3 is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets one of the pre-
defined outcomes as described in Section 8.1.2. 
8.3.3.2.2. Assessment of causality 
The investigator is obligated to assess the relationship between study vaccines and the 
occurrence of each AE/SAE using clinical judgement. In case of concomitant 
administration of multiple vaccines/products, if possible, the investigator should specify 
if the AE could be causally related to a specific vaccine/product administered (i.e. 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine(s)/product(s) cannot be determined the investigator should indicate the 
AE to be related to all products. 
Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study vaccines will be considered and investigated. The investigator will also consult the 
IB to determine his/her assessment. 
There may be situations when a SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK Biologicals. However, it is very 
important that the investigator always makes an assessment of causality for every event 
prior to submission of the Expedited Adverse Events Report to GSK Biologicals. The 
investigator may change his/her opinion of causality in light of follow-up information and 
update the SAE information accordingly. The causality assessment is one of the criteria 
used when determining regulatory reporting requirements. 
All solicited local (injection site) reactions will be considered causally related to 
vaccination. Causality of all other AEs should be assessed by the investigator using the 
following question: 

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Is there a reasonable possibility that the AE may have been caused by the study 
vaccine(s)? 
YES 
: 
There is a reasonable possibility that the study vaccine(s) contributed to 
the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study vaccine(s). There are other, more likely 
causes and administration of the study vaccine(s) is not suspected to 
have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 8.1.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE. 
Possible contributing factors include: 
• Medical history. 
• Other medication. 
• Protocol required procedure. 
• Other procedure not required by the protocol. 
• Lack of efficacy of the vaccines, if applicable. 
• Erroneous administration. 
• Other cause (specify). 
8.3.3.3. 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• Recovered/resolved. 
• Recovering/resolving. 
• Not recovered/not resolved. 
• Recovered with sequelae/resolved with sequelae. 
• Fatal (SAEs only). 
8.3.3.4. 
Medically attended visits 
For each solicited and unsolicited symptom the patient experiences, the patient will be 
asked if he/she received medical attention defined as hospitalisation, or an otherwise 
unscheduled visit to or from medical personnel for any reason, including emergency 
room visits. This information will be recorded in the eCRF.  

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8.4. 
Reporting of serious adverse events, pregnancies, and 
other events 
8.4.1. 
Prompt reporting of serious adverse events, pregnancies, and 
other events to GSK Biologicals 
SAEs that occur in the time period defined in Section 8.3 will be reported promptly to 
GSK within the timeframes described in Table 27, once the investigator determines that 
the event meets the protocol definition of a SAE. 
Pregnancies that occur in the time period defined in Section 8.3 will be reported promptly 
to GSK within the timeframes described in Table 27, once the investigator becomes 
aware of the pregnancy. 
AESIs that occur in the time period defined in Section 8.3 will be reported promptly to 
GSK within the timeframes described in Table 27, once the investigator determines that 
the event meets the protocol definition of an AESI. 
Table 27 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK Biologicals 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
Electronic Expedited Adverse 
Events Report 
Pregnancies  
2 weeks* 
electronic pregnancy report 
2 weeks* 
electronic pregnancy report  
AESIs 
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 an 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. 
8.4.2. 
Contact information for reporting serious adverse events, 
pregnancies and AESIs (liver disease-related AEs, hematological 
AESIs and pIMDs)  
Study Contact for Reporting 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 Biologicals Clinical Safety & Pharmacovigilance 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: ogm28723@gsk.com 

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8.4.3. 
Completion and transmission of SAE reports to GSK Biologicals 
Once an investigator becomes aware that a SAE has occurred in a study patient, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event. Even if the investigator does 
not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated 
WITHIN 24 HOURS. 
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE. 
8.4.3.1. 
Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the SPONSOR INFORMATION) or to GSK 
Biologicals Clinical Safety and Pharmacovigilance department within 24 hours.  
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system.  
8.4.4. 
Completion and transmission of pregnancy reports to GSK 
Biologicals 
Once the investigator becomes aware that a patient is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 2 WEEKS. 
Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the pregnancy 
report. 
8.4.5. 
Reporting of AESIs to GSK Biologicals 
Once an AESI is diagnosed (serious or non-serious) in a study patient, the investigator (or 
designate) must complete the information in the electronic Expedited Adverse Events 
Report WITHIN 24 HOURS after he/she becomes aware of the diagnosis. The report 
allows to specify that the event is 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 

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event. For pIMDs, this will be done in accordance with the pIMD 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 8.4.3.1 for back-up system in case the electronic reporting system does 
not work. 
8.4.6. 
Updating of SAE, pregnancy, and AESI information after removal 
of write access to the patient’s eCRF 
When additional SAE, pregnancy, or AESI information is received after removal of the 
write access to the patient’s eCRF, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
SPONSOR INFORMATION) or to GSK Biologicals Clinical Safety and 
Pharmacovigilance department within the designated reporting time frames specified in 
Table 27. 
8.4.7. 
Regulatory reporting requirements for serious adverse events  
The investigator will promptly report all SAEs to GSK in accordance with the procedures 
detailed in Section 8.4.1. GSK Biologicals has a legal responsibility to promptly notify, 
as appropriate, both the local regulatory authority and other regulatory agencies about the 
safety of a product under clinical investigation. Prompt notification of SAEs by the 
investigator to the Study Contact for Reporting SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of other patients are met. 
Investigator safety reports are prepared according to the current GSK policy and are 
forwarded to investigators as necessary. An investigator safety report is prepared for a 
SAE(s) that is both attributable to the study vaccines and unexpected. The purpose of the 
report is to fulfil specific regulatory and GCP requirements, regarding the product under 
investigation. 

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8.5. 
Follow-up of adverse events, serious adverse events, 
pregnancies, AESIs and handling of abnormal parameters 
8.5.1. 
Follow-up of adverse events and serious adverse events  
8.5.1.1. 
Follow-up during the study 
After the initial AE/SAE report, the investigator is required to proactively follow each 
patient and provide additional relevant information on the patient’s condition to GSK 
Biologicals (within 24 hours for SAEs; refer to Table 27). 
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 patient. 
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until 30 
days after the last vaccination. 
8.5.1.2. 
Follow-up after the patient is discharged from the study 
The investigator will follow patients: 
• 
with SAEs, serious or non-serious AESIs, or patients withdrawn from the study as a 
result of an AE, until the event has resolved, subsided, stabilised, disappeared, or 
until the event is otherwise explained, or the patient is lost to follow-up.  
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK Biologicals using a paper/ electronic 
Expedited Adverse Events Report and/or pregnancy report as applicable. 
GSK Biologicals may request that the investigator performs or arranges the conduct of 
additional clinical examinations/tests and/or evaluations to elucidate as fully as possible 
the nature and/or causality of the AE or SAE. The investigator is obliged to assist. If a 
patient dies during participation in the study or during a recognised follow-up period, 
GSK Biologicals will be provided with any available post-mortem findings, including 
histopathology. 
8.5.2. 
Follow-up of pregnancies 
Pregnant patients will be followed to determine the outcome of the pregnancy. At the end 
of the pregnancy, whether full-term or premature, information on the status of the mother 
and child will be forwarded to GSK Biologicals using the electronic pregnancy report and 
the Expedited Adverse Events Report if applicable. Generally, the follow-up period 
doesn’t need to be longer than six to eight weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE. 

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8.5.3. 
Handling of abnormal biochemistry and hematology parameters 
Throughout the study period, in case of ALT > 3 X ULN, every attempt should be made 
to have the patient return to the study site as soon as possible to: 
• Repeat the biochemistry and hematology tests on newly collected blood samples, 
preferably within 48-72 hours, to confirm the abnormalities and to determine if they 
are increasing or decreasing. If deemed necessary, the retests could be performed 
locally, at the discretion of the investigator. The normal laboratory ranges of the local 
laboratory and the results should be recorded in the eCRF. 
• enquire details of the signs/symptoms, e.g. appearance or worsening of fatigue, 
nausea, vomiting, abdominal pain, jaundice, fever. 
• If the liver biochemistry parameter abnormality is confirmed or symptoms persist, the 
patient should be under appropriate monitoring, at the discretion of the investigator, 
which may include but not limited to: 
• Repeat the tests two or three times weekly. Frequency of retesting can decrease to 
once a week or less if abnormalities stabilize or the trial drug has been discontinued 
and the patient is asymptomatic,  
• Obtain a more detailed history of symptoms and concurrent diseases,  
• Query for possible exposure to medication/herbal substance or environmental 
chemical agents or alcohol use or special diets that may have altered these 
parameters, 
• Perform additional clinical examinations and/or testing as appropriate to identify the 
possible cause of the abnormal parameters.  
Patients with other hematology/biochemistry parameters of Grade 3 and above have to 
repeat the relevant tests at least once a week until returned to normal or Grade 1 values. 
During the primary phase, 
• Patients with confirmed ALT > 384 U/L (i.e. > 8 X ULN) (repeated testing preferably 
within 48-72 hours) will be withdrawn from vaccination. If the result is not 
confirmed, tests will be repeated until ALT level decreases to < 72 U/L (i.e. < 1.5 X 
ULN). Patients with ALT < 72 U/L (i.e. < 1.5 X ULN) will be eligible for the next 
vaccine administration.  
• Patients with confirmed ALT > 241 U/L (i.e. > 5 X ULN) (repeated testing preferably 
within 48-72 hours) that persists for 2 weeks will be withdrawn from vaccination. If 
the result is not confirmed, tests will be repeated until ALT level decreases to < 72 
U/L (i.e. < 1.5 X ULN). Patients with ALT < 72 U/L (i.e. < 1.5 X ULN) will be 
eligible for the next vaccine administration. 
• Patients with confirmed ALT > 144 U/L (i.e. > 3 X ULN) and INR > 1.5 (repeated 
testing preferably within 48-72 hours) will be withdrawn from vaccination. If the 
result is not confirmed, tests will be repeated until ALT level decreases to < 72 U/L 
(i.e. < 1.5 X ULN) and INR decreases to < 1.2. Patients with ALT < 72 U/L (i.e. < 1.5 
X ULN) and INR < 1.2 will be eligible for the next vaccine administration.  

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• Patients with confirmed ALT > 144 U/L (i.e. > 3 X ULN) and bilirubin > 44 µmol/L 
(> 2 X ULN) (repeated testing preferably within 48-72 hours) will be withdrawn from 
vaccination. If the result is not confirmed, tests will be repeated until ALT level 
decreases to < 72 U/L (i.e. < 1.5 X ULN) and bilirubin level decreases to < 22 µmol 
/L (i.e. < 1 X ULN). Patients with ALT < 72 U/L (i.e. < 1.5 X ULN) and bilirubin < 
22 µmol/L (i.e. < 1 X ULN) will be eligible for the next vaccine administration. 
The interval between the two vaccine doses may then be extended to up to maximum 12 
weeks. 
8.6. 
Treatment of adverse events 
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of a SAE / AESI 
should be recorded in Expedited Adverse Event Report of the patient’s eCRF (refer to 
Section 6.7). 
8.7. 
Subject card 
Study patients 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 patient. In 
an emergency situation this card serves to inform the responsible attending physician that 
the patient is in a clinical study and that relevant information may be obtained by 
contacting the investigator. 
Patients must be instructed to keep subject cards in their possession at all times during the 
study duration. 
8.8. 
Holding rules and safety monitoring 
8.8.1. 
Internal Safety Review Committee (iSRC) 
This study will be overseen by an iSRC operating under a charter. Core members of the 
iSRC will include a GSK Biologicals’ safety physician, a hepatologist, a Clinical 
Research and Development Lead, and a biostatistician who are not otherwise involved in 
the conduct of the Therapeutic HBV studies. The iSRC will conduct the safety review 
using unblinded data. 
The iSRC will determine whether any of the predefined study holding rules (see Section 
8.8.3) are met or whether there is any other safety signal during the planned iSRC 
evaluation (see Section 8.8.2). In addition to the planned iSRC evaluation, ad hoc iSRC 
reviews can be triggered in case any safety concern is observed. 
An external (non-GSK) expert with clinical expertise in hepatology will work together 
with the iSRC to review the safety data and contribute to the decision-making process to 
hold or continue the study.  

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If no safety signal is observed, the favourable outcome of the safety evaluation 
authorising the investigator to proceed with vaccination of patients will be documented 
and provided in writing to the investigators. 
If a holding rule is met, the study will be put on hold. All vaccinations will cease 
immediately, but all other procedures relating to safety, immunology, efficacy and 
disease monitoring will continue. Following an internal review, Company will then 
decide to suspend, modify or continue the conduct of the study. This decision will be 
documented and provided in writing to the investigators. If following this internal safety 
review, the Sponsor deems it appropriate to restart the enrolment, this can be done 
following approval of a substantial amendment by the regulatory authorities. 
8.8.2. 
Details on the staggered vaccination and dose escalation 
The study will be conducted following a staggered design overseen by the iSRC (see 
Figure 4).  
Within each Step (see Figure 3): 
• A maximum of
patients per group (e.g. 
 
 will first be randomized for vaccination and followed for 2 days. When all these 
patients have completed Visit 2 (i.e. 2-day post Dose 1), iSRC will review all the 
available safety data. If the iSRC considers it appropriate to continue, the 
randomization of the remaining patients in each group can start. If ≥
patients 
randomized at the same study site on the same day, these patients should be 
vaccinated sequentially with at least 60 minutes apart to allow monitoring of any 
acute event, such as anaphylactic reaction. 
• Prior to the administration of the Dose 2, Dose 3 and Dose 4 to the first patient, a 
favorable outcome of the iSRC evaluation of data up to 30 days after Dose 1, Dose 2 
and Dose 3, respectively, should be available. 
iSRC: internal Safety Review Committee; p-v: post-vaccination. 
For the second dose vaccination, there will be at least 8 days apart between the time the initially recruited patients (i.e. 
 complete administration of Dose 2 and the remaining patients within 
each step start receiving Dose 2. This will allow a completion of 7-day safety follow up of Dose 2 by initially recruited 
patients before dosing of Dose 2 to the remaining patients. 
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Dose-escalation between steps will be done as follows (See Figure 4): 
• Step A (low dose of each vaccine): Approximately
patients will be randomised for 
vaccination in Step A. When all these patients have completed Visit 8 (i.e. 14-day 
post Dose 2), the iSRC will review all the available safety data. If the iSRC considers 
it appropriate to continue the study, Step B treatment randomization and 
administration can start. Note that safety assessment of at least
patients in Step A 
with available data up to Visit 8 i.e. 14 days post-vaccination Dose 2, may be 
considered sufficient prior moving to Step B, if approved by local authorities. Refer 
to Section 8.8.3.2 for considerations to conclude Step A with
patients instead of
patients initially planned.  
• Step B (prime-boost with ChAd155-hIi-HBV and MVA-HBV and sequential 
administration with HBc-HBs/AS01B-4): Approximately
patients from Step B will 
first be randomised for vaccination. When they have completed Visit 8 (i.e. 14-day 
post Dose 2), the iSRC will review all the available safety data. If the iSRC considers 
it appropriate to continue the study, the treatment randomisation and administration to 
the remaining patients in Step B can start.  
• Step C (prime-boost with ChAd155-hIi-HBV and MVA-HBV and co-administration 
with HBc-HBs/AS01B-4): After Step B enrolment is complete, Step C treatment 
randomization and administration can start.  
• Prior to initiating the randomization for each step, the study team will review the 
number of subjects available for that step. 
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8.8.3. 
Holding rules 
8.8.3.1. 
Holding rules definitions and monitoring 
The following safety holding rules (Table 28) will be checked by iSRC during each 
safety evaluation. Meeting any of these holding rules during the primary phase will 
trigger a hold of vaccination in the clinical study, irrespective of the number of patients 
enrolled and/or the timing of the event relative to vaccination. 
• Holding rules 1, 2 and 3 will be assessed by the iSRC during the safety evaluation. 
• Holding rules 1 and 3 will also be monitored by the investigator on a continuous 
basis irrespective of the number of patients enrolled. If an investigator detects one of 
the holding rules mentioned above, he/she will immediately put the enrolment or the 
vaccination on hold and he/she will immediately inform the Sponsor and enter the 
data in the eCRF. It is the Sponsor’s responsibility to put the enrolment or the 
vaccination on hold at all sites. 

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Table 28 
Holding rules 
Holding 
Rule 
Event 
Number of 
patients 
1a 
Death or any life-threatening SAE 
≥ 1 
1b 
Any SAE that is considered as related to the vaccine in an investigational group 
≥ 1 
1c 
Any withdrawal from the study (by investigator or patient request) following a Grade 3 AE 
that cannot reasonably be attributed to a cause other than vaccination  
≥ 1 
1d 
Any local or general solicited AE leading to hospitalization, or fever > 40°C (104°F) that 
cannot reasonably be attributed to a cause other than vaccination, or necrosis at the 
injection site, within the 7-day (days 1-7) post-vaccination period  
≥ 1 
2a 
Any Grade 3 solicited local AE (lasting 48h or more) in an investigational group, within the 
7-day (day 1-7) post-vaccination period  
At least 25% 
AND ≥ 2 in a 
vaccine group 
2b 
Any Grade 3 solicited general AE (lasting 48h or more) in an investigational group, that 
cannot reasonably be attributed to a cause other than vaccination, within the 7-day (day 1-
7) post-vaccination period 
At least 25% 
AND ≥ 2 in a 
vaccine group 
2c 
Any Grade 3 unsolicited AE in an investigational group, that cannot reasonably be 
attributed to a cause other than vaccination, within the 7-day (day 1-7) post-vaccination 
period or  
Any Grade 3 abnormality in pre-specified hematological or biochemical laboratory 
parameters in an investigational group within the 7-day (day 1-7) post-vaccination period 
At least 25% 
AND ≥ 2 in a 
vaccine group 
3a 
Any acute exacerbation or severe hepatitis flare (intermittent elevation of ALT to more than 
10 times the ULN) * 
≥ 1 
3b 
Any acute exacerbation or moderate hepatitis flare for more than 2 weeks (intermittent 
elevation of ALT to > 5 to < 10 X ULN) * 
≥ 1 
3c 
Any ALT flare (ALT > 3XULN) with other substantial liver biochemical change defined as an 
increase in serum bilirubin to ≥2 x ULN and/or international normalized ratio (INR) >1.5 * 
≥ 1 
3d 
Any hepatic decompensation defined as the occurrence of 1 or more of the following 
events: ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, 
or hepatic encephalopathy 
≥ 1 
3e 
Any reactivation of chronic hepatitis B as characterized by HBV-DNA breakthrough 
accompanied with 1 or more of the following: ALT elevation to > 3 X ULN, substantial 
biochemical changes, or hepatic decompensation as defined above 
≥ 1 
3f 
Any AE related to spontaneous local or general bleeding AND Thrombocytopenia < 
50,000/mm3 
≥ 1 
* The abnormal value should be confirmed by an additional testing preferably within 48-72 hours; if no additional value 
is available within one week, the initial value will be considered as confirmed. ULN for ALT = 48 U/L (Q2 Solutions 
Laboratory); ULN for bilirubin = 22 µmol/L (Q2 Solutions Laboratory). In case the test is repeated locally, the reference 
range of the local laboratory should be used and recorded. 
8.8.3.2. 
Risk assessment for the holding rules 
Figure 5 presents the probability of not meeting defined holding rule for 
 patients 
per study group. 
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Figure 5 
Safety holding rules with associated probabilities  
 
 

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The above Figure 5 illustrates that, with 
 patients in a group: 
• For holding rules 1 and 3, using a cut-off of 
, there is around 90% chance that 
the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 35% and around 60% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 10%. 
• For holding rule 2, using a cut-off of 
 there is only around 60% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true incidence 
rate of 35% and around 90% chance that the holding rule is not met in a vaccine 
group if the corresponding event has true incidence rate of 10%. 
• For holding rules 1 and 3, using a cut-off of 
 there is around 82% chance that 
the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 35% and around 66% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 10%.  
• For holding rule 2, using a cut-off of 
, there is around 44% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true incidence 
rate of 35% and around 95% chance that the holding rule is not met in a vaccine 
group if the corresponding event has true incidence rate of 10%.  
Table 29 provides the impact on the probability of detecting holding rule with
patients 
as compared to
patients : 
• There is a decrease in sensitivity of detecting a holding rule event, meaning that there 
is 5% to 7% decrease in probability of detecting a holding rule event in
patient 
among 4 patients as compared to
patients and 3% to 14% decrease in probability of 
detecting a holding rule in
patients among
patients as compared to
patients. 
• If the study had continued to vaccinate
patients in Step A 
patients per group), 
considering the incidence rates of 25% [95%CI: 0.63;80.59] observed in
patients 
patients per group), the probability to have an event meeting a holding rule 
criterion will be below 50% [49%=Upper limit of 1-sided 67% CI] with 67% of 
confidence. 
• No AEs meeting holding rule events were reported up to 14 days post-vaccination 
Dose 2. Therefore, if the study had continued to enrol up to
patients, the additional 
safety data are very unlikely to change the observed safety profile. 
Table 29 
Probability of meeting holding rule with 
 patients  
True Incidence rates 
Probability of meeting holding rule 
10% 
41% 
34% 
8% 
5% 
15% 
56% 
48% 
16% 
11% 
20% 
67% 
59% 
26% 
18% 
25% 
76% 
68% 
37% 
26% 
30% 
83% 
76% 
47% 
35% 
35% 
89% 
82% 
57% 
44% 
40% 
92% 
87% 
66% 
52% 
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By Data lock point of 24 April 2020, 
patients received at least one dose of study 
treatment in Step A. Among them
patients completed the study treatment and
patients received at least 2 doses of study treatment. To date, no safety concerns were 
raised and no holding rule was met as confirmed by iSRC based on the safety review. 
Refer to IB Edition 4 Supplement for details.  
Considering that no events that could trigger a holding rule were reported up to 14 days 
post-vaccination Dose 2, if the study had to continue to enrol up to
patients in Step A, 
the additional safety data would be very unlikely to change the observed safety profile. 
The likelihood of detection of holding rule based on 
 patients among
patients 
versus
patients per group (i.e.
patients versus
patients in total in Step A) has been 
thoroughly evaluated.  
Therefore it is proposed that safety assessment of at least
patients in Step A with 
available data up to Visit 8 i.e. 14 days post-vaccination Dose 2, may be considered 
sufficient prior moving to Step B.  
For sites that participate in Step A, this will be implemented, when approved by local 
authorities. For sites that do not participate in Step A, safety assessment of Step A 
patients only or assessment of cumulative data of Step A and first patients in Step B will 
be considered prior starting the Step B, depending on the country feedback. 
Figure 6 presents the probability of not meeting defined holding rule for
patients per 
study group.  
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The above Figure 6 illustrates that, with
patients in a group: 
• For holding rules 1 and 3, using a cut-off of 
, there is around 88% chance that 
the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 10% and around 45% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 5%. 
• For holding rule 2, using a cut-off of 
, there is around 90% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true incidence 
rate of 20% and around 10% chance that the holding rule is not met in a vaccine 
group if the corresponding event has a true incidence rate of 20%. 
• For holding rule 2, using a cut-off of 
, there is around 70% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true incidence 
rate of 30% and there is around 96% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 10%. 
The above Figure 7 illustrates that, with
patients in a group: 
• For holding rules 1 and 3, using a cut-off of 
, there is around 90% chance that 
the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 5% and around 10% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 5%. 
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• For holding rule 2, using a cut-off of 
, there is around 90% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true incidence 
rate of 10% and around 10% chance that the holding rule is not met in a vaccine 
group if the corresponding event has a true incidence rate of 10%. 
• For holding rule 2, using a cut-off of 
, there is around 90% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true incidence 
rate of 35% and there is around 99% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 10%. 
9. 
PATIENT COMPLETION AND WITHDRAWAL 
9.1. 
Patient completion 
A patient who returns for the concluding visit foreseen in the protocol is considered to 
have completed the study. 
9.2. 
Patient withdrawal 
Patients withdrawn after randomization will not be replaced. 
9.2.1. 
Patient withdrawal from the study 
From an analysis perspective, a ‘withdrawal’ from the study refers to any patient who did 
not come back for the concluding visit foreseen in the protocol.  
All data collected until the date of withdrawal/last contact of the patient will be used for 
the analysis. 
A patient 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 patient from the date of withdrawal/last contact. 
Investigators will make an attempt to contact those patients who do not return for 
scheduled visits or follow-up. Specific actions to be taken by the Investigator to re-
establish the contact with the patient may include up to 3 telephone calls and/or emails 
and a certified letter to the last known address.  
Information relative to the withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a patient from the study was made by 
the patient himself/herself or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal: 
• Serious adverse event. 
• Unsolicited non-serious adverse event. 
• Solicited adverse event 
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• Protocol violation (specify). 
• Consent withdrawal, not due to an adverse event*. 
• Moved from the study area. 
• Lost to follow-up. 
• Sponsor study termination. 
• Other (specify). 
*In case a patient is withdrawn from the study because he/she has withdrawn consent, the 
investigator will document the reason for withdrawal of consent, if specified by the 
patient in the eCRF. 
Patients who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from patients who are withdrawn for other reasons. Investigators will 
follow patients who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 8.5.1.2). 
9.2.2. 
Patient withdrawal from study vaccines 
A ‘withdrawal’ from the study vaccines refers to any patient who does not receive the 
complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A patient withdrawn from the study vaccines may not necessarily be 
withdrawn from the study as further study procedures or follow-up may be performed 
(safety or immunogenicity) if planned in the study protocol. For the purpose of this study, 
all study procedures except study vaccines administration, its related procedures 
(treatment number allocation, etc.) remain applicable to the patients.  
If vaccination cannot be administered within a maximum of 111 days between 
subsequent vaccinations (refer to Table 6), patient should discontinue study vaccination 
and management of follow up visits in the primary phase (Epoch 002) should be 
performed as described below and in Section 5.6.18:  
• For patients who discontinued vaccination after vaccination Dose 1, Visits 10, 12, 13, 
14 and 17-22 should be performed, as defined in Table 4 and Table 5, for follow up 
on safety and laboratory parameters. 
• For patients who discontinued vaccination after vaccination Dose 2, Visits 14 and 17-
22 should be performed, as defined in Table 4 and Table 5, for follow up on safety 
and laboratory parameters.  
• For patients who discontinued vaccination after vaccination Dose 3, Visits 18-22 
should be performed, as defined in Table 5, for follow up on safety and laboratory 
parameters.  
• For all patients who discontinued study vaccination, the planned visits in the follow 
up phase (Epoch 003) should be performed as defined in Table 5.  

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Information relative to premature discontinuation of the study vaccines will be 
documented on the Vaccine Administration screen of the eCRF. The investigator will 
document whether the decision to discontinue further vaccination/treatment was made by 
the patient himself/herself or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal: 
• Serious adverse event. 
• Unsolicited non-serious adverse event. 
• Solicited adverse event 
• Not willing to be vaccinated 
• Other (specify). 
9.3. 
Screening and baseline failures 
A patient is considered to be a Screening failure if the patient signs the ICF, but 
withdraws before randomization to study treatment. The following information will be 
collected for Screening failures: 
• Informed consent 
• Inclusion/exclusion criteria 
• Demographic data 
• Medical history 
• Physical examination 
• Blood samples for Screening tests 
• SAEs related to study participation, to concomitant use of GSK products or any fatal 
SAEs 
• Screening failure details  
10. 
STATISTICAL METHODS 
10.1. 
Primary endpoints 
• Occurrence of AEs from vaccination up to Day 337: 
− 
Occurrence of each solicited local and general symptoms within 7 days after 
each vaccination (from day of vaccination to six days after vaccination). 
− 
Occurrence of unsolicited AEs within 30 days after each vaccination (from day 
of vaccination to 29 days after vaccination). 
− 
Occurrence of hematological, biochemical or urinalysis laboratory abnormalities 
within 30 days after each vaccination (from day of vaccination to 29 days after 
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− 
Occurrence of SAEs up to six months after the last dose (Day 337, Visit 22). 
− 
Occurrence of pIMDs up to six months after the last dose (Day 337, Visit 22). 
− 
Occurrence of liver-disease related AEs up to six months after the last dose (Day 
337, Visit 22). 
− 
Occurrence of hematological AESIs up to six months after the last dose (Day 
337, Visit 22). 
− 
Occurrence of medically attended events (MAEs) up to six months after the last 
dose (Day 337, Visit 22). 
10.2. 
Secondary endpoints 
Immunogenicity 
Immunogenicity with respect to HBV components of the viral vectored vaccines and 
adjuvanted proteins vaccines, at predefined time points (see Table 4 and Table 5). 
• Anti-HBc antibodies: seropositivity and concentration. 
• Anti-HBs antibodies: seroconversion and concentration; anti-HBs ≥10 mIU/ml and 
≥100 mIU/ml. 
• Frequency of HBc- and HBs- specific CD4+ T-cells and CD8+ T-cells; CD4+ T-cells 
responder, CD8+ T-cells responder. 
Efficacy 
• qHBsAg: number of patients with ≥ 0.5 log decrease, ≥ 1-log decrease, HBsAg loss 
and log-changes since pre-vaccination.  
• Number of patients with HBsAg loss and anti-HBs seroconversion.  
• Mean qHBsAg in each group.  
Safety 
• Occurrence of AEs from vaccination up to Day 841:  
− 
Occurrence of any SAEs throughout the study period, 
− 
Occurrence of SAEs causally related to an investigational vaccine throughout 
the study period, 
− 
Occurrence of MAEs throughout the study period, 
− 
Occurrence of pIMDs throughout the study period, 
− 
Occurrence of liver disease-related AEs throughout the study period, 
− 
Occurrence of spontaneous local or general bleeding with thrombocytopenia (< 
50,000 platelets/mm3), 
− 
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− 
Occurrence of AEs and SAEs leading to study withdrawal. 
• Pregnancy and pregnancy outcome throughout the study period. 
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11. 
ADMINISTRATIVE MATTERS 
To comply with ICH GCP administrative obligations relating to data collection, 
monitoring, archiving data, audits, confidentiality, public disclosure requirements and 
publications must be fulfilled.  
11.1. 
electronic Case Report Form instructions 
A validated GSK defined electronic data collection tool will be used as the method for 
data collection.  
In all cases, patient initials will not be collected nor transmitted to GSK. Patient data 
necessary for analysis and reporting will be entered/transmitted into a validated database 
or data system. Clinical data management will be performed in accordance with 
applicable GSK standards and data cleaning procedures. 
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While completed eCRFs are reviewed by a GSK Biologicals’ Site Monitor at the study 
site, omissions or inconsistencies detected by subsequent eCRF review may necessitate 
clarification or correction by the investigator or appropriately qualified designee. In all 
cases, the investigator remains accountable for the study data.  
The investigator will be provided with a CD-ROM of the final version of the data 
generated at the investigational site once the database is archived and the study report is 
complete and approved by all parties. 
11.2. 
Study Monitoring by GSK Biologicals 
GSK will monitor the study to verify that, amongst other items, the:  
• Data are authentic, accurate, and complete. 
• Safety and rights of patients are being protected. 
• Study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements.  
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents. 
The investigator must ensure provision of reasonable time, space and qualified personnel 
for monitoring visits. 
Direct access to all study-site related and source data is mandatory for the purpose of 
monitoring review. The monitor will perform an eCRF review and a Source Document 
Verification (SDV). By SDV we understand verifying eCRF entries by comparing them 
with the source data that will be made available by the investigator for this purpose.  
The Source Documentation Agreement Form describes the source data for the different 
data in the eCRF. This document should be completed and signed by the site monitor and 
investigator and should be filed in the investigator’s study file. Any data item for which 
the eCRF will serve as the source must be identified, agreed and documented in the 
source documentation agreement form.  
Upon completion or premature discontinuation of the study, the monitor will conduct site 
closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations, GCP, and GSK procedures. 
11.3. 
Record retention 
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere) in a safe and 
secure location. The records must be easily accessible, when needed (e.g. audit or 
inspection), and must be available for review in conjunction with assessment of the 
facility, supporting systems, and staff. Where permitted by applicable laws/regulations or 
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other than hard copy (e.g. microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions 
are legible and are a true and accurate copy of the original and meet accessibility and 
retrieval standards, including re-generating a hard copy, if required. Furthermore, the 
investigator must ensure that an acceptable back-up of the reproductions exists and that 
there is an acceptable quality control procedure in place for making these reproductions. 
GSK will inform the investigator/institution of the time period for retaining these records 
to comply with all applicable regulatory requirements. The minimum retention time will 
meet the strictest standard applicable to a particular site, as dictated by ICH GCP, any 
institutional requirements, applicable laws or regulations, or GSK standards/procedures, 
otherwise, the minimum retention period will default to 25 years after completion of the 
study report. 
The investigator/institution must notify GSK of any changes in the archival 
arrangements, including, but not limited to archival at an off-site facility, transfer of 
ownership of the records in the event the investigator leaves the site.  
11.4. 
Quality assurance 
To ensure compliance with GCP and all applicable regulatory requirements, GSK may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory 
inspection of this study. Such audits/inspections can occur at any time during or after 
completion of the study. If an audit or inspection occurs, the investigator and institution 
agree to allow the auditor/inspector direct access to all relevant documents and to allocate 
his/her time and the time of his/her staff to the auditor/inspector to discuss findings and 
any relevant issues. 
11.5. 
Posting of information on publicly available clinical trial 
registers and publication policy 
GSK assures that the key design elements of this protocol will be posted on the GSK 
website and in publicly accessible database(s) such as clinicaltrials.gov, in compliance 
with the current regulations. 
GSK also assures that results of this study will be posted on the GSK website and in 
publicly accessible regulatory registry(ies) within the required time-frame, in compliance 
with the current regulations. The minimal requirement is to have primary endpoint 
summary results disclosed at latest 12 months post primary PCD and to have secondary 
endpoint disclosed at latest 12 months after the LSLV as described in the protocol. 
As per EU regulation, summaries of the results of GSK interventional studies (phase I-
IV) in adult population conducted in at least one EU member state will be posted on 
publicly available EMA registers within 12 months of EoS (as defined in the protocol) in 
the concerned EU member state. However, where, for scientific reasons detailed in the 
protocol, it is not possible to submit a summary of the results within one year in the 
concerned EU member state, the summary of results shall be submitted as soon as it is 
available. In this case, the protocol shall specify when the results are going to be 
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GSK also aims to publish the results of these studies in searchable, peer reviewed 
scientific literature and follows the guidance from the International Committee of 
Medical Journal Editors. 
11.6. 
Provision of study results to investigators 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location. 
GSK Biologicals will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the study 
patients, as appropriate. 
11.7. 
Data Sharing 
Under the framework of the SHARE initiative, results of GSK studies may be combined 
with non- GSK studies, to investigate further about the study product(s) and other 
product(s), and /or the disease/condition under investigation and related diseases and 
conditions. 
11.8. 
Pharmacogenomics 
By United States federal regulation, annual reports must include relevant 
pharmacogenomics results experiment. Refer to the US Guidance for industry 
“Pharmacogenomic data submissions” for more information on the process and format 
for submission of such data. 
12. 
COUNTRY SPECIFIC REQUIREMENTS 
12.1. 
Germany 
Explanatory statement concerning Gender Distribution (Article 7, paragraph 2 (12) 
of the German GCP ORDER). 
For this TH HBV VV-001 study, there is no intention to conduct specific analyses 
investigating the relationship between gender and the safety, immunogenicity and 
efficacy of the investigational HBV vaccines. Recruitment will include both males and 
females. To not expose pregnant women and their foetuses/children to an early-phase 
investigational vaccine, females enrolled in this trial will either be of non-childbearing 
potential (i.e., hysterectomy, bilateral ovariectomy or be premenarchal or 
postmenopausal), or if she is of childbearing potential, she must have a negative 
pregnancy test at the Screening and practice adequate contraception from Screening until 
12 weeks after completion of the vaccine series (Refer to the study protocol, Section 4.2 
“Inclusion criteria” and Section 4.3 “Exclusion criteria”). The recruitment will be closed 
to females who are pregnant or lactating. Similarly, patients becoming or deciding to 
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According to the Hepatitis B annual epidemiological report by European Centre for 
Disease Prevention and Control, male-to-female ratio of acute or chronic hepatitis B was 
1.5 to 1 [European Centre for Disease Prevention and Control, 2016]. In Germany, the 
prevalence of acute or chronic HBV infection (as evident by anti-HBc positive and 
HBsAg positive) among men was 0.5% (0.2–1.1) and among women was 0.2% (0.1–0.4); 
the relatively high prevalence among men as compared to women was statistically not 
significant [Poethko-Müller, 2013]. With respect to the nucleot(s)ide treatment, there is 
no gender differences in the safety outcomes or efficacy [Summary of product 
characteristics for Entecavir; Prescribing information for Tenofovir disoproxil fumarate]. 
Liver ultrasound 
In case liver ultrasound is not possible, another imaging method may be used at the 
discretion of the investigator. However, study related application of radioactive 
substances or ionizing radiation (including X-rays) needs approval by Federal Office for 
Radiation Protection according § 23 StrlSchV respectively § 28a RöV. 
Remote Source Data Verification (rSDV) during exceptional situations in Germany 
Frequent instream monitoring of safety data by the central study team at GSK is required 
for this study. Instream review of study data items and processes should be considered 
during exceptional situations/circumstances, such as with pandemics like COVID-19, 
focusing on key data points, patient assessments and processes that are critical to ensure 
the rights, safety and well-being of study participants and the integrity of the study and 
data. Prior to any rSDV activity a written agreement by the Investigator will be obtained. 
The agreement includes the extent and the method of rSDV activities. Monitoring Plan 
and Study-Specific Risk Register will be updated to include rSDV activities and clinical 
research associates (CRAs) will be guided for the conduct of rSDV. 
Option 1 Transfer of redacted Source Documentation 
Process for transfer and review of redacted source documentation provided by the site: 
• The CRA instructs study site on the source data needed for the remote SDV activities. 
• The CRA instructs site staff they must pseudonymize the requested documentation, 
do a quality check that anonymized (redacted) areas cannot be read, and then delivers 
the documentation to the CRA in an encrypted form of communication (the site 
should have a documented process). 
• The minimum requirements regarding quality of the copies will be agreed with the 
site upfront: 
− 
For the scanning of paper documents resolution will be a minimum of 300 dots 
per inch (dpi). 
− 
For the scanning of photographs and images resolution will be 600 dots per inch 
(dpi) minimum. 
− 
Colour scanners must be able to produce copies that match the original. 
− 
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− 
Documents will be saved as portable document format (PDF). 
− 
In order to maintain quality standards, a captured image will not be subjected to 
non-uniform scaling (i.e. sizing) or re-sampling to a lower resolution. 
• 
Redacted source document scans will be sent to the CRA via email using one of the 
following secure options: 
a. 
Transport Layer Security (TLS) connection: 
TLS connections are intended to support significant mail flow between GSK and external 
partners in a secure manner. 
b. GSK Secure 
In cases where only a handful of users are communicating or the volume of emails is low, 
the use of GSK secure, the GSK ad-hoc message encryption solution is recommended. 
c. 
Password protected PDF attachment 
− 
A password protected scan (PDF) will be attached to an email. The password to 
open the attachment will be sent in a separate email. 
• 
The CRA may use the secure email website to assess whether the sites email address 
is secure (i.e. encrypted). 
 
• 
Prior to starting remote SDV the CRA ensures that the provided documents are 
complete and do not contain any Personal Information (PI). 
− 
In case the CRA detects any PI that has not been redacted, the CRA informs the 
study site and deletes the files (incl. the Recycle bin). 
− 
A Data Breach must be reported Data Breach Web Report Form. 
• 
Use of an external PC screen is recommended. The CRA will not generate any 
copies from the source data received. 
• 
Source data verification/review will be conducted according to the process outlined 
in the GSK Monitoring SOP. 
• 
After completion of SDV activities, the CRA deletes all copies/images of subject 
data received from the site. This includes the deletion of the recycle bin and any 
temporary files. 
• 
A statement confirming that all documents were destroyed will be provided by the 
CRA via email to the site. 
• 
Details of what was monitored remotely will be documented in the appropriate 
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Option 2 – Review of Subject Source Documentation remotely 
Process for use of Webcams, WebEx, MS Teams for viewing subject source remotely: 
• 
The CRA ensures that the site personnel sharing information with GSK has authority 
to do so.  
• 
Remote SDV activities will be performed exclusively by the assigned site monitor. 
• 
Prior to conducting any remote SDV activities the CRA ensures that a written 
informed consent, covering the proposed SDV activities, has been signed by the 
study patient. 
• 
For CRAs using GSK laptops, only use GSK approved video conferencing tools (e.g. 
MS Teams or GSK WebEx). Live image transmission is fully encrypted and 
protected for authorised user. By using these systems, it will be assured that data will 
be viewed only but not transmitted/stored. 
• 
For functional service provider (FSP)/Local contract research organisation (CRO) 
CRAs not using GSK laptops, only MS Teams via RAA (Remote Access 
Application) may be used for meetings between the CRA and the site. WebEx is not 
permitted from non-GSK laptops. Other tools like FaceTime, WhatsApp or Zoom are 
not permitted since they do not have sufficient encryption features. GSK does not 
have enterprise contract/privacy agreement with these providers. 
• 
Prior to the remote monitoring visit, the CRA instructs study site on the specific data 
needed for the remote SDV. 
• 
Source data verification will be conducted according to the process outlined in the 
Monitoring SOP. 
• 
The use of a headset is required, do not use computer audio. 
• 
The CRA does not capture screens or take pictures of screens to ensure we are not 
transferring content outside of clinical sites. 
• 
WebEx or Teams do not store or have access to any data, GSK staff is not allowed to 
make or store any screenshots or save any data which has been shared.  
• 
Details of what was monitored remotely will be documented in the appropriate 
section of the MVR. 
In case of technical malfunctions or if the security of the transmission is no longer 
ensured, we will pause rSDV activities. GSK Issue Management Procedures will be 
initiated. 
12.2. 
France 
This section includes requirements of French Public Health Code / specific local GSK 
requirements and identifies, item per item, the mandatory modifications or additional 
information applicable to the study. 
1. Concerning the « SELECTION OF STUDY POPULATION AND WITHDRAWAL 
CRITERIA»  

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• The following vulnerable subject populations will be excluded: minors, protected 
subjects, adult subjects not in condition to express their consent, subjects deprived of 
liberty, subjects receiving psychiatric cares, subjects hospitalized in a Health and 
Social Establishment for other purpose than the participation to the study. 
• A subject will be eligible for inclusion in this study if he /she is either affiliated to or 
beneficiary of a social security category (French Public Health Code law L.1121-8-1). 
(exception for a participant to a non-interventional study if authorised by the Ethics 
Committee). It is the investigator’s responsibility to ensure and to document (in the 
source document - subject notes) that the subject: 
− 
is either affiliated to or beneficiary of a social security category;  
− 
has got an authorisation by the Ethics Committee. 
2. Concerning the “STATISTICAL CONSIDERATIONS AND DATA ANALYSES” 
and specially in the “SAMPLE SIZE ASSUMPTIONS” 
The expected number of subjects to be recruited in France is declared to the French 
regulatory authority. 
3. Concerning the “STUDY GOVERNANCE CONSIDERATIONS” 
• In section “Regulatory and Ethical Considerations, including the Informed Consent 
Process” 
− 
Concerning the process for informing the subject and/or his/her legally 
authorized representative, the following text is added: 
French Patient Informed Consent Form is a document which summarizes the main 
features of the study and allows collection of the subject and/or his/her legally 
authorized representative written consent in triplicate (quadriplicate for minor 
subject). It also contains a reference to the authorisation of ANSM and the approval 
from the French Ethics Committee and the maintenance of confidentiality of the 
returned consent form by GlaxoSmithKline France. 
− 
Concerning the process for obtaining subject informed consent: 
When a research involving human being is carried out on a minor / on an adult in the 
care of a “tutelle” guardian, consent is given by their legal representative and, if the 
committee mentioned in article L. 1123-1 considers that the research in question, 
because of the seriousness of the restraints or the specificity of the medical acts 
involved, entails a serious risk of affecting their private life or the integrity of their 
body, consent is given by the family council if it has been instated, or by the judge of 
“tutelle” guardians. 
When research involving human being is carried out on an adult in the care of a 
"curatelle" guardian, consent is given by the subject assisted by his guardian. 
However, if the adult in the care of a "curatelle" guardian is invited to participate in 
research which the committee mentioned in article L. 1123-1 considers, because of 
the seriousness of the restraints or the specificity of the medical acts involved, to 
entail a serious risk of affecting their private life or the integrity of their body, the 
matter is submitted to the judge of guardians who decides whether the adult is 

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capable of giving her/his consent. In the case of incapacity, the judge will decide 
whether or not to authorise the research involving human being. 
− 
Concerning the management of the Patient Informed Consent Forms, the 
following text is added: 
The first copy of the Patient Informed Consent Form is kept by the investigator. The 
second copy is kept by the Medical Director of GlaxoSmithKline France and the last 
copy(ies) is(are) given to the subject or their legally authorized representative(s). 
The second copy of all the consent forms will be collected by the Clinical Research 
Assistant (CRA) under the Investigator’s control, and placed in a sealed envelope 
bearing only: 
− 
the study number,  
− 
the identification of the Centre: name of the principal investigator and centre 
number, 
− 
the number of informed consents, 
− 
the date,  
− 
and the principal investigator’s signature. 
Then, the CRA hands the sealed envelope over to the Medical Director, for 
confidential recording, under the responsibility of the Medical Director. 
• NOTIFICATION TO THE HOSPITAL DIRECTOR 
In accordance with Article L1123-13 of the French Public Health Code, the Hospital 
Director is informed of the commitment to the trial in her/his establishment. The 
Hospital Director is supplied with the protocol and any information needed for the 
financial disposition, the name of the investigator(s), the number of sites involved in 
his establishment and the estimated time schedule of the trial (R.1123-69). 
• INFORMATION TO THE HOSPITAL PHARMACIST 
In accordance with Article R.1123-70 of the French Public Health Code, the Hospital 
Pharmacist is informed of the commitment to the trial in her/his establishment. The 
Pharmacist is supplied with a copy of the protocol (which allows her/him to dispense 
the drug(s) of the trial according to the trial methodology), all information 
concerning the product(s) of the trial (e.g. included in the CIB), the name of the 
investigator(s), the number of sites involved in her/his establishment and the 
estimated time schedule of the trial. 
4. Concerning the “ DATA MANAGEMENT ” the following text is added: 
• Within the framework of this clinical trial, data regarding the identity of the 
investigators and/or co-investigators and/or the pharmacists if applicable, involved in 
this clinical trial, and data regarding the subjects recruited in this clinical trial (subject 
number, treatment number, subjects status with respect to the clinical trial, dates of 
visit, medical data) will be collected and computerized in GlaxoSmithKline data 
bases by GlaxoSmithKline Laboratory or on its behalf, for reasons of follow up, 
clinical trial management and using the results of said clinical trial. According to the 
Data Protection French Law n° 78-17 of 6th January 1978, each of these people 

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aforesaid has a right of access, correction and opposition on their own data through 
GlaxoSmithKline Laboratory (Clinical Operations Department). 
• DEMOGRAPHIC DATA 
In accordance with the Data Protection French Law n° 78-17 of 6th January 1978 – 
article 8, the ethnic origin can only be collected if the collection of this data is strictly 
necessary and relevant for the purpose of the study. 
• TESTING OF BIOLOGICAL SAMPLES 
In accordance with the French Public Health Code law – article L1211-2, a 
biological sample without identified purpose at the time of the sample and subject’s 
preliminary information is not authorized. 
5. Monitoring visits 
The Health Institution and the Investigator agree to receive on a regular basis a 
Clinical Research Assistant (CRA) of GLAXOSMITHKLINE or of a service 
provider designated by GLAXOSMITHKLINE. The Health Institution and the 
Investigator agree to be available for any phone call and to systematically answer to 
all correspondence regarding the Study from GLAXOSMITHKLINE or from a 
service provider designated by GLAXOSMITHKLINE. In addition, the Health 
Institution and the Investigator agree that the CRA or the service provider designated 
by GLAXOSMITHKLINE have direct access to all the data concerning the Study 
(test results, medical record, etc …). This consultation of the information by 
GLAXOSMITHKLINE is required to validate the data registered in the electronic 
Case Report Form (eCRF), in particular by comparing them directly to the source 
data. In accordance with the legal and regulatory requirements, the strictest 
confidentiality will be respected. 
6. Data entry into the eCRF 
The Health Institution and the Investigator agree to meet deadlines, terms and 
conditions of the Study’s electronic Case Report Form (eCRF) use here below: 
The Health Institution and the Investigator undertake: 
• That the Investigator and the staff of the investigator center make themselves 
available to attend the training concerning the computer system dedicated to the 
electronic Case Report Form (eCRF) of the Study provided by 
GLAXOSMITHKLINE or by a company designated by GLAXOSMITHKLINE. 
• That the Investigator and the staff of the investigator center use the IT Equipment 
loaned and/or the access codes only for the purpose of which they are intended and 
for which they have been entrusted to them, namely for the Study achievement, to the 
exclusion of any other use. 
• That the Investigator and the staff of the investigator center use the IT Equipment 
loaned according to the specifications and manufacturer’s recommendations which 
will have been provided by GLAXOSMITHKLINE. 
• To keep the IT Equipment and/or access codes in a safe and secure place and to 
authorize only the use of this IT Equipment by investigator center staff designated by 
the principal investigator to enter the data of the Study. 

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• To be responsible for the installation and payment of the required Internet 
connections needed for the use of the IT Equipment, Computer systems and/or access 
codes. 
• To return at the end of the Study the IT Equipment and/or access codes to 
GLAXOSMITHKLINE or to any company designated by GLAXOSMITHKLINE 
and any training material and documentation. The IT Equipment cannot under any 
circumstances be kept by the Health Institution or the Investigator for any reason 
whatsoever.  
7. CTR publication 
It is expressly specified that GLAXOSMITHKLINE and/or the Sponsor can make 
available to the public the results of the Study by the posting of the said results on a 
website of the GLAXOSMITHKLINE GROUP named Clinical Trial Registered 
(CTR) including the registration of all the clinical trials conducted by the 
GLAXOSMITHKLINE Group and this before or after the publication of such results 
by any other process. 
8. Data Protection French Law of 6th January 1978 (CNIL) 
In accordance with the Data Protection French Law of 6 January 1978, computer 
files used by GLAXOSMITHKLINE to monitor and to follow the implementation 
and the progress of the Study are declared with CNIL by GLAXOSMITHKLINE. 
The Investigator has regarding the processing data related to her/him a right of 
access, of rectification and of opposition with GLAXOSMITHKLINE in accordance 
with the legal provisions. This information can be transferred or be accessed to other 
entities of GLAXOSMITHKLINE Group, what the Investigator agrees by the 
signature of the present Protocol. 
9. Investigational Product Accountability, Reconciliation, and Destruction 
In specific situations (if the site has 1- an approval from the French Regulatory 
Agency (ANSM) and 2- a GSK written endorsement letter) where institutional 
practices dictate that the site disposes of and/or destroys IP prior to allowing the 
“monitor’ to verify and document IP accountability, the following applies: 
“During the conduct of the Study, Investigational Product (IP) will be destroyed by 
the Institution prior to a GlaxoSmithKline “monitor” conducting final investigational 
product accountability. Institution agrees that such destruction will comply with 
Institution’s investigational product accountability procedures and will provide 
GlaxoSmithKline with investigational product accountability logs and supporting 
documentation to verify adherence to ‘Bonnes Pratiques Cliniques’ (decision dated 
on the 24th of November 2006). 

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13. 
REFERENCES 
Agnandji ST, Lell B, Soulanoudjingar SS, et al. First results of phase 3 trial of 
RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011;365:1863-1875. 
Al-Mahtab M, Akbar MF, Aquilar JC, et al. Therapeutic potential of a combined hepatitis 
B virus surface and core antigen vaccine in patients with chronic hepatitis B. Hepatol Int. 
2013;7(4):981-9. 
Asante KP, Abdulla S, Agnandji S, et al. Safety and efficacy of the RTS, S/AS01E 
candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 
19 month follow-up of a randomised, open-label, phase 2 trial. Lancet Infect Dis. 
2011;11:741–749. 
Baerlecken NT, Nothdorft S, Stummvoll GH, et al. Autoantibodies against CD74 in 
spondyloarthritis. Ann Rheum Dis. 2014;73(6):1211-14. 
Bain C, Honnet G & Veron L. Biological activity of TG4040, a novel HCV therapeutic 
vaccine, in treatment-naive HCV chronic patients: interim results of biomarker and 
immunomonitoring analyses. 16th International Symposium on Hepatitis C Virus & 
Related Viruses. Nice, France; 2009. 
Baraliakos X, Baerlecken N, Witte T, et al. High prevalence of anti-CD74 antibodies 
specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with 
axial spondyloarthritis. Ann Rheum Dis. 2014;73(6):1079-82. 
Barnes E, Folgori A, Capone S, et al. Novel Adenovirus-Based Vaccines Induce Broad 
and Sustained T-cell Responses to HCV in Man. Sci Transl Med. 2012;4:1-11. 
Block TM, Locarnini S, McMahon BJ, Rehermann B, Peters MG. Use of current and new 
endpoints in the evaluation of experimental hepatitis B therapeutics. Clin Infect Dis. 2017 
Feb 12. doi: 10.1093/cid/cix129. 
Boni C, Laccabue D, Lampertico P, et al. Restored function of HBV-specific T cells after 
long-term effective therapy with nucleos(t)ide analogues. Gastroenterology. 
2012;143:963-73. 
Bowness P. HLA-B27. Annu Rev Immunol. 2015;33:29-48. 
Capone S, Naddeo M, D’Alise M, et al. Fusion of HCV nonstructural antigen to MHC 
class II-associated invariant chain enhances T-cell responses induced by vectored 
vaccines in nonhuman primates. Mol Ther. 2014;22(5):1039-47. 
Castéra L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, 
Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. 
Gastroenterology. 2005;128(2):343-50. 

CONFIDENTIAL 
204852 (TH HBV VV-001) 
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153 
Cavenaugh JS, Awi D, Mendy M, et al. Partially Randomized, Non-Blinded Trial of 
DNA and MVA Therapeutic Vaccines Based on Hepatitis B Virus Surface Protein for 
Chronic HBV Infection. PLoS ONE. 2011;6:1-14. 
Centers for Disease Control and Prevention Metropolitan Atlanta Congenital Defects 
Program (CDC MACDP) guidelines. Birth defects and genetic diseases branch 6-digit 
code for reportable congenital anomalies; 
http://www.cdc.gov/ncbddd/birthdefects/documents/MACDPcode0807.pdf 
Chlibek R, Bayas JM, Collis H, et al. Safety and immunogenicity of an AS01-adjuvanted 
varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years 
of age. J Infect Dis. 2013;208(12):1953-61. 
Chlibek R, Smetana J, Pauksens K, et al. Safety and immunogenicity of three different 
formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older 
adults: A phase II, randomized, controlled study. Vaccine. 2014;32:1745-1753. 
Chong CH & Lim SG. When can we stop nucleoside analogues in patients with chronic 
hepatitis B? Liver Int. 2017;37 Suppl 1:52-58. 
Christian BA, Poi M, Jones JA, et al. The combination of milatuzumab, a humanized 
anti-CD74 antibody, and veltuzumab, a humanized anti-CD20 antibody, demonstrates 
activity in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Br J 
Haematol. 2015;169(5):701-10. 
Cornberg M, Wong VW, Locarnini S, Brunetto M, Janssen HL, Chan HL. The role of 
quantitative hepatitis B surface antigen revisited. J Hepatol. 2017;66(2):398-411. 
Cottingham MG, Carroll MW. Recombinant MVA vaccines: dispelling the myths. 
Vaccine. 2013;31:4247-51. 
Cunningham AL, Lal H, Kovac M, et al. Efficacy of the Herpes zoster subunit vaccine in 
adults 70 years of age or older. N Engl J Med. 2016;375(11):1019-1032. 
Currier JR, Ngauy V, de Souza MS, et al. Phase I safety and immunogenicity evaluation 
of MVA-CMDR, a multigenic, recombinant modified vaccinia Ankara-HIV-1 vaccine 
candidate. PloS One. 2010;5:e13983. 
Didierlaurent AM, Collignon C, Bourguignon P, et al. Enhancement of Adaptive 
Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells. 
J Immunol. 2014;193:1920-1930. 
Earl PL, Cotter C, Moss B, et al. Design and evaluation of multi-gene, multi-clade HIV-1 
MVA vaccines. Vaccine. 2009;27:5885-95. 
EMA Guideline on the exposure to medicinal products during pregnancy: need for post-
authorization data (Doc. Ref. EMEA/CHMP/313666/2005 ) ‘adopted at Community level 
in May 2006); 
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_g
uideline/2009/11/WC500011303.pdf 

CONFIDENTIAL 
204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
22 June 2023 
154 
European Association for Study of Liver (EASL) & Asociacion Latinoamericana para el 
Estudio del Higado (ALEH). EASL-ALEH Clinical Practice Guidelines: Non-invasive 
tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237-64. 
European Association for the Study of the Liver (EASL). EASL 2017 Clinical Practice 
Guidelines on the management of hepatitis B virus infection. J. Hepatol. 2017;67(2):370-
398. 
European Centre for Disease Prevention and Control. Annual Epidemiological Report 
2016 – Hepatitis B. Stockholm: ECDC; 2016. Available from: 
http://ecdc.europa.eu/en/healthtopics/hepatitisb/Pages/Annualepidemiologicalreport2016.
aspx 
Ewer K, Rampling T, Venkatraman N, et al. A monovalent chimpanzee adenovirus Ebola 
vaccine boosted with MVA. N Engl J Med. 2016;374(17):1635-46. 
Folgori A, Capone S, Ruggeri L, et al. A T-cell HCV vaccine eliciting effective 
immunity against heterologous virus challenge in chimpanzees. Nat Med. 2006;12:190-7. 
Fontaine H, Kahi S, Chazallon C, et al. Anti-HBV DNA vaccination does not prevent 
relapse after discontinuation of analogues in the treatment of chronic hepatitis B: a 
randomised trial—ANRS HB02 VAC-ADN. Gut. 2015;64:139–147. 
Fournillier A, Gerossier E, Evlashev A, et al. An accelerated vaccine schedule with a 
poly-antigenic hepatitis C virus MVA-based candidate vaccine induces potent, long 
lasting and in vivo cross-reactive T cell responses. Vaccine. 2007;25:7339-53. 
Green CA, Scarselli E, Sande CJ, et al. Chimpanzee adenovirus- and MVA-vectored 
respiratory syncytial virus vaccine is safe and immunogenic in adults. Sci Transl Med. 
2015;7(300):300ra126. 
Greinacher A, Langer F, Makris M, et al. Vaccine-induced immune thrombotic 
thrombocytopenia (VITT): Update on diagnosis and management considering different 
resources. J Thromb Haemost. 2022;20(1):149-156.  
Guerra S, Gonzalez JM, Climent N, et al. Selective induction of host genes by MVA-B, a 
candidate vaccine against HIV/AIDS. J Virol.2010;84:8141-52. 
Habersetzer F, Zarsky JP, Leroy V, et al. A novel vectorized HCV therapeutic vaccine 
(TG4040): results of a phase 1 study in naive patients chronically infected by HCV. J 
Hepatol. 2009 Supplement 1;50:S18. 
Halfon P, Munteanu M & Poynard T. FibroTest-ActiTest as a non-invasive marker of 
liver fibrosis. Gastroenterol Clin Biol. 2008;32(6 Suppl 1):22-39. 
Heathcote J, McHutchison J, Lee S, et al. A pilot study of the CY-1899 T-cell vaccine in 
subjects chronically infected with hepatitis B virus. The CY1899 T Cell Vaccine Study 
Group. Hepatology. 1999;30:531-6. 

CONFIDENTIAL 
204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
22 June 2023 
155 
Howie SR. Blood sample volumes in child health research: review of safe limits. Bulletin 
of the World Health Organization. 2011;89:46-53. 
Jung MC, Grüner N, Zachoval R, et al. Immunological monitoring during therapeutic 
vaccination as a prerequisite for the design of new effective therapies: induction of a 
vaccine-specific CD4+ T-cell proliferative response in chronic hepatitis B carriers. 
Vaccine. 2002;20(29-30):3598-612. 
Kaufman JL, Niesvizky R, Stadtmauer EA, et al. Phase I, multicentre, dose-escalation 
trial of monotherapy with milatuzumab (humanized anti-CD74 monoclonal antibody) in 
relapsed or refractory multiple myeloma. Br J Haematol. 2013;163(4):478-86. 
Kelly C, Swadling L, Capone S, et al. Chronic hepatitis C viral infection subverts 
vaccine-induced T-cell immunity in humans. Hepatology. 2016; 63(5):1455–1470. 
Kranidioti H, Manolakopoulos S & Khakoo SI. Outcome after discontinuation of 
nucleot(s)ide analogues in chronic hepatitis B: relapse rate and associated factors. Ann 
Gastroenterol. 2015;28(2):173-181. 
Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster 
subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087-2096. 
Lampertico P. Oral antiviral therapy for HBeAg negative chronic hepatitis B: better stop 
or continue? Gut. 2014;64(4):526-528. 
Leroux-Roels I, Koutsoukos M, Clementa F, et al. Strong and persistent CD4+ T-cell 
response in healthy adults immunized with a candidate HIV-1 vaccine containing gp120, 
Nef and Tat antigens formulated in three Adjuvant Systems. Vaccine. 2010;28(43):7016-
24. 
Leroux-Roels I, Leroux-Roels G, Clement F, et al. A phase 1/2 clinical trial evaluating 
safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate 
in young and older adults. J Infect Dis. 2012;206:1280-1290. 
Leroux-Roels G, Leroux-Roels I, Clement F, et al. Evaluation of the immune response to 
RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines: randomized, double-blind study in 
malaria-naïve adults. Hum Vaccines Immunother. 2014;10:2211-2219. 
Leroux-Roels G, Marchant A, Levy J, et al. Impact of adjuvants on CD4+ T cell and B 
cell responses to a protein antigen vaccine: Results from a phase II, randomized, 
multicenter trial. Clin Immunol. 2016;169:16-27. 
Leroy V, Angus P, Bronowicki JP, et al. Daclatasvir, sofosbuvir, and ribavirin for 
hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study 
(ALLY-3+). Hepatology. 2016;63(5):1430-41. 
Lok AS, Lai CL, Leung N, et al. Long-term safety of lamivudine treatment in patients 
with chronic hepatitis B. Gastroenterology. 2003;125(6):1714-22. 

CONFIDENTIAL 
204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
22 June 2023 
156 
Lok AS, Pan CQ, Han SH, et al. Randomized phase II study of GS-4774 as a therapeutic 
vaccine in virally suppressed patients with chronic hepatitis B. J Hepatol. 
2016;65(3):509-16. 
Lusingu J, Olotu A, Leach A, et al. Safety of the malaria vaccine candidate, 
RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian children. PloS One. 
2010;5:e14090. 
Maini MK, Boni C, Lee CK, et al. The role of virus-specific CD8(+) cells in liver 
damage and viral control during persistent hepatitis B virus infection. J Exp Med. 
2000;191(8):1269-80. 
Martin P, Furman RR, Rutherford S, et al. Phase I study of the anti-CD74 monoclonal 
antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas. 
Leuk Lymphoma. 2015;12:1-6. 
Mensah VA, Gueye A, Ndiaye M, et al. Safety, immunogenicity and efficacy of prime-
boost vaccination with ChAd63 and MVA encoding ME-TRAP against plasmodium 
falciparum infection in adults in Senegal. PLoS One. 2016;11(12):e0167951. 
Michel ML, Deng Q & Mancini-Bourgine M. Therapeutic vaccines and immune-based 
therapies for the treatment of chronic hepatitis B: Perspectives and challenges. J Hepatol. 
2011;54:1286-96. 
Michel ML, Bourgine M, Fontaine H, et al. Therapeutic vaccines in treating chronic 
hepatitis B: the end of the beginning or the beginning of the end? Med Microbiol 
Immunol. 2015;204(1):121-129. 
Mikkelsen M, Holst PJ, Bukh J, et al. Enhanced and Sustained CD8+ T-cell Responses 
with an Adenoviral Vector-Based Hepatitis C Virus Vaccine Encoding NS3 Linked to the 
MHC Class II Chaperone Protein Invariant Chain. J Immunol. 2011;186:2355-64. 
Omosa-Manyonyi G, Mpendo J, Ruzagira E, et al. A Phase I Double Blind, Placebo-
Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-
1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy 
HIV-Uninfected African Adults. PLoS One. 2015;10(5):e0125954. 
Penn-Nicholson A, Geldenhuys H, Burny W, et al. Safety and immunogenicity of 
candidate vaccine M72/AS01E in adolescents in a TB endemic setting. Vaccine. 
2015;33:4025-4034. 
Phillips S, Chokshi S, Riva A, et al. CD8(+) T cell conctrol of hepatitis B virus 
replication: direct comparison between cytolytic and noncytolytic functions. J Immunol. 
2010;184(1):287-95. 
Poethko-Müller C, Zimmermann R, Hamouda O, et al. Die Seroepidemiologie der 
Hepatitis A, B und C in Deutschland. Ergebnisse der Studie zur Gesundheit Erwachsener 
in Deutschland (DEGS1). Bundesgesundheitsbl. 2013;56:707-715. 

CONFIDENTIAL 
204852 (TH HBV VV-001) 
Protocol Amendment 11 Final 
22 June 2023 
157 
Prescribing information for Tenofovir disoproxil fumarate. Accessible at: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021356s042,022577s002lbl.
pdf 
Sheehy SH, Duncan CJ, Elias SC, et al. Phase Ia Clinical Evaluation of the Safety and 
Immunogenicity of the Plasmodium falciparum Blood- Stage Antigen AMA1 in ChAd63 
and MVA Vaccine Vectors. PLoS One. 2012;7:1-14. 
Song IH, Heldmann F, Rudwaleit M, et al. Different response to rituximab in tumor 
necrosis factor blocker-naive patients with active ankylosing spondylitis and in patients 
in whom tumor necrosis factor blockers have failed: a twenty-four-week clinical trial. 
Arthritis Rheum. 2010;62(5):1290-7. 
Stein R, Mattes MJ, Cardillo TM, et al. CD74: a new candidate target for the 
immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007;13(18 Pt 2):5556s-5563s. 
Summary of product characteristics for Entecavir. Accessible at: 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000623/WC500051984.pdf 
Swadling L, Capone S, Antrobus RD, et al. A human vaccine strategy based on 
chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional 
HCV-specific T cell memory. Sci Transl Med. 2014;6(261):261ra153. 
Swadling L, Halliday J, Kelly C, et al. Highly-immunogenic virally-vectored T-cell 
vaccines cannot overcome subversion of the T-cell response by HCV during chronic 
infection. Vaccines. 2016;4 (3) pii:E27. 
Tapia MD, Sow SO, Lyke KE, et al. Use of ChAd3-EBO-Z Ebola virus vaccine in 
Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, 
single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation 
trial, and a nested, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 
2016;16:31-42. 
Thiele M, Madsen BS, Hansen JF, et al. Accuracy of the enhanced liver fibrosis test vs 
FibroTest, elastography, and indirect markers in detection of advanced fibrosis in patients 
with alcoholic liver disease. Gastroenterology. 2018;154(5):1369-1379. 
Van Braeckel E, Bourguignon P, Koutsoukos M, et al. An adjuvanted polyprotein HIV-1 
vaccine induces polyfunctional cross-reactive CD4+ T cell responses in seronegative 
volunteers. Clin Infect Dis. 2011;52(4):522-31. 
Vandepapelière P, Lau GK, Leroux-Roels G, et al. Therapeutic vaccination of chronic 
hepatitis B patients with virus suppression by antiviral therapy: a randomized, controlled 
study of co-administration of HBsAg/AS02 candidate vaccine and lamivudine. Vaccine. 
2007;25:8585-97. 

CONFIDENTIAL 
204852 (TH HBV VV-001) 
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22 June 2023 
158 
Webster GJ, Reignat S, Brown D, et al. Longitudinal Analysis of CD8+ T Cells Specific 
for Structural and Nonstructural Hepatitis B Virus Proteins in Patients with Chronic 
Hepatitis B: Implications for Immunotherapy. J Virol. 2004;78:5707-19. 
White SJ, Freedman LS. Allocation of patients to treatment groups in a controlled clinical 
study. Br J Cancer. 1978;37:849-857. 
World Health Organization (WHO). Global hepatitis report 2017, April 2017. 
http://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/ 
Yang FQ, Yu YY, Wang GQ, et al. A pilot randomized controlled trial of dual-plasmid 
HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients 
under lamivudine chemotherapy. J Viral Hepat. 2012;19:581-593. 
Zaiss DM, Boog CJ, van Eden W, et al. Considerations in the design of vaccines that 
induces CD8 T-cells mediated immunity. Vaccine. 2010;28:7716-22. 
Zent O, Arras-Reiter C, Broeker M, et al. Immediate allergic reactions after vaccinations 
– a post-marketing surveillance review. Eur J Pediatr. 2002;161(1):21-5. 
Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by 
measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48-
54. 
Zoutendijk R, Hansen BE, Van Vuuren AJ, et al. Serum HBsAg decline during longterm 
potent nucleos(t)ide analogue therapy for chronic hepatitis B and prediction of HBsAg 
loss. J Infect Dis. 2011;204:415-418. 

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APPENDIX A 
LABORATORY ASSAYS 
1. Anti-HBs Ig tot (CLIA) - ADVIA Centaur anti-HBs2 (Siemens Healthcare) 
The ADVIA Centaur Anti-HBS2 assay is a sandwich immunoassay using direct, 
chemiluminometric technology. HBsAg (ad and ay) are covalently coupled to magnetic 
latex particles in the Solid Phase. In the Lite Reagent, the HBs Ag (ad and ay) is labelled 
with acridinum ester. Non-magnetic latex particles are added from the ancillary well. The 
sample is incubated simultaneously with Lite Reagent, Solid Phase and Ancillary 
Reagent. Antibody-antigen complexes will form if anti-HBs is present in the sample. A 
direct relationship exist between the amount of anti-HBs activity present in the patient 
sample and the amount of relative light units (RLUs) detected by the system. 
Note: ad et ay are two different subtypes of S antigen 
2. Anti-HBc 
Not yet developed 
4. qHBsAg – HBsAg assay (Abbott) 
The Abbott HBsAg assay is a two-step immunoassay using chemiluminescent 
paramagnetic microparticles (CMIA) technology for the quantitative determination of 
HBsAg. In the first step, sample is mixed with microparticles coated with anti-HBs; 
antibody-antigen will form if HBsAg is present in the sample. In the second step, 
acridium-labeled anti-HBs conjugate is added. A direct relationship exists between the 
amount of HBsAg present in the sample and the RLU detected by the system. 
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5. qHBsAg – HBsAg assay (Abbott) with pre-treatment 
Immune complexes (Ag-Ab complexes) can be present in the sample. Those immune 
complexes can interfere with the HBsAg dosage. In order to avoid this interference, 
sample is pre-treated with a chaotropic agent that dissolves the immune complexes. After 
this pre-treatment, sample is used as described in the previous section. 
7. HBV DNA assay 
Cobas® HBV assay for use on the Cobas 4800 System (ROCHE) or equivalent will be 
used for the detection and the quantification of HBV DNA in serum. 
It is an in vitro nucleic acid amplification test for the quantitation of hepatitis B virus 
DNA in human EDTA plasma or serum of HBV-infected individuals. This test is 
intended for use as an aid in the management of patients with chronic HBV infection 
undergoing anti-viral therapy. The test can be used to measure HBV DNA levels at 
baseline and during treatment to aid in assessing response to treatment. 
Primers and probe target the highly conserved pre-core and core regions of the HBV 
genome. The test covers all known HBV genotypes (A-H) and the HBV viral load is 
reported as IU/ml. 
This assay, commercialized by ROCHE, is CE-approved. Performance characteristics of 
the assay were evaluated by the manufacturer and are summarized into the kit package 
insert. 
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11. CFC Assay  
This assay is applied to measure the frequency of antigen-specific T-lymphocytes in 
peripheral blood. Blood samples are collected by venipuncture and PBMCs are prepared 
by certified laboratories by centrifugation onto a Lymphoprep™ cushion within 24 hours 
following collection. PBMC suspensions are stored in liquid nitrogen until analysis. To 
measure T-cell responses elicited by the vaccine candidate, samples are thawed and 
cultured overnight in the presence of costimulatory antibodies (anti-CD28 and anti-
CD49d) without stimulation (background control) or with peptide pools (15mer 
overlapping by 11) covering the sequence of the relevant antigens (HBs, HBc, 
 
. Cells are then immunostained for surface phenotypic markers 
(CD4 and CD8), permeabilized and then immunostained for CD3 and activation markers 
(the costimulatory molecules CD40L and 4-1BB and the cytokines IL-2, IFN-γ, TNF-α, 
IL-13, IL-17). Analysis is performed by multiparametric flow cytometry, and the results 
are expressed after background subtraction as frequencies of antigen specific CD4+ (or 
CD8+) T-cells producing various combinations of the activation markers assessed per 
million CD4+ (or CD8+) T-cells. 
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APPENDIX B 
CLINICAL LABORATORIES 
Table 34 
GSK Biologicals’ laboratories 
Table 35 
Outsourced laboratories 
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APPENDIX C 
TOXICITY GRADING FOR HEMATOLOGY, 
BIOCHEMISTRY AND URINALYSIS 
PARAMETERS 
Component 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hematology   
Hemoglobin (g/dl) male 
13.5 - 12.5  12.4 - 10.5  10.4 - 8.5  
< 8.5 
Hemoglobin change from baseline male (g/dl) 
< 1.5 
1.6 - 2 
2.1 - 5 
> 5 
Hemoglobin (g/dl) female 
12 -11 
10.9 - 9.5 
9.4 - 8 
< 8 
Hemoglobin change from baseline female (g/dl) 
< 1.5 
1.6 - 2 
2.1 - 5 
> 5 
WBC (cell/mm3) increase 
10,800 - 
15,000 
15,001 - 
20,000 
20,001 - 
25,000 
> 25,000 
WBC (cell/mm3) decrease 
3,500 - 
2,500 
2,499 - 
1,500 
1,499 - 
1,000 
< 1,000 
Lymphocyte (cell/mm3) decrease 
1,000 - 750 749 - 500  499 - 250  
< 250 
Neutrophils (cell/mm3) decrease 
2,000 - 
1,500 
1,499 - 
1,000 
999 - 500 
< 500 
Eosinophils (cell/mm3)  
650 - 1,500 1,501 - 
5,000 
> 5,000 
hypereosin
ophilic 
syndrome 
Platelet (cell/mm3) decrease 
140,000 - 
125,000 
124,000 - 
100,000 
99,000 - 
25,000 
< 25,000 
INR increase  
1.1 - < 1.5 
x ULN 
1.5 - < 2.0 
x ULN 
2.0 - 3.0 x 
ULN 
> 3.0 x 
ULN 
Biochemistry 
ALT (increase by factor) 
1.1 - 2.5 x 
ULN 
2.6 - 5 x 
ULN 
5.1 - 10 x 
ULN 
> 10 x ULN 
AST (increase by factor) 
1.1 - 2.5 x 
ULN 
2.6 - 5 x 
ULN 
5.1 - 10 x 
ULN 
> 10 x ULN 
ALP (increase by factor) 
1.1 - 2.0 x 
ULN 
2.1 - 3 x 
ULN 
3.1 - 10 x 
ULN 
> 10 x ULN 
Total Bilirubin, if LFT normal (increase by factor) 
1.1 - 1.5 x 
ULN 
1.6 - 2 x 
ULN 
2.1 - 3.0 x 
ULN 
> 3 x ULN 
Total Bilirubin, if LFT abnormal (increase by factor) 
1.1 - 1.25 x 
ULN 
1.26 - 1.5 
x ULN 
1.51 - 1.75 
x ULN 
> 1.75 x 
ULN 
GGT (increase by factor) 
> 1.25 - 2.5 
x ULN 
> 2.5 - 5 x 
ULN 
5.1 - 10 x 
ULN 
> 10 x ULN 
Creatinin (increase by factor) 
1.1 - 1.5 x 
ULN 
1.6 - 2.0 x 
ULN 
2.1 - 2.5 x 
ULN 
> 2.5 x 
ULN or 
dialysis 
required 
Urinalysis* 
Protein  
trace 
1 + 
2 + 
> 2+ 
Glucose 
trace 
1 + 
2 + 
> 2+ 
Blood (microscopic) – red blood cells per high power field 
(rbc/hpf)  
1 -1 0 
11 - 50  
> 50 and/or 
gross blood 
hospitalize
d for 
packed red 
blood cell 
(PRBC) 
transfusion 
* For urinalysis the primary testing method used in the clinical trials is urine dipstick. This method of testing does not 
allow for precise conversion of the results of blood in urine into FDA grading. Therefore blood in urine results are 
reported based on dipstick scale (small + refers to ≥ 25 ery/µL, moderate ++ refers to ≥ 80 ery/µL, large +++ refers to 
≥ 200 ery/µL). 

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APPENDIX D 
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. 
• 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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APPENDIX E 
UPDATED BRIGHTON COLLABORATION CASE 
DEFINITION FOR THROMBOSIS WITH 
THROMBOCYTOPENIA SYNDROME (TTS)  
(The current interim case definition, v10.16.4 dated 11 November 2021 is provided 
below. Please refer to https://brightoncollaboration.us/thrombosis-with-
thrombocytopenia-syndrome-interim-case-definition/ for the most updated version of the 
case definition.) 
Beginning in February, 2021, multiple European countries (e.g., Austria, Denmark, 
Norway, Germany, UK) and Australia have reported cases of thrombosis with 
thrombocytopenia syndrome (TTS) in persons who received the Astra-Zeneca (AZ) 
COVID-19 vaccine (1-3, 10) and more recently in the US with the Janssen vaccine (11). 
In May 2021, a draft interim case definition was proposed by the Brighton Collaboration. 
Since that time, understanding of this condition and its relationship to vaccines has 
evolved. Recent work by Andreas Greinacher and others now allow revision of the 
original case definition and level of certainty algorithm [Greinacher, 2022]. The goal of 
this case definition is to facilitate harmonized studies of this outcome. This supplements 
guidelines published by WHO provided information on case identification for treatment. 
The Case Definition (CD) Level of Certainty (LOC) is determined based on a series of 
clinical conditions defined below. 
Condition A: ☐ Platelet count <150 X 109/L and of new onset with no known recent 
exposure to heparin (within the last 30 days) 
Condition B1: ☐ Presence of thrombosis/thromboembolism confirmed by ≥ 1 of the 
following (Check all that apply below) 
☐ Imaging Study 
• 
Ultrasound – Doppler 
• 
CT scan – contrast / angiography 
• 
Magnetic resonance venography or arteriography 
• 
Echocardiogram 
• 
Perfusion V/Q scan 
• 
Conventional angiography / digital subtraction angiography 
☐ Surgical procedure – that confirmed presence of a thrombus (e.g. thrombectomy) 
☐ Pathologic examination – including biopsy or autopsy 
Condition B2: ☐ Severe and persistent headache onset ≥5d post vaccination with 
elevated D-DIMER >8x ULN (Upper limits of normal) 

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Condition C: ☐ Clinical presentation suggests one of the specific clinical syndromes 
below? (Check the most appropriate) NOTE: the italicized signs/symptoms in brackets 
after each are suggestive of the syndrome but not an exhaustive list; some of them should 
be present. Diagnosis of the syndrome by a clinical specialist is also acceptable 
☐ Cerebral venous sinus thrombosis / other Cerebral venous thrombosis (new onset of 
unexplained headache, often severe, typically persisting; focal cerebral dysfunction; 
encephalopathy; seizure; blurred vision; double vision) 
☐ Deep vein thrombosis (new onset swelling usually but not always in lower extremities; 
localized swelling accompanied by pain [may be crampy in nature] and tenderness; 
reddened/discoloured/warm skin; pitting edema) 
☐ Pulmonary thromboembolism (sudden onset: shortness of breath[at rest or on 
exertion], pleuritic chest pain [sudden, intense, sharp, stabbing or burning in nature, made 
worse by breathing/coughing/sneezing/laughing], cough +/- hemoptysis), tachypnea, 
tachycardia, arrhythmia, cyanosis, hypotension) 
☐ Intra-abdominal thrombosis. (abdominal pain [may be out of proportion to physical 
exam findings], bloating, nausea, vomiting, diarrhea, bloody stools, ascites, 
hepatomegaly if hepatic vein location) 
☐ Ischemic Stroke (sudden onset of focal neurologic deficits such as difficulty with 
speech [dysphasia or dysarthria], hemiparesis, ataxic gait abnormal eye movements, 
facial paresis) 
☐ Myocardial infarction (chest pain [often crushing in nature], shortness of breath, 
arrhythmias, cyanosis, sudden death) 
☐ Arterial Thrombosis 
Condition D: ☐ One or more of these imaging or lab findings supportive of the diagnosis 
of thrombosis / thromboembolism? (Check all that apply) 
☐ Echocardiogram or doppler ultrasound 
☐ Computed tomography without contrast or MRI 
☐ D-dimer (Elevated above upper limit of normal for age) 
Condition E: ☐ At least one of these Lab findings that are strongly supportive of the 
diagnosis of platelet-activating antibody mediated thrombosis? (Check all that apply) 
☐ D-dimer > 4 times ULN for age 
☐ Positive anti-platelet factor 4 (PF4) assay: specific anti-PF4 ELISA (note: rapid tests 
are insensitive for these antibodies) or functional test with addition of PF4 

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TTS Case Definition Level of Certainty Determination 
If yes to (A and B1) or yes to (A and B2): then is Level 1 
If no to (B1 and B2)_and_[If yes to A plus yes to (C and E)] then is level 1 
If no to (B1 and B2)_and_[If yes to A plus yes to (C and D)] then is level 2 
If no to (B1 and B2)_and_[If yes to A plus [(yes to C) and (no to D and E)] then is level 
3If there is insufficient information to determine the conditions needed to a level of 
certainty of 1, 2 or 3 then the level of certainty is level 4  
If there is sufficient information to determine the conditions A, B, C, D, and E but the 
aggregate of the conditions do not meet the LOC 1, 2, or 3 then the LOC is Level 5; Not a 
Case of TTS. 

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APPENDIX F 
AMENDMENTS AND ADMINISTRATIVE 
CHANGES TO THE PROTOCOL 
eTrack study number 
and Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
1 
Amendment date: 
22 May 2018 
Co-ordinating author: 
, Scientific Writer (XPE Pharma & 
Science for GSK Biologicals) 
Rationale/background for changes:  
List of changes 
On the cover page, the list of contributing authors has been updated with 4 new 
contributors: 
• 
 and 
, Study Delivery Leads 
• 
 and
, Clinical Safety Representatives 
• 
 and 
 Oversight Data Managers 
• 
 and 
, Clinical and Epidemiology Project Leads 
In Section 5.5 Outline of study procedures, Table 3 has been updated: 
Table 3 List of study procedures: Screening and primary phase (Screening Visit to 
Visit 17) 
Type of contact Screening 
Visit 
Visit 
1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 
7 
Visit 
8 
Visit 
9 
Visit 
10 
Visit 
11 
Visit 
12 
Visit 
13 
Visit 
14 
Visit 
15 
Visit 
16 
Visit 
17 
Physical 
examination/vital 
signs m  
● 
● 
O 
O 
O 
O 
● 
O 
O 
O 
● 
O 
O 
O 
● 
O 
O 
O 
m At Screening, a physical examination should be performed based on the clinical history of the patient. 
Physical examination at each subsequent study visit will be performed only if the patient indicates during 
questioning and test result review that there might be some underlying pathology(ies) or if deemed 
necessary by the Investigator or delegate. At Screening and at each vaccination, vital signs (including 
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systolic/diastolic blood pressure, heart rate and respiratory rate after at least 10 minutes of rest) should be 
collected. Collected information needs to be recorded in the eCRF. 
In Section 8.3.3.2.1 Assessment of intensity, additional information on intensity 
grading of local redness/swelling and fever has been provided: 
The maximum intensity of local injection site redness/swelling will be scored at GSK 
Biologicals as follows: 
Grade 0 
≤ 20 mm 
Grade 1 
> 20 mm to ≤ 50 mm 
Grade 2 
> 50 mm to ≤ 100 mm 
Grade 3 
> 100 mm 
Fever will be scored as follows: 
 
Celsius 
Fahrenheit 
Grade 1 
38.0 to 38.4°C 
100.4 to 101.1°F 
Grade 2 
38.5 to 38.9°C 
101.2 to 102.0°F 
Grade 3 
≥ 39°C 
≥ 102.1°F 

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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
2 
Amendment date: 
17 December 2018 
Co-ordinating author: 
, Scientific Writer (XPE 
Pharma & Science for GSK Biologicals) 
Rationale/background for changes:  
PPD
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List of changes 
On the cover page, the list of contributing authors has been updated: 
• 
 and 
, Clinical Research Development Leads 
• 
 and 
, Clinical Laboratory Science 
Representatives, Clinical Readout Team Leaders 
• 
 and 
, Laboratory Science Representatives, 
Laboratory Study Managers 
• 
 and 
, Clinical Trial Supply Managers, 
In the Synopsis and in Section 1.2.2, ‘immunogens’ has been changed to ‘antigens’ for 
clarity. 
Two different doses of ChAd155-hIi-HBV (5x109 and 5x1010 vp) and MVA-HBV 
(2x107 and 2x108 pfu) will be assessed and were selected based on available clinical 
data with ChAd3- and MVA-based vectored vaccines using other antigens. 
In the Synopsis and in Section 2.2, the secondary objective related to the proof-of-
principle has been clarified. The Table 26 was edited accordingly. 
2) If tThere is at least a 10-fold difference in mean qHBsAg concentration between a 
vaccine group at Day 337 and the respective control group (i.e. a lower limit of the 
80% CI of the GMC concentration ratio > 1) (i.e. the criterion is to observe a point 
estimate of at least 10-fold decrease between the groups with statistical significance, 
i.e., 80% CI on the ratio not including 1). 
Table 26 Power to demonstrate a defined fold-decrease (i.e. log-difference) between 
two groups with
and
evaluable patients per group respectively, SD varying from 
0.5 to 0.9 – one-sided alpha = 10% 
True fold decrease 
N per group 
SD 
Power 
1-log decrease (i.e.10-fold decrease) 
 
0.5 
100% 
0.9 
97% 
In the Synopsis and in Section 3, the control groups have been clarified: 
• 
Control: 
− Group B2 
− Group B3 
− Group C2 
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Safety assessment: Group A3 (placebo control) will be used for Step A. For Step 
B and Step C, Group B3 and C2 data obtained up to Day 113 (placebo control 
up to Day 113) will be used respectively. 
For PoP efficacy objective: For Step B and Step C, Group B3 and C2 data 
obtained up to Day 113 (placebo control up to Day 113) will be used as placebo 
control, respectively. 
In the Synopsis and Section 3, an error in the timepoints for collecting blood samples 
for serum repository has been corrected. This is now aligned with Table 3 and Table 4: 
− Blood samples for serum repository will be collected on Day 1, 75, 121, 136, 
195, 361, 541 71, 113, 127, 183, 337, 505 and 841. 
In the Synopsis and in Section 10.2, one secondary endpoint was adapted to be aligned 
with the laboratory assays: 
Frequency of HBc- and HBs- specific CD4+ T-cells and CD8+ T-cells; CD4+ T-cells 
responder, CD8+ T-cells responder, number of CD4+ T-cells per million cells, CD8+ T-
cells per million cells. 
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The list of abbreviations has been updated: 
APRI 
Aspartate Transaminase to Platelets Ratio Index 
CCLIA 
Competitive Chemiluminescent Immunoassay 
CFC 
Cytokine Flow Cytometry 
CKD-EPI 
Chronic Kidney Disease Epidemiologic Collaboration 
CLIA 
Chemiluminescent Immunoassay 
CMI 
Cell-Mediated Immunogenicity Immunity 
CMIA 
Chemiluminescent Microparticle Immunoassay 
ELISA 
Enzyme Linked Immunosorbent Assay 
ES 
Exposed Set 
kPa 
KiloPascal 
METAVIR 
Meta-Analysis of Histological Data in Viral Hepatitis 
PCR 
Polymerase Chain Reaction 
Pfu 
Plaque Forming Unit 
TVC 
Total Vaccinated Cohort 
In the Glossary of Terms, the definition of menopause and post-menopause has been 
clarified: 
 
Menopause is the age associated with complete 
cessation of menstrual cycles, menses, and implies the 
loss of reproductive potential by ovarian failure. A 
practical definition accepts menopause after 1 year 
without menses with an appropriate clinical profile at 
the appropriate age e.g. > 45 years. 
A postmenopausal state is defined as no menses for 
12 months without an alternative medical cause. A 
blood sample for simultaneous follicle-stimulating 
hormone and estradiol levels may be collected at the 
discretion of the investigator to confirm non-
reproductive potential. 
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In Section 1.1.2, clarification has been provided: 
GSK Biologicals’ new vaccination strategy relies on a heterologous prime-boost 
approach with HBV viral vector vaccines (ChAd155-hIi-HBV followed by MVA-
HBV) with sequential or co-administration of AS01B-4-adjuvanted HBc-HBs proteins. 
In Section 1.2.2, justification on the cut-off of FibroTest and Fibroscan for the 
inclusion criteria has been provided: 
Among the different available strategies, algorithms combining TE and serum 
biomarkers appear to be the most attractive and validated one [Leroy, 2016; Castéra, 
2005]. In patients with viral hepatitis C, when TE and serum biomarkers results are in 
accordance, the diagnostic accuracy is increased for detecting significant fibrosis but 
not for cirrhosis. In cases of unexplained discordance, a liver biopsy should be 
performed if the results would change the patient management. In this FTIH, such 
strategy will be adopted to exclude CHB patients with significant fibrosis and cirrhosis. 
In a prospective study of chronic hepatitis C (CHC), a significant positive correlation 
was observed between liver stiffness as measured by FibroScan and fibrosis stages as 
determined by on biopsy [Ziol, 2005]. The distinctive cut-off values of 9.6 kiloPascal 
(kPa) and 14.5 kPa in diagnosis of extensive fibrosis (METAVIR F3) and cirrhosis 
(METAVIR F4), respectively. In another prospective study in CHC patients, the 
performance of FibroScan was compared with FibroTest, aspartate transaminase to 
platelets ratio index (APRI) and liver biopsy [Castéra, 2005]. FibroScan and 
FibroTest have shown similar accuracy in estimating the liver fibrosis staging. The 
best performance was obtained by combining the FibroScan and FibroTest, The 
most discriminant cut-off value for advanced fibrosis (METAVIR F3) were 
determined as 9.5 kPa and 12.5 kPa for cirrhosis (METAVIR F4). In a meta-
analysis of the FibroTest diagnostic value, it was found that FibroTest had a higher 
or similar prognostic value compared with biopsy in patients with CHB, CHC and 
alcoholic liver disease (ALD) [Halfon, 2008]. In another prospective study in 
patients with alcoholic liver disease, FibroTest has been show to identify advanced 
liver fibrosis with high diagnostic accuracy [Thiele, 2018]. The cutoff score 0.58 
ruled out advanced fibrosis with an negative predictive value (NPV) of 97%. In a 
Phase III study on the combination of several direct antiviral agents (DAAs) in 
treating genotype 3 chronic HCV infection with advanced liver disease, liver biopsy, 
Fibroscan and FibroTest plus APRI were used to define the liver fibrosis stage of the 
study population [Leroy, 2016]. Advanced fibrosis was defined as a METAVIR score 
of F3 or an Ishak score of 4 on liver biopsy, or a FibroScan ≥ 9.6 kPa but <14.6 kPa, 
or a FibroTest score of 0.58-0.74 plus an APRI score above 1 but below 2. Cirrhosis 
was defined as a METAVIR score of F4 or an Ishak score > 4 on liver biopsy, a liver 
stiffness value ≥14.6 kPa, or a FibroTest result ≥ 0.75 plus APRI ≥ 2. Where 
different testing methods yielded conflicting results, biopsy data took precedence. If 
biopsy data were not available, a FibroScan result took precedence over the 
FibroTest/APRI result. In this study, we adopt both Fibroscan and FibroTest to rule 
out patients with advanced liver fibrosis or cirrhosis. Only patients with FibroScan < 
9.6 kPa or FibroTest score < 0.59, will be included in this FTIH study. 

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In Section 1.2.2, an error has been corrected: 
Route of administration: The choice of the intramuscular route for ChAd155-hIi-
HBV is based on the assumption that no co-infection of natural human Adenovirus 
could occur at this site. Furthermore, there is a large body of data from clinical trials in 
humans using replication defective Ad5- and Ad6-based HIV vaccines injected 
intramuscularly showing an excellent safety profile, no viral shedding, and high levels 
of immunogenicity. MVA-NSmutHBV will also be given by the intramuscular route 
following several studies on other MVA vector vaccines demonstrating similar 
immunogenicity but less local reactivity when MVA vectors were administered by the 
intramuscular compared to the subcutaneous route. 
The ChAd155-hIi-HBV includes a DNA sequence coding for CD74, also called the 
invariant chain (hIi). Since hIi is a self-antigen expressed throughout the immune 
system by B cells, activated T-cells, dendritic cells, monocytes and macrophages and 
widely expressed in the thymus, it should be well tolerated immune tolerance to this 
antigen should be well established. 
Single dose studies of milatuzumab in monkeys showed no adverse effects but did 
transiently decrease circulating B and T lymphocytes and natural killer cells 
[Kaufman, 2013; Christian, 2015; Martin 2015; Stein, 2007]. 
Nevertheless, the risk that the ChAd155-hIi-HBV vaccine induces an immune response 
against the hIi and a pIMD cannot be entirely ruled out. 
 
 
 
 
 
In Section 3, information related to the ancillary TH HBV VV-031 HBS:001 study, 
where shedding of ChAd1555-hIi-HBV will be assessed, has been added: 
• 
 
 
 
• 
Ancillary study: To evaluate the shedding potential of the replication 
incompetent ChAd155-hIi-HBV vaccine, an ancillary study has been set-up and 
described in a separate study protocol TH HBV VV-031 HBS:001. This ancillary 
study will be performed on a subset of patients recruited in Step B. Biological 
samples (throat swab and urine samples) from these subjects will be collected at 
Visit 1, 2, 3, 4 and 5. 
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In Section 4.2: 
The authorized ALT level at screening has been clarified: 
• 
Documented normal level of ALT as per local clinical diagnosis for at least 24 
months AND at Screening test ALT ≤ 48 U/L < ULN. Small fluctuations of ALT 
(≤ 1.5 X ULN) are allowed provided ALT ≤ < 48 U/L at Screening. If no results 
are available, two Screening tests need to be performed at least 2 weeks apart. 
ULN are to be defined according to local laboratory reference range. 
The inclusion criterion related to previous diagnosis of advanced liver fibrosis and 
cirrhosis has been clarified according to the definition provided in Section 1.2.2: 
• 
No clinical diagnosis of advanced liver fibrosis and cirrhosis (F3 or F4 by 
METAVIR scoring system or ≥ 4 by Ishak scoring system) within the previous 24 
months. 
In Section 4.3, the exclusion criteria related to the use of immunosuppressants and to 
the documented evidence of other active cause of hepatitis have been updated: 
• 
Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs (including but not limited 
to IFN) during the period starting six months prior to the first vaccine dose. For 
corticosteroids, this will mean prednisone ≥ 10 20 mg/day or equivalent. Inhaled 
and topical steroids are allowed. 
• 
Documented evidence of other currently active cause of hepatitis (e.g. auto-
immune hepatitis as per Screening test, primary biliary cirrhosis; primary 
sclerosing cholangitis, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's 
disease). 
In Section 5.2.2 and 5.2.2.1.1, the minimization procedure has been clarified: 
Section 5.2.2: 
SBIR: 
 
No 
 
X Yes: HbsAg concentration at Screening will be used as 
a minimization factor (<1000 IU/ml and ≥ 1000 IU/ml) 
for Step B and Step C randomization. 
Section 5.2.2.1.1: 
Allocation of the patient to a study group at the investigator site will be performed 
using a randomization system on internet (SBIR). The randomization algorithm will 
use a minimization procedure [White, 1978] accounting for HbsAg concentration 
(<1000 IU/ml and ≥ 1000 IU/ml) measured at Screening. The minimization 
procedure will be applied for patients enrolled in the steps B and C. 
After obtaining the signed and dated ICF from the patient and having checked the 
eligibility of the patient, the site staff in charge of the vaccine administration will 
access SBIR. Upon receiving the patient identification number and HbsAg 
concentration, the randomization system will determine the study group and will 
provide the treatment number to be used for the first dose. 

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In Table 6 (Section 5.7.2) and Table 11 (Section 5.7.4.1), the hematological 
components to be tested as part of CBC have been clarified in the footnotes. 
(CBC) includes erythrocytes, leukocytes, neutrophils, lymphocytes, eosinophils, 
basophils, monocytes, platelets, hemoglobin and hematocrit. 
In Table 3: 
• 
Four timepoints for the procedure “Recording of unsolicited AEs” have been 
added on Days 31, 87, 143 and 199. 
• 
Four timepoints for the procedure “Recording of solicited AEs” have been added 
on Days 8, 64, 120 and 176. 
• 
Two timepoints for the procedure “Blood sampling for CMI response” have been 
changed from Days 120 and 176 to Days 127 and 183. 
• 
 
 
• 
The blood volume to be collected for HBV, HCV, HDV and HIV serology has 
been changed to 18,5 ml. 
• 
The blood volume to be collected for measurement of autoimmune antibodies has 
been changed to 13,5 ml. 
• 
The symbol “~” has been added before each volume to be collected. This change 
was also made on Table 4. 
Table 3 List of study procedures: Screening and primary phase (Screening Visit to 
Visit 17) 
 
Type of 
contact 
Screening 
Visit 
Visit 
1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 
7 
Visit 
8 
Visit 
9 
Visit 
10 
Visit 
11 
Visit 
12 
Visit 
13 
Visit 
14 
Visit 
15 
Visit 
16 
Visit 
17 
Time points 
Day -29  Day 
1  
Day 
3  
Day 
8  
Day 
15  
Day 
31  
Day 
57  
Day 
64  
Day 
71  
Day 
87  
Day 
113  
Day 
120  
Day 
127  
Day 
143  
Day 
169  
Day 
176  
Day 
183  
Day 
199 
Sampling time 
point(s) 
Screening Pre 
Post-Vacc 1 
Post-Vacc 2 
Post-Vacc 3 
Post-Vacc 4 
Biospecimen 
sampling 
 
Blood sampling 
for 
biochemistry 
(~3.5 ml) b,g,k 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling 
for 
biochemistry 
(AFP) (~3.5 ml) 
k 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling 
for FibroTest 
(~8.5 ml) k 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Type of 
contact 
Screening 
Visit 
Visit 
1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 
7 
Visit 
8 
Visit 
9 
Visit 
10 
Visit 
11 
Visit 
12 
Visit 
13 
Visit 
14 
Visit 
15 
Visit 
16 
Visit 
17 
Time points 
Day -29  Day 
1  
Day 
3  
Day 
8  
Day 
15  
Day 
31  
Day 
57  
Day 
64  
Day 
71  
Day 
87  
Day 
113  
Day 
120  
Day 
127  
Day 
143  
Day 
169  
Day 
176  
Day 
183  
Day 
199 
Sampling time 
point(s) 
Screening Pre 
Post-Vacc 1 
Post-Vacc 2 
Post-Vacc 3 
Post-Vacc 4 
Biospecimen 
sampling 
 
Blood sampling 
for 
hematological 
tests/CBC 
(~2.0 ml) c,g 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling 
for 
hematological 
tests/INR (~4.5 
ml) c,g 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling 
for 
autoimmune 
antibodies 
(~13.5 8.5 ml)  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling 
for HBV, HCV, 
HDV and HIV 
serology (~18.5 
ml)  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling 
for qHBsAg 
(~3.5 ml) 
● 
● 
 
 
 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
● 
Blood sampling 
for HBV-DNA 
and new viral 
markers (~10 
ml) 
● 
 
 
 
 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
● 
Blood sampling 
for CMI 
response (~20 
ml) d 
 
● 
 
 
● 
 
● 
● 
● 
 
● 
● 
● 
 
● 
● 
● 
 
Blood sampling 
for humoral 
response to 
HBV antigens 
(~3.5 ml) e 
 
● 
 
 
● 
 
 
 
● 
 
● 
 
● 
 
 
 
● 
 
Blood sampling 
for serum 
repository 
(~3.5 ml)  
 
● 
 
 
 
 
 
 
● 
 
● 
 
● 
 
 
 
● 
 
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Type of 
contact 
Screening 
Visit 
Visit 
1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 
7 
Visit 
8 
Visit 
9 
Visit 
10 
Visit 
11 
Visit 
12 
Visit 
13 
Visit 
14 
Visit 
15 
Visit 
16 
Visit 
17 
Time points 
Day -29  Day 
1  
Day 
3  
Day 
8  
Day 
15  
Day 
31  
Day 
57  
Day 
64  
Day 
71  
Day 
87  
Day 
113  
Day 
120  
Day 
127  
Day 
143  
Day 
169  
Day 
176  
Day 
183  
Day 
199 
Sampling time 
point(s) 
Screening Pre 
Post-Vacc 1 
Post-Vacc 2 
Post-Vacc 3 
Post-Vacc 4 
Biospecimen 
sampling 
 
Safety assessment 
Recording of 
unsolicited AEs 
within 30 days 
post-
vaccination 
(Day 1-30) 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Recording of 
solicited AEs 
(Days 1-7 post-
vaccination) 
self-reported 
by the patient 
 
● 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
 
Table 4 List of study procedures: primary phase (Visit 18 to Visit 22), follow-up phase 
(Visit 23 to Visit 26) and unscheduled visits 
Type of contact 
Visit 
18 
Visit 
19 
Visit 
20 
Visit 
21 
Visit 
22 
Visit 
23 
Visit 
24 
Visit 
25 
Visit 
26 
Unscheduled 
visit 
Time points 
Day 
225  
Day 
253  
Day 
281  
Day 
309  
Day 
337  
Day 
421  
Day 
505  
Day 
673  
Day 
841  
 
Sampling time point(s) 
Post-Vacc 4 
 
Biospecimen sampling 
 
 
Blood sampling for biochemistry (~3.5 ml) a, 
h,i 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for biochemistry (AFP) 
(~3.5 ml) i 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for FibroTest (~8.5 ml) i 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for hematological tests/CBC 
(~2.0 ml) b, h 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for hematological tests/INR 
(~4.5 ml) b,h 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Blood sampling for qHBsAg (~3.5 ml)  
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
Blood sampling for HBV-DNA and new viral 
markers (~10 ml)  
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
Blood sampling for CMI response (~20 ml) c 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for humoral response to 
HBV antigens (~3.5 ml) d 
 
 
 
 
● 
 
● 
 
● 
 
Blood sampling for serum repository (~3.5 
ml)  
 
 
 
 
● 
 
● 
 
● 
 
Urine sampling for urine chemistry (dipstick) 
e 
● 
● 
● 
● 
● 
 
 
 
 
 

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Table 4 List of study procedures: primary phase (Visit 18 to Visit 22), follow-up phase 
(Visit 23 to Visit 26) and unscheduled visits 
Type of contact 
Visit 
18 
Visit 
19 
Visit 
20 
Visit 
21 
Visit 
22 
Visit 
23 
Visit 
24 
Visit 
25 
Visit 
26 
Unscheduled 
visit 
Time points 
Day 
225  
Day 
253  
Day 
281  
Day 
309  
Day 
337  
Day 
421  
Day 
505  
Day 
673  
Day 
841  
 
Sampling time point(s) 
Post-Vacc 4 
 
In Section 5.6.5, information on the high barrier to resistance treatment to be collected 
has been clarified: 
• 
History and ongoing Current treatment with high barrier to resistance Nas, e.g. 
ETV, TDF or TAF (drug name, route, start date and end date, if applicable), 
In Section 5.6.12, the blood volumes to be collected for the measurement of 
autoimmunes antibodies and for viral serology have been changed to 13.5 ml and 18.5 
ml, respectively. The total volume of blood across the full study period, the highest 
volume per visit and the highest volume over a 8-week period have been adapted. 
• 
Autoimmune antibodies: ~8.513.5 ml, 
• 
Viral serology (HBV, HCV, HDV and HIV): ~8.518.5 ml, 
The volume of blood to be collected from each patient during the 2.5 year study period 
(from Screening to Day 841) is approximately 883.5 875.5 ml. Among all visits, the 
highest volume of blood on a single visit will be approximately 64 51 ml (on Day -29) 
and the highest volume of blood over 8-week will be approximately 186 145 ml (from 
Day 57 to Day 113), which are below the safe limits as recommended by the WHO 
[Howie, 2011]. 
In Table 6 (Section 5.7.2), 
• 
Two timepoints for the blood sampling for CMI response have been changed from 
Days Visit 11 and Visit 15 to Visit 12 and Visit 16. 
• 
 
 
• 
The blood volume to be collected for HBV, HCV, HDV and HIV serology has 
been changed to 18,5 ml. 
• 
The blood volume to be collected for measurement of autoimmune antibodies has 
been changed to 13,5 ml. 
• 
The symbol “~” has been added before each volume to be collected. 
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Table 6 Biological samples 
Sample type 
Component 
Time point 
Quantity 
Unit 
Cohort/subset 
Blood 
HBV, HCV, HDV and 
HIV serology  
Screening 
~8.518.5 
ml 
All patients 
Autoimmune antibodies 
Screening 
~8.513.5 
ml 
Biochemistry 
(FibroTest) * 
Screening, Visit 22, Visit 24 
and Visit 26 
~8.5 
ml 
Biochemistry (AFP) * 
Screening, Visit 22, Visit 24 
and Visit 26 
~3.5 
ml 
Biochemistry (ALT, 
AST, ALP, GGT, 
Bilirubin and Creatinine) 
* 
All visits 
~3.5 
ml 
Hematology (CBC) **  
All visits 
~2.0 
ml 
Hematology (INR) 
All visits 
~4.5 
ml 
HBV-DNA and new viral 
markers  
Screening, Visit 5, Visit 6, Visit 
9, Visit 10, Visit 13, Visit 14 
Visit 17, Visit 18, Visit 19, Visit 
20, Visit 21, Visit 22, Visit 23, 
Visit 24, Visit 25 and Visit 26 
~10 
ml 
qHBsAg 
Screening, Visit 1, Visit 5, Visit 
6, Visit 9, Visit 10, Visit 13, 
Visit 14, Visit 17, Visit 18, Visit 
19, Visit 20, Visit 21, Visit 22, 
Visit 23, Visit 24, Visit 25 and 
Visit 26 
~3.5 
ml 
CMI response 
Visit 1, Visit 4, Visit 6, Visit 7, 
Visit 8, Visit 10, Visit 11, Visit 
12, Visit 14, Visit 15, Visit 16, 
Visit 22, Visit 24 and Visit 26 
~20 
ml 
Humoral response to 
HBV antigens 
Visit 1, Visit 4, Visit 8, Visit 10, 
Visit 12, Visit 16, Visit 22, Visit 
24 and Visit 26 
~3.5 
ml 
Serum repository 
Visit 1, Visit 8, Visit 10, Visit 
12, Visit 16, Visit 22, Visit 24 
and Visit 26 
~3.5 
ml 
 
Urine  
Urine chemistry 
All visits up to Visit 22 
included. 
NA 
NA 
Information in Table 7, Table 8, Table 9 and Table 10 has been presented so that it is now 
aligned with internal standards: 
Hematology, biochemistry, autoimmune antibodies and urine chemistry assessments will 
be performed at GSK Biologicals or at a laboratory designated by GSK Biologicals using 
commercial tests (see Table 7). 
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Table 7 Hematology, biochemistry, autoimmune antibody and urine tests 
System 
Discipline 
Component 
Method 
Scale 
Laboratory 
Whole 
blood 
Hematology 
CBCErythrocytes (Red Blood 
Cells) 
As per Q2 
Solutions 
practice 
Quantitative 
Q2 Solutions  
Leukocytes (White Blood 
Cells) 
Quantitative 
Neutrophils 
Quantitative 
Lymphocytes 
Quantitative 
Eosinophils 
Quantitative 
Basophils 
Quantitative 
Monocytes 
Quantitative 
Platelets 
Quantitative 
Hemoglobin 
Quantitative 
Hematocrit 
Quantitative 
INR Prothrombin Time 
International Normalised Ratio 
(INR) 
Quantitative 
Serum 
Biochemistry 
ALT, AST, ALP, GGT, Bilirubin 
and Creatinine Alanine 
Aminotransferase (ALT) 
Quantitative 
Aspartate Aminotransferase 
(AST) 
Quantitative 
Alkaline Phosphatase (ALP) 
Quantitative 
Gamma Glutamyl Transferase 
(GGT) 
Quantitative 
Total Bilirubin 
Quantitative 
Creatinine 
Quantitative 
AFP Alpha-fetoprotein 
Quantitative 
FibroTest 
Quantitative 
Autoimmune 
antibodies 
Antinuclear antibodies (ANAs) 
Qualitative 
Smooth-muscle antibodies 
(SMAs) 
Qualitative 
Liver-kidney microsomal type 1 
Ab.IgG (LKM-1) 
Qualitative 
Anti-liver cytosol 1 (anti LC1) 
antibodies 
Quantitative 

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Table 8 HBV, HCV, HDV and HIV serology and HBV virology assays 
Syste
m 
Disciplin
e 
Component 
Method 
Kit/ 
manufactur
er 
Unit 
Cut-
off 
Scale 
Laborator
y 
Serum 
HBV 
serology 
Hepatitis B 
Virus.Surface Ab 
(Anti-HBs) a 
CMIA  
Alinity anti-
HBs (Abbott)  mIU/m
L  
10  
Ordinal  
CEVAC 
Hepatitis B 
Virus.Surface 
Ag (qHBsAg) 
Architect 
HbsAg 
assay 
CMIA 
N/A 
IU/ml 
0.05
c 
Quantitativ
e 
Hepatitis B 
Virus.e Ag 
(HbeAg)a 
As per Q2 
Solutions 
practice 
CLIA 
N/A 
N/A 
0.8 
Qualitative 
Q2 
Solutions 
Hepatitis B 
Virus.Core Ab 
(Angi-HBc)  a 
As per Q2 
Solutions 
practice 
CMIA  
N/A 
N/A 
0.5  
Qualitative 
Hepatitis B 
Virus.e Ab (Anti-
Hbe)a 
As per Q2 
Solutions 
practice 
CCLIA 
N/A 
N/A 
0.8 
Qualitative 
HCV 
serology 
Hepatitis Virus 
C Ab (Anti-HCV) 
a 
As per Q2 
Solutions 
practice 
CMIA  
N/A 
N/A 
0.8 
Qualitative 
Q2 
Solutions 
HDV 
serology 
Hepatitis Virus 
D Ab (Anti-HDV)a 
As per Q2 
Solutions 
practice 
ELISA  
N/A 
N/A 
0.9 
Qualitative 
Q2 
Solutions 
HIV 
serology 
Human 
Immunodeficien
cy Virus Ab 
(Anti-HIV) a 
As per Q2 
Solutions 
practice 
CMIA  
N/A 
N/A 
1 
N/A 
Qualitative 
Q2 
Solutions 
HBV 
virology 
Hepatitis B 
Virus DNA  
(HBV DNA) 
QPCR  
Cobas® 
HBV 
assay 
N/A 
IU/mL  
10  
Quantitativ
e  
DDL 
Diagnostic 
Laborator
y 
HBV DNA whole 
sequencingb 
Sequencin
g 
N/A 
N/A 
N/A 
N/A 
a This test will be performed at Screening only. 
b This test will be performed in case of virological breakthrough. 
c This cut-off will be used at Screening. For other time points, the cut-off might change based on supplementary 
validation experiments. 

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The cut-off for HBV DNA measured by qPCR will be 10 IU/mL. 
Table 9 Humoral Immunity (Antibody determination) 
System 
Component 
Method 
Kit / Manufacturer 
Unita 
Cut-offa 
Laboratory ba 
Serum 
Anti-HBs Ig tot 
Hepatitis B 
Virus.Surface 
Ab  
CLIA  
ADVIA Centaur anti-
HBs2 (Siemens 
Healthcare)  
mIU/ml  6.2  
GSK Biologicals’ 
laboratory or 
laboratory 
designated by 
GSK 
Anti-HBc 
Hepatitis B 
Virus Core Ab 
To be 
developed dc 
TBD 
TBD 
TBD 
a Assay cut-off and unit might be subject to change during the course of the study (e.g. in case of requalification, 
revalidation or standardization). In this case, this will be documented in the clinical report. 
ba GSK Biologicals laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium 
or Marburg, Germany. Refer to APPENDIX B for the laboratory addresses. 
bc Exploratory test that will be performed depending on availability of assays and scientific relevance. 
cd This assay will be developed in the course of the study.  
Table 10 Cell mediated immunity 
System 
Component 
Challenge 
Method 
Unit 
Laboratorya 
PBMC 
(HBs-specific 
(CD4+/CD8+) T-cells) 
HBs peptide pool 
CFC  
ICS 
Events per 
million T-cells 
GSK Biologicals’ 
laboratory or 
laboratory designated 
by GSK 
HBc-specific 
(CD4+/CD8+) T-cells 
HBc peptide pool 
CFC 
ICS 
Events per 
million T-cells 
 
In Section 5.7.3, corrections have been made: 
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In Table 12, timepoints for evaluating HbsAg 
 have been adapted and the 
priority ranks were deleted: 
Table 12 Evaluation of serum HBV antigens 
Sample 
type 
Type of contact and 
time point 
Study 
group 
No 
Patients 
Component 
Components 
priority rank 
Serum 
Screening, Visit 1, Visit 
5, Visit 6, Visit 9, Visit 
10, Visit 13, Visit 14, 
Visit 17, Visit 18, Visit 
19, Visit 20, Visit 21, 
Visit 22, Visit 23, Visit 
24, Visit 25 and Visit 26 
All study 
groups 
HbsAg 
1 
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Table 14 Evaluation of humoral immunogenicity 
Type of contact and time point 
Sub 
groups 
No. 
patients 
Component 
Components 
priority rank 
Visit 1, Visit 4, Visit 8, Visit 10, Visit 12, Visit 
16, Visit 22, Visit 24 and Visit 26 
All study 
groups 
Anti-HBc 
2 
Anti-HBs Ig total 
1 
In Table 15:  
• 
Two timepoints for the blood sampling for CMI response have been changed from 
Days Visit 11 and Visit 15 to Visit 12 and Visit 16. 
• 
 
 
Table 15 Evaluation of cell-mediated immunogenicity 
Type of contact and time point 
Sub 
groups 
No. 
patients 
Component 
Components 
priority rank 
Visit 1, Visit 4, Visit 6, Visit 7, Visit 8, Visit 
10, Visit 1112, Visit 14, Visit 1516, Visit 22, 
Visit 24 and Visit 26 
All study 
groups 
HBc-specific ICS 
(CD4+/CD8+) T-cells 
1 
HBs-specific ICS 
(CD4+/CD8+) T-cells 
2 
 
In Section 6.4, the wording related to disposal of the dressing has been adapted: 
After each vaccination, the injection site will be covered with a dressing in order to 
absorb any virus that may leak out through the needle track. The dressing will be 
removed only after 30 minutes and will be disposed as GMO waste by autoclaving or 
in accordance with the applicable guidelines/standard operating procedures at the 
investigator’s site. 
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In Section 6.7.1, Nas with high barrier to resistance have been added to the list of 
concomitant medications to be recorded: 
• 
Nucleos(t)ide analogues with high barrier to resistance (e.g. ETV, TDF, TAF) 
that the patient takes to control chronic hepatitis B. 
In Section 6.7.2, the daily dose of prednisone that may lead to elimination from the 
per-protocol analyses has been changed from 20 mg to 10 mg: 
• 
Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this 
will mean prednisone ≥ 20 10 mg/day or equivalent. Inhaled and topical steroids 
are allowed. 
In Section 8.5.3, a mistake in the ALT level has been corrected: 
• 
Patients with confirmed ALT within 144 - 239 240 U/L (i.e. > 3 to ≤< 5 X ULN) 
and INR > 1.5 (repeated testing preferably within 48-72 hours) will be withdrawn 
from vaccination. If the result is not confirmed, tests will be repeated until ALT 
level decreases to < 72 U/L (i.e. < 1.5 X ULN) and INR decreases to < 1.15. 
Patients with ALT < 72 U/L (i.e. < 1.5 X ULN) and INR < 1.15 will be eligible for 
the next vaccine administration. 
In Section 8.8.2, a footnote has been added to Figure 3 to provide additional 
information on the staggered enrolment. 
For the second dose vaccination, there will be at least 8 days apart between the 
initially recruited subjects (i.e. 
 and the 
remaining subjects within in each step 
In Section 8.8.3.2, the wording related to the risk assessment for holding rules has been 
clarified: 
Figure 5 and Figure 6 present the probability of not meeting defined holding rule for
 patients per study group, respectively. 
The above Figure 5 illustrates that, with
patients in a group: 
• 
For holding rules 1 and 3, using a cut-off of 
, there is around 90% chance that 
the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 35% and around 60% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 10%. 
• 
For holding rule 2, using a cut-off of 
, there is only around 60% chance that 
the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 35% and around 90% chance that the holding rule is not met in a 
vaccine group if the corresponding event has true incidence rate of 10%. 
The above Figure 6 illustrates that, with
patients in a group: 
• 
For holding rules 1 and 3, using a cut-off of 
, there is around 88% chance 
that the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 10% and around 45% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 5%. 
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• 
For holding rules 2, using a cut-off of 
, there is around 90% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 20% and around 10% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 20%. 
• 
For holding rules 2, using a cut-off of 
, there is around 70% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 30% and there is around 96% chance that the holding rule is 
not met in a vaccine group if the corresponding event has a true incidence rate 
of 10%. Around 30% chance that the holding rule is not met in a vaccine group if 
the corresponding event has a true incidence rate of 30%. 
The above Figure 7 illustrates that, with
patients in a group: 
• 
For holding rules 1 and 3, using a cut-off of 
, there is around 90% chance 
that the holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 5% and around 10% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 5%. 
• 
For holding rules 2, using a cut-off of 
, there is around 90% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 10% and around 10% chance that the holding rule is not met in a 
vaccine group if the corresponding event has a true incidence rate of 10%. 
• 
For holding rule 2, using a cut-off of 
, there is around 90% chance that the 
holding rule is met in a vaccine group if the corresponding event has a true 
incidence rate of 35% and there is around 99% chance that the holding rule is 
not met in a vaccine group if the corresponding event has a true incidence rate 
of 10%. Around 10% chance that the holding rule is not met in a vaccine group if 
the corresponding event has a true incidence rate of 35%. 
In Section 10.5.1, 10.5.2, 10.8 and 10.9, the naming of the cohort has been aligned with 
CDISC requirements (i.e. TVC was changed to Exposed Set [ES] and ATP was 
changed to Per Protocol Set [PPS]). 
Section 10.5.1: 
10.5.1 Exposed Set Total vaccinated cohort 
The Total vaccinated cohort Exposed set (TVCES) will include all patients with study 
vaccine administration documented: 
• 
A safety/reactogenicity analysis based on the TVC ES will include all patients 
who received at least one vaccine dose. 
• 
An efficacy/immunogenicity analysis based on TVC ES will include all 
vaccinated patients for whom efficacy/immunogenicity data are available. 
The TVC ES analysis will be performed per treatment actually administered at Dose 1. 
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Section 10.5.2: 
The per-protocol cohort for efficacy/immunogenicity will include all evaluable 
patients, i.e., those who were included in the TVC ES and: 
Section 10.8: 
The analysis will be performed the same way for each step A, B or C. The primary 
analysis will be performed on the per-protocol cohort for efficacy/immunogenicity and 
if, in any study group, the percentage of vaccinated patients with serological results 
excluded from the per-protocol cohort is at least 15%, a second analysis will be 
performed on the TVC ES.  
Section 10.9: 
The analysis will be performed the same way for each step A, B or C including patients 
from the TVC ES. 
In Section 10.6, the sentence related to cut-off presentation was deleted for alignment 
with changes in Table 8 and 9: 
• 
Immunogenicity 
− The cut-off value is defined by the laboratory before the analysis and is 
described in Section 5.7.3. 
− A seronegative patient is a patient whose titre is below the cut-off value. 
In Section 10.8.1, statistical analysis of CMI has been added: 
• 
CMI results will be presented by group using descriptive statistics (N, geometric 
mean [GM], min, Q1, median, Q3, max). 
In Section 10.8.1, the possibility to perform additional statistical analyses has been 
mentioned: 
If sufficient patients are available for the analysis, additional descriptive analysis 
may be performed by categories of baseline HbsAg concentration and HBV 
genotype. 
In Section 10.9.1, the wording related to 2 safety analyses has been corrected/adapted: 
• 
The number of patients who experienced FibroScan TE score ≥ 9.6 8.1 kPa and 
FibroTest score ≥ 0.59 at Day 337, 505 and 841 will be reported. 
• 
The number of patients who developed hepatocellular carcinoma experienced 
liver mass on liver imaging examination and/or α-fetoprotein > 50 mg/ml at Day 
337, 505 and 841 will be reported. 
In Section 12 Country specific requirements, a new subsection for France (Section 
12.2) has been added: 
Section 12.2. France 

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This section includes requirements of French Public Health Code / specific local 
GSK requirements and identifies, item per item, the mandatory modifications or 
additional information applicable to the study. 
1. Concerning the « SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA»  
• 
The following vulnerable subject populations will be excluded: minors, protected 
subjects, adult subjects not in condition to express their consent, subjects 
deprived of liberty, subjects receiving psychiatric cares, subjects hospitalized in a 
Health and Social Establishment for other purpose than the participation to the 
study. 
• 
A subject will be eligible for inclusion in this study if he /she is either affiliated 
to or beneficiary of a social security category (French Public Health Code law 
L.1121-8-1). (exception for a participant to a non-interventional study if 
authorised by the Ethics Committee). It is the investigator’s responsibility to 
ensure and to document (in the source document - subject notes) that the 
subject: 
− 
is either affiliated to or beneficiary of a social security category;  
− 
has got an authorisation by the Ethics Committee. 
2. Concerning the “STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES” and specially in the “SAMPLE SIZE ASSUMPTIONS” 
The expected number of subjects to be recruited in France is declared to the French 
regulatory authority. 
3. Concerning the “STUDY GOVERNANCE CONSIDERATIONS” 
• 
In section “Regulatory and Ethical Considerations, including the Informed 
Consent Process” 
− 
Concerning the process for informing the subject and/or his/her legally 
authorized representative, the following text is added: 
French Patient Informed Consent Form is a document which summarizes the 
main features of the study and allows collection of the subject and/or his/her 
legally authorized representative written consent in triplicate (quadriplicate for 
minor subject). It also contains a reference to the authorisation of ANSM and 
the approval from the French Ethics Committee and the maintenance of 
confidentiality of the returned consent form by GlaxoSmithKline France. 
− 
Concerning the process for obtaining subject informed consent: 
When a research involving human being is carried out on a minor / on an adult 
in the care of a “tutelle” guardian, consent is given by their legal representative 
and, if the committee mentioned in article L. 1123-1 considers that the research 
in question, because of the seriousness of the restraints or the specificity of the 
medical acts involved, entails a serious risk of affecting their private life or the 
integrity of their body, consent is given by the family council if it has been 
instated, or by the judge of “tutelle” guardians. 

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When research involving human being is carried out on an adult in the care of a 
"curatelle" guardian, consent is given by the subject assisted by his guardian. 
However, if the adult in the care of a "curatelle" guardian is invited to 
participate in research which the committee mentioned in article L. 1123-1 
considers, because of the seriousness of the restraints or the specificity of the 
medical acts involved, to entail a serious risk of affecting their private life or the 
integrity of their body, the matter is submitted to the judge of guardians who 
decides whether the adult is capable of giving her/his consent. In the case of 
incapacity, the judge will decide whether or not to authorise the research 
involving human being. 
− 
Concerning the management of the Patient Informed Consent Forms, the 
following text is added: 
The first copy of the Patient Informed Consent Form is kept by the investigator. 
The second copy is kept by the Medical Director of GlaxoSmithKline France 
and the last copy(ies) is(are) given to the subject or their legally authorized 
representative(s). 
The second copy of all the consent forms will be collected by the Clinical 
Research Assistant (CRA) under the Investigator’s control, and placed in a 
sealed envelope bearing only: 
− 
the study number,  
− 
the identification of the Centre: name of the principal investigator and 
centre number, 
− 
the number of informed consents, 
− 
the date,  
− 
and the principal investigator’s signature. 
Then, the CRA hands the sealed envelope over to the Medical Director, for 
confidential recording, under the responsibility of the Medical Director. 
• 
NOTIFICATION TO THE HOSPITAL DIRECTOR 
In accordance with Article L1123-13 of the French Public Health Code, the Hospital 
Director is informed of the commitment to the trial in her/his establishment. The 
Hospital Director is supplied with the protocol and any information needed for the 
financial disposition, the name of the investigator(s), the number of sites involved in 
his establishment and the estimated time schedule of the trial (R.1123-69). 
• 
INFORMATION TO THE HOSPITAL PHARMACIST 
In accordance with Article R.1123-70 of the French Public Health Code, the 
Hospital Pharmacist is informed of the commitment to the trial in her/his 
establishment. The Pharmacist is supplied with a copy of the protocol (which allows 
her/him to dispense the drug(s) of the trial according to the trial methodology), all 
information concerning the product(s) of the trial (e.g. included in the CIB), the 
name of the investigator(s), the number of sites involved in her/his establishment and 
the estimated time schedule of the trial. 

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4. Concerning the “ DATA MANAGEMENT ” the following text is added: 
• 
Within the framework of this clinical trial, data regarding the identity of the 
investigators and/or co-investigators and/or the pharmacists if applicable, 
involved in this clinical trial, and data regarding the subjects recruited in this 
clinical trial (subject number, treatment number, subjects status with respect to 
the clinical trial, dates of visit, medical data) will be collected and computerized 
in GlaxoSmithKline data bases by GlaxoSmithKline Laboratory or on its behalf, 
for reasons of follow up, clinical trial management and using the results of said 
clinical trial. According to the Data Protection French Law n° 78-17 of 6th 
January 1978, each of these people aforesaid has a right of access, correction 
and opposition on their own data through GlaxoSmithKline Laboratory 
(Clinical Operations Department). 
• 
DEMOGRAPHIC DATA 
In accordance with the Data Protection French Law n° 78-17 of 6th January 1978 – 
article 8, the ethnic origin can only be collected if the collection of this data is strictly 
necessary and relevant for the purpose of the study. 
• 
TESTING OF BIOLOGICAL SAMPLES 
In accordance with the French Public Health Code law – article L1211-2, a 
biological sample without identified purpose at the time of the sample and subject’s 
preliminary information is not authorized. 
5. Monitoring visits 
The Health Institution and the Investigator agree to receive on a regular basis a 
Clinical Research Assistant (CRA) of GLAXOSMITHKLINE or of a service provider 
designated by GLAXOSMITHKLINE. The Health Institution and the Investigator 
agree to be available for any phone call and to systematically answer to all 
correspondence regarding the Study from GLAXOSMITHKLINE or from a service 
provider designated by GLAXOSMITHKLINE. In addition, the Health Institution 
and the Investigator agree that the CRA or the service provider designated by 
GLAXOSMITHKLINE have direct access to all the data concerning the Study (test 
results, medical record, etc …). This consultation of the information by 
GLAXOSMITHKLINE is required to validate the data registered in the electronic 
Case Report Form (eCRF), in particular by comparing them directly to the source 
data. In accordance with the legal and regulatory requirements, the strictest 
confidentiality will be respected. 
6. Data entry into the eCRF 
The Health Institution and the Investigator agree to meet deadlines, terms and 
conditions of the Study’s electronic Case Report Form (eCRF) use here below: 
The Health Institution and the Investigator undertake: 
• 
That the Investigator and the staff of the investigator center make themselves 
available to attend the training concerning the computer system dedicated to the 

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electronic Case Report Form (eCRF) of the Study provided by 
GLAXOSMITHKLINE or by a company designated by GLAXOSMITHKLINE. 
• 
That the Investigator and the staff of the investigator center use the IT 
Equipment loaned and/or the access codes only for the purpose of which they 
are intended and for which they have been entrusted to them, namely for the 
Study achievement, to the exclusion of any other use. 
• 
That the Investigator and the staff of the investigator center use the IT 
Equipment loaned according to the specifications and manufacturer’s 
recommendations which will have been provided by GLAXOSMITHKLINE. 
• 
To keep the IT Equipment and/or access codes in a safe and secure place and to 
authorize only the use of this IT Equipment by investigator center staff 
designated by the principal investigator to enter the data of the Study. 
• 
To be responsible for the installation and payment of the required Internet 
connections needed for the use of the IT Equipment, Computer systems and/or 
access codes. 
• 
To return at the end of the Study the IT Equipment and/or access codes to 
GLAXOSMITHKLINE or to any company designated by 
GLAXOSMITHKLINE and any training material and documentation. The IT 
Equipment cannot under any circumstances be kept by the Health Institution or 
the Investigator for any reason whatsoever.  
7. CTR publication 
It is expressly specified that GLAXOSMITHKLINE and/or the Sponsor can make 
available to the public the results of the Study by the posting of the said results on a 
website of the GLAXOSMITHKLINE GROUP named Clinical Trial Registred 
(CTR) including the registration of all the clinical trials conducted by the 
GLAXOSMITHKLINE Group and this before or after the publication of such results 
by any other process. 
8. Data Protection French Law of 6th January 1978 (CNIL) 
In accordance with the Data Protection French Law of 6 January 1978, computer 
files used by GLAXOSMITHKLINE to monitor and to follow the implementation 
and the progress of the Study are declared with CNIL by GLAXOSMITHKLINE. 
The Investigator has regarding the processing data related to her/him a right of 
access, of rectification and of opposition with GLAXOSMITHKLINE in accordance 
with the legal provisions. This information can be transferred or be accessed to other 
entities of GLAXOSMITHKLINE Group, what the Investigator agrees by the 
signature of the present Protocol. 
9. Investigational Product Accountability, Reconciliation, and Destruction 
In specific situations (if the site has 1- an approval from the French Regulatory 
Agency (ANSM) and 2- a GSK written endorsement letter) where institutional 
practices dictate that the site disposes of and/or destroys IP prior to allowing the 
“monitor’ to verify and document IP accountability, the following applies: 

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“During the conduct of the Study, Investigational Product (IP) will be destroyed by 
the Institution prior to a GlaxoSmithKline “monitor” conducting final 
investigational product accountability. Institution agrees that such destruction will 
comply with Institution’s investigational product accountability procedures and will 
provide GlaxoSmithKline with investigational product accountability logs and 
supporting documentation to verify adherence to ‘Bonnes Pratiques Cliniques’ 
(decision dated on the 24th of November 2006). 
In Section 13, references have been added: 
Halfon P, Munteanu M & Poynard T. FibroTest-ActiTest as a non-invasive marker 
of liver fibrosis. Gastroenterol Clin Biol. 2008;32(6 Suppl 1):22-39. 
Thiele M, Madsen BS, Hansen JF, et al. Accuracy of the enhanced liver fibrosis test 
vs FibroTest, elastography, and indirect markers in detection of advanced fibrosis in 
patients with alcoholic liver disease. Gastroenterology. 2018;154(5):1369-1379. 
White SJ, Freedman LS. Allocation of patients to treatment groups in a controlled 
clinical study. Br J Cancer. 1978;37:849-857. 
Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis 
by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 
2005;41:48-54. 
In Appendix A Laboratory assays: 
• 
Mentions of “Architect” assay were removed. The Abbott platform to be used for 
measurement of HbsAg may either be the “Architect” or the “Alinity”. Referring 
to the “Abbott” platform covers both options. 
• 
Mention of the ‘Lumipulse G’ assay has been removed. 
• 
Description of the CFC assay has been added. 
4. qHBsAg – Architect HbsAg assay (Abbott) 
The architect Abbott HbsAg assay is a two-step immunoassay using chemiluminescent 
paramagnetic microparticles (CMIA) technology for the quantitative determination of 
HbsAg. In the first step, sample is mixed with microparticles coated with anti-HBs; 
antibody-antigen will form if HbsAg is present in the sample. In the second step, 
acridium-labeled anti-HBs conjugate is added. A direct relationship exists between the 
amount of HbsAg present in the sample and the RLU detected by the system. 
5. qHBsAg – Architect HbsAg assay (Abbott) with pre-treatment 
Immune complexes (Ag-Ab complexes) can be present in the sample. Those immune 
complexes can interfere with the HbsAg dosage. In order to avoid this interference, 
sample is pre-treated with Sodium Thiocyanate (NaSCN), a chaotropic agent that 
dissolves the immune complexes. After this pre-treatment, sample is used as described 
in the previous section. 

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6. 
 
11. CFC Assay 
This assay is applied to measure the frequency of antigen-specific T-lymphocytes in 
peripheral blood. Blood samples are collected by venipuncture and PBMCs are 
prepared by certified laboratories by centrifugation onto a Lymphoprep™ cushion 
within 24 hours following collection. PBMC suspensions are stored in liquid 
nitrogen until analysis. To measure T-cell responses elicited by the vaccine 
candidate, samples are thawed and cultured overnight in the presence of 
costimulatory antibodies (anti-CD28 and anti-CD49d) without stimulation 
(background control) or with peptide pools (15mer overlapping by 11) covering the 
sequence of the relevant antigens (HBs, HBc, 
 Cells 
are then immunostained for surface phenotypic markers (CD4 and CD8), 
permeabilized and then immunostained for CD3 and activation markers (the 
costimulatory molecules CD40L and 4-1BB and the cytokines IL-2, IFN-γ, TNF-α, 
IL-13, IL-17). Analysis is performed by multiparametric flow cytometry, and the 
results are expressed after background subtraction as frequencies of antigen specific 
CD4+ (or CD8+) T-cells producing various combinations of the activation markers 
assessed per million CD4+ (or CD8+) T-cells. 
In Appendix C Toxicity grading for hematology and biochemistry parameters, an error 
has been corrected: 
Platelet (cell/mm3) decrease 
14,000140,000 
- 125,000 
124,000 - 
100,000 
99,000 - 
25,000 
< 25,000 
 
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eTrack study number 
and Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
3 
Amendment date: 
6 August 2019 
Co-ordinating author: 
, Scientific Writer (Modis for GSK 
Biologicals) 
List of changes 
On the cover page, the list of contributors has been updated: 
• 
 and 
, Clinical Safety 
Representatives 
• 
 and 
, Study Data Managers 
• 
 and 
, Public Disclosure Representatives 
On the Sponsor Information page, information related to contact details for emergency 
unblinding have been added: 
1. GSK Biologicals’ Central Safety Physician On-Call Contact information 
for Emergency Unblinding 
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GSK Biologicals Central Safety Physician Phone contact: refer to protocol Section 
5.3.1. 
In the list of abbreviations, he following abbreviations were removed because not used 
in the text: 
Th1 
T-helper Type 1 
UPR 
Unfolded Protein Reponse 
In Section 1.3.1.4, minor edits was made for alignment with the changes in the 
eligibility criteria: 
Considering the risk of hepatic failure that may be triggered by vaccine-induced 
immune response, this FTIH will be conducted in CHB adult (18-65 years of age) 
patients at low risk of hepatitis flares, i.e. in those patients under NA therapy since at 
least 24 months, well-controlled (HBV DNA suppressed and alanine transaminase 
[ALT] normalized within the past since at least 24 months) and with no advanced liver 
fibrosis or cirrhosis of any stage. 
In Section 3 and in the Synopsis, correction regarding blinding in Epoch 001 
(Screening) was made: 
Study Epochs 
Blinding 
Epoch 001 
Single-blind Not 
applicable 
Epoch 002 
Single-blind 
Epoch 003 
Single-blind 
In Section 3 and in the Synopsis, the following clarification has been provided: 
Safety monitoring: Internal Safety Review Committee (iSRC). An external expert 
with clinical expertise in hepatology will work together with the iSRC to review the 
safety data and contribute to the decision-making process to hold or continue the 
study. 
In Section 4.2, the following inclusion criterion was modified: 
• 
Documented HBV viral suppression as per local clinical diagnosis for at least 
within the previous 24 months AND at Screening test HBV DNA < 10 IU/ml. If 
no results are available, two Screening tests need to be performed at least 2 weeks 
apart. Small fluctuations of HBV DNA (≤ 100 IU/ml) are allowed provided HBV 
DNA is < 10 IU/ml at Screening and was clearly not rising during the previous 24 
months.  
• 
Documented normal level of ALT as per local clinical diagnosis for at least within 
the previous 24 months AND at Screening test ALT ≤ 48 U/L. Small fluctuations 
of ALT (≤ 1.5 X ULN) are allowed provided ALT ≤ 48 U/L at Screening. If no 
results are available, two Screening tests need to be performed at least 2 weeks 
apart. ULN are to be defined according to local laboratory reference range. 

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• 
No clinical diagnosis of advanced liver fibrosis and cirrhosis (e.g. F3 or F4 by 
METAVIR scoring system or ≥ 6 by Ishak scoring system) within the previous 24 
months. 
In Section 4.3, the following eligibility criteria were modified: 
• 
Medical history of advanced fibrosis and cirrhosis.  
• 
Suspicion of or confirmed HCC or any other liver cancer in medical history or at 
Screening: 
− Elevated α-fetoprotein > 50 mg ng/ml. 
• 
Hematology and biochemistry parameters outside normal clinical range at 
Screening: 
Hematology: 
− Hemoglobin < 12.0 g/dl (for females) or < 13.85 g/dl (for males) 
INR > 1.15 1.2 
• 
Body Mass Index (BMI) > 30 35 kg/m² at Screening. 
A new section (Section 5.3.1) on emergency unblinding was added: 
Unblinding a participant’s individual intervention number should occur ONLY in case 
of a medical emergency when knowledge of the intervention is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention via SBIR, 
an automated Internet-based system. 
As back up process, the investigator has the option of contacting a GSK Biologicals’ 
Helpdesk (refer to the Table 3) if he/she needs help performing the unblinding (i.e. 
he/she cannot access the automated Internet-based system). 
A non-investigator physician (e.g. physician from emergency room) or participant/care 
giver/family member may also request emergency unblinding either via the 
investigator (preferred option) or via the GSK Biologicals’ Helpdesk (back up 
process).  
Where applicable, the patient/participant card lists contact information for both the 
investigator and GSK Biologicals’ Helpdesk. 
Table 3 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Phone: +32.2.656.68.04 
Fax: +32.2.401.25.75 
E-mail: rix.ugrdehelpdesk@gsk.com 

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In Section 8.5.3, abnormal parameters related to INR have been adapted to reflect the 
changes in eligibility criteria: 
• 
Patients with confirmed ALT within 144 - 240 U/L (i.e. > 3 to ≤ 5 X ULN) and 
INR > 1.5 (repeated testing preferably within 48-72 hours) will be withdrawn from 
vaccination. If the result is not confirmed, tests will be repeated until ALT level 
decreases to < 72 U/L (i.e. < 1.5 X ULN) and INR decreases to < 1.15 1.2. 
Patients with ALT < 72 U/L (i.e. < 1.5 X ULN) and INR < 1.15 1.2 will be 
eligible for the next vaccine administration. 
In Section 8.8.1, the following paragraph has been added: 
An external (non-GSK) expert with clinical expertise in hepatology will work 
together with the iSRC to review the safety data and contribute to the decision-
making process to hold or continue the study. 
In Section 10.11.1, the following clarification was made: 
Stepwise safety analyses for iSRC review will be done as described in Section 8.8.1. 
These analyses will be performed by project independent statistician in order to keep 
GSK study team blinded as much as possible until up to the end of the defined step 
procedures. 
In Appendix C, the lab value for toxicity grading of eosinophils was corrected (typo 
error) and a footnote related to blood in urine analysis was added: 
Eosinophils (cell/mm3)  
600 
650 - 
1,500 
1,501 - 
5,000 
> 5,000 hypereosinophilic 
syndrome 
Blood (microscopic) – red blood cells per high power field (rbc/hpf) 
 
1 -1 0 11 - 50  > 50 
and/or 
gross 
blood 
hospitalized for 
packed red blood 
cell (PRBC) 
transfusion 
 

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eTrack study number 
and Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
4 
Amendment date: 
29 April 2020 
Co-ordinating author: 
, Scientific Writer (Modis for GSK 
Biologicals) 
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List of changes 
On the cover page, the list of contributors has been updated: 
• 
 and 
, Scientific Writers, Modis for GSK 
Biologicals 
On the cover page, the list of contributors has been updated: 
• 
 and 
, Clinical Research Development 
Leads 
• 
 and 
, Study 
Delivery Leads 
• 
, Bio-Statistician 
• 
 and 
, Clinical Trial 
Supply Managers 
• 
, and 
, Study Data Managers 
• 
 and 
, Public Disclosure 
Representatives 
In the list of abbreviations, the following abbreviation was added because its use in the 
text: 
COVID-19 
Coronavirus Disease 2019 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
WHO 
World Health Organisation 
In section 2.2, a typo has been corrected. 
Proof-of-principle (PoP) will be achieved if  
At least
% of patients (i.e. a lower limit of the 80% CI of at least 15%) in one 
vaccine group show a at least 10-fold decrease (i.e. 1-log difference) in qHBsAg 
or show HbsAg loss at Day 337 versus Day 1, or  
In Section 3, the following text and cross-reference to the new section (Section 5.6.17) 
was added to provide flexibility to certain study procedures during special 
circumstances, such as COVID-19 pandemic: 
During special circumstances (e.g., Coronavirus disease [COVID-19] pandemic), 
certain study procedures should be adapted to protect patient’s welfare, and as far as 
possible ensure the potential benefit to the patient and promote data integrity 
(Section 5.6.17). 
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In Section 3, a cross-reference to the new section (Section 5.6.17) was added to Figure 
1 to provide flexibility to certain study procedures during special circumstances, such 
as COVID-19 pandemic: 
Refer to Section 5.6.17 for study procedures to be adapted during special 
circumstances. 
In Section 5.5, a cross-reference to the new section (Section 5.6.17) was added to 
provide flexibility to certain study procedures during special circumstances, such as 
COVID-19 pandemic: 
For study procedures to be adapted during special circumstances, refer to Section 
5.6.17. 
In Section 5.5, a cross-reference to the new section (Section 5.6.17) was added to 
Tables 4-5 to provide flexibility to certain study procedures during special 
circumstances, such as COVID-19 pandemic: 
Refer to Section 5.6.17 for study procedures to be adapted during special 
circumstances.  
In Section 5.5, a cross-reference to the new section (Section 5.6.17) was added to 
Tables 4 for the management of study visits if subsequent vaccination cannot be 
administered within an interval of 56- 60 days due to special circumstances: 
If subsequent vaccination cannot be administered within an interval of 56 - 60 days 
due to special circumstances, please refer Section 5.6.17. ) 
In Section 5.5, footnotes “n” and “o” were added to Tables 4 for procedures that are 
not applicable in case vaccination was not administered at vaccination visit or at 
preceding vaccination visit: 
n Procedure not applicable if vaccination could not be administered at that 
vaccination visit.  
o Procedure not applicable if vaccination was not administered at preceding 
vaccination visit. 
k If procedure has not been performed at the respective timepoints, it should be done 
at earliest convenience. 
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In Section 5.5, footnote “c” and cross-reference to the new section (Section 5.6.17) 
were added to Table 6 to provide additional criteria to be considered during special 
circumstances, such as COVID-19 pandemic: 
In case of special circumstances, this interval between two subsequent doses can be 
extended up to 84 days. If more than 84 days elapsed from administration of the 
previous vaccine dose, study vaccination should continue provided that maximum 
interval of 111 days between doses is respected.  
In Section 5.6.17, added new, to provide guidance on adapting study procedures during 
special circumstances, such as COVID-19 pandemic: 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance 
from local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, 
the following measures may be implemented for enrolled patients of the impacted 
countries or sites:  
• 
Study visits may be replaced by a telephone call, other means of virtual contact 
or home visit, if appropriate to collect the safety information (AEs and 
concomitant medications/vaccinations), unless a patient presents symptoms or 
reports AEs that necessitate a site visit in Investigator’s judgement. 
• 
Diary cards may be transmitted from and to the site by electronic means and/or 
conventional mail. 
• 
The screening activities and vaccine administration may be put on hold in line 
with specific local guidance or when deemed necessary by the Investigator or by 
Sponsor. Notification to Ethical Committees / Independent Review Boards and 
Competent Authorities should be made as appropriate. When it deems 
appropriate to resume the screening activities and vaccine administration, this 
can be done following notification to the Ethical Committees / Independent 
Review Boards and Competent Authorities and approvals as needed.  
• 
Maximum interval between study vaccinations: If despite best efforts it is not 
possible to administer subsequent dose of study vaccine as defined in the 
protocol (see Table 6), a maximum dose interval of 111 days between two 
subsequent doses should be used. The maximum interval has been determined 
based on experience with Ebola ChAd-MVA prime-boost in Phase I study 
[Tapia, 2016]. In this study, MVA-BN-Filo booster vaccine given 11 – 16 weeks 
(79 - 111 days) after priming with ChAd3-EBO-Z was well tolerated and 
immunogenic eliciting both anamnestic antibody responses and robust 
multifunctional CD4 and CD8 memory T-cell responses.  
• 
Discontinuation from study vaccination: If a maximum interval of 111 days 
since previous vaccination is exceeded, vaccination should be discontinued. 
• 
Adaptation of study visits when subsequent vaccination cannot be administered 
as defined in the protocol i.e. at interval of 56 – 60 days: 
• 
If subsequent vaccination cannot be administered within an interval of 56 - 60 
days, only the visits specified in Table 7 should be performed at least every 4 
weeks after the previous vaccination to follow up on safety and laboratory 

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parameters. For management of those visits, refer to Table 7. Data collected at 
those visits should be encoded using unscheduled visit form in eCRF until the 
vaccination is resumed within a maximum of 111 days interval from the 
previous vaccination.  
• 
If subsequent vaccination can be administered within maximum interval of 111 
days from the date of previous dose administration, the visit related to this 
vaccination should be performed and further visits should follow as defined in 
Table 4, Table 5 and Table 6. Vaccination visit and subsequent visits should be 
encoded as regular visits in eCRF. 
• 
If subsequent vaccination cannot be administered within maximum interval of 
111 days from the date of previous dose administration, patient should 
discontinue study vaccination and management of follow up visits in the primary 
phase (Epoch 002) should be performed as indicated in Table 7 and described 
below: 
For patients who discontinued vaccination after vaccination Dose 1, Visits 10, 
12, 13, 14 and 17-22 should be performed for follow up on safety and laboratory 
parameters. 
For patients who discontinued vaccination after vaccination Dose 2, Visits 14 
and 17-22 should be performed for follow up on safety and laboratory 
parameters.  
For patients who discontinued vaccination after vaccination Dose 3, Visits 18-22 
should be performed for follow up on safety and laboratoryparameters.  
Data collected at the above mentioned visits should be encoded as regular visits 
in eCRF.  
For all patients who discontinued study vaccination, the planned visits in the 
follow up phase (Epoch 003) should be performed as defined by protocol. 
• 
Biological samples may be collected at a different location* other than the study 
site or at patient’s home, in line with applicable local guidance. Biological 
samples should not be collected if they cannot be processed in a timely manner 
or appropriately stored until the intended use. 
• 
In case a Grade 3 laboratory parameter abnormality is detected, an unscheduled 
visit should be performed, per protocol planned as a site visit. However, 
Investigator should practice his/her medical judgement on the clinical relevance 
of any abnormality and manage this according to the local clinical practice and 
local guideline concerning the COVID-19. If the site visit restriction is in place, 
the Investigator should contact the concerned patient in a remote manner (e.g. 
phone contact or home visit, if appropriate) to collect the safety information. 
Whenever possible and in line with applicable local guidance, the Investigator 
should arrange the clinical and laboratory examination at a different location* 
other than the study site that is accessible for the concerned patient. 
* It is the investigator’s responsibility to identify an alternate location. The 
investigator should ensure that this alternate location meets ICH GCP 
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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 European Medicines Agency Guidance on the 
Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic 
(version 2, 27 March, 2020) for more details. 
Impact on the per protocol set for immunogenicity and efficacy will be determined 
on a case by case basis. Due to potential increase of the drop-out rate, to ensure 
sufficient number of evaluable patients: 
• 
Allowed intervals between two subsequent vaccinations, that constitute criterion 
for per protocol set, has been extended from 56 - 60 days to 84 days;  
• 
An increase of maximum 15% in sample size in Step B and in Step C can be 
anticipated. 
Table 7 
Study visits of Epoch 002 to be performed if subsequent vaccination 
cannot take place within allowed interval of 56 - 60 days from previous vaccination  
Epoch 
Epoch 002 
Study Phase 
Primary Phase 
Type of 
contact 
Visit 
1  
 
Visits 
2-5 
 
Visit 
6 
 
Visit 
7 
 
Visit 
8 
 
Visit 
9 
 
Visit 
10 
 
Visit 
11 
 
Visit 
12 
 
Visit 
13 
 
Visit 
14  
 
Visit 
15 
 
Visit 
16 
 
Visit 
17 
 
Visit 
18 
 
Visit 
19 
 
Visit 
20 
 
Visit 
21 
 
Visit 
22 
 
Time points Day 
1  
Day 3 
- Day 
31  
Day 
57  
Day 
64  
Day 
71  
Day 
87  
Day 
113  
Day 
120 
Day 
127 
Day 
143 
Day 
169  
Day 
176 
Day 
183 
Day 
199 
Day 
225 
Day 
253 
Day 
281 
Day 
309 
Day 
337 
Previous 
vaccination 
Dose  
 
Dose 1 
Dose 
1 
N 
Un 
C 
C Un MV* C 
N 
N 
MV 
C 
C 
N 
N 
N 
N 
N 
N 
Dose 2 
 
 
Dose 
2 
N 
N 
N 
Un 
C Un Un MV* C 
C 
N 
N 
N 
N 
N 
N 
Dose 3 
 
 
 
 
 
 Dose 
3 
N 
N 
N 
Un 
C 
C Un N* 
N 
N 
N 
N 
Dose 4 
 
 
 
 
 
 
 
 
 
 Dose 
4 
N 
N 
N 
N 
N 
N 
N 
N 
N: Visit including procedures as defined for this visit in Table 4. Visit should be encoded as regular visit in 
eCRF. 
Un: Visit performed in special circumstances (e.g. remotely, home visit) including as many procedures as 
possible as defined for this visit in Table 4. Visit should be encoded using Unscheduled visit form in eCRF. 
C: Visit cancelled if subsequent vaccination was not yet administered. 
MV: Modified Visit applicable for patient who discontinued from study vaccination. This visit excludes 
vaccination-related procedures while maintaining all non vaccination-related procedures. For details, refer 
to Table 4. Visit should be encoded using vaccination visit form in eCRF. 
* Discontinuation of study vaccination may apply, if interval of 111 days from the date of previous dose 
administration is exceeded. This should be determined based on the actual date of the previous dose 
administration. 
Note: 
1. If the above visits are performed in special circumstances (e.g. remotely, home visit), as many 
procedures as possible should be done (refer to Table 4 and Table 5). 
2. If subsequent vaccination can be administered within maximum interval of 111 days from the date of 
previous dose administration, the visit related to this vaccination should be performed and further visits 

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should follow as defined in Table 4, Table 5 and Table 6. Vaccination and subsequent visits should be 
encoded as regular visits in eCRF. 
3. If subsequent vaccination cannot be administered within a maximum interval of 111 days from the date of 
previous dose administration, patient should discontinue study vaccination and follow up visits should be 
performed as indicated above. The timepoints from vaccination Dose 1, Dose 2 and Dose 3 at which patient 
should be considered as discontinued from study vaccination are marked with * in the above table and 
should be determined based on the actual date of the previous dose administration. 
4. Management of visits for patient who completed Dose 4 vaccination is shown for completeness. 
In Section 8.1.6, added new, to include COVID cases in the safety reporting:  
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 8.1.2) related to COVID-19 infection, the following verbatim 
terms should be used according to World Health Organisation (WHO) definition 
(Please refer to APPENDIX D): 
• 
Suspected COVID-19 infection; or 
• 
Probable COVID-19 infection; or 
• 
Confirmed COVID-19 infection 
Information pertaining to COVID-19 infection should be entered in the dedicated 
eCRF page. 
In Section 9.2.2, a typo was corrected and a cross-reference was added the new section 
(Section 5.6.17) for management of study visits in patients who discontinued study 
vaccination due special circumstances: 
A ‘withdrawal’ from the study vaccines refers to any patient who does not receive the 
complete treatment, i.e. when no further planned dose is administered from the date of 
withdrawal. A patient withdrawn from the study vaccines may not necessarily be 
withdrawn from the study as further study procedures or follow-up may be performed 
(safety or immunogenicity) if planned in the study protocol. For the purpose of this 
study, all study procedures* excepting study vaccines administration, its related 
procedures (treatment number allocation, etc.) remain applicable to the patients.  
* For management of study visits in patients who discontinued study vaccination due 
special circumstances, refer to Section 5.6.17. 
In Section 10.4.1, cross-reference was added to the new section (Section 5.6.17) for 
additional sample size considerations due to impact of special circumstances: 
* Refer to Section 5.6.17 for sample size considerations that may be adapted due to 
impact of special circumstances.  
In Appendix D, added new, to provide case definition for COVID-19 infection: 
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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. 
 

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eTrack study number 
and Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
5 
Amendment date: 
20 May 2020 
Co-ordinating author: 
, Scientific Writer (Modis for GSK 
Biologicals) 
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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
6 
Amendment date: 
16 March 2021 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
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List of changes 
On the cover page, the names of co-ordinating author and contributing authors have 
been updated: 
• 
, Scientific Writer 
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• 
 
Clinical Laboratory Science Representatives, Clinical Readout Team Leaders. 
• 
, 
Study Data Managers 
• 
, Global Regulatory Leads 
The following note has been added in the sponsor signatory approval page: 
Note: Not applicable if an alternative signature process (e.g. electronic signature or 
email approval) is used to get the sponsor approval. 
List of abbreviations: The following abbreviation was added:  
mRNA 
messenger Ribonucleic Acid 
In section 4.3, the following exclusion criteria have been updated: 
• 
Administration of adenovirus/adenovector-based or MVA-based vaccine within 
the last 12 months except for adenovirus/adenovector-based COVID-19 vaccines 
that could be administered up to 30 day prior to the first study vaccine dose. 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 14 days before each dose and ending 30 days after 
each dose of vaccines, with the exception of influenza vaccine that may be given 
at any time except within a 7-day period before or after each vaccine dose and 
COVID-19 vaccine that may be given at any time except within a 30-day period 
before or after each vaccine dose apart from COVID-19 mRNA based-vaccines 
that may be administered any time except for the period of 14 days before and 30 
days after each study vaccine dose. 
Note: If the type of COVID-19 vaccine is unknown, the allowed interval of 30 
days before or after each study vaccine dose should be followed. 
In Section 5.2.2, the following wording has been added for SBIR: 
SBIR: 
 
No 
 
X Yes: hBsAg concentration at Screening will be used as 
a minimization factor (<1000 IU/ml and ≥ 1000 IU/ml) 
for Step B and Step C randomization except for the 
patients needed for the first iSRC review in Step C 
 
In Section 5.2.2.1.1, the following wording has been added: 
Allocation of the patient to a study group at the investigator site will be performed 
using a randomization system on internet (SBIR). The randomization algorithm will 
use a minimization procedure [White, 1978] accounting for hBsAg concentration 
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(<1000 IU/ml and ≥ 1000 IU/ml) measured at Screening. The minimization procedure 
will be applied for patients enrolled in the steps B and C except for the patients needed 
for the first iSRC review in Step C to ensure to have not more than
patients in a 
treatment group as required for the iSRC evaluations. 
In Table 3, for Belgium, France Germany, Hongkong, Spain, Taiwan and Thailand, 
prefix numbers for contact information for emergency blinding have been added. The 
list of toll free numbers are presented in a tabular format. 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Phone: +32 2 656 68 04 
Country 
Toll-free number 
Belgium, France, Germany, Spain, Taiwan 
00 800 4344 1111 
Hongkong 
006 800 4344 1111 
Thailand 
001 800 4344 1111 
United Kingdom 
0800 056 7221 
Fax: +32 2 401 25 75 
E-mail: rix.ugrdehelpdesk@gsk.com 
In Table 4, Table 5 and Section 5.6.7, the wording related to liver ultrasound has been 
updated: 
• 
If liver ultrasound is not possible, alternative liver imaging examination (e.g. 
magnetic resonance or computerized tomography) may be performed at the 
discretion on the investigator. If it is not possible to perform a liver ultrasound at 
screening, a routine ultrasound performed within 180 days prior to the 
vaccination visit 1, can be used for eligibility assessment. For Germany, please 
see the country-specific requirements in Section 12. 
In Table 4, the following footnote has been updated: 
q The minimum requirements at Visits 2, 5, 9, 13 and 17 are safety assessment 
including, but not limited to, recording of solicited symptoms, unsolicited AEs within 
30 days post-vaccination, SAEs, MAEs, AESIs, SAEs related to study participation, or 
to a concurrent GSK medication/vaccine, AEs/SAEs leading to study withdrawal, 
pregnancy and pregnancy outcome, intercurrent medical conditions leading to 
elimination from per-protocol analyses and concomitant medications/vaccinations. The 
collection of data for safety assessment can be performed remotely (e.g. via phone 
contact). Other study procedures including biological samples collection and physical 
examination are optional at the discretion of the Investigator. However, efforts should 
be made for the patients needed for the first iSRC review in Step C to perform Visit 2 
at the site to allow collection of biological samples for safety evaluation by iSRC. For 
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patients participating to TH HBV VV-031 HBS:001 study, biological samples 
collection specific to that study remains mandatory for Visits 2 and 5. 
In Table 4, Section 5.6.12, Table 9, Table 14, wording related to obtaining an 
additional buccal swab sample has been added. 
In the event of DNA extraction failure, a replacement buccal swab sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent. 
In Section 5.6.18, the following points are updated: 
• 
Biological samples may be collected at a different location* other than the study 
site or at patient’s home, in line with applicable local guidance. Biological samples 
should not be collected if they cannot be processed in a timely manner or 
appropriately stored until the intended use. In case of anticipated delay or 
urgency in obtaining the biological sample result to follow safety parameters 
post-vaccination, the investigator is recommended to collect an additional 
biological sample for local testing. If such sample is required, it is important that 
the sample for central testing is obtained at the same time. 
• 
Impact on the per protocol set for immunogenicity and efficacy will be determined 
on a case by case basis. Due to potential increase of the drop-out rate and 
potential administration of COVID-19 vaccines during study participation 
(outside of study procedures), to ensure sufficient number of evaluable patients: 
− Allowed intervals between two subsequent vaccinations, that constitute 
criterion for per protocol set, has been extended from 53 - 63 days to 84 days;  
− An increase of maximum 15% in sample size in Step B and in Step C can be 
anticipated. 
A table summarizing the recommendations on spacing between COVID-19 vaccine 
and study vaccination based on type of COVID-19 vaccine has been added. 
Recommendations on spacing between COVID-19 vaccine and study vaccination 
based on type of COVID-19 vaccine are outlined in Table 8. Note that the interval 
between two subsequent study vaccine doses can be extended up to 84 days to 
accommodate COVID-19 vaccinations 
Table 8 
Recommendations on spacing between COVID-19 vaccine and 
study vaccination by type of COVID-19 vaccine 
COVID-19 vaccine 
Prior study vaccination 
During study 
vaccination 
After study vaccination 
mRNA based 
14 days before first study 
vaccine dose 
At least 14 days before 
or 30 days after study 
vaccination 
30 days after last 
vaccine dose 
Adenovector-
based 
30 days before first study 
vaccine dose 
At least 30 days before 
or after study 
vaccination 
30 days after last 
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Protein-based 
adjuvanted 
30 days before first study 
vaccine dose 
At least 30 days before 
or after study 
vaccination 
30 days after last 
vaccine dose 
Other 
technologies 
30 days before first study 
vaccine dose 
At least 30 days before 
or after study 
vaccination 
30 days after last 
vaccine dose 
In Table 12 and Table 13, priority ranking for humoral immunity and cell-mediated 
immunity component testing has been added, respectively. 
Table 12: Humoral Immunity (antibody determination) 
System 
Component 
Method 
Components priority 
rank 
Laboratory a 
Serum 
Hepatitis B Virus.Surface Ab  
CLIA  
1 
GSK Biologicals’ 
laboratory or 
laboratory designated 
by GSK 
Hepatitis B Virus Core Ab 
To be developed b 
2 
Table 13: Cell-mediated immunity 
System 
Component 
Challenge 
Method 
Component 
priority rank 
Laboratorya 
PBMC 
HBc-specific (CD4+/CD8+) T-cells 
HBc peptide pool 
CFC 
1 
GSK Biologicals’
laboratory or 
laboratory 
designated by 
GSK 
HBs-specific (CD4+/CD8+) T-cells 
HBs peptide pool 
CFC 
2 
In Section 6.7.1, the following point has been added: 
• 
Any COVID-19 vaccine administered in the period starting 12 months prior to 
the vaccination visit 1 and ending at the last study visit. 
In Section 6.7.2, the following points have been updated: 
• 
A vaccine not foreseen by the study protocol administered during the period 
starting 14 days before each dose and ending 30 days after administration of the 
last vaccine(s) dose*, with the exception of annual influenza vaccine or pandemic 
influenza vaccine and COVID-19 vaccine (COVID-19 vaccines may be given at 
any time except within a 30-day period before or after each vaccine dose apart 
from COVID-19 mRNA based-vaccines that may be administered any time 
except for the period of 14 days before and 30 days after each study vaccine 
dose). 
Note: If the type of COVID-19 vaccine is unknown, the allowed interval of 30 
days before or after each study vaccine dose should be followed. 
In case an emergency mass vaccination for an unforeseen public health threat 
(e.g.: a pandemic) is organised by the public health authorities, outside the routine 
immunisation program, the time period described above can be reduced if, 
necessary for that vaccine provided it is licensed and used according to its Product 
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Information Summary of Product Characteristics (SmPC) or Prescribing 
Information and according to the local governmental recommendations and 
provided a written approval of the Sponsor is obtained 
In section 8.8.2, ‘i.e.’ has been changed to ‘e.g.’ 
A maximum of
patients per group (i.e. e.g. N=6 in Step A; 
 
 will first be randomized for vaccination and followed for 2 days. When all 
these patients have completed Visit 2 (i.e. 2-day post Dose 1), iSRC will review all the 
available safety data. If the iSRC considers it appropriate to continue, the 
randomization of the remaining patients in each group can start. If ≥
patients 
randomized at the same study site on the same day, these patients should be vaccinated 
sequentially with at least 60 minutes apart to allow monitoring of any acute event, such 
as anaphylactic reaction. 
In section 10.4.2, the following was updated: 
• 
An interim analysis may be performed when CMI samples 14 days post-
vaccination Dose 2 are tested and results are available for as many patients as 
possible but at least
patients vaccinated in Step B and available data of all 
patients in Step A. Considering that
% patients may be eliminated from analysis 
set, the aim is to have approximately at least
evaluable patients of Step B 
patients in group B1,
patients in group B2 and group B3) 
In section 10.11.1, the following was updated: 
• 
An interim analysis may be performed when CMI samples up to 14 days post-
vaccination Dose 2 (Day 71) are tested and results are available for as many 
patients as possible but at least approximately
patients vaccinated in Step B 
and available data of all patients in Step A. There will be no statistical adjustment 
done as this analysis is not related to confirmatory objective of the study. This 
analysis will be documented in a statistical report. 
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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
7 
Amendment date: 
30 July 2021 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
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List of changes 
• 
Throughout the document, the phase of the study was changed from Phase I to 
Phase I/II. 
• 
On the cover page, the names of contributing authors have been updated: 
− 
 
 Study Delivery Leads 
− 
, Laboratory Science 
Representatives, Laboratory Study Managers 
− 
, Public 
Disclosure Representatives 
List of abbreviations: The following abbreviations were added:  
CRA 
Clinical Research Associate 
TTS 
Thrombosis with Thrombocytopenia Syndrome 
In synopsis and Section 3, the following wording has been added under sampling 
schedule: 
• 
 
 
 
 
• 
Blood samples in case of a TTS event should be collected within 2 weeks of the 
diagnosis of the TTS for exploratory testing. This blood sample can be collected 
at the next study visit or at an unscheduled visit in case the next study visit is >2 
weeks from the TTS diagnosis. The blood sample collection for TTS event 
reported during the follow-up phase is optional. 
In Section 1.2.1, the following wordings were modified: 
The aims of the study are as followsThis study aims:  
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• 
Phase I Dose-escalation safety lead-in (Step A and Step B) aims to assess safety 
of a low dose (Step A) and a target dose (Step B) of the vaccine, both in a 
sequential regimen; 
• 
Phase II Regimen-finding that assesses the target doses of the vaccines given in 
different regimens in Step B and Step C, aims: 
− To evaluate the safety profile of sequential regimen in Step B (with or without 
adjuvanted proteins i.e. group B1 and B3 respectively), adjuvanted proteins 
given alone (group B2) and co-administration regimens in Step C the 
vaccines in adult patients with hBeAg negative chronic HBV infection and with 
no advanced liver fibrosis or cirrhosis who are virally suppressed on NA 
treatment for at least 24months. As this is a Phase I study, patients will remain 
under NA therapy throughout the study, 
− To evaluate whether one or more vaccine regimens tested will induce a 
decrease in serum hBsAg concentration (proof-of-principle [PoP]), 
− To evaluate the added value of the adjuvanted proteins on top of viral vector 
vaccines, 
− To evaluate the best vaccination regimen for the administration of the 
adjuvanted proteins (i.e. either sequentially to or co-administered with the viral 
vectored vaccines), 
− To evaluate the added value of 3 boost doses versus one boost dose of MVA-
HBV co-administered with adjuvanted proteins (group C1 and C2), 
− To assess the induction of HBV-specific CD8+ and CD4+ T-cell responses and 
antibody responses by different vaccine regimens. 
In Table 4, the following footnote related to TTS has been added: 
• 
In case of a TTS event, an additional blood sample should be collected within 2 
weeks of the diagnosis of the TTS for exploratory testing. This blood sample can 
be collected at the next study visit or at an unscheduled visit in case the next 
study visit is >2 weeks from the TTS diagnosis. For more information, please 
refer to Section 5.7.2. 
In Table 5, the following footnote related to TTS has been added: 
• 
In case of a TTS event, collection of an additional blood sample within 2 weeks 
of the diagnosis of the TTS for exploratory testing is optional. This blood sample 
can be collected at the next study visit or at an unscheduled visit in case the next 
study visit is >2 weeks from the TTS diagnosis. For more information, please 
refer to Section 5.7.2. 
In Section 5.6.18, additional wordings related to COVID-19 vaccines were added: 
In view of the current medical need for COVID-19 vaccination, 
guidance/recommendations from National Authorities should apply first and 
foremost if/when existing. 

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Recommendations on spacing between COVID-19 vaccine and study vaccination 
based on type of COVID-19 vaccine are outlined in Table 8. Note that the interval 
between two subsequent study vaccine doses can be extended up to 84 days to 
accommodate COVID-19 vaccinations. 
Table 8 
Recommendations on spacing between COVID-19 vaccine and study 
vaccination by type of COVID-19 vaccine 
COVID-19 vaccine 
Prior study vaccination 
During study vaccination 
After study vaccination 
mRNA based 
14 days before first study 
vaccine dose 
At least 14 days before or 30 
days after study vaccination 
30 days after last vaccine 
dose 
Adenovector-
based 
30 days before first study 
vaccine dose 
At least 30 days before or 
after study vaccination 
30 days after last vaccine 
dose 
Protein-based 
adjuvanted 
30 days before first study 
vaccine dose 
At least 30 days before or 
after study vaccination 
30 days after last vaccine 
dose 
Other 
technologies 
30 days before first study 
vaccine dose 
At least 30 days before or 
after study vaccination 
30 days after last vaccine 
dose 
Whenever multiple types of COVID-19 vaccine are offered, a COVID-19 vaccine that 
is not adenovector-based may be considered as a better choice. 
In Table 9, the following footnote and text was updated: 
• 
 
 
 
 
In Section 5.7.2., the following wording related to TTS has been added: 
• 
In case of a TTS event, an additional blood sample (~3.5ml) should be collected 
within 2 weeks of the diagnosis of the TTS. This blood sample can be collected 
at the next study visit or at an unscheduled visit in case the next study visit is >2 
weeks from the TTS diagnosis. Additional blood sample collection for TTS event 
reported during the follow-up phase is optional. This serum sample (if available) 
as well as the samples collected for repository, as already specified in the 
protocol, will be used for exploratory testing and better understanding of the 
pathogenesis of TTS event. Since scientific knowledge on TTS pathology and 
biomarkers for TTS risks in relation to adenovector-based vaccines is evolving, 
this exploratory testing is not to guide TTS management and no assay details are 
specified in the protocol. This testing will be performed at a laboratory 
designated by GSK Biologicals. 
In Table 12, the following assay details were added and the footnote was modified: 
System 
Component 
Method 
Components 
priority rank 
Laboratory a 
Serum 
Hepatitis B Virus.Surface Ab  
CLIA  
1 
GSK Biologicals’ 
laboratory or 
laboratory 
designated by GSK 
Hepatitis B Virus Core Ab 
To be developed b 
ELISA 
2 
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Chimpanzee Adenovirus 
Type 155 Ab  
Seroneutralizing 
assay 
4 
a GSK Biologicals laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium 
or Marburg, Germany. Refer to APPENDIX B for the laboratory address. 
b This assay will be developed in the course of the study. 
In Table 13, the following footnote was modified: 
a GSK Biologicals laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium 
or Marburg, Germany. 
In Table 18 and Table 19, the following footnote was added: 
Under Section 8.1.5.2, a sub-section related to TTS has been added: 
Recently, following COVID-19 vaccines, thrombosis with thrombocytopenia 
syndrome (TTS), in some cases accompanied by bleeding, has been observed very 
rarely following vaccination with adenovector-based COVID-19 vaccines. This 
includes severe cases presenting as venous thrombosis, including unusual sites such 
as cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial 
thrombosis, concomitant with thrombocytopenia. Some cases had a fatal outcome. 
The majority of these cases occurred within the first two weeks following 
adenovector-based COVID-19 vaccination and mostly in women under 60 years of 
age. 
Currently available data are insufficient to either disprove or confirm that TTS is a 
class effect for adenovector-based vaccines. As of May 2021, no TTS event has been 
reported in any GSK studies using adenovector-based vaccines. However, as a 
precautionary measure, safety information related to occurrence of TTS will be 
collected in this study and additional blood sample will be asked from a patient 
reporting TTS. 
Individuals diagnosed with thrombocytopenia during the entire vaccination phase 
(from dose 1 till 1 month post-last dose) and follow-up phase should be actively 
investigated for signs of thrombosis. Similarly, individuals who present with 
thrombosis during the entire vaccination phase (from dose 1 till 1 month post-last 
dose) and follow-up phase should be evaluated for thrombocytopenia. For diagnostic 
algorithm and clinical management of TTS, clinical guidelines and local 
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recommendations should be followed. For case definition of TTS, please refer to the 
Brighton Collaboration Case Definition provided in Appendix E. 
In case a confirmed TTS event is reported during this study, patients will be queried 
for additional information which will be documented in the eCRF by the investigator 
and an additional blood sample should be collected within 2 weeks of the diagnosis 
of the TTS for exploratory testing and better understanding of the pathogenesis. 
Additional blood sample collection for TTS event reported during the follow-up 
phase is optional. Since scientific knowledge on TTS pathology and biomarkers for 
TTS risks in relation to adenovector-based vaccines is evolving, this exploratory 
testing is not to guide TTS management and no assay details are specified in the 
protocol. 
In Section 10.3, the following text was modified: 
In Section 10.4.2, the following wording was added: 
Subsequent interim analyses on CMI samples 14 days post-vaccination Dose 2 may 
be performed for all patients in Step B and all patients in Step C (as many patients as 
possible in case of visit delay). 
In Section 10.11.1, the following wordings were updated: 
The sequence of analyses will be managed the same way in each defined step: 
• 
Stepwise safety analyses for iSRC review will be done as described in Section 8.8. 
These analyses will be performed by project independent statistician in order to 
keep GSK study team blinded as much as possible until the end of the defined step 
procedures. 
• 
An interim analysis may be performed when CMI samples up to 14 days post-
vaccination Dose 2 (Day 71) are tested and results are available for 
− as many patients as possible but at least
patients vaccinated in Step B and 
available data of all patients in Step A. There will be no statistical adjustment 
done as this analysis is not related to confirmatory objective of the study. This 
analysis will be documented in a statistical report. 
− all patients in Step B* and, 
− all patients in Step C* 
− *In case of visit delay, analysis may be performed for as many patients as 
possible with data available at the time of the analysis. Analysis for remaining 
patients will be performed at the time of the next analysis. 
• 
An interim analysis will be performed when core efficacy data up to 6 months post 
Dose 4 (Day 337) of all patients in Step B will be available. There will be no 
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statistical adjustment done as the analysis will be performed on the final data. This 
analysis will be documented in a statistical report. Clinical study report may be 
written if deemed necessary for regulatory consultation. 
• 
A final analysis of safety/immunogenicity/efficacy endpoints will be performed 
when all safety/reactogenicity and core assays data up to 6 months post Dose 4 
(Day 337) are cleaned and available. At this point, the project GSK statistician will 
be unblinded (i.e. will have access to the individual patient treatment 
assignments), but no individual listings will be provided in order to keep the 
individual blinding. This analysis will be documented in a statistical report. 
Clinical study report may be written if deemed necessary for regulatory 
consultation. 
In section 12, the following country specific wording for Germany was added: 
Remote Source Data Verification (rSDV) during exceptional situations in Germany 
Frequent instream monitoring of safety data by the central study team at GSK is 
required for this study. Instream review of study data items and processes should be 
considered during exceptional situations/circumstances, such as with pandemics like 
COVID-19, focusing on key data points, patient assessments and processes that are 
critical to ensure the rights, safety and well-being of study participants and the 
integrity of the study and data. Prior to any rSDV activity a written agreement by the 
Investigator will be obtained. The agreement includes the extent and the method of 
rSDV activities. Monitoring Plan and Study-Specific Risk Register will be updated to 
include rSDV activities and clinical research associates (CRAs) will be guided for the 
conduct of rSDV. 
Option 1 Transfer of redacted Source Documentation 
Process for transfer and review of redacted source documentation provided by the 
site: 
• 
The CRA instructs study site on the source data needed for the remote SDV 
activities. 
• 
The CRA instructs site staff they must pseudonymize the requested 
documentation, do a quality check that anonymized (redacted) areas cannot be 
read, and then delivers the documentation to the CRA in an encrypted form of 
communication (the site should have a documented process). 
• 
The minimum requirements regarding quality of the copies will be agreed with 
the site upfront: 
− 
For the scanning of paper documents resolution will be a minimum of 300 
dots per inch (dpi). 
− 
For the scanning of photographs and images resolution will be 600 dots per 
inch (dpi) minimum. 
− 
Colour scanners must be able to produce copies that match the original. 

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− 
A4 format as final size without loss of information. 
− 
Documents will be saved as portable document format (PDF). 
− 
In order to maintain quality standards, a captured image will not be 
subjected to non-uniform scaling (i.e. sizing) or re-sampling to a lower 
resolution. 
• 
Redacted source document scans will be sent to the CRA via email using one of 
the following secure options: 
d. Transport Layer Security (TLS) connection: 
TLS connections are intended to support significant mail flow between GSK and 
external partners in a secure manner. 
e. 
GSK Secure 
In cases where only a handful of users are communicating or the volume of emails is 
low, the use of GSK secure, the GSK ad-hoc message encryption solution is 
recommended. 
f. 
Password protected PDF attachment 
− 
A password protected scan (PDF) will be attached to an email. The 
password to open the attachment will be sent in a separate email. 
• 
The CRA may use the secure email website to assess whether the sites email 
address is secure (i.e. encrypted). 
 
• 
Prior to starting remote SDV the CRA ensures that the provided documents are 
complete and do not contain any Personal Information (PI). 
− 
In case the CRA detects any PI that has not been redacted, the CRA informs 
the study site and deletes the files (incl. the Recycle bin). 
− 
A Data Breach must be reported Data Breach Web Report Form. 
• 
Use of an external PC screen is recommended. The CRA will not generate any 
copies from the source data received. 
• 
Source data verification/review will be conducted according to the process 
outlined in the GSK Monitoring SOP. 
• 
After completion of SDV activities, the CRA deletes all copies/images of subject 
data received from the site. This includes the deletion of the recycle bin and any 
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• 
A statement confirming that all documents were destroyed will be provided by 
the CRA via email to the site. 
• 
Details of what was monitored remotely will be documented in the appropriate 
section of the Monitoring Visit Report (MVR). 
Option 2 – Review of Subject Source Documentation remotely 
Process for use of Webcams, WebEx, MS Teams for viewing subject source 
remotely: 
• 
The CRA ensures that the site personnel sharing information with GSK has 
authority to do so.  
• 
Remote SDV activities will be performed exclusively by the assigned site 
monitor. 
• 
Prior to conducting any remote SDV activities the CRA ensures that a written 
informed consent, covering the proposed SDV activities, has been signed by the 
study patient. 
• 
For CRAs using GSK laptops, only use GSK approved video conferencing tools 
(e.g. MS Teams or GSK WebEx). Live image transmission is fully encrypted and 
protected for authorised user. By using these systems, it will be assured that data 
will be viewed only but not transmitted/stored. 
• 
For functional service provider (FSP)/Local contract research organisation 
(CRO) CRAs not using GSK laptops, only MS Teams via RAA (Remote Access 
Application) may be used for meetings between the CRA and the site. WebEx is 
not permitted from non-GSK laptops. Other tools like FaceTime, WhatsApp or 
Zoom are not permitted since they do not have sufficient encryption features. 
GSK does not have enterprise contract/privacy agreement with these providers. 
• 
Prior to the remote monitoring visit, the CRA instructs study site on the specific 
data needed for the remote SDV. 
• 
Source data verification will be conducted according to the process outlined in 
the Monitoring SOP. 
• 
The use of a headset is required, do not use computer audio. 
• 
The CRA does not capture screens or take pictures of screens to ensure we are 
not transferring content outside of clinical sites. 
• 
WebEx or Teams do not store or have access to any data, GSK staff is not 
allowed to make or store any screenshots or save any data which has been 
shared.  
• 
Details of what was monitored remotely will be documented in the appropriate 
section of the MVR. 
In case of technical malfunctions or if the security of the transmission is no longer 
ensured, we will pause rSDV activities. GSK Issue Management Procedures will be 
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In Table 33, the following was modified: 
Laboratory 
Address 
GSK Biological’s Clinical Laboratory Sciences, 
Rixensart  
Biospecimen Reception - B7/44 
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 Biological’s Clinical Laboratory Sciences, 
Marburg 
GSK Vaccines GmbH  
Emil-von-Behring-Str. 76 
35041 Marburg 
Deutschland/ Germany 
In Table 34, the following was modified: 
Laboratory 
Address 
CEVAC - University of Gent 
Corneel Heymanslaan 10 
9000 Gent 
De Pintelaan, 185 Gent 
Belgium 
Brighton collaboration case definition is added in Appendix E. 
Since at least mid-February 2021, multiple European countries (e.g., Austria, 
Denmark, Norway, Germany, UK) and Australia have reported cases of thrombosis 
with thrombocytopenia syndrome (TTS) in persons who received the Astra-Zeneca 
(AZ) COVID-19 vaccine [Greinacher, 2021; Schultz, 2021; ATAGI, 2021; Scully, 
2021] and more recently in the US with the Janssen vaccine [Cines, 2021]. There is 
currently no standard case definition (CD) for TTS accepted for use by all countries. 
On 3 April 2021, the British Society of Haematology published its Updated Guidance 
on Management Version 1.0 with CD for possible, probable, and definite cases of 
TTS [British Society of Haematology, 2021]. This document is oriented towards 
identification and treatment of cases rather than being designed for epidemiologic 
studies, especially initial case finding, however. Therefore, there is an urgent need 
for the latter a draft of which is included in 4 below. 
Since its inception in 1999, the Brighton Collaboration has sought to advance the 
science of vaccine safety by developing standard CD for adverse events following 
immunizations (AEFI’s) [Bonhoeffer, 2002]. To date, >60 CD’s have been 
developed, such as fever, seizure, anaphylaxis, intussusception, narcolepsy, etc. 
Individual CD for thrombosis [Draft Brighton Collaboration Case Definition of 
Thrombosis and Thromboembolism, 2021] and for thrombocytopenia [Wise, 2007] 
have also been developed. 
• 
Based on this experience, we propose a two-step process (see proposed process 
below) to develop both: 
− 
A “draft interim case definition” to facilitate identifying a cohort of 
individuals with this clinical entity (see interim/working CD for TTS below 
for process; interim case definition thrombosis thrombocytopenia syndrome 
version 16 below for draft); who could then be studied using a common study 
protocol and assessment tools. 

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− 
While others have called this new syndrome Vaccine-induced immune 
thrombotic thrombocytopenia (VITT) [Greinacher, 2021; Schultz, 
2021]; this assumes a causal mechanism. We have elected to use ‘TTS’ 
[ATAGI, 2021] for this initial case finding purpose. 
− 
To this end, vaccination with a SARS-2-CoV vaccine would not be 
required to enter this cohort but clearly vaccine exposure information 
would be collected on these individuals along with other variables and 
laboratory tests that have yet to be fully identified (see final CD below). 
− 
A final Brighton case definition (see final CD below) 
• 
When new clinical syndromes or diseases are first identified, standard CD are 
needed for both clinical (e.g., appropriate diagnosis, treatment) and public 
health (e.g. epidemiologic studies, and data harmonization) purposes. This is 
especially true for rare events where any misclassification will hinder scientific 
progress. The process for developing a final standard CD for a new illness 
usually takes some time requiring serial improvements of working or interim CD 
as full knowledge accumulates. The US CDC CD for what came to be called 
Acquired Immuno-Deficiency Syndrome (AIDS) for example was initially 
developed in 1981 and revised in 1985, 1987, and 1993 [British Society of 
Haematology, 2021]. The Chinese CD for COVID-19 changed seven times from 
15 January 2020 to 30 March 2020 [Bonhoeffer, 2002]. 
• 
The Brighton CD’s are usually tiered into three levels of available evidence, 
level one (high), level two (medium), and level three (low). This gradient in 
evidence might be acquired from clinical trials (high) or routine passive 
surveillance (low); or alternatively, tertiary referral hospital (high) vs. basic 
rural clinic (low). We try generally to avoid use of the terms Definite, Probable, 
Possible in this context as these terms are also commonly used for the strength 
of causal link (see below), but are making an exception here as they are more 
concise and meaningful than not using them. 
• 
Because Brighton’s overall interest is in accurate understanding of whether the 
vaccine exposure causes the AEFI or not; and because most AEFI’s lack a 
unique clinical or laboratory marker to establish a causal link, the only way of 
demonstrating this causal link is by showing that vaccinated persons have a 
higher rate of the AEFI than unvaccinated persons in an unbiased manner 
(either from clinical trials or epidemiologic studies). Process-wise, the data for 
this rate comparison is usually best attained by first finding all possible cases of 
the specific AEFI or adverse event of special interest (AESI), then separately 
ascertaining their vaccine exposure status in a blinded manner, before linking 
the two. As Brighton CD are designed to find all possible cases of meaning the 
CD in an unbiased manner relative to vaccine exposure, they do not include 
vaccine exposure as part of the CD. 
Proposed process: 
• 
For interim/working CD for TTS: We initially proposed identifying a small 
number (e.g. 3) haematologists familiar with the recent cases of TTS in 

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UK/Europe to join a similar number of Brighton Thrombosis CD WG members. 
In practice, however, we found it too challenging to get busy clinicians together 
across multiple time zones in a hurry on short notice. Alternatively, we used a 
pre-organized meeting of the International Network of Special Immunization 
Services (INSIS) on this topic on 6 April 2021 (and subsequent days via email) 
to draft the interim version and are now sharing it for broad peer review. We 
hope to finalize the interim CD within 1-2 weeks. Our initial focus is on cases 
with both thrombocytopenia and thrombosis. We recognize that it is possible that 
some individuals may experience either thrombosis or thrombocytopenia alone, 
but evaluation of this will be done separately. 
• 
For a final CD: we will: 
− review as complete a description as possible of identified TTS cases; 
− create a list of variables we wish to collect on them; we are merging 
questionnaires from UK, EMA, Canada, and others and will then develop a 
consensus document based upon peer review. 
− organize and distribute the work to collect this information on each possible 
TTS case in a timely manner. For this process, we can create a distributed 
database file, merging all the de-identified data from each country, 
protecting confidentiality yet allowing for needed analyses. 
− analyse the data to refine the Working CD with the goal of developing a 
formal final Brighton CD as swiftly as possible. 
Note: While this interim case definition focuses on identifying cases that have both 
thrombocytopenia and thrombosis, it is possible that patients with this condition are 
part of a spectrum which may include thrombocytopenia alone as well as patients 
with thrombosis without thrombocytopenia. The existing Brighton CD can be used to 
identify and classify those patients for further study. The US CDC has elected to 
prioritize previously identified manifestations including CVST and splanchnic vein 
thrombosis for signal evaluation [Shimabukuro, 2021]. However, here we have 
purposely used a broader definition to allow definition of what might be a broader 
spectrum of disease. In addition, in this revision we have attempted to address how 
heparin exposure should be addressed in identifying cases. Since exposure to 
heparin can cause heparin induced thrombocytopenia thrombosis (HITT) syndrome 
which clinically is similar to TTS, there was a consensus that cases should be 
stratified as to whether they had been exposed to heparin within 100 days of onset of 
their symptoms. We have therefore introduced levels 1-H, 2-H and 3-H for cases 
with heparin exposure in that time window. This heparin exposure could occur 
either before or after any vaccine exposure, if any. 
Interim Case Definition Thrombosis Thrombocytopenia Syndrome version 16 
Any patient presenting with both acute venous or arterial thrombosis and new onset 
thrombocytopenia [Wise, 2007] (as confirmed by both the Brighton Case Definitions 
for thrombocytopenia and thrombosis [Draft Brighton Collaboration Case Definition 

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of Thrombosis and Thromboembolism, 2021; Wise, 2007]1. The Brighton 
Collaboration case definition for thrombocytopenia [Wise, 2007] requires a platelet 
count of less than 150 000/ µl.2 Either one of the two Thrombocytopenia levels of 
certainty, Level 1 or Level 2, is sufficient to satisfy the condition of 
Thrombocytopenia for the TTS case definition. 
• 
The Brighton Collaboration case definition for thrombosis [Draft Brighton 
Collaboration Case Definition of Thrombosis and Thromboembolism, 2021] is 
still undergoing final review. Currently the criteria for meeting the definition 
with level one certainty require confirmation by imaging, surgical, or pathology 
findings as specified below. Level two and three criteria are for a probable and 
possible case, respectively. The case definitions for probable and possible cases 
support case screening, identification, and inclusion from countries that may 
not have access to more sophisticated diagnostic studies. 
• 
TTS cases will be classified regarding level of certainty based upon the Brighton 
level of certainty achieved for thrombosis. 
• 
Cases will also be stratified as to whether the individual has had recent 
1exposure to heparin. 
Level 1 BC Thrombosis Thrombocytopenia Syndrome Case Criteria 
A platelet count of less than 150 000/ µl of new onset without history of receipt of 
heparin within 100 days3 
AND 
Imaging study, surgical, or pathology findings consistent with 
thrombosis/thromboembolism 
• 
Imaging studies include any of the following, depending on the location of the 
lesion4 
− Ultrasound – Doppler 
                                                 
1 Note: Anti-PF-4 antibodies have been included in clinical case definitions designed to identify patients 
for treatment. Since our goal here is to provide an interim case definition to further our 
understanding of the syndrome via epidemiologic studies, these tests have not been included is the 
interim case definition, but this information will be collected on the cases identified. 
2 For level one of the thrombocytopenia definition, either a blood smear to rule out platelet clumping or 
symptomatology in terms of bleeding is required. However, since with the TTS syndrome, the clinical 
manifestation is thrombosis and not bleeding and all cases will have thrombosis to meet the TTS 
definition, the requirement for a blood smear has been eliminated here. 
3 No heparin within the last 100 days. Please see references for choice of this interval 
4 Imaging will depend on location and whether venous or arterial thrombosis is present. With venogram 
for venous thrombosis and head CT or CT angiogram or MRI/MRI angiogram for arterial lesions. 

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− Computed Tomography (CT scan) – contrast/angiography 
− Magnetic resonance venography (MRV) or arteriography (MRA) 
− Echocardiogram 
− Perfusion V/Q scan 
− Conventional angiography/Digital subtraction angiography 
OR 
• 
Procedure that confirms the presence of a thrombus (e.g. Thrombectomy) 
OR 
• 
Pathology consistent with thrombosis/thromboembolism including biopsy or 
autopsy 
Most appropriate imaging test depends on the location of the lesion. Any of the tests 
listed may be used as available based on radiologist/expert interpretation. 
Beyond the presence of thrombocytopenia, additional abnormal laboratory clotting 
study results are not required for confirmation as they can be normal in presence of 
thrombotic/thromboembolic events. When present, they can be supportive of the 
diagnosis, including: 
• 
D-dimer elevated above the upper limit of normal for age 
• 
Shortened PT, PTT– below the lower limit of normal for age 
Level 1-H BC Thrombosis Thrombocytopenia Syndrome Case Criteria is the same as 
Level 1 except that the case has a history of heparin exposure within 100 days of 
symptom onset. 
Level 2 BC Thrombosis Thrombocytopenia Syndrome Criteria (modified) - Probable 
Case 
• 
a platelet count of less than 150 000/ µl of new onset without recent history of 
receiving heparin within 100 days 
AND 
A Clinical Presentation Consistent with Thrombosis or Thromboembolism Event, 
including 
• 
Specific clinical syndromes including any of the following 
− Deep vein thrombosis (DVT) – symptoms will depend on the location of the 
thrombosis, for example: swelling, pain, redness, or warmth of an extremity; 
headache, visual disturbance, seizures for sinus vein thrombosis; abdominal 
pain for intraabdominal thrombosis 

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− Pulmonary thromboembolism (PE) - sudden onset shortness of breath, 
pleuritic chest pain, sudden death/pulseless electrical activity arrest [Wells 
criteria for scoring –based on clinical findings] 
− Stroke 
− Myocardial infarction 
− Arterial thrombosis 
AND 
• 
Supporting Imaging or laboratory (D-dimer) findings suggestive but not 
definitive of thrombosis/thromboembolism including any of the following 
− Chest radiograph 
− Echocardiogram 
− Computed tomography without contrast 
OR 
− D-dimer - elevated above the upper limit of normal for age 
Level 2-H BC Thrombosis Thrombocytopenia Syndrome Case Criteria is the same as 
Level 2 except that the case has a history of heparin exposure within 100 days of 
symptom onset. 
Level 3 BC Thrombosis Criteria- Possible Case (Modified) 
• 
a platelet count of less than 150 000/ μl of new onset without recent history of 
receiving heparin within 100 days. 
AND 
Clinical Presentation Consistent with Thrombosis or Thromboembolism Event, 
including any of the following 
Specific clinical syndromes (see full list in the flow diagram below): 
• 
Deep vein thrombosis (DVT) – symptoms will depend on the location of the 
thrombosis, for example: swelling, pain, redness, or warmth of an extremity; 
headache, visual disturbance, seizures for sinus vein thrombosis; abdominal 
pain for intraabdominal thrombosis. 
• 
Pulmonary thromboembolism (PE) - sudden onset shortness of breath, pleuritic 
chest pain, sudden death/pulseless electrical activity arrest (Wells criteria for 
scoring –based on clinical findings) 
• 
Stroke 
• 
Myocardial infarction 

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• 
Arterial thrombosis 
Level 3-H BC Thrombosis Thrombocytopenia Syndrome Case Criteria is the same as 
Level 3 except that the case has a history of heparin exposure within 100 days of 
symptom onset. 
Figure 8: Decision tree algorithm for case-finding of Thrombocytopenia Thrombosis 
Syndrome (TTS) 
 
 

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Acknowledgement 
We thank in advance the voluntary contributions of all the colleagues who make 
development of Brighton Collaboration CDs possible. We hope to post a list such 
contributors for TTS CD when ready. 
References 
ATAGI statement on AstraZeneca vaccine in response to new vaccine safety 
concerns. https://www.health.gov.au/news/atagi-statement-on-astrazeneca-vaccine-in-
response-to-new- vaccine- safety-concerns (accessed Apr. 10, 2021). 
Bonhoeffer J, Kohl K, Chen R, Duclos P, Heijbel H, Heininger U, Jefferson T, 
Loupi E. The Brighton Collaboration: addressing the need for standardized case 
definitions of adverse events following immunization (AEFI). Vaccine. 2002 Dec 
13;21(3-4):298-302. doi: 10.1016/s0264-410x(02)00449-8. PMID: 12450705. 
British Society of Haematology. Guidance produced from the Expert Haematology 
Panel (EHP) focused on syndrome of Thrombosis and Thrombocytopenia occurring 
after coronavirus Vaccination. Updated Guidance on Management. Version 1.0. 
https://b-s- h.org.uk/media/19512/guidance-version-10-on-mngmt-of- thrombosis-
with-thrombocytopenia- occurring-after-c-19-vaccine_20210401.pdf (accessed Apr. 
10, 2021). 
Cines DB, Bussell JB SARS-CoV-2 Vaccine Induced Thrombotic 
Thrombocytopenia. N Engl J Med. 2021. DOI: 10.1056/NEJMe2106315. 
Draft Brighton Collaboration Case Definition of Thrombosis and 
Thromboembolism, 2021. https://brightoncollaboration.us/draft-case-definition-of-
thrombosis-and-thromboembolism/. 
Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle P, Eichinger SE. A 
Prothrombotic Thrombocytopenic Disorder Resembling Heparin-Induced 
Thrombocytopenia Following Coronavirus- 19 Vaccination. NEJM, 2021/04/09. 
https://www.nejm.org/doi/full/10.1056/NEJMoa2104840. 
Schultz NiH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen Fridtjof, 
Ahlen MT et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 

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Vaccination. NEJM, 2021/04/09 
https://www.nejm.org/doi/full/10.1056/NEJMoa2104882. 
Scully M, Singh D, Lown R, et al. Pathologic antibodies to platelet factor 4 after 
ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021. DOI: 
10.1056/NEJMoa2105385. 
Shimabukuro, T. 2021. Update: Thrombosis with thrombocytopenia syndrome (TTS) 
following COVID-19 vaccination. [PowerPoint presentation slide 15]. Available at: 
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-
Shimabukuro- 508.pdf. (Accessed: May 14, 2021). 
Wise RP, Bonhoeffer J, Beeler J, Donato H, Downie P, Matthews D, et al; Brighton 
Collaboration Thrombocytopenia Working Group. Thrombocytopenia: case 
definition and guidelines for collection, analysis, and presentation of immunization 
safety data. Vaccine. 2007 Aug 1;25(31):5717-24. 
https://doi.org/10.1016/j.vaccine.2007.02.067. Epub 2007 Mar 12. PMID: 17493712. 

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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
8 
Amendment date: 
8 November 2021 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
List of changes 
On the cover page, the names of contributing authors have been updated: 
• 
, Clinical 
Safety Representatives. 
• 
 
, Study Data Managers. 
In Section 4.3, the following exclusion criterion has been modified. 
• Administration of adenovirus/adenovector-based or MVA-based vaccine within the 
last 12 months except for adenovirus/adenovector-based COVID-19 vaccines that 
could be administered up to 30 days prior to the first study vaccine dose 
(applicable for all patients except for the patients in France) OR Administration 
of adenovirus/adenovector-based or MVA-based vaccine within the last 12 
months (applicable for the patients in France only). 
In Table 8, the following wording has been added for adenovector-based vaccines 
COVID-19 vaccine 
Prior study vaccination 
During study vaccination 
After study vaccination 
mRNA based 
14 days before first study 
vaccine dose 
At least 14 days before or 30 
days after study vaccination 
30 days after last 
vaccine dose 
Adenovector-
based 
30 days before first study 
vaccine dose (applicable 
for all patients except for 
the patients in France) OR 
12 months before first 
study vaccine dose 
(applicable for the 
patients in France only). 
At least 30 days before or 
after study vaccination 
30 days after last 
vaccine dose 
PPD
PPD
PPD
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Protein-based 
adjuvanted 
30 days before first study 
vaccine dose 
At least 30 days before or 
after study vaccination 
30 days after last 
vaccine dose 
Other 
technologies 
30 days before first study 
vaccine dose 
At least 30 days before or 
after study vaccination 
30 days after last 
vaccine dose 

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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
9 
Amendment date: 
16 June 2022 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
List of changes 
On the cover page, the names of contributing authors have been updated: 
• 
 
 Clinical Safety Representatives 
• 
 
, Study Data Managers 
• 
, Global Regulatory 
Leads 
• 
 
 Public Disclosure Representatives. 
In Sponsor signatory approval page, the sponsor details were updated: 
Dorota Borys, MD 
Clinical and Epidemiology R&D Project Lead 
Therapeutic Hepatitis B (CHB-TI) and Pneumococcal vaccines,  
GlaxoSmithKline Biologicals, SA 
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In Synopsis and Section 2.2, the following was modified in the secondary objectives: 
• To assess the immunogenicity of escalating doses of the HBV viral vector vaccines 
(prime-boost) and/or adjuvanted proteins vaccines in patients with chronic HBV 
infection who are virally suppressed on NA therapy.  
• To assess the efficacy of escalating doses of the HBV viral vector vaccines (prime-
boost) and/or adjuvanted proteins vaccines in patients with chronic HBV infection 
who are virally suppressed on NA therapy. 
In synopsis and Section 10.1, the Day and Visit details were added in the primary 
endpoints: 
• Occurrence of serious adverse events (SAEs) up to six months after the last dose 
(Day 337, Visit 22). 
• Occurrence of potential immune-mediated diseases (pIMDs) up to six months after 
the last dose (Day 337, Visit 22). 
• Occurrence of liver-disease related AEs up to six months after the last dose (Day 
337, Visit 22). 
• Occurrence of hematological adverse events of special interest (AESIs) up to six 
months after the last dose (Day 337, Visit 22). 
• Occurrence of medically attended events (MAEs) up to six months after the last 
dose (Day 337, Visit 22). 
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The following abbreviation was added in the list of abbreviations: 
Pol 
Polymerase 
In Section 1.3, the following wordings were added: 
Although clinical data on similar type of vaccines are available that are supportive to 
the use of each vaccine in the proposed vaccine regimen (see Sections 1.2.2 and 1.3.1), 
none of the investigational vaccines to be used in this study have been administered in 
humans yet prior the study start. Therefore, safety and efficacy of the proposed 
vaccine regimen are unknown until the data are generated. 
Please refer to the current Investigator Brochure for the summary of potential risks and 
benefits of the ChAd155-hIi-HBV, MVA-HBV and HBc-HBs/AS01B-4 and for the 
data generated during the study. 
In Section 4.2, the following inclusion criterion was updated: 
• Documented medical history of hBeAg-negative CHB prior to onset of NA therapy 
(applicable to all patients in Step A and Step B and to some patients in Step C) or 
documented medical history of hBeAg-negative CHB over a period of at least 24 
months prior screening (applicable to some patients in Step C only). 
In Table 3, the following was added: 
The Helpdesk is available by phone, fax and email 
Phone (for countries where the toll-free number is not available): +32 2 656 68 04 
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In Table 11, laboratory details were updated 
System 
Discipline 
Component 
Method 
Scale 
Laboratory 
Serum 
HBV 
serology 
Hepatitis B 
Virus.Surface Ab 
(Anti-HBs)a 
CMIA  
Qualitative 
GSK 
Biologicals’ 
laboratory or 
laboratory 
designated 
by GSK 
Hepatitis B 
Virus.Surface Ag 
(HBsAg) 
CMIA  
Quantitative  
Hepatitis B Virus.e Ag  
(HBeAg)a 
CLIA  
Qualitative 
Q2 Solutions 
Hepatitis B Virus.Core 
Ab (Anti-HBc) a 
CMIA  
Qualitative 
Hepatitis B Virus.e Ab  
(Anti-HBe)a 
CCLIA  
Qualitative 
HBV DNA whole 
sequencingb 
Sequencing 
N/A 
In Table 13, Pol-specific details were added: 
System 
Component 
Challenge 
Method 
Component 
priority rank 
Laboratorya 
PBMC 
HBc-specific 
(CD4+/CD8+) T-cells 
HBc peptide pool 
CFC 
1 
GSK Biologicals’ 
laboratory or 
laboratory 
designated by GSK 
HBs-specific 
(CD4+/CD8+) T-cells 
HBs peptide pool 
CFC 
2 
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In Table 19, 
Sample 
type 
Type of contact and time point 
Sub 
groups 
No. patients b 
Component 
Components 
priority rank 
Blood for 
CMI 
response 
Visit 1, Visit 4, Visit 6, Visit 7, Visit 
8, Visit 10, Visit 12, Visit 14, Visit 
16, Visit 22, Visit 24 and Visit 26 
All 
study 
groups 
HBc-specific 
(CD4+/CD8+) T-cells 
1 
HBs-specific 
(CD4+/CD8+) T-cells 
2 
3 
4 
5 
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In Section 8.4.2, the email address for GSK Biologicals Clinical Safety & 
Pharmacovigilance was updated: 
Email address: ogm28723@gsk.com Rix.CT-safety-vac@gsk.com 
In Section 10.4.1, the following wording was added: 
Endpoint 1 - “HBsAg loss percentage of responders in one group” 
A sample of size of 
evaluable patients in the vaccine investigational group, with a 
one-sided alpha level of 10% will allow to conclude, with a power of at least 70% on a 
vaccine effect (i.e. at least 15% of responders, meaning a lower limit of the 80% CI of 
at least 15%) when having 30% responders in the vaccine group. Table 30 below 
provides the power to demonstrate at least 1-log decrease for a range of true 
response rates and sample sizes. 
Table 30: Power to demonstrate at least a 1-log decrease (i.e. 10-fold decrease) in 
qHBsAg or shows HBsAg loss at Day 337 versus Day 1 
  
True response rate 
Power to demonstrate 80% CI LL >=15% 
 
 
 
20% 
23.9 
16.4 
14.8 
25% 
48.5 
31.3 
24.3 
30% 
71.8 
48.4 
35.2 
35% 
87.6 
64.8 
46.7 
40% 
95.6 
78.2 
58.0 
Power to demonstrate 80% CI LL >=10% 
 
 
 
 
15% 
28.9 
17.7 
7.3 
20% 
57.2 
35.1 
14.8 
25% 
79.7 
53.8 
24.3 
30% 
92.3 
70.3 
35.2 
35% 
97.6 
82.7 
46.7 
40% 
99.4 
90.9 
58.0 
N = Number of evaluable patients 
PASS – Test for one proportion using exact test 
Table 32: Power to demonstrate a defined fold-decrease (i.e. log-difference) between 
two groups with 
 evaluable patients per group respectively, SD varying from 
0.5 to 0.9 – one-sided alpha = 10% 
True-fold decrease 
N per group 
SD 
Power 
1-log decrease (i.e.10-fold decrease) 
0.5 
100% 
0.9 
97% 
0.7-log decrease (i.e. 5-fold decrease) 
0.5 
100% 
0.9 
88% 
0.5-log decrease (i.e.3.2-fold decrease) 
0.5 
97% 
0.9 
68% 
1-log decrease (i.e.10-fold decrease) 
0.5 
99.8% 
0.9 
86.3% 
0.7-log decrease (i.e. 5-fold decrease) 
0.5 
95.6% 
0.9 
65.0% 
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0.5-log decrease (i.e.3.2-fold decrease) 
0.5 
80.4% 
0.9 
46.9% 
PASS – Two-Sample T-Test Power Analysis – H1: Mean < Mean Control 
• 
An interim analysis may be performed on all available efficacy data, when at 
least approximately 50% of the patients (i.e.
patients i.e
evaluable patients 
in the B1 treatment group and
evaluable patients in the control group) in Step 
B have completed Visit 17 (Day 199) and data are available for the analysis.  
• 
If deemed necessary for the internal decision making, an additional interim 
analysis may be performed on all available efficacy data, when at least 
approximately 50% of the patients (i.e.
 patients) in Step C have completed 
Visit 17 (Day 199) and data are available for the analysis. 
Otherwise mentioned, for all the planned analysis with CI, a 95% CI will be 
computed. 
In Section 10.4.2, the following text and table were modified: 
First interim analysis may be performed when CMI samples 14 days post-vaccination 
Dose 2 are tested and results are available for as many patients as possible but at least 
patients vaccinated in Step B and available data of all patients in Step A. 
Considering that
% patients may be eliminated from analysis set, the aim is to have 
at least
evaluable patients of Step B 
patients in group B1
patients in group B2 
and group B3). 
Table 33: Exact 80% CI around observed percentage of CMI responders, considering a 
range of 
evaluable patients 
Observed percentage of CMI 
responders 
Exact 80% CI (%) 
20.0% 
[5.5-45.0] 
30.0% 
[11.6-55.2] 
40.0% 
[18.8-64.6] 
50.0% 
[26.7-73.3] 
60.0% 
[35.4-81.2] 
70.0% 
[44.8-88.4] 
80.0% 
[55.0-94.5] 
90.0% 
[66.3-99.0] 
20.0% 
[9.0-36.0] 
30.0% 
[16.6-46.7] 
40.0% 
[24.9-56.7] 
50.0% 
[33.8-66.2] 
60.0% 
[43.3-75.1] 
70.0% 
[53.3-83.4] 
80.0% 
[63.9-91.0] 
90.0% 
[75.5-97.3] 
20.0% 
[10.9-32.5] 
30.0% 
[19.0-43.2] 
40.0% 
[27.7-53.3] 
50.0% 
[37.0-63.0] 
60.0% 
[46.7-72.3] 
70.0% 
[56.8-81.0] 
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80.0% 
[67.5-89.1] 
90.0% 
[79.1-96.3] 
Subsequent interim analyses on CMI samples 14 days post-vaccination Dose 2 and 14 
days post-vaccination dose 4 may be performed for all patients in Step B and all 
patients in Step C (as many patients as possible in case of visit delay). 
In Section 10.8.1, the following was added: 
• The percentage of participants with 95% confidence intervals in each group who 
achieve Sustained Virological Response (SVR defined as HBsAg concentration 
<LLOQ and HBV DNA <LLOQ) for 24 weeks after the end of vaccination (Visit 
22, Day 337) will be performed.  
• The percentage of participants who achieve qHBsAg decrease (≥0.5 log decrease, 
≥1-log decrease), and log-changes since baseline will be tabulated by group. 
• The number and percentage of participants who experienced HBV DNA 
virologic breakthrough (defined at 1-log increase from nadir in HBV DNA or 
HBV DNA becoming quantifiable after being below the LLOQ) will be reported 
and time to onset will be summarised. 
• The number and percentage of participants with HBsAg reversion and/or HBV 
DNA reversion will be tabulated. Time to reversion will be summarised. 
• Number and percentage of HBc-, HBs- 
 specific CD4+/CD8+ T-cell 
responders will be computed for the vaccine by groups. 
If sufficient patients are available for the analysis, efficacy analysis may be 
performed by categories of baseline HBsAg concentration, HBV genotype and subset 
of patients of this study meeting the eligibility criteria of the study TH HBV ASO-
001.  
The SAP will include a more technical and detailed description of the statistical 
analyses. 
PoP 
• In step B and step C, 80% CIs of qHBsAg GMC ratios between groups receiving 
candidate study vaccine at six months post last vaccine dose (Day 337, Visit 22) 
and placebo will be computed using an ANCOVA model on the logarithm 10 
transformation of the concentrations. The ANCOVA model will include the 
vaccine group and country as fixed effects and the pre-vaccination titer as 
covariate. Lower limit of the CI above 1 will also be considered as indicator of 
PoP. 
Exploratory group comparisons 
• Additional exploratory group comparisons will be performed to evaluate the added 
value of the adjuvanted proteins on the top of viral vectored vaccines and to 
evaluate the best vaccination regimen for the administration of the adjuvanted 
proteins (i.e. either sequentially to or co-administered with the viral vectored 
vaccines).  
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• The qHBsAg GMC ratio between groups at six months post last vaccine dose (Day 
337, Visit 22) will be computed with CIs using an ANCOVA model on the 
logarithm 10 transformation of the concentrations. The ANCOVA model will 
include the vaccine group and the country as fixed effects and the pre-vaccination 
titer as covariate. 
• The difference between the groups in percentage of patients with at least a 10-fold 
decrease (i.e. 1-log difference) in qHBsAg or HBsAg loss at Day 337 versus Day 1 
will be computed with CIs. 
These comparisons will be descriptive with the aim to characterize the difference in 
efficacy between the groups and will not be adjusted for multiplicity. 
If sufficient patients are available for the analysis, additional descriptive analysis may 
be performed by categories of baseline HBsAg concentration, HBV genotype and 
history of HBeAg-negative CHB (documented prior to onset of NA therapy or over a 
period of at least 24 months prior screening). 
The SAP will include a more technical and detailed description of the statistical 
analyses. 
In Section 10.11.1, the following points were added: 
• An interim analysis may be performed when CMI samples up to 14 days post-
vaccination Dose 4 (Day 183) are tested and results are available for 
− 
all patients in Step B* and, 
− 
all patients in Step C* 
• *In case of visit delay, analysis may be performed for as many patients as 
possible with data available at the time of the analysis. Analysis for 
remaining patients will be performed at the time of the next analysis. 
• An interim analysis may be performed on available efficacy data, when at least 
50% of the patients 
patients) in Step B have completed Visit 17 (Day 199) and 
efficacy data are available for the analysis. This analysis will be documented in a 
statistical report.  
• If deemed necessary for internal decision making, an interim analysis may be 
performed on available efficacy data, when at least approximately 50% of the 
patients (i.e.
patients) in Step C have completed Visit 17 (Day 199) and 
efficacy data are available for the analysis. This analysis will be documented in a 
statistical report.  
• A final analysis of follow-up for safety/immunogenicity/efficacy will be performed 
when all data up to Day 841 are cleaned and available. This analysis may be 
performed for combined Step A and Step B and separately for Step C. Individual 
listings will be provided at this stage. This analysis will be documented in a 
statistical report. 
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An integrated clinical study report containing all data will be written and made 
available to the investigators. 
All the interim analyses will be performed by project independent statistician in order 
to keep GSK central study team blinded as much as possible. 
In Section 13, the following reference was added: 
Greinacher A, Langer F, Makris M, et al. Vaccine-induced immune thrombotic 
thrombocytopenia (VITT): Update on diagnosis and management considering 
different resources. J Thromb Haemost. 2022;20(1):149-156. 
 
This assay is applied to measure the frequency of antigen-specific T-lymphocytes in 
peripheral blood. Blood samples are collected by venipuncture and PBMCs are 
prepared by certified laboratories by centrifugation onto a Lymphoprep™ cushion 
within 24 hours following collection. PBMC suspensions are stored in liquid nitrogen 
until analysis. To measure T-cell responses elicited by the vaccine candidate, samples 
are thawed and cultured overnight in the presence of costimulatory antibodies (anti-
CD28 and anti-CD49d) without stimulation (background control) or with peptide pools 
(15mer overlapping by 11) covering the sequence of the relevant antigens (HBs, HBc, 
 Cells are then immunostained for surface 
phenotypic markers (CD4 and CD8), permeabilized and then immunostained for CD3 
and activation markers (the costimulatory molecules CD40L and 4-1BB and the 
cytokines IL-2, IFN-γ, TNF-α, IL-13, IL-17). Analysis is performed by 
multiparametric flow cytometry, and the results are expressed after background 
subtraction as frequencies of antigen specific CD4+ (or CD8+) T-cells producing 
various combinations of the activation markers assessed per million CD4+ (or CD8+) 
T-cells. 
In Table 35, the following was deleted: 
CEVAC - University of Gent 
Corneel Heymanslaan 10 
9000 Gent 
Belgium 
In Appendix C, the heading was modified and the following footnote was added: 
Appendix C: Toxicity Grading For Hematology, Biochemistry and Urinalysis 
Parameters 
* For urinanalysis the primary testing method used in the clinical trials is urine 
dipstick. This method of testing does not allow for precise conversion of the results of 
blood in urine into FDA grading. Therefore blood in urine results are reported based 
on dipstick scale (small + refers to ≥ 25 ery/µL, moderate ++ refers to ≥ 80 ery/µL, 
large +++ refers to ≥ 200 ery/µL). 
In Appendix E, the case definition for Brighton Collaboration has been updated: 
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(The current interim case definition, v10.16.4 dated 11 November 2021 is provided 
below. Please refer to https://brightoncollaboration.us/thrombosis-with-
thrombocytopenia-syndrome-interim-case-definition/ for the most updated version of 
the case definition.) 
Beginning in February, 2021, multiple European countries (e.g., Austria, Denmark, 
Norway, Germany, UK) and Australia have reported cases of thrombosis with 
thrombocytopenia syndrome (TTS) in persons who received the Astra-Zeneca (AZ) 
COVID-19 vaccine (1-3, 10) and more recently in the US with the Janssen vaccine 
(11). In May 2021, a draft interim case definition was proposed by the Brighton 
Collaboration. Since that time, understanding of this condition and its relationship 
to vaccines has evolved. Recent work by Andreas Greinacher and others now allow 
revision of the original case definition and level of certainty algorithm [Greinacher, 
2022]. The goal of this case definition is to facilitate harmonized studies of this 
outcome. This supplements guidelines published by WHO provided information on 
case identification for treatment. 
The Case Definition (CD) Level of Certainty (LOC) is determined based on a series 
of clinical conditions defined below. 
Condition A: ☐ Platelet count <150 X 109/L and of new onset with no known recent 
exposure to heparin (within the last 30 days) 
Condition B1: ☐ Presence of thrombosis/thromboembolism confirmed by ≥ 1 of the 
following (Check all that apply below) 
☐Imaging Study 
• Ultrasound – Doppler 
• CT scan – contrast / angiography 
• Magnetic resonance venography or arteriography 
• Echocardiogram 
• Perfusion V/Q scan 
• Conventional angiography / digital subtraction angiography 
☐ Surgical procedure - that confirmed presence of a thrombus (e.g. thrombectomy) 
☐ Pathologic examination – including biopsy or autopsy 
Condition B2: ☐ Severe and persistent headache onset ≥5d post vaccination with 
elevated D-DIMER >8x ULN (Upper limits of normal) 
Condition C: ☐ Clinical presentation suggests one of the specific clinical syndromes 
below? (Check the most appropriate) NOTE: the italicized signs/symptoms in 
brackets after each are suggestive of the syndrome but not an exhaustive list; some 

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of them should be present. Diagnosis of the syndrome by a clinical specialist is also 
acceptable 
☐ Cerebral venous sinus thrombosis / other Cerebral venous thrombosis (new onset 
of unexplained headache, often severe, typically persisting; focal cerebral 
dysfunction; encephalopathy; seizure; blurred vision; double vision) 
☐ Deep vein thrombosis (new onset swelling usually but not always in lower 
extremities; localized swelling accompanied by pain [may be crampy in nature] and 
tenderness; reddened/discoloured/warm skin; pitting edema) 
☐ Pulmonary thromboembolism (sudden onset: shortness of breath[at rest or on 
exertion], pleuritic chest pain [sudden, intense, sharp, stabbing or burning in nature, 
made worse by breathing/coughing/sneezing/laughing], cough +/- hemoptysis), 
tachypnea, tachycardia, arrhythmia, cyanosis, hypotension) 
☐ Intra-abdominal thrombosis. (abdominal pain [may be out of proportion to 
physical exam findings], bloating, nausea, vomiting, diarrhea, bloody stools, ascites, 
hepatomegaly if hepatic vein location) 
☐ Ischemic Stroke (sudden onset of focal neurologic deficits such as difficulty with 
speech [dysphasia or dysarthria], hemiparesis, ataxic gait abnormal eye movements, 
facial paresis) 
☐ Myocardial infarction (chest pain [often crushing in nature], shortness of breath, 
arrhythmias, cyanosis, sudden death) 
☐ Arterial Thrombosis 
Condition D: ☐ One or more of these imaging or lab findings supportive of the 
diagnosis of thrombosis / thromboembolism? (Check all that apply) 
☐ Echocardiogram or doppler ultrasound 
☐ Computed tomography without contrast or MRI 
☐ D-dimer (Elevated above upper limit of normal for age) 
Condition E: ☐ At least one of these Lab findings that are strongly supportive of the 
diagnosis of platelet-activating antibody mediated thrombosis? (Check all that apply) 
☐ D-dimer > 4 times ULN for age 
☐ Positive anti-platelet factor 4 (PF4) assay: specific anti-PF4 ELISA (note: rapid 
tests are insensitive for these antibodies) or functional test with addition of PF4 

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TTS Case Definition Level of Certainty Determination 
If yes to (A and B1) or yes to (A and B2): then is Level 1 
If no to (B1 and B2)_and_[If yes to A plus yes to (C and E)] then is level 1 
If no to (B1 and B2)_and_[If yes to A plus yes to (C and D)] then is level 2 
If no to (B1 and B2)_and_[If yes to A plus [(yes to C) and (no to D and E)] then is 
level 3If there is insufficient information to determine the conditions needed to a 
level of certainty of 1, 2 or 3 then the level of certainty is level 4  
If there is sufficient information to determine the conditions A, B, C, D, and E but 
the aggregate of the conditions do not meet the LOC 1, 2, or 3 then the LOC is Level 
5; Not a Case of TTS. 
Since at least mid-February 2021, multiple European countries (e.g., Austria, Denmark, 
Norway, Germany, UK) and Australia have reported cases of thrombosis with 
thrombocytopenia syndrome (TTS) in persons who received the Astra-Zeneca (AZ) 
COVID-19 vaccine [Greinacher, 2021; Schultz, 2021; ATAGI, 2021; Scully, 2021] 
and more recently in the US with the Janssen vaccine [Cines, 2021]. There is currently 
no standard case definition (CD) for TTS accepted for use by all countries. On 3 April 
2021, the British Society of Haematology published its Updated Guidance on 
Management Version 1.0 with CD for possible, probable, and definite cases of TTS 
[British Society of Haematology, 2021]. This document is oriented towards 
identification and treatment of cases rather than being designed for epidemiologic 
studies, especially initial case finding, however. Therefore, there is an urgent need for 
the latter a draft of which is included in 4 below. 
Since its inception in 1999, the Brighton Collaboration has sought to advance the 
science of vaccine safety by developing standard CD for adverse events following 
immunizations (AEFI’s) [Bonhoeffer, 2002]. To date, >60 CD’s have been developed, 
such as fever, seizure, anaphylaxis, intussusception, narcolepsy, etc. Individual CD for 
thrombosis [Draft Brighton Collaboration Case Definition of Thrombosis and 
Thromboembolism, 2021] and for thrombocytopenia [Wise, 2007] have also been 
developed. 
• Based on this experience, we propose a two-step process (see proposed process 
below) to develop both: 
• A “draft interim case definition” to facilitate identifying a cohort of individuals 
with this clinical entity (see interim/working CD for TTS below for process; 
interim case definition thrombosis thrombocytopenia syndrome version 16 below 
for draft); who could then be studied using a common study protocol and 
assessment tools. 
• While others have called this new syndrome Vaccine-induced immune thrombotic 
thrombocytopenia (VITT) [Greinacher, 2021; Schultz, 2021]; this assumes a causal 
mechanism. We have elected to use ‘TTS’ [ATAGI, 2021] for this initial case 
finding purpose. 

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• To this end, vaccination with a SARS-2-CoV vaccine would not be required to 
enter this cohort but clearly vaccine exposure information would be collected on 
these individuals along with other variables and laboratory tests that have yet to be 
fully identified (see final CD below). 
• A final Brighton case definition (see final CD below) 
• When new clinical syndromes or diseases are first identified, standard CD are 
needed for both clinical (e.g., appropriate diagnosis, treatment) and public health 
(e.g. epidemiologic studies, and data harmonization) purposes. This is especially 
true for rare events where any misclassification will hinder scientific progress. The 
process for developing a final standard CD for a new illness usually takes some 
time requiring serial improvements of working or interim CD as full knowledge 
accumulates. The US CDC CD for what came to be called Acquired Immuno-
Deficiency Syndrome (AIDS) for example was initially developed in 1981 and 
revised in 1985, 1987, and 1993 [British Society of Haematology, 2021]. The 
Chinese CD for COVID-19 changed seven times from 15 January 2020 to 30 
March 2020 [Bonhoeffer, 2002]. 
• The Brighton CD’s are usually tiered into three levels of available evidence, level 
one (high), level two (medium), and level three (low). This gradient in evidence 
might be acquired from clinical trials (high) or routine passive surveillance (low); 
or alternatively, tertiary referral hospital (high) vs. basic rural clinic (low). We try 
generally to avoid use of the terms Definite, Probable, Possible in this context as 
these terms are also commonly used for the strength of causal link (see below), but 
are making an exception here as they are more concise and meaningful than not 
using them. 
• Because Brighton’s overall interest is in accurate understanding of whether the 
vaccine exposure causes the AEFI or not; and because most AEFI’s lack a unique 
clinical or laboratory marker to establish a causal link, the only way of 
demonstrating this causal link is by showing that vaccinated persons have a higher 
rate of the AEFI than unvaccinated persons in an unbiased manner (either from 
clinical trials or epidemiologic studies). Process-wise, the data for this rate 
comparison is usually best attained by first finding all possible cases of the specific 
AEFI or adverse event of special interest (AESI), then separately ascertaining their 
vaccine exposure status in a blinded manner, before linking the two. As Brighton 
CD are designed to find all possible cases of meaning the CD in an unbiased 
manner relative to vaccine exposure, they do not include vaccine exposure as part 
of the CD. 
Proposed process: 
• 
For interim/working CD for TTS: We initially proposed identifying a small number 
(e.g. 3) haematologists familiar with the recent cases of TTS in UK/Europe to join 
a similar number of Brighton Thrombosis CD WG members. In practice, however, 
we found it too challenging to get busy clinicians together across multiple time 
zones in a hurry on short notice. Alternatively, we used a pre-organized meeting of 
the International Network of Special Immunization Services (INSIS) on this topic 
on 6 April 2021 (and subsequent days via email) to draft the interim version and 

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are now sharing it for broad peer review. We hope to finalize the interim CD within 
1-2 weeks. Our initial focus is on cases with both thrombocytopenia and 
thrombosis. We recognize that it is possible that some individuals may experience 
either thrombosis or thrombocytopenia alone, but evaluation of this will be done 
separately. 
• For a final CD: we will: 
• review as complete a description as possible of identified TTS cases; 
• create a list of variables we wish to collect on them; we are merging questionnaires 
from UK, EMA, Canada, and others and will then develop a consensus document 
based upon peer review. 
• organize and distribute the work to collect this information on each possible TTS 
case in a timely manner. For this process, we can create a distributed database file, 
merging all the de-identified data from each country, protecting confidentiality yet 
allowing for needed analyses. 
• analyse the data to refine the Working CD with the goal of developing a formal 
final Brighton CD as swiftly as possible. 
Note: While this interim case definition focuses on identifying cases that have both 
thrombocytopenia and thrombosis, it is possible that patients with this condition are 
part of a spectrum which may include thrombocytopenia alone as well as patients with 
thrombosis without thrombocytopenia. The existing Brighton CD can be used to 
identify and classify those patients for further study. The US CDC has elected to 
prioritize previously identified manifestations including CVST and splanchnic vein 
thrombosis for signal evaluation [Shimabukuro, 2021]. However, here we have 
purposely used a broader definition to allow definition of what might be a broader 
spectrum of disease. In addition, in this revision we have attempted to address how 
heparin exposure should be addressed in identifying cases. Since exposure to heparin 
can cause heparin induced thrombocytopenia thrombosis (HITT) syndrome which 
clinically is similar to TTS, there was a consensus that cases should be stratified as to 
whether they had been exposed to heparin within 100 days of onset of their symptoms. 
We have therefore introduced levels 1-H, 2-H and 3-H for cases with heparin exposure 
in that time window. This heparin exposure could occur either before or after any 
vaccine exposure, if any. 
Interim Case Definition Thrombosis Thrombocytopenia Syndrome version 16 
Any patient presenting with both acute venous or arterial thrombosis and new onset 
thrombocytopenia [Wise, 2007] (as confirmed by both the Brighton Case Definitions 
for thrombocytopenia and thrombosis [Draft Brighton Collaboration Case Definition of 
Thrombosis and Thromboembolism, 2021; Wise, 2007]5. The Brighton Collaboration 
                                                 
5 Note: Anti-PF-4 antibodies have been included in clinical case definitions designed to identify patients for 
treatment. Since our goal here is to provide an interim case definition to further our understanding of 
 

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case definition for thrombocytopenia [Wise, 2007] requires a platelet count of less than 
150 000/ µl.6 Either one of the two Thrombocytopenia levels of certainty, Level 1 or 
Level 2, is sufficient to satisfy the condition of Thrombocytopenia for the TTS case 
definition. 
• The Brighton Collaboration case definition for thrombosis [Draft Brighton 
Collaboration Case Definition of Thrombosis and Thromboembolism, 2021] is still 
undergoing final review. Currently the criteria for meeting the definition with level 
one certainty require confirmation by imaging, surgical, or pathology findings as 
specified below. Level two and three criteria are for a probable and possible case, 
respectively. The case definitions for probable and possible cases support case 
screening, identification, and inclusion from countries that may not have access to 
more sophisticated diagnostic studies. 
• TTS cases will be classified regarding level of certainty based upon the Brighton 
level of certainty achieved for thrombosis. 
• Cases will also be stratified as to whether the individual has had recent 1exposure 
to heparin. 
Level 1 BC Thrombosis Thrombocytopenia Syndrome Case Criteria 
A platelet count of less than 150 000/ µl of new onset without history of receipt of 
heparin within 100 days7 
AND 
Imaging study, surgical, or pathology findings consistent with 
thrombosis/thromboembolism 
• Imaging studies include any of the following, depending on the location of the 
lesion8 
• Ultrasound – Doppler 
• Computed Tomography (CT scan) – contrast/angiography 
• Magnetic resonance venography (MRV) or arteriography (MRA) 
                                                 
the syndrome via epidemiologic studies, these tests have not been included is the interim case 
definition, but this information will be collected on the cases identified. 
6 For level one of the thrombocytopenia definition, either a blood smear to rule out platelet clumping or 
symptomatology in terms of bleeding is required. However, since with the TTS syndrome, the clinical 
manifestation is thrombosis and not bleeding and all cases will have thrombosis to meet the TTS 
definition, the requirement for a blood smear has been eliminated here. 
7 No heparin within the last 100 days. Please see references for choice of this interval 
8 Imaging will depend on location and whether venous or arterial thrombosis is present. With venogram for 
venous thrombosis and head CT or CT angiogram or MRI/MRI angiogram for arterial lesions. 

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• Echocardiogram 
• Perfusion V/Q scan 
• Conventional angiography/Digital subtraction angiography 
OR 
• Procedure that confirms the presence of a thrombus (e.g. Thrombectomy) 
OR 
• Pathology consistent with thrombosis/thromboembolism including biopsy or 
autopsy 
Most appropriate imaging test depends on the location of the lesion. Any of the tests 
listed may be used as available based on radiologist/expert interpretation. 
Beyond the presence of thrombocytopenia, additional abnormal laboratory clotting 
study results are not required for confirmation as they can be normal in presence of 
thrombotic/thromboembolic events. When present, they can be supportive of the 
diagnosis, including: 
• D-dimer elevated above the upper limit of normal for age 
• Shortened PT, PTT– below the lower limit of normal for age 
Level 1-H BC Thrombosis Thrombocytopenia Syndrome Case Criteria is the same as 
Level 1 except that the case has a history of heparin exposure within 100 days of 
symptom onset. 
Level 2 BC Thrombosis Thrombocytopenia Syndrome Criteria (modified) - Probable 
Case 
• a platelet count of less than 150 000/ µl of new onset without recent history of 
receiving heparin within 100 days 
AND 
A Clinical Presentation Consistent with Thrombosis or Thromboembolism Event, 
including 
• Specific clinical syndromes including any of the following 
• Deep vein thrombosis (DVT) – symptoms will depend on the location of the 
thrombosis, for example: swelling, pain, redness, or warmth of an extremity; 
headache, visual disturbance, seizures for sinus vein thrombosis; abdominal pain 
for intraabdominal thrombosis 
• Pulmonary thromboembolism (PE) - sudden onset shortness of breath, pleuritic 
chest pain, sudden death/pulseless electrical activity arrest [Wells criteria for 
scoring –based on clinical findings] 
• Stroke 

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• Myocardial infarction 
• Arterial thrombosis 
AND 
• Supporting Imaging or laboratory (D-dimer) findings suggestive but not definitive 
of thrombosis/thromboembolism including any of the following 
• Chest radiograph 
• Echocardiogram 
• Computed tomography without contrast 
OR 
• D-dimer - elevated above the upper limit of normal for age 
Level 2-H BC Thrombosis Thrombocytopenia Syndrome Case Criteria is the same as 
Level 2 except that the case has a history of heparin exposure within 100 days of 
symptom onset. 
Level 3 BC Thrombosis Criteria- Possible Case (Modified) 
• a platelet count of less than 150 000/ µl of new onset without recent history of 
receiving heparin within 100 days. 
AND 
Clinical Presentation Consistent with Thrombosis or Thromboembolism Event, 
including any of the following 
Specific clinical syndromes (see full list in the flow diagram below): 
• Deep vein thrombosis (DVT) – symptoms will depend on the location of the 
thrombosis, for example: swelling, pain, redness, or warmth of an extremity; 
headache, visual disturbance, seizures for sinus vein thrombosis; abdominal pain 
for intraabdominal thrombosis. 
• Pulmonary thromboembolism (PE) - sudden onset shortness of breath, pleuritic 
chest pain, sudden death/pulseless electrical activity arrest (Wells criteria for 
scoring –based on clinical findings) 
• Stroke 
• Myocardial infarction 
• Arterial thrombosis 
Level 3-H BC Thrombosis Thrombocytopenia Syndrome Case Criteria is the same as 
Level 3 except that the case has a history of heparin exposure within 100 days of 
symptom onset. 

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Figure 8 
Decision tree algorithm for case-finding of Thrombocytopenia 
Thrombosis Syndrome (TTS) 
 
 

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Acknowledgement 
We thank in advance the voluntary contributions of all the colleagues who make 
development of Brighton Collaboration CDs possible. We hope to post a list such 
contributors for TTS CD when ready. 
References 
ATAGI statement on AstraZeneca vaccine in response to new vaccine safety concerns. 
https://www.health.gov.au/news/atagi-statement-on-astrazeneca-vaccine-in-response-to-
new- vaccine- safety-concerns (accessed Apr. 10, 2021). 
Bonhoeffer J, Kohl K, Chen R, Duclos P, Heijbel H, Heininger U, Jefferson T, Loupi 
E. The Brighton Collaboration: addressing the need for standardized case definitions of 
adverse events following immunization (AEFI). Vaccine. 2002 Dec 13;21(3-4):298-
302. doi: 10.1016/s0264-410x(02)00449-8. PMID: 12450705. 
British Society of Haematology. Guidance produced from the Expert Haematology 
Panel (EHP) focused on syndrome of Thrombosis and Thrombocytopenia occurring 
after coronavirus Vaccination. Updated Guidance on Management. Version 1.0. 
https://b-s- h.org.uk/media/19512/guidance-version-10-on-mngmt-of- thrombosis-with-
thrombocytopenia- occurring-after-c-19-vaccine_20210401.pdf (accessed Apr. 10, 
2021). 
Cines DB, Bussell JB SARS-CoV-2 Vaccine Induced Thrombotic Thrombocytopenia. 
N Engl J Med. 2021. DOI: 10.1056/NEJMe2106315. 
Draft Brighton Collaboration Case Definition of Thrombosis and Thromboembolism, 
2021. https://brightoncollaboration.us/draft-case-definition-of-thrombosis-and-
thromboembolism/. 
Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle P, Eichinger SE. A 
Prothrombotic Thrombocytopenic Disorder Resembling Heparin-Induced 
Thrombocytopenia Following Coronavirus- 19 Vaccination. NEJM, 2021/04/09. 
https://www.nejm.org/doi/full/10.1056/NEJMoa2104840. 

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Schultz NiH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen Fridtjof, Ahlen 
MT et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. 
NEJM, 2021/04/09 https://www.nejm.org/doi/full/10.1056/NEJMoa2104882. 
Scully M, Singh D, Lown R, et al. Pathologic antibodies to platelet factor 4 after 
ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021. DOI: 10.1056/NEJMoa2105385. 
Shimabukuro, T. 2021. Update: Thrombosis with thrombocytopenia syndrome (TTS) 
following COVID-19 vaccination. [PowerPoint presentation slide 15]. Available at: 
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-
Shimabukuro- 508.pdf. (Accessed: May 14, 2021). 
Wise RP, Bonhoeffer J, Beeler J, Donato H, Downie P, Matthews D, et al; Brighton 
Collaboration Thrombocytopenia Working Group. Thrombocytopenia: case definition 
and guidelines for collection, analysis, and presentation of immunization safety data. 
Vaccine. 2007 Aug 1;25(31):5717-24. https://doi.org/10.1016/j.vaccine.2007.02.067. 
Epub 2007 Mar 12. PMID: 17493712. 

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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
10 
Amendment date: 
23 September 2022 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
List of changes 
On the cover page, the names of contributing authors have been updated: 
• 
, 
Laboratory Science Representatives, Laboratory Study Managers 
• 
, Clinical and Epidemiology R&D 
Project Leads 
In Sponsor signatory approval page, the sponsor details were updated 
Dietrich Bosse, MD 
Dorota Borys, MD 
Clinical and Epidemiology R&D Project Lead 
Therapeutic Hepatitis B (CHB-TI) and Pneumococcal vaccines, 
GlaxoSmithKline Biologicals, SA 
In Section 8.1.5.2.1, the following wording was modified: 
Recently, following COVID-19 vaccines, thrombosis with thrombocytopenia 
syndrome (TTS), in some cases accompanied by bleeding, has been observed very 
rarely following vaccination with adenovector-based COVID-19 vaccines. This 
includes severe cases presenting as venous thrombosis, including unusual sites such as 
cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial 
thrombosis, concomitant with thrombocytopenia. Some cases had a fatal outcome. The 
majority of these cases occurred within the first two three weeks following 
adenovector-based COVID-19 vaccination and mostly in women individuals under 60 
years of age. 
PPD
CCI
PPD
PPD

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In Appendix E, the title was updated: 
Updated Brighton Collaboration Case Definition for Thrombosis with 
Thrombocytopenia Syndrome (TTS). 

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eTrack study number and 
Abbreviated Title 
204852 (TH HBV VV-001) 
Amendment number: 
11 
Amendment date: 
22 June 2023 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
List of changes: 
On the cover page, the names of co-ordinating and contributing authors have been 
updated: 
• 
 Scientific Writers, 
Modis for GSK Biologicals 
• 
, Scientific Writer 
• 
, Clinical Research Development 
Science Leads 
• 
, Lead Statistician 
• 
, Bio-Study Statistician 
• 
 
, Clinical Laboratory Science Representatives, Clinical Readout Team 
Leaders 
• 
 
, Clinical Safety Representatives 
• 
 
Clinical Trial Supply Managers 
• 
 
Global Regulatory Leads 
• 
, Global Patent 
Representatives 
• 
, Clinical and Epidemiology R&D 
Project Leads (CPLs) 
In Sponsor signatory approval page, the following details were updated 
Dietrich Bosse, MD 
Clinical and Epidemiology R&D Project Lead 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
CCI

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Therapeutic Hepatitis B (CHB-TI) vaccines, GlaxoSmithKline Biologicals, SA 
In Section 5.5., the following footnote has been added for the list of procedures table 4 
and 5: 
In Table 4: 
AE: Adverse events; AESI: Adverse event of special interest; AFP: alpha-fetoprotein; CBC: complete blood count; 
CMI: cell-mediated immunity; DNA: Deoxyribonucleic acid; eCRF: electronic Case Report Form GSK: 
GlaxoSmithKline; HBV: hepatitis B virus; HCV: hepatitis C virus; HDV: hepatitis D virus; HIV: human 
immunodeficiency virus; HLA: human leukocyte antigen; hIi: human invariant chain; INR: international normalized 
ratio; MAE: medically attended event; ml: milliliter; pIMDs: potential immune-mediated diseases; qHBsAg: 
quantitative hepatitis B surface antigen; SAE: serious adverse event; Vacc: vaccination. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
^ If subsequent vaccination cannot be administered within an interval of 53 - 63 days due to special circumstances 
or any other reasons, please refer to Section 5.6.18.  
Refer to Section 5.6.18 for study procedures to be adapted during special circumstances.  
a Women of childbearing potential are to have a pregnancy test prior to study vaccination (either a blood or urine 
test, depending on local clinical requirement). For women of non-childbearing potential, the specific reason for not 
performing a pregnancy test needs to be documented in the eCRF (current tubal ligation, hysterectomy, 
ovariectomy, post-menopause or other). 
b For biochemical tests to be performed, please refer to Table 10 and Table 15. 
c For information about hematological tests to be performed, please refer to Table 10 and Table 15. 
d Blood sampling for CMI response will be collected from patients in centres with access to the PBMC processing 
facilities. For information about CMI response assays to be performed, please refer to Table 13 and Table 19.  
e For information about humoral response assays to be performed, please refer to Table 12 and Table 18 
f For information about urinalysis tests to be performed, please refer to Table 10 and Table 15. Routine urinalysis 
is done by dipstick. A microscopic examination and albumin to creatinine ratio (ACR) should be done 
(locally) if there is blood or protein reported from urine dipstick. If urine albumin and/or creatinine values 
are <LLOQ due to which the ACR cannot be calculated, it should be documented in the eCRF. 
g Additional blood sampling for biochemical/hematological testing may need to be performed in case of abnormal 
lab parameters. For more information, please refer to Section 8.5.3. 
h For more information please refer to Section 6.7. 
i For more information, please refer to Section 6.8. 
j If liver ultrasound is not possible, alternative liver imaging examination (e.g. magnetic resonance or computerized 
tomography) may be performed at the discretion on the investigator. If it is not possible to perform a liver ultrasound 
at screening, a routine ultrasound performed within 180 days prior to the vaccination visit 1, can be used for 
eligibility assessment. For Germany, please see the country-specific requirements in Section 12. 
k Blood samples for creatinine, FibroTest and Liver kidney microsomal type 1 (LKM-1) autoantibody tests should be 
collected after a minimum 8 hour fast. 
l 
 
 
m At Screening, a physical examination should be performed based on the clinical history of the patient. Physical 
examination at each subsequent study visit will be performed only if the patient indicates during questioning and 
test result review that there might be some underlying pathology(ies) or if deemed necessary by the Investigator or 
delegate. At Screening and at each vaccination, vital signs (including systolic/diastolic blood pressure, heart rate 
and respiratory rate after at least 10 minutes of rest) should be collected. Collected information needs to be 
recorded in the eCRF. 
n Procedure not applicable if vaccination could not be administered at that vaccination visit.  
o Procedure not applicable if vaccination was not administered at preceding vaccination visit.  
q The minimum requirements at Visits 2, 5, 9, 13 and 17 are safety assessment including, but not limited to, 
recording of solicited symptoms, unsolicited AEs within 30 days post-vaccination, SAEs, MAEs, AESIs, SAEs 
related to study participation, or to a concurrent GSK medication/vaccine, AEs/SAEs leading to study withdrawal, 
pregnancy and pregnancy outcome, intercurrent medical conditions leading to elimination from per-protocol 
CCI
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analyses and concomitant medications/vaccinations. The collection of data for safety assessment can be performed 
remotely (e.g. via phone contact). Other study procedures including biological samples collection and physical 
examination are optional at the discretion of the Investigator. However, efforts should be made for the patients 
needed for the first iSRC review in Step C to perform Visit 2 at the site to allow collection of biological samples for 
safety evaluation by iSRC. For patients participating to TH HBV VV-031 HBS:001 study, biological samples 
collection specific to that study remains mandatory for Visits 2 and 5. 
r The randomization is performed after screening and prior Visit 1. All eligibility criteria should be confirmed before 
vaccination at Day 1 visit (i.e. Visit 1).  
s In the sites/countries where a home nursing is possible according to local regulations, the patients may be offered 
the option to have a home visit. Only selected visits will have the option to be performed as a home visit, these may 
include biological samples collection, patients’ assessments and data collection. The full specifications of the home 
nursing services will be outlined in the SPM. 
t The screening window is extended from 90 days to 180 days except for CBC, INR, liver chemistry and HBV-DNA 
for which testing should be repeated if the interval between blood sampling at screening visit and the first dose 
vaccination at Visit 1 exceeds 90 days. 
v In case of a TTS event, an additional blood sample should be collected within 2 weeks of the diagnosis of the TTS 
for exploratory testing. This blood sample can be collected at the next study visit or at an unscheduled visit in case 
the next study visit is >2 weeks from the TTS diagnosis. For more information, please refer to Section 5.7.2. 
In Table 5: 
AE: Adverse events; AESI: Adverse event of special interest; AFP: alpha-fetoprotein; CBC: complete blood count; 
CMI: cell-mediated immunity; DNA: Deoxyribonucleic acid; eCRF: electronic Case Report Form; GSK: 
GlaxoSmithKline; HBV: hepatitis B virus; INR: international normalized ratio; MAE: medically attended event; ml: 
milliliter; pIMDs: potential immune-mediated diseases; qHBsAg: quantitative hepatitis B surface antigen; SAE: 
serious adverse event; Vacc: vaccination. 
Note: The double-line border following Visit 22 indicates the analyses which will be performed on all data (i.e. data 
that are as clean as possible) obtained up to Visit 22. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
Refer to Section 5.6.18 for study procedures to be adapted during special circumstances. 
a For information about biochemical and biomarkers tests to be performed, please refer to Table 10 and Table 15. 
For information about virological tests to be performed, please refer to Table 11. 
b For information about hematological tests to be performed, please refer to Table 10 and Table 15. 
c For information about CMI response assays to be performed, please refer to Table 13 and Table 19. 
d For information about humoral response assays to be performed, please refer to Table 12 and Table 18. 
e For information about urinalysis tests to be performed, please refer to Table 10 and Table 15. Routine urinalysis 
is done by dipstick. A microscopic examination and albumin to creatinine ratio (ACR) should be done 
(locally) if there is blood or protein reported from urine dipstick. If urine albumin and/or creatinine values 
are <LLOQ due to which the ACR cannot be calculated, it should be documented in the eCRF. 
f For detailed information, please refer to Section 6.7. 
g For detailed information, please refer to Section 6.8. 
h Additional blood sampling for biochemical/hematological testing may need to be performed in case of abnormal lab 
parameters. For more information, please refer to Section 8.5.3. 
i Blood samples for creatinine and FibroTest tests should be collected after a minimum 8 hour fast.  
j If liver ultrasound is not possible, alternative liver imaging examination (e.g. magnetic resonance or computerized 
tomography) may be performed at the discretion on the investigator. If it is not possible to perform a liver ultrasound 
at screening, a routine ultrasound performed within 180 days prior to the vaccination visit 1, can be used for 
eligibility assessment. For Germany, please see the country-specific requirements in Section 12. 
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k If procedure has not been performed at the respective timepoints, it should be done at earliest convenience.  
l For patients in Step A: the minimum requirements of Visits 19 and 21 are safety assessment including recording of 
solicited symptoms, unsolicited AEs within 30 days post-vaccination, SAEs, MAEs, AESIs, SAEs related to study 
participation, or to a concurrent GSK medication/vaccine, AEs/SAEs leading to study withdrawal, pregnancy and 
pregnancy outcome, intercurrent medical conditions leading to elimination from per-protocol analyses and 
concomitant medications/vaccinations. The safety assessment can be performed via telephone contact. Other study 
procedures including biological samples collection and physical examination are optional at the discretion of the 
Investigator. For patients in Step B and Step C, Visits 19 and 21 are cancelled. 
m In the sites/countries where a home nursing is possible according to local regulations, the patients may be offered 
the option to have a home visit. Only selected visits will have the option to be performed as a home visit, these may 
include biological samples collection, patients’ assessments and data collection. The full specifications of the home 
nursing services will be outlined in the SPM. 
n Procedure to be performed in addition to the other procedures only if Unscheduled visit is planned in order to 
check for contraindication to the subsequent vaccination in case no biological samples have been collected since 
the previous vaccination visit due to special circumstances. Please refer to Section 5.6.18. 
o In case of a TTS event, collection of an additional blood sample within 2 weeks of the diagnosis of the TTS for 
exploratory testing is optional. This blood sample can be collected at the next study visit or at an unscheduled visit 
in case the next study visit is >2 weeks from the TTS diagnosis. For more information, please refer to Section 5.7.2. 
In Section 8.1.5.2.1, the following changes are made: 
Recently, following COVID-19 vaccines, thrombosis with thrombocytopenia 
syndrome (TTS), in some cases accompanied by bleeding, has been observed very 
rarely following vaccination with adenovector-based COVID-19 vaccines. This 
includes severe cases presenting as venous thrombosis, including unusual sites such as 
cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial 
thrombosis, concomitant with thrombocytopenia. Some cases had a fatal outcome. The 
majority of these cases occurred within the first two weeks following adenovector-
based COVID-19 vaccination and mostly in women under 60 years of age (applicable 
for all patients except for the patients in Belgium). OR The majority of these cases 
occurred within the first three weeks following adenovector-based COVID-19 
vaccination and mostly in individuals under 60 years of age (applicable for the 
patients in Belgium only). 
 

Signature Page for  204852 TMF-16238057 v1.0
Signature Page for TMF-16238057 v1.0
Reason for signing: Approved
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Role: Approver
Date of signature: 23-Jun-2023 10:39:32 GMT+0000
PPD