A Phase 1, Observer-blind, Randomised, Controlled, Single-centre Study to Evaluate the Safety, Reactogenicity, and Immune Responses to an Adjuvanted and Non-adjuvanted Conjugate Vaccine Against Salmonella Typhi and Salmonella Paratyphi A in Healthy Adults 18 to 50 Years of Age in Europe
Phase: PHASE1
Conditions: Typhoid Fever
Sponsor: GlaxoSmithKline

Protocol Amendment 2
Study ID:  205480
Official Title of Study: A Phase 1, observer-blind, randomised, controlled, single-
centre study to evaluate the safety, reactogenicity, and immune responses to an 
adjuvanted and non-adjuvanted conjugate vaccine against Salmonella Typhi and 
Salmonella Paratyphi A in healthy adults 18 to 50 years of age in Europe
NCT number: NCT05613205
Date of Document: 25-Aug-2023

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
1 
CLINICAL STUDY PROTOCOL 
SPONSOR: 
GLAXOSMITHKLINE BIOLOGICALS SA (GSK) 
RUE DE L’INSTITUT 89, 
1330 RIXENSART, BELGIUM 
Primary study intervention 
and number 
• 
Vi-CRM197+O:2-CRM197, Typhoid and 
Paratyphoid A conjugate vaccine (Bivalent) 
(GSK3536867A) 
• 
ADJ+Vi-CRM197+O:2-CRM197, Adjuvanted 
Typhoid and Paratyphoid A conjugate vaccine 
(Bivalent)  
Other study interventions 
• 
Typhoid Vi polysaccharide vaccine (TYPHIM 
VI) 
• 
 
 
 
eTrack study number and 
abbreviated title 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-
CRM GVGH-001 (H02_01TP)) 
EudraCT number 
2021-002029-19 
Date of protocol 
Final: 23 August 2022 
Date of protocol amendment 
Amendment 1 Final: 25 May 2023 
Amendment 2 Final: 21 August 2023 
Title 
A Phase 1, observer-blind, randomised, controlled, 
single-centre study to evaluate the safety, 
reactogenicity, and immune responses to an 
adjuvanted and non-adjuvanted conjugate vaccine 
against Salmonella Typhi and Salmonella Paratyphi 
A in healthy adults 18 to 50 years of age in Europe 
Brief title 
Safety and immunogenicity of a novel conjugate 
vaccine against Salmonella Typhi and Salmonella 
Paratyphi A in healthy adults 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.1 
©2022 GSK group of companies or its licensor. 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
2 
Protocol Amendment 2 Sponsor Signatory Approval 
eTrack study number and 
abbreviated title 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-
CRM GVGH-001 (H02_01TP)) 
EudraCT number 
2021-002029-19 
Date of protocol 
Final: 23 August 2022 
Date of protocol amendment 
Amendment 1 Final: 25 May 2023 
Amendment 2 Final: 21 August 2023 
Title  
A Phase 1, observer-blind, randomised, controlled, 
single-centre study to evaluate the safety, 
reactogenicity, and immune responses to an 
adjuvanted and non-adjuvanted conjugate vaccine 
against Salmonella Typhi and Salmonella Paratyphi 
A in healthy adults 18 to 50 years of age in Europe 
Sponsor signatory 
Ashwani Kumar Arora, GVGH Head of Clinical 
Development & Regulatory Affairs 
Signature 
 
 
 
Date 
 
Note: Not applicable if an alternative signature process (e.g., electronic signature or 
email approval) is used to get the Sponsor approval 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
3 
Protocol Amendment 2 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments, or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals SA. 
• 
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.  
• 
That I will comply with the terms of the site agreement. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To supervise any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site. 
• 
To ensure that any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site are qualified to perform those trial-related 
duties and functions. 
• 
To ensure that vaccine dilution and possibly necessary labelling of clinical study 
materials at the study site will be performed according to GSK Biologicals 
instructions only by trained site staff with appropriate qualifications as required by 
local laws and regulations. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the participant and/or the participant’s legally acceptable representative. 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• 
To co-operate with representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the Sponsor to 
obtain and supply, as necessary, details about the Investigator’s ownership interest in 
the Sponsor or the investigational intervention(s), and more generally about his/her 
financial ties with the Sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
4 
Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study.  
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
5 
eTrack study number and 
abbreviated title 
205480 (TYPH-PARATYPH A CONJ VI-CRM 
O2-CRM GVGH-001 (H02_01TP)) 
EudraCT number 
2021-002029-19 
Date of protocol 
Final: 23 August 2022 
Date of protocol amendment 
Amendment 1 Final: 25 May 2023 
Amendment 2 Final: 21 August 2023 
Title 
A Phase 1, observer-blind, randomised, controlled, 
single-centre study to evaluate the safety, 
reactogenicity, and immune responses to an 
adjuvanted and non-adjuvanted conjugate vaccine 
against Salmonella Typhi and Salmonella Paratyphi 
A in healthy adults 18 to 50 years of age in Europe 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
6 
SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA (GSK),  
Rue de l’Institut 89, 1330 Rixensart, Belgium.  
2. Sponsor medical expert for the study 
Refer to the local study contact information document. 
3. Sponsor study monitor 
Refer to IQVIA study contact list. 
4. Sponsor study contact for reporting of a Serious Adverse Events (SAEs) 
Refer to IQVIA study contact list. 
5. Contact for emergency unblinding 
Refer to IQVIA Study Plans. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
7 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Amendment 2 (21 August 2023): 
This amendment is considered non-substantial based on the criteria defined in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall rationale for the current Amendment: 
The main reasons for this amendment are to update the information on the IgG ELISA 
testing method and to add clarification regarding baseline samples for each corresponding 
post-vaccination laboratory evaluation in the primary endpoint table. 
LIST OF MAIN CHANGES IN THE PROTOCOL AND THEIR RATIONALE: 
Section # and title 
Description of change 
Brief rationale 
Section 1 Synopsis, 
Section 3 (Objective and 
Endpoints), Table 3 (Study 
objectives and endpoints), 
Section 9.4(Statistical 
analyses), Sub-section 
9.4.1 Primary endpoints 
(s), 
 
 
Clarification regarding the baseline 
for each post-vaccination laboratory 
estimation has been added. 
This clarifies the baseline for each post 
vaccination laboratory estimation 
Section 9.4 (Statistical 
analyses), Sub-section 
9.4.2 Secondary 
endpoints (s) 
“Number” has been added in the 
statistical analysis methods column 
for completeness, for the last 
endpoint calculating within-subject 
increase of at least 4-fold in Anti-O:2 
IgG antibody concentrations, as 
measured by ELISA, per study group. 
For completeness and harmonization with 
other statistical analysis methods. 
Section 10.2 (Appendix 2: 
Clinical laboratory tests) 
Deleted information related to 
VaccZyme Human anti-Vi IgG kit 
As VaccZyme kit will no longer be used in 
the study, information regarding VaccZyme 
is replaced with a generalized description of 
an IgG ELISA assay 
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
8 
TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
List of main changes in the protocol and their rationale: ........................................... 7 
1. 
PROTOCOL SUMMARY ........................................................................................ 14 
1.1. 
Synopsis ..................................................................................................... 14 
1.2. 
Schema ...................................................................................................... 17 
1.3. 
Schedule of Activities (SoA) ........................................................................ 18 
2. 
INTRODUCTION .................................................................................................... 22 
2.1. 
Study rationale ............................................................................................ 22 
2.2. 
Background ................................................................................................ 23 
2.3. 
Benefit/Risk assessment ............................................................................. 23 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 25 
4. 
STUDY DESIGN .................................................................................................... 27 
4.1. 
Overall design ............................................................................................. 27 
4.2. 
Scientific rationale for study design ............................................................. 29 
4.2.1. 
Rationale for choice of vaccination route and schedule ................ 29 
4.2.2. 
Rationale for choice of follow-up period ....................................... 30 
4.2.3. 
Rationale for choice of study population ...................................... 30 
4.2.4. 
Rationale for choice of active comparator .................................... 30 
4.3. 
Justification for dose ................................................................................... 30 
4.4. 
End of Study definition ................................................................................ 31 
5. 
STUDY POPULATION ........................................................................................... 31 
5.1. 
Inclusion criteria .......................................................................................... 31 
5.2. 
Exclusion criteria ......................................................................................... 32 
5.2.1. 
Medical conditions ....................................................................... 32 
5.2.2. 
Prior/Concomitant therapy ........................................................... 33 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 34 
5.2.4. 
Other exclusions .......................................................................... 34 
5.3. 
Lifestyle considerations ............................................................................... 34 
5.4. 
Screen failures ............................................................................................ 34 
5.5. 
Criteria for temporarily delaying study intervention administration ............... 35 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 35 
6.1. 
Study interventions administered ................................................................ 35 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 37 
6.3. 
Measures to minimise bias: randomisation and blinding ............................. 37 
6.3.1. 
Participant identification ............................................................... 37 
6.3.2. 
Intervention allocation to the participant ....................................... 37 
6.3.3. 
Allocation of participants to assay subsets ................................... 38 
6.3.4. 
Blinding and unblinding ................................................................ 38 
6.3.4.1. 
Emergency unblinding ................................................ 39 
6.3.4.2. 
Unblinding prior to regulatory reporting of SAEs ......... 39 
6.4. 
Study intervention compliance .................................................................... 39 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
9 
6.5. 
Dose modification ....................................................................................... 39 
6.6. 
Continued access to study intervention after the end of the study ............... 39 
6.7. 
Treatment of overdose ................................................................................ 40 
6.8. 
Concomitant therapy ................................................................................... 40 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 40 
7.1. 
Discontinuation of study intervention ........................................................... 40 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration .............................................................................. 41 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 41 
7.3. 
Lost to follow-up.......................................................................................... 42 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 42 
8.1. 
Immunogenicity assessments ..................................................................... 44 
8.1.1. 
Biological samples ....................................................................... 44 
8.1.2. 
Laboratory assays ....................................................................... 45 
8.1.3. 
Immunological read-outs .............................................................. 45 
8.1.4. 
Cytology ...................................................................................... 45 
8.1.5. 
Clinical safety laboratory assessments ........................................ 46 
8.1.6. 
Immunological correlates of protection ......................................... 46 
8.2. 
Safety assessments .................................................................................... 46 
8.2.1. 
Pre-vaccination procedures ......................................................... 46 
8.2.1.1. 
Collection of demographic data .................................. 46 
8.2.1.2. 
Medical history ........................................................... 46 
8.2.1.3. 
Physical examination .................................................. 47 
8.2.1.4. 
Pregnancy test ........................................................... 47 
8.2.1.5. 
Pre-vaccination body temperature .............................. 47 
8.2.1.6. 
Warnings and precautions to vaccination ................... 47 
8.2.2. 
Study holding rules and safety monitoring.................................... 48 
8.2.2.1. 
Staggered vaccination ................................................ 48 
8.2.2.2. 
Outcome of safety evaluation ..................................... 51 
8.2.2.3. 
Study holding rules ..................................................... 51 
8.3. 
AEs, SAEs, and other safety reporting ........................................................ 53 
8.3.1. 
Time period and frequency for collecting AE, SAE, and 
other safety information ............................................................... 53 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies, and 
other events ................................................................................. 54 
8.3.2.1. 
Clinically significant abnormal laboratory 
findings ....................................................................... 54 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies, 
and other events .......................................................................... 55 
8.3.4. 
Treatment of expedited AEs......................................................... 55 
8.3.5. 
Participant card ............................................................................ 56 
8.3.6. 
Medical device deficiencies ......................................................... 56 
8.3.6.1. 
Detection, follow-up, and prompt reporting of 
medical device deficiency ........................................... 56 
8.3.6.2. 
Regulatory reporting of medical device 
deficiency when used as combination product ............ 57 
8.4. 
Pharmacokinetics ....................................................................................... 57 
8.5. 
Genetics and/or Pharmacogenomics .......................................................... 57 
8.6. 
Biomarkers ................................................................................................. 57 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
10 
8.7. 
Immunogenicity........................................................................................... 57 
8.8. 
Health outcomes ......................................................................................... 57 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 57 
9.1. 
Statistical hypotheses ................................................................................. 57 
9.2. 
Sample size determination .......................................................................... 57 
9.2.1. 
Statistical consideration for safety assessment ............................ 58 
9.2.2. 
Statistical considerations on immunogenicity assessment ........... 58 
9.3. 
Analysis sets ............................................................................................... 59 
9.3.1. 
Criteria for elimination from analysis ............................................ 60 
9.3.1.1. 
Intercurrent medical conditions ................................... 60 
9.4. 
Statistical analyses ..................................................................................... 61 
9.4.1. 
Primary endpoint(s) (Amended, 21 August 2023) ........................ 61 
9.4.2. 
Secondary endpoint(s) ................................................................. 62 
.................................................................... 62 
9.5. 
Interim analyses .......................................................................................... 63 
9.5.1. 
Sequence of analyses.................................................................. 63 
9.5.2. 
Statistical consideration for interim analysis ................................. 63 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 63 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 63 
10.1.1. 
Regulatory and ethical considerations ......................................... 63 
10.1.2. 
Financial disclosure ..................................................................... 64 
10.1.3. 
Informed consent process ............................................................ 64 
10.1.4. 
Data protection ............................................................................ 65 
10.1.5. 
Committee structure .................................................................... 65 
10.1.6. 
Dissemination of clinical study data ............................................. 66 
10.1.7. 
Data quality assurance ................................................................ 66 
10.1.8. 
Source documents ....................................................................... 67 
10.1.9. 
Study and site start and closure ................................................... 68 
10.1.10. Publication policy ......................................................................... 69 
10.2. 
Appendix 2: Clinical laboratory tests (Amended, 21 August 2023) .............. 69 
10.2.1. 
Protocol-required safety laboratory assessments ......................... 70 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of AE .................. 71 
10.3.1. 
Definition of an AE ....................................................................... 71 
10.3.1.1. Events Meeting the AE Definition ............................... 71 
10.3.1.2. Events NOT Meeting the AE Definition ....................... 72 
10.3.2. 
Definition of an SAE ..................................................................... 72 
10.3.3. 
Solicited events............................................................................ 73 
10.3.4. 
Unsolicited AEs............................................................................ 74 
10.3.5. 
Adverse events of special interest................................................ 74 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 74 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs ..................... 74 
10.3.7.1. Pregnancy .................................................................. 74 
10.3.8. 
Recording and follow-up of AEs, SAEs, and pregnancies ............ 75 
10.3.8.1. Time period for collecting and recording AEs, 
SAEs, and pregnancies .............................................. 75 
10.3.8.2. Follow-up of AEs, SAEs, pregnancies, or any 
other events of interest ............................................... 76 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
11 
10.3.8.2.1. Follow-up during the study ...................... 76 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study ...................... 76 
10.3.8.2.3. Follow-up of pregnancies ........................ 76 
10.3.8.3. Updating of SAE and pregnancy information 
after removal of write access to the 
participant’s eCRF ...................................................... 77 
10.3.9. 
Assessment of intensity and toxicity ............................................. 77 
10.3.9.1. Assessment of intensity .............................................. 77 
10.3.9.2. Assessment of causality ............................................. 78 
10.3.9.3. Medically attended visits ............................................. 79 
10.3.9.4. Assessment of outcomes............................................ 80 
10.3.10. Reporting of SAEs, pregnancies, and other events ...................... 80 
10.3.10.1. Events requiring expedited reporting to 
Sponsor or designee .................................................. 80 
10.3.10.2. Backup system in case the electronic reporting 
system does not work ................................................. 80 
10.4. 
Appendix 4: Contraceptive guidance and collection of pregnancy 
information .................................................................................................. 81 
10.4.1. 
Definitions .................................................................................... 81 
10.4.1.1. Woman of childbearing potential (WOCBP) ................ 81 
10.4.1.1.1. Women not considered as women 
of childbearing potential .......................... 81 
10.4.2. 
Contraception guidance ............................................................... 82 
10.4.3. 
Collection of pregnancy information ............................................. 83 
10.4.3.1. Female participants who become pregnant ................ 83 
10.5. 
Appendix 5: Genetics .................................................................................. 83 
10.6. 
Appendix 6: Definition of medical device AE, adverse device effect 
(ADE), serious adverse device effect (SADE) and unanticipated 
SADE (USADE) .......................................................................................... 83 
10.6.1. 
Definition of medical device AE and ADE..................................... 83 
10.6.2. 
Definition of medical device SAE, SADE and USADE .................. 84 
10.6.3. 
Recording and reporting of medical device AE, ADEs, 
SADEs and USADE ..................................................................... 84 
10.6.4. 
Reporting of medical device deficiencies for Associated 
Person ......................................................................................... 85 
10.7. 
Appendix 7 Country-specific requirements .................................................. 85 
10.8. 
Appendix 8: List of Asian countries considered endemic for typhoid 
fever ........................................................................................................... 85 
10.9. 
Appendix 9: Toxicity grading scale for safety laboratory assessment .......... 86 
10.10. Appendix 10: Abbreviations and Glossary of terms ..................................... 86 
10.10.1. List of abbreviations ..................................................................... 86 
10.10.2. Glossary of terms ......................................................................... 89 
10.11. Appendix 11: Protocol amendment history .................................................. 94 
11. REFERENCES ..................................................................................................... 101 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
12 
LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities (SoA) ................................................................... 18 
Table 2 
Intervals between study visits ................................................................. 22 
Table 3 
Study objectives and endpoints (Amended, 21 August 2023) ................. 25 
Table 4 
Study groups, intervention, and blinding ................................................. 29 
Table 5 
Study interventions administered ........................................................... 36 
Table 6 
Intervals between study visits under special circumstances (e.g., 
COVID-19 pandemic) ............................................................................. 44 
Table 7 
Biological samples ................................................................................. 44 
Table 8 
Laboratory assays .................................................................................. 45 
Table 9 
Immunological read-outs ........................................................................ 45 
Table 10 
Safety evaluation schedule .................................................................... 50 
Table 11 
Study holding rules ................................................................................. 52 
Table 12 
Timeframes for collecting and reporting of safety information ................. 53 
Table 13 
Timeframes for submitting SAE and pregnancy reports.......................... 55 
Table 14 
Probability to observe at least 1 AE according to sample size and 
AE rate ................................................................................................... 58 
Table 15 
95% confidence intervals for seroresponse in participants 
receiving the full dose of the vaccine ...................................................... 59 
Table 16 
Analysis sets .......................................................................................... 59 
Table 17 
Protocol-required safety laboratory assessments ................................... 70 
Table 18 
Solicited administration-site events ........................................................ 73 
Table 19 
Solicited systemic events ....................................................................... 73 
Table 20 
Intensity scales for solicited events in adults .......................................... 77 
Table 21 
Highly effective contraceptive methods .................................................. 82 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
13 
LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 28 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
14 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale: 
A monovalent typhoid conjugate vaccine consisting of a fragmented Typhoid Vi antigen 
conjugated to Cross-Reacting Material 197 (fVi-CRM197) was previously developed by 
the Novartis Vaccines Institute for Global Health (NVGH), now GSK Vaccines Institute 
for Global Health (GVGH). In 2013, this technology was transferred to Biological E Ltd 
(BioE, Hyderabad, India) who conducted several clinical studies using this formulation, 
which led to marketing approval as the BioE Typhoid Conjugate Vaccine (TYPHIBEV) 
in January 2020, by the Central Drugs Standard Control Organisation of the Government 
of India (MF/BIO/20/000001) and to WHO pre-qualification in Q4 2020.  
A novel Typhoid and Paratyphoid A conjugate vaccine (bivalent), abbreviated hereinafter 
as Vi-CRM197+O:2-CRM197, aimed to prevent both typhoid and paratyphoid enteric fever 
in infants and older age groups, was developed recently by GVGH. This candidate 
vaccine is based on chemical conjugation of the Vi polysaccharide for Salmonella Typhi 
and the O:2 polysaccharide for Salmonella Paratyphi A, with the carrier protein 
Corynebacterium diphtheriae CRM197 widely used for production of several conjugate 
vaccines licensed worldwide. In 2013, the technology for this vaccine had been also out 
licensed to BioE for further development and commercialisation in certain endemic 
countries. GVGH is still responsible for the development of Vi-CRM197+O:2-CRM197 to 
achieve proof of concept. This includes the conduct of toxicology studies and Phase 
1/Phase 2 clinical studies.  
The purpose of this first-time-in-human (FTIH) study is to evaluate the safety and 
immunogenicity profile of a low and a full dose of Vi-CRM197+O:2-CRM197, formulated 
with (ADJ+Vi-CRM197+O:2-CRM197) or without Aluminium adjuvant (Vi-CRM197+O:2-
CRM197), administered in 2 doses, a priming dose and a booster dose, 24 weeks apart, in 
healthy adults 18 to 50 years of age in Europe. Subsequent studies are planned for 
endemic countries. The current study is sponsored by GSK and managed by GVGH. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
15 
Objectives and endpoints: 
Objectives 
Endpoints 
Primary 
Evaluate the safety profile of the Vi-
CRM197+O:2-CRM197 vaccine, with and 
without adjuvant. 
• 
Percentage of participants with solicited administration-site 
events during 7 days after each vaccination, on the days of 
vaccination and the 6 subsequent days (study intervention 
administered on Day 1 and Day 169), per study group. 
• 
Percentage of participants with solicited systemic events 
during 7 days after each vaccination, on the days of 
vaccination and the 6 subsequent days (study intervention 
administered on Day 1 and Day 169), per study group. 
• 
Percentage of participants with unsolicited adverse events 
(AE) during 28 days after each vaccination, on the days of 
vaccination and 27 subsequent days (study intervention 
administered on Day 1 and Day 169), per study group. 
• 
Percentage of participants with any serious adverse event 
(SAE) from first vaccination until 28 days after second study 
intervention administration (Day 1 to Day 197), per study 
group. 
• 
Percentage of participants with AEs/SAEs leading to 
withdrawal from the study or withholding further study 
intervention administration, from first study intervention 
administration until 28 days after second study intervention 
administration (Day 1 to Day 197), per study group. 
• 
Percentage of participants with deviations from normal or 
baseline† values of haematological, renal, and hepatic panel 
test results at 7 days after each vaccination (Day 8 and Day 
176), per study group. 
Secondary 
Evaluate the long-term safety profile of the 
Vi-CRM197+O:2-CRM197 vaccine, with and 
without adjuvant. 
• 
Percentage of participants with any SAE from 28 days after 
second vaccination (Day 197) up to Day 337, per study 
group. 
• 
Percentage of participants with AEs/SAEs leading to 
withdrawal from the study from 28 days after second 
vaccination (Day 197) up to Day 337, per study group. 
Evaluate the immunogenicity profile of the 
typhoid and paratyphoid A components of 
the Vi-CRM197+O:2-CRM197 vaccine, with 
and without adjuvant, using enzyme-linked 
immunoassay (ELISA). 
• 
Geometric mean concentration (GMC) of anti-Vi antigen 
Immunoglobulin G (IgG) antibody concentrations as 
measured by ELISA, before first vaccination (Day 1), 28 
days after first vaccination (Day 29), before second 
vaccination (Day 169), 7 days after second vaccination (Day 
176), and 28 days after second vaccination (Day 197), per 
study group. 
• 
GMC of Anti-O:2 IgG antibody concentrations, as measured 
by ELISA, before first vaccination (Day 1), 28 days after first 
vaccination (Day 29), before second vaccination (Day 169), 
7 days after second vaccination (Day 176), and 28 days 
after second vaccination (Day 197), per study group. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
16 
Objectives 
Endpoints 
Evaluate different seroresponse rates to the 
typhoid and paratyphoid A component of the 
Vi-CRM197+O:2-CRM197 vaccine, with and 
without adjuvant. 
• 
Percentage of participants achieving anti-Vi antigen IgG 
antibody concentrations ≥4.3 µg/mL*, as measured by 
ELISA, before first vaccination (Day 1), 28 days after first 
vaccination (Day 29), before second vaccination (Day 169), 
7 days after second vaccination (Day 176), and 28 days 
after second vaccination (Day 197), per study group. 
• 
Percentage of participants achieving anti-Vi antigen IgG 
antibody concentrations ≥2.0 µg/mL**, as measured by 
ELISA, before first vaccination (Day 1), 28 days after first 
vaccination (Day 29), before second vaccination (Day 169), 
7 days after second vaccination (Day 176), and 28 days 
after second vaccination (Day 197), per study group. 
• 
Percentage of participants achieving at least 4-fold*** 
increase in Anti-O:2 IgG antibody concentrations, as 
measured by ELISA, at 28 days after first vaccination (Day 
29), before second vaccination (Day 169), 7 days after 
second vaccination (Day 176), and 28 days after second 
vaccination (Day 197) compared to first vaccination baseline 
(Day 1), per study group. 
*This threshold, estimated to be protective against typhoid fever, 
was established in previous studies [Szu, 2013; WHO, 2020] and 
then used in the registration of Vi conjugated vaccine in India. 
**This threshold, estimated to be protective against typhoid fever, 
was defined as a short-term threshold in a previous study [Szu, 
2014]. 
***This threshold is chosen as a clinically meaningful threshold 
that, in the absence of an established correlate of protection, 
could allow quantitative decisions to be made for further 
development of this component of the vaccine. 
†Baseline for post-first vaccination at Day 8 is Day 1 (can also be screening blood draw, if performed within 3 
days of first vaccination), and baseline for post-second vaccination at Day 176 is Day 169. 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
17 
1.2. 
Schema 
 
 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
18 
1.3. 
Schedule of Activities (SoA) 
Table 1 
Schedule of Activities (SoA) 
Type of contact 
Screening 
period 
Visit 1 
(Priming Vacc) 
Sentinel 
participant 
safety 
phone 
contact 
Reminder 
phone 
contact 1 
Visit 2 
Visit 3 
Visit 4 
(Booster 
Vacc) 
Reminder 
phone contact 
2 
Visit 5 
Visit 6 
Follow-up 
safety 
phone 
contact 
Time points 
Day -21 to 
Day -1 
Day 1 
Day 2  
Day 4 
Day 8 
Day 29 
Day 169 
Day 172 
Day 176 Day 197 
Day 337 
Informed consent (Section 
10.1.3) 
● 
 
 
 
 
 
 
 
 
 
 
Check of inclusion/exclusion 
criteria (Sections 5.1 and 5.2) 
● 
● 
 
 
 
 
● 
 
 
 
 
Collection of demographic data 
(Section 8.2.1.1) 
● 
 
 
 
 
 
 
 
 
 
 
Medical history (Section 8.2.1.2) 
● 
 
 
 
 
 
 
 
 
 
 
Physical examination (including 
vital sign assessment and body 
temperature measurement) 
(Section 8.2.1.3) 
● 
● 
 
 
 
 
● 
 
 
 
 
Symptom-directed physical 
examination (Section 8.2.1.3) 
 
 
 
 
○ 
○ 
 
 
○ 
○ 
 
Height and weight measurement 
(Section 8.2.1.3) 
● 
 
 
 
 
 
 
 
 
 
 
Randomisation (Section 6.3) 
 
● 
 
 
 
 
 
 
 
 
 
Study intervention 
Check of contraindications and 
warnings, and precautions to 
vaccination (Sections 7.1.1 and 
8.2.1.6) 
○ 
○ 
 
 
 
 
○ 
 
 
 
 
Check of criteria for temporary 
delay for enrolment and/or study 
intervention administration 
(Section 5.5) 
○ 
○ 
 
 
 
 
○ 
 
 
 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
19 
Type of contact 
Screening 
period 
Visit 1 
(Priming Vacc) 
Sentinel 
participant 
safety 
phone 
contact 
Reminder 
phone 
contact 1 
Visit 2 
Visit 3 
Visit 4 
(Booster 
Vacc) 
Reminder 
phone contact 
2 
Visit 5 
Visit 6 
Follow-up 
safety 
phone 
contact 
Time points 
Day -21 to 
Day -1 
Day 1 
Day 2  
Day 4 
Day 8 
Day 29 
Day 169 
Day 172 
Day 176 Day 197 
Day 337 
Pregnancy test (Section 8.2.1.4) 
●1 
●2 
 
 
 
 
●2 
 
 
 
 
Study intervention allocation 
(Section 6.3) 
 
● 
 
 
 
 
 
 
 
 
 
Administration of the Vi-
CRM197+O:2-CRM197 vaccine 
(low or full dose, with or without 
Alum), or control  
 
●3 
 
 
 
 
●4 
 
 
 
 
Laboratory assessments 
Blood sampling for antibody 
determination (~10 mL) 
 
●5 
 
 
 
● 
●5 
 
● 
● 
 
Blood collection for assay 
standard generation (~15 mL) 
 
 
 
 
 
 
 
 
 
● 
 
Blood sampling for safety 
Screening laboratory assays 
(refer to Table 17) (~20 mL)  
● 
 
 
 
 
 
 
 
 
 
 
Blood sampling for safety 
laboratory assays 
(haematological and clinical 
chemistry analyses) (~13.5 mL) 
 
●5,6 
 
 
● 
 
●5 
 
● 
 
 
Safety assessments 
Recording of any concomitant 
medication/vaccination (Section 
6.8) 
● 
● 
●7 
 
● 
● 
● 
 
● 
● 
 
Recording of any intercurrent 
medical conditions (Section 
9.3.1) 
 
● 
●7 
 
● 
● 
● 
 
● 
● 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
20 
Type of contact 
Screening 
period 
Visit 1 
(Priming Vacc) 
Sentinel 
participant 
safety 
phone 
contact 
Reminder 
phone 
contact 1 
Visit 2 
Visit 3 
Visit 4 
(Booster 
Vacc) 
Reminder 
phone contact 
2 
Visit 5 
Visit 6 
Follow-up 
safety 
phone 
contact 
Time points 
Day -21 to 
Day -1 
Day 1 
Day 2  
Day 4 
Day 8 
Day 29 
Day 169 
Day 172 
Day 176 Day 197 
Day 337 
Recording of solicited events in 
the participant paper Diary (Days 
1-7 post-vaccination) (Section 
10.3.8) 
 
○ 
 
 
 
 
○ 
 
 
 
 
Recording of unsolicited AEs in 
the source document (Days 1-28 
post-vaccination) (Section 10.3.8) 
 
○ 
○7 
 
○ 
 
○ 
 
○ 
 
 
Transcription of unsolicited AEs 
in the eCRF by the Investigator or 
delegate 
 
● 
● 
 
● 
● 
● 
 
● 
● 
 
Safety surveillance (including 
vital sign assessment and body 
temperature measurement) 
(60 minutes post-vaccination) 
(Section 10.3.8) 
 
● 
 
 
 
 
● 
 
 
 
 
Reporting of SAEs (Section 
10.3.8) 
 
● 
●7 
 
● 
● 
● 
 
● 
● 
● 
Reporting of SAEs related to 
study participation or concurrent 
GSK medication/ vaccine 
● 
● 
●7 
 
● 
● 
● 
 
● 
● 
● 
Reporting of pregnancies and 
pregnancy outcomes (Section 
10.3.8) 
 
● 
 
 
● 
● 
● 
 
● 
● 
 
Recording of AEs/SAEs leading 
to withdrawal 
 
● 
 
 
● 
● 
● 
 
● 
● 
● 
Diary cards 
Distribution of diary cards  
 
○ 
 
 
 
 
○ 
 
 
 
 
Phone call for diary card 
completion reminder (Section 
10.3.8) 
 
 
 
● 
 
 
 
● 
 
 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
21 
Type of contact 
Screening 
period 
Visit 1 
(Priming Vacc) 
Sentinel 
participant 
safety 
phone 
contact 
Reminder 
phone 
contact 1 
Visit 2 
Visit 3 
Visit 4 
(Booster 
Vacc) 
Reminder 
phone contact 
2 
Visit 5 
Visit 6 
Follow-up 
safety 
phone 
contact 
Time points 
Day -21 to 
Day -1 
Day 1 
Day 2  
Day 4 
Day 8 
Day 29 
Day 169 
Day 172 
Day 176 Day 197 
Day 337 
Safety phone call to sentinel 
participants 1-day post-
vaccination to check for any 
holding rule events or SAEs 
(Section 8.2.2) 
 
 
● 
 
 
 
 
 
 
 
 
Diary card transcription in the 
eCRF by Investigator or delegate 
 
 
 
 
● 
 
 
 
● 
 
 
Return of diary cards  
 
 
 
 
● 
 
 
 
● 
 
 
Participant study conclusion 
(Section 4.4) 
 
 
 
 
 
 
 
 
 
 
● 
1A blood pregnancy test will be performed. 
2A urine pregnancy test will be performed. 
3TYPHIM VI will be the control vaccination at Visit 1 (Day 1) 
4
will be the control vaccination at Visit 4 (Day 169) 
5Blood collection will be performed prior to vaccination 
6If a blood sample has been collected during Screening in the 3 days before the date of first vaccination, another safety blood sample does not need to be collected on Visit 1. 
7All information needs to be verified at the site during an ad hoc Visit. Refer to Section 8.2.2 for details on safety monitoring.  
AE=adverse event; eCRF=electronic case report form; SAE=serious adverse event; VACC=vaccination 
Note: The double-line border following Day 29 and Day 197 indicates the interim analyses, which will be performed on all data obtained up to Day 29 (28 days after first vaccination in 
Step 2) and Day 197 (28 days after second vaccination in Step 2). The double-line borders following Day 337 indicate the final analysis in these participants, which will be performed on 
all data obtained up to Day 337. 
● 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. 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
22 
Table 2 
Intervals between study visits  
2. 
INTRODUCTION 
2.1. 
Study rationale 
A monovalent typhoid conjugate vaccine consisting of a fragmented Typhoid Vi antigen 
conjugated to Cross-Reacting Material 197 (fVi-CRM197) was previously developed by 
the Novartis Vaccines Institute for Global Health (NVGH), now GSK Vaccines Institute 
for Global Health (GVGH). In 2013, this technology was transferred to Biological E Ltd 
(BioE, Hyderabad, India) who conducted several clinical studies using this formulation, 
which led to marketing approval as the BioE Typhoid Conjugate Vaccine (TYPHIBEV) 
in January 2020, by the Central Drugs Standard Control Organisation of the Government 
of India (MF/BIO/20/000001) and to WHO pre-qualification in Q4 2020.  
A novel Typhoid and Paratyphoid A conjugate vaccine (bivalent), abbreviated hereinafter 
as Vi-CRM197+O:2-CRM197, aimed to prevent both typhoid and paratyphoid enteric fever 
in infants and older age groups, was developed recently by GVGH. This candidate 
vaccine is based on chemical conjugation of the Vi polysaccharide for Salmonella Typhi 
and the O:2 polysaccharide for Salmonella Paratyphi A, with the carrier protein 
Corynebacterium diphtheriae CRM197 widely used for production of several conjugate 
vaccines licensed worldwide. In 2013, the technology for this vaccine had been also out 
licensed to BioE for further development and commercialisation in certain endemic 
countries. GVGH is still responsible for the development of Vi-CRM197+O:2-CRM197 to 
achieve proof of concept. This includes the conduct of toxicology studies and Phase 
1/Phase 2 clinical studies.  
The purpose of this first-time-in-human (FTIH) study is to evaluate the safety and 
immunogenicity profile of a low and a full dose of Vi-CRM197+O:2-CRM197, formulated 
with (ADJ+Vi-CRM197+O:2-CRM197) or without Aluminium adjuvant (Vi-CRM197+O:2-
CRM197), administered in 2 doses, a priming dose and a booster dose, 24 weeks apart, in 
healthy adults 18 to 50 years of age in Europe. Subsequent studies are planned for 
endemic countries. The current study is sponsored by GSK and managed by GVGH. 
Interval 
Planned Visit interval  
Allowed interval range 
Visit 1 → Visit 2 
7 days 
7 days – 10 days 
Visit 1 → Visit 3 
28 days 
28 days – 33 days 
Visit 1 → Visit 4 
168 days 
158 days – 178 days 
Visit 4 → Visit 5 
7 days 
7 days – 10 days 
Visit 4 → Reminder phone call 2 
3 days 
1 day – 3 days 
Visit 4 → Visit 6 
28 days 
28 days – 33 days 
Visit 4 → Follow-up safety phone contact  
168 days 
154 days – 182 days 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
23 
2.2. 
Background 
Despite improved sociosanitary conditions in the last decade, enteric fever remains a 
major cause of disability and death, with billions of people likely to be exposed to 
Salmonella enterica pathogens causing typhoid and paratyphoid fever. In the 2017 Global 
Burden of Disease (GBD) study, approximately 14.3 million cases of enteric fever were 
reported, which caused approximately 135 900 deaths (116 800 due to typhoid fever and 
19 100 due to paratyphoid fever) [GBD 2017 Typhoid and Paratyphoid Collaborators, 
2019]. In 2017, paratyphoid fever was responsible for 23.7% of all cases of enteric fever, 
which was similar to an earlier 1990 GBD estimate of 21.3% [GBD 2017 Typhoid and 
Paratyphoid Collaborators, 2019]. High incidence countries for paratyphoid fever include 
Nepal [Zellweger, 2017], Bangladesh [Owais, 2010; Saha, 2018], Pakistan [Owais, 
2010], and India [John, 2016]. Most blood cultures positive for Salmonella Typhi or 
Salmonella Paratyphi from clinical and laboratory records in Asian endemic countries are 
resistant to fluoroquinolones, with a high proportion also resistant to ampicillin, 
chloramphenicol, and trimethoprim-sulfamethoxazole [Barkume, 2018]. 
In this study, participants will be administered 2 vaccinations using a 0–6-month 
schedule (a priming dose and a booster dose) and a dose-escalation approach with 2 
different doses (low and full), with or without adjuvant. TYPHIM VI (Typhoid Vi 
polysaccharide vaccine) will be used as control for the first vaccination, and 
 
(booster immunisation vaccine against tetanus, diphtheria, and pertussis) as control for 
the second vaccination. Dose escalation will be performed by evaluating first a low dose 
formulated without adjuvant containing 5 µg of Vi-CRM197 (1/5 of the licensed vaccine) 
and 5 µg of O:2-CRM197 followed by an evaluation of a low dose formulated with 
adjuvant containing 5 µg of Vi-CRM197 (1/5 of the licensed vaccine) and 5 µg of O:2-
CRM197. Subsequently, a full dose formulated with and without adjuvant containing 
25 µg of Vi-CRM197 (same as the licensed monovalent vaccine) and 25 µg of O:2-
CRM197 will be evaluated. Depending on interim and final analyses results, additional 
studies will be planned in endemic countries for enteric fever. 
Please refer to the current Investigator Brochure (IB) for information regarding 
preclinical studies of Vi-CRM197+O:2-CRM197 and ADJ+Vi-CRM197+O:2-CRM197. 
2.3. 
Benefit/Risk assessment 
The safety and immunogenicity of the first generation monovalent Vi-CRM197 candidate 
vaccine was assessed in previous Phase 1 and 2 clinical studies in adults, children, and 
infants from Salmonella Typhi endemic and non-endemic countries [van Damme, 2011; 
Bhutta, 2014]. 
The second-generation fragmented Typhoid Vi antigen conjugated to CRM197 vaccine, 
which is the same component as in Vi-CRM197+O:2-CRM197 without adjuvant, to be used 
in this study, was tested in Phase 1 (CTRI/2018/01/011500) and Phase 2/3 clinical studies 
(CTRI/2018/11/016419, CTRI/2019/07/020451, CTRI/2020/03/023712) sponsored by 
BioE. These completed studies led to licensing of the vaccine in India in January 2020 
and to WHO pre-qualification in Q4-2020. There are no clinical studies with the use of 
the paratyphoid A component of the investigational vaccine. 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
24 
Aluminium Hydroxide (Alum) is a well-known, safe, and widely used adjuvant in 
licensed vaccines. It has been added to the Vi-CRM197+O:2-CRM197 vaccine to enhance 
the immune response to the O:2-CRM197 component, with the possibility that it can lead 
to antigen sparing and eventually achieve a single-dose licensed vaccine. 
Intramuscular vaccination commonly precipitates a transient and self-limiting local 
inflammatory reaction. This may typically include pain at the injection site, redness, and 
swelling. As with all injectable vaccines, appropriate medical treatment and supervision 
will be readily available in case of a rare anaphylactic event following administration of 
the vaccine. 
Blood sampling procedures planned in the study may result in bruising at the sampling 
site. There is also a rare possibility of bleeding, fainting, infection, or nerve injury. Safe 
sampling procedures will be applied by appropriately trained and qualified site staff to 
minimise distress and sampling errors. The amount of blood to be taken for sampling is 
within the locally accepted range for the study age group and is not expected to be 
harmful to the participant’s health. 
By taking part in the study, the participants will contribute to the process of developing 
therapies in an area of unmet need. They may also help provide valuable data about the 
tolerability and immunogenicity of the investigational vaccine and its potential ability to 
provide clinical protection. Administration of control vaccines can also provide some 
benefits to the participants such as protection against tetanus, diphtheria, and pertussis 
 and prevention of typhoid fever (TYPHIM VI). Participants can gain 
medical advice about their health status through the medical evaluations and laboratory 
assessments done during the study.  
Detailed information about the known and expected benefits and risks and expected AEs 
of Vi-CRM197+O:2-CRM197 and ADJ+Vi-CRM197+O:2-CRM197 can be found in the IB. 
Detailed information about the known and expected benefits and risks and expected AEs 
of 
 and TYPHIM VI can be found in the Prescribing information/Summary 
of Product Characteristics (SmPC). 
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
25 
3. 
OBJECTIVES AND ENDPOINTS  
Table 3 
Study objectives and endpoints (Amended, 21 August 2023) 
Objectives 
Endpoints 
Primary 
Evaluate the safety profile of the Vi-
CRM197+O:2-CRM197 vaccine, with and without 
adjuvant. 
• 
Percentage of participants with solicited administration-
site events during 7 days after each vaccination, on the 
days of vaccination and the 6 subsequent days (study 
intervention administered on Day 1 and Day 169), per 
study group. 
• 
Percentage of participants with solicited systemic events 
during 7 days after each vaccination, on the days of 
vaccination and the 6 subsequent days (study 
intervention administered on Day 1 and Day 169), per 
study group. 
• 
Percentage of participants with unsolicited adverse 
events (AE) during 28 days after each vaccination, on the 
days of vaccination and 27 subsequent days (study 
intervention administered on Day 1 and Day 169), per 
study group. 
• 
Percentage of participants with any serious adverse 
event (SAE) from first vaccination until 28 days after 
second study intervention administration (Day 1 to Day 
197), per study group. 
• 
Percentage of participants with AEs/SAEs leading to 
withdrawal from the study or withholding further study 
intervention administration, from first study intervention 
administration until 28 days after second study 
intervention administration (Day 1 to Day 197), per study 
group. 
• 
Percentage of participants with deviations from normal or 
baseline† values of haematological, renal, and hepatic 
panel test results at 7 days after each vaccination (Day 8 
and Day 176), per study group. 
Secondary 
Evaluate the long-term safety profile of the Vi-
CRM197+O:2-CRM197 vaccine, with and without 
adjuvant. 
• 
Percentage of participants with any SAE from 28 days 
after second vaccination (Day 197) up to Day 337, per 
study group.  
• 
Percentage of participants with AEs/SAEs leading to 
withdrawal from the study from 28 days after second 
vaccination (Day 197) up to Day 337, per study group. 
Evaluate the immunogenicity profile of the 
typhoid and paratyphoid A components of the 
Vi-CRM197+O:2-CRM197 vaccine, with and 
without adjuvant, using enzyme-linked 
immunoassay (ELISA). 
• 
Geometric mean concentration (GMC) of anti-Vi antigen 
Immunoglobulin G (IgG) antibody concentrations as 
measured by ELISA, before first vaccination (Day 1), 28 
days after first vaccination (Day 29), before second 
vaccination (Day 169), 7 days after second vaccination 
(Day 176), and 28 days after second vaccination (Day 
197), per study group. 
• 
GMC of Anti-O:2 IgG antibody concentrations, as 
measured by ELISA, before first vaccination (Day 1), 28 
days after first vaccination (Day 29), before second 
vaccination (Day 169), 7 days after second vaccination 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
26 
Objectives 
Endpoints 
(Day 176), and 28 days after second vaccination (Day 
197), per study group. 
Evaluate different seroresponse rates to the 
typhoid and paratyphoid A component of the Vi-
CRM197+O:2-CRM197 vaccine, with and without 
adjuvant. 
• 
Percentage of participants achieving anti-Vi antigen IgG 
antibody concentrations ≥4.3 µg/mL*, as measured by 
ELISA, before first vaccination (Day 1), 28 days after first 
vaccination (Day 29), before second vaccination (Day 
169), 7 days after second vaccination (Day 176), and 28 
days after second vaccination (Day 197), per study 
group. 
• 
Percentage of participants achieving anti-Vi antigen IgG 
antibody concentrations ≥2.0 µg/mL**, as measured by 
ELISA, before first vaccination (Day 1), 28 days after first 
vaccination (Day 29), before second vaccination (Day 
169), 7 days after second vaccination (Day 176), and 28 
days after second vaccination (Day 197), per study 
group. 
• 
Percentage of participants achieving at least 4-fold*** 
increase in Anti-O:2 IgG antibody concentrations, as 
measured by ELISA, at 28 days after first vaccination 
(Day 29), before second vaccination (Day 169), 7 days 
after second vaccination (Day 176), and 28 days after 
second vaccination (Day 197) compared to first 
vaccination baseline (Day 1), per study group. 
*This threshold, estimated to be protective against typhoid 
fever, was established in previous studies [Szu, 2013; WHO, 
2020] and then used in the registration of Vi conjugated vaccine 
in India. 
**This threshold, estimated to be protective against typhoid 
fever, was defined as a short-term threshold in a previous study 
[Szu, 2014]. 
***This threshold is chosen as a clinically meaningful threshold 
that, in the absence of an established correlate of protection, 
could allow quantitative decisions to be made for further 
development of this component of the vaccine. 
†Baseline for post-first vaccination at Day 8 is Day 1 (can also be screening blood draw, if performed within 3 
days of first vaccination), and baseline for post-second vaccination at Day 176 is Day 169. 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
27 
4. 
STUDY DESIGN 
4.1. 
Overall design 
This is a Phase 1 observer-blind, controlled, self-contained, randomised, single-centre, 
dose-escalation study with 3 Steps (Step 1a, Step 1b, and Step 2). A total of 96 
participants in 7 study groups, including 17 sentinel participants, are planned to be 
enrolled in the study. Figure 1 shows a visual representation of the study design and 
Table 4 shows a description of the study intervention groups. 
An electronic case report form (eCRF) and a paper Diary will be used for data collection, 
which will include biological sampling (blood) and safety follow-ups.  
The study design, the enrolment, and the monitoring procedures will follow GSK safety 
standards for FTIH clinical studies (Refer to Sections 8.2.2 and 10.1.5 for details on 
staggered vaccination, safety monitoring, and holding rules).  
The primary completion date will be at Visit 6 (Day 197), 28 days after administration of 
the second study intervention (booster vaccination). An extended safety follow-up will be 
performed until 6 months after this second study intervention administration (Day 337) 
for collection of SAEs. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
28 
Figure 1 
Study design overview  
 
 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
29 
Table 4 
Study groups, intervention, and blinding  
Study groups 
Number of 
participants 
Age 
(Min-
Max) 
Study intervention(s)  
Blinding 
FSFV → 
IA 1*  
IA 1* → 
LSLV) 
Step 1a low 
dose without 
Alum 
12 
18 – 
50 
years 
2 intramuscular vaccinations (Day 
1 and Day 169) with low dose of Vi-
CRM197+O:2-CRM197 without Alum 
Observer-
blind 
Single-blind*  
Step 1a control 
6 
1 intramuscular vaccination (Day 1) 
with TYPHIM VI and 1 
intramuscular vaccination (Day 
169) with 
  
Step 1b low 
dose with Alum 
12 
2 intramuscular vaccinations (Day 
1 and Day 169) with low dose of 
ADJ+Vi-CRM197+O:2-CRM197 with 
Alum  
Step 1b control 
6 
1 intramuscular vaccination (Day 1) 
with TYPHIM VI and 1 
intramuscular vaccination (Day 
169) with 
 
Step 2 full dose 
without Alum  
24 
2 intramuscular vaccinations (Day 
1 and Day 169) with full dose of Vi-
CRM197+O:2-CRM197 without Alum 
Step 2 full dose 
with Alum 
24 
2 intramuscular vaccinations (Day 
1 and Day 169) with full dose of 
ADJ+Vi-CRM197+O:2-CRM197 with 
Alum 
Step 2 control 
12 
1 intramuscular vaccination (Day 1) 
with TYHPIM VI and 1 
intramuscular vaccination (Day 
169) with 
 
FSFV = first subject first visit; IA = interim analysis; LSLV = last subject last visit 
*Refer to Sections 6.3.4 and 9.5.1 for additional details on change of blinding during the interim analysis  
4.2. 
Scientific rationale for study design 
4.2.1. 
Rationale for choice of vaccination route and schedule 
Previous clinical studies (CTRI/2018/11/016419, CTRI/2019/07/020451, 
CTRI/2020/03/023712) with the typhoid component of the Vi-CRM197+O:2-CRM197 
vaccine have shown sufficient immunogenicity and an acceptable safety profile with a 
single intramuscular injection, which led to the licensing of the vaccine in India.  
According to results from preclinical studies in mice [Micoli, 2012; Micoli, 2020] with 
each component of the Vi-CRM197+O:2-CRM197 vaccine, 2 injections may be needed in 
clinical studies to achieve optimal immunogenicity of the paratyphoid A component. An 
interval of 6 months between 2 vaccinations is expected to boost the immune response 
from the second vaccination. The selected schedule is considered appropriate for this 
FTIH study.  
CCI
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
30 
4.2.2. 
Rationale for choice of follow-up period 
No adverse events of special interest are planned to be collected in this study; the 
investigational vaccine does not contain any novel adjuvant and the Vi-CRM197 
component is already registered in India with no particular safety concern observed 
during its development (refer to the IB). No particular safety concerns have been 
identified in other licensed Vi-based vaccines against typhoid fever.  
A 6-month follow-up period after the first study intervention administration will allow 
the identification of any possible late-occurring AEs. A follow-up of 28 days after the 
second study intervention administration will allow collection of unsolicited AEs and any 
other event as indicated in Table 12. An extended 6-month safety follow-up after the 
second study intervention administration will collect any late-occurring SAE and 
AEs/SAEs leading to withdrawal or study discontinuation.  
4.2.3. 
Rationale for choice of study population 
Healthy adults in Europe have been chosen since enteric fever caused by typhoid and 
paratyphoid A is not endemic in this population. Therefore, it is expected that participants 
will not have pre-existing antibodies, which may interfere with the immunogenicity 
evaluation of the candidate vaccine. This study population has also been chosen on the 
basis of being a low-risk population for the assessment of safety of a FTIH vaccine. The 
age of participants selected for this study is consistent with planned clinical development 
of the vaccine.  
4.2.4. 
Rationale for choice of active comparator 
The safety profiles of both TYPHIM VI and 
 are well characterised. 
Additionally, both comparator vaccines are not likely to be part of the routine vaccination 
schedule of study participants, hence, all participants may receive benefit of vaccination 
by participation in the study. 
TYPHIM VI, which is licensed in Europe, has been chosen as a comparator, rather than 
the TYPHIBEV vaccine (not licensed in Europe) or any other conjugated typhoid 
vaccines. This is consistent with the primary objective being safety in this FTIH clinical 
study.  
4.3. 
Justification for dose 
The full dose for the typhoid, Vi-CRM197 component, to be used in this study is the same 
as the dose of the monovalent vaccine licensed for protection against typhoid fever 
among individuals aged 6 months to 45 years in 2020 in India and WHO pre-qualified in 
the same year. That dose was shown in a Phase 2/3 clinical study 
(CTRI/2018/11/016419) to be comparable in terms of safety and immunogenicity to a 
licensed Typhoid Vi-Tetanus Toxoid conjugate vaccine (Typbar-TCV, Bharat Biotech) 
when administered to healthy adults, children, and infants.  
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
31 
Two injections with the highest dose of the paratyphoid A, O:2-CRM197 component to be 
used in this study have shown a robust immune response in mice, rats, and rabbits. 
Results from a repeat-dose toxicology study in rabbits are available in the IB to confirm 
the safety of the highest antigen doses. There are no clinical safety data with the use of 
the paratyphoid A component of the vaccine in humans. 
Although a 4-fold decrease in antigen was preferred from the full dose to the low dose, a 
5-fold decrease has been chosen instead for reasons of practical feasibility of the volume 
to be administered. Fractional dosing will be used for administration of the low dose due 
to the lack of a commercially available diluent.  
Aluminium Hydroxide (Alum) has been added to this vaccine as an adjuvant to enhance 
the immune response to the O:2-CRM197 component, with the expectation that it will lead 
to antigen sparing and the use of an effective single-dose vaccine in humans. Adjuvant 
effects have been shown in animal studies but still need to be confirmed in human 
studies.  
4.4. 
End of Study definition 
A participant is considered to have completed the study if he/she returns for the last Visit 
or is available for the last scheduled procedure as described in the protocol. 
End of Study (EoS): Last Subject Last Visit (safety phone contact, Day 337).  
5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardise the scientific 
integrity, regulatory acceptability of the study or safety of the participant. 
5.1. 
Inclusion criteria 
All participants must satisfy ALL the following criteria at study entry: 
• 
Participants 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 participant prior to performance of any 
study specific procedure. 
• 
Healthy participants as established by medical history, clinical examination, and 
Screening laboratory investigations.  
• 
Participant satisfying Screening requirements. 
• 
Participant seronegative for human immunodeficiency virus, hepatitis B, and 
hepatitis C at Screening. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
32 
• 
A male or female participant between, and including, 18 and 50 years of age at the 
time of the first study intervention administration. 
• 
Female participants of non-childbearing potential may be enrolled in the study. Non-
childbearing potential is defined as pre-menarche, current bilateral tubal ligation or 
occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Refer to Section 
10.4.1 for definitions of women of childbearing potential, menarche, and menopause. 
• 
Female participants of childbearing potential may be enrolled in the study if the 
participant: 
− 
has practiced adequate contraception for 1 month prior to study intervention 
administration, and 
− 
has a negative pregnancy test on the day of study intervention administration, 
and 
− 
has agreed to continue adequate contraception during the entire treatment period 
and for 1 month after completion of the study intervention administration series.  
5.2. 
Exclusion criteria 
The following criteria should be checked at the time of study entry. The potential 
participant MUST NOT be included in the study if ANY exclusion criterion applies: 
5.2.1. 
Medical conditions 
• 
Progressive, unstable, or uncontrolled clinical conditions. 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine. 
• 
Hypersensitivity, including allergy, to medicinal products or medical equipment 
whose use is foreseen in this study. 
• 
Clinical conditions representing a contraindication to intramuscular vaccination and 
blood draws. 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required). 
• 
Any behavioural or cognitive impairment or psychiatric disease that, in the opinion 
of the Investigator, may interfere with the participant’s ability to participate in the 
study. 
• 
Acute* or chronic illness, clinically significant pulmonary, cardiovascular, hepatic, 
or renal functional abnormality, as determined by physical examination or laboratory 
screening tests. 
*Participants with a minor illness (such as mild diarrhoea or mild upper respiratory 
infection) without fever may be enrolled at the discretion of the Investigator. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
33 
• 
Any clinically significant* haematological (haemoglobin level, white blood cell, 
lymphocyte, neutrophil, eosinophil, platelet, red blood cell count and erythrocyte 
mean corpuscular volume) and/or biochemical (alanine aminotransferase [ALT], 
aspartate aminotransferase [AST], creatinine, and total protein) laboratory 
abnormality.  
*The Investigator should use his/her clinical judgement to decide which 
abnormalities are clinically significant. 
• 
Confirmed positive COVID-19 test during the period starting 14 days before the first 
administration of study vaccines (Day -14 to Day 1).  
• 
Any other clinical condition that, in the opinion of the Investigator, might pose 
additional risk to the participant due to participation in the study. 
• 
Confirmed or suspected autoimmune diseases (e.g., vitiligo, autoimmune thyroiditis). 
5.2.2. 
Prior/Concomitant therapy 
• 
Previous administration of any type of Typhoid vaccine (Ty21a, Vi-PS, or Typhoid 
conjugate vaccine). 
• 
Use of any investigational or non-registered product (drug, vaccine, or medical 
device) other than the study interventions during the period starting 30 days before 
the first administration of study vaccines (Day -30 to Day 1), or planned use during 
the study period. 
• 
A vaccine not foreseen by the study protocol administered during the period starting 
at -14 days before the first dose (-21 days in the case of live vaccines) and ending 28 
days after the last dose of study intervention administration*, with the exception of 
flu and COVID-19 vaccines, administered during the period starting at 7 days before 
and 7 days after each dose (14 days before and 14 days after in case of live 
vaccines). 
*In case emergency mass vaccination for an unforeseen public health threat (e.g., a 
pandemic) is recommended and/or organised by public health authorities outside the 
routine authorisation programme, the time period described above can be reduced if, 
necessary for that vaccine, provided it is used according to the local governmental 
recommendations and that the Sponsor is notified accordingly. When regulations 
allow, the recommended time intervals for administration of these vaccines are at 
least 7 days before or 7 days after (at least 14 days before or 14 days after in case of 
live vaccines) each dose of study intervention administration. 
• 
Administration of long-acting immune-modifying drugs at any time during the study 
period (e.g., infliximab). 
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the administration of the first dose of 
study intervention or planned administration during the study period. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
34 
• 
Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 3 
months prior to the first study intervention dose. For corticosteroids, this will mean 
prednisone equivalent ≥20 mg/day for adult participants. Inhaled and topical steroids 
are allowed. 
5.2.3. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug/invasive medical device). 
5.2.4. 
Other exclusions  
• 
History of travel to countries of Asia that are considered endemic* for enteric fever 
in the last 3 years. 
*Refer to Section 10.8 for the list of countries; this also includes travel during the 
study duration. 
• 
Pregnant or lactating female. 
• 
Female participants planning to become pregnant or planning to discontinue 
contraceptive precautions. 
• 
History of or current chronic* alcohol consumption and/or drug abuse. 
*Chronic alcohol consumption is defined as one or more of the following: a) a 
prolonged period of frequent and heavy alcohol use, b) the inability to control 
drinking once it has begun, c) physical dependence manifested by withdrawal 
symptoms when the individual stops using alcohol, d) tolerance or the need to use 
increasing amounts of alcohol to achieve the same effects, e) and a variety of social 
and/or legal problems arising from alcohol use. 
• 
Any study personnel or immediate dependents, family, or household member. 
5.3. 
Lifestyle considerations 
Not applicable 
5.4. 
Screen failures 
A screening failure is an individual who consents to participate in this study but is not 
entered in the study (was not randomised, did not receive a study intervention, and did 
not undergo a post-screening procedure). 
The Investigator will maintain a screening log to record details of all participants 
screened and to confirm eligibility or record reasons for the screening failure. No 
laboratory data will be retained in the eCRF for participants identified as screening 
failures. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
35 
5.5. 
Criteria for temporarily delaying study intervention 
administration 
Study intervention administration may be postponed within the permitted time interval 
until transient conditions cited below are resolved:  
• 
Participants with haematological/biochemical values out of normal range which are 
expected to be temporary may be rescreened/re-vaccinated at a later date, within the 
allowed time interval. 
• 
Acute disease and/or fever at the time and/or study intervention administration. Refer 
to the SoA (Section 1.3) for definition of fever and preferred location for measuring 
temperature in this study.  
• 
Participants with a minor illness (such as mild diarrhoea, mild upper respiratory 
infection) without fever may be dosed at the discretion of the Investigator.  
• 
Participants with a positive COVID-19 test before a planned study intervention 
administration will be allowed to receive the study intervention only if at least 14 
days have passed since the first positive test. 
• 
Participants receiving flu and COVID-19 vaccines, administered during the period 
starting at 7 days before and 7 days after each planned dose (14 days before and 14 
days after in case of live vaccines). 
• 
Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to study 
intervention administration. 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY  
Refer to the Glossary of terms for the definition of study intervention. 
6.1. 
Study interventions administered  
Table 5 shows the study vaccines that will be administered in the study. The 
investigational vaccines, Vi-CRM197+O:2-CRM197 and ADJ+Vi-CRM197+O:2-CRM197, 
will be administered in 2 different doses depending on Step. The low dose will be 
administered by fractional dosing (0.1 mL) retrieved from the same 0.5 mL vial 
presentation as the full dose. The licensed vaccines, TYPHIM VI and 
 will 
be administered as per their SmPC.  
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
36 
Table 5 
Study interventions administered 
*The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the study intervention in the non-dominant arm, an injection in the dominant arm may be 
performed 
Study intervention 
name: 
TYP04A (Low Dose 
Vi-CRM197+O:2-
CRM197) 
TYP04B (Full Dose 
Vi-CRM197+O:2-
CRM197) 
TYP03A (Low Dose 
ADJ+Vi-CRM197+O:2-
CRM197) 
TYP03B (Full Dose 
ADJ+Vi-CRM197+O:2-
CRM197) 
TYPHIM VI (Sanofi 
Pasteur) 
DTP01A (
 
Study intervention 
formulation: 
Presentation: 
vial, solution for 
injection 
vial, solution for 
injection 
vial, solution for 
injection 
vial, solution for 
injection 
pre-filled syringe, 
solution for injection 
pre-filled syringe, 
suspension for injection 
Type: 
Investigational 
Investigational 
Investigational 
Investigational 
Comparator 
Comparator 
Product category: 
Biologic 
Biologic 
Biologic 
Biologic 
Combination Product 
Combination product 
Route of 
administration:  
intramuscular 
Administration site: 
• 
Location 
Deltoid 
• 
Directionality  
Upper 
• 
Laterality* 
Non-dominant 
Number of doses to 
be administered: 
2 per participant 
2 per participant 
2 per participant 
2 per participant 
1 per participant  
1 per participant 
Volume to be 
administered: 
0.1 mL 
0.5 mL 
0.1 mL 
0.5 mL 
0.5 mL 
0.5 mL 
Packaging and 
labelling: 
Refer to the Study Procedures Manual for more details 
Responsible for 
manufacture: 
CCI
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
37 
Study participants must be observed closely for at least 60 minutes after the 
administration of the study interventions. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis or syncope. 
6.2. 
Preparation/Handling/Storage/Accountability 
The study interventions must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s).  
Only authorised study personnel should be allowed access to the study interventions. 
Storage conditions will be assessed by a IQVIA Clinical Research Associate during pre-
study activities. Refer to the Study Procedures Manual for more details on storage and 
handling of the study interventions. 
6.3. 
Measures to minimise bias: randomisation and blinding  
6.3.1. 
Participant identification 
Participant identification numbers will be assigned sequentially to the participants who 
have consented to participate in the study, according to the range of participant 
identification numbers allocated to the study centre. 
6.3.2. 
Intervention allocation to the participant 
Allocation of the participant to a study group will be performed using envelopes prior to 
first study intervention administration, according to a randomisation schedule generated 
prior to the study by an independent statistician.  
The target will be to enrol approximately 96 eligible participants, 18 to 50 years of age, 
who will be randomly assigned to the different study groups, according to Step: 
Step 1a: 18 adults will be assigned in a 2:1 ratio to the following study groups 
• 
“Step 1a low dose without Alum” (approximately 12 participants) 
• 
“Step 1a control” (approximately 6 participants) 
Step 1b: 18 adults will be assigned in a 2:1 ratio to the following study groups 
• 
“Step 1b low dose with Alum” (approximately 12 participants) 
• 
“Step 1b control” (approximately 6 participants) 
Step 2: 60 adults will be assigned in a 2:2:1 ratio to the following study groups 
• 
“Step 2 full dose without Alum” (approximately 24 participants) 
• 
“Step 2 full dose with Alum” (approximately 24 participants) 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
38 
• 
“Step 2 control” (approximately 12 participants) 
Refer to the IQVIA Lab Manual and Pharmacy Manual for additional information about 
the study intervention number allocation. 
6.3.3. 
Allocation of participants to assay subsets 
6.3.4. 
Blinding and unblinding  
Data will be collected in an observer-blind manner until the first interim analysis (to be 
performed 28 days after first study intervention administration in Step 2). From the first 
interim analysis (refer to Section 9.5.1) until EoS, the study will be considered single-
blind, with the participant and Investigator remaining blinded. Study interventions will be 
prepared and administered by qualified study personnel who will not participate in data 
collection, evaluation, review, or the entry of any study endpoint (i.e., reactogenicity, 
safety, immunogenicity). 
Investigators will remain blinded to each participant’s assigned study intervention 
throughout the course of the study. All activities involving vaccine handling (e.g., re-
labelling of clinical study materials at the study site) and vaccine administration will be 
performed by unblinded site staff according to instructions and training provided by GSK 
or delegated contract research organisation staff before study start. The site staff 
responsible for these activities will be personnel who are respectively qualified according 
to applicable local laws and regulations. Preparation and administration of the vaccine(s) 
should be performed at a location different from the location where clinical assessment 
and evaluation is performed. The participant will be instructed not to look at the injection 
syringe while the study intervention is administered. The unblinded site staff will be also 
responsible for completing the Vaccine Administration Log and Vaccine Accountability 
Log to ensure final accountability. Refer to the IQVIA Pharmacy Manual for further 
details on blinding procedures and management. 
In case a participant’s intervention assignment is unblinded, the participant’s continuation 
in the study will be evaluated on a case-by-case basis between the Investigator and GSK. 
The participant should still be followed up for safety if a study intervention has been 
performed. 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no link between the study intervention group and the identity of the participant. 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
39 
6.3.4.1. 
Emergency unblinding 
Unblinding a participant’s individual study intervention should occur ONLY in case of a 
medical emergency when this information is essential for the clinical management or 
welfare of the participant. 
In case of emergency, the Investigator can have unrestricted, immediate, and direct 
access to the participant’s study intervention information via emergency unblinding 
envelopes.  
A physician other than the Investigator (e.g., an emergency room physician) or 
participant/care giver/family member may also request emergency unblinding via the 
Investigator. The participant card provides contact information for the Investigator and 
his/her back up. 
6.3.4.2. 
Unblinding prior to regulatory reporting of SAEs 
GSK policy requires unblinding of any unexpected SAE which is attributable/suspected 
to be attributable to the study interventions, prior to regulatory reporting. Global Safety 
(GS) is responsible for unblinding the study intervention assignment within the 
timeframes defined for expedited reporting of SAEs (refer to the Section 10.3.10.1).  
In addition, GSK GS staff may unblind the intervention assignment for any participant 
with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or a SAE that is fatal 
or life threatening. For SAEs requiring expedited reporting to 1 or more regulatory 
agencies, a copy of the report containing participant’s intervention assignment may be 
sent to investigators in accordance with local regulations and/or GSK policy. 
6.4. 
Study intervention compliance 
Participants will receive the study interventions directly from the Investigator or 
designee, under medical supervision. The date and time of administration of each study 
intervention dose in the clinic will be recorded in the source documents. 
6.5. 
Dose modification 
Not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study 
During the study conclusion Visit/Contact, the Investigator will ask each participant if 
they are interested in participating in a long-term study. If a participant is not interested in 
joining the long-term study the reason for refusal will be documented, when available, in 
the participant’s eCRF. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
40 
6.7. 
Treatment of overdose 
Not applicable. 
6.8. 
Concomitant therapy 
At each study Visit, the Investigator or his/her delegate should question the participant 
about all medications/products taken, and vaccinations received by the participant. 
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 the period of 28 days post-vaccination.  
• 
Relevant medications/products such as vaccines, immunoglobulin, blood products, 
immunosuppressors, and immunomodulators, administered during the period starting 
from the administration of the first dose of the study intervention and ending on Visit 
6 (Day 197).  
• 
Any vaccination administered in the period starting 30 days before the first dose of 
study vaccine and ending on Visit 6 (Day -30 to Day 197). 
• 
Prophylactic medication (i.e., medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination). 
• 
All concomitant medication associated with an adverse event, including 
vaccines/products, except vitamins and dietary supplements, administered after the 
first dose of study intervention (Day 1 to Day 197). 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines (refer to Sections 5.2.2 
and 9.3.1 for further details). 
• 
All concomitant medication which may explain/cause/be used to treat an SAE 
including vaccines/products, as defined in Sections 8.3.1 and 10.3.8.2. These must 
also be recorded in the Expedited Adverse Event Report. 
The IQVIA Clinical Research Associate should be contacted if there are any questions 
regarding concomitant or prior therapy. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
‘Discontinuation’ of study intervention refers to any participant who has not received all 
planned doses of study intervention. A participant who discontinued study intervention 
may continue other study procedures (e.g., safety or immunogenicity), planned in the 
study protocol at the discretion of the Investigator.  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
41 
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• 
Adverse event requiring expedited reporting to GSK 
• 
Unsolicited non-serious adverse event  
• 
Solicited adverse event 
• 
Not willing to be vaccinated 
• 
Other (specify). 
Participants who discontinue study intervention will not be replaced. 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration 
The eligibility for subsequent study intervention administration must be confirmed before 
administering any additional dose.  
Participants who meet any of the criteria listed below or criteria listed in sections 5.2.1 
and 5.2.2 should not receive additional doses of study intervention. Such participants 
should be encouraged to continue other study procedures, at the investigators’ discretion 
(Section 10.3.8.2). All relevant criteria for discontinuation of study intervention 
administration must be recorded in the eCRF.  
• 
Participants who experience any SAE judged to be possibly or probably related to 
study intervention or non-study concomitant vaccine/product, including 
hypersensitivity reactions. 
• 
Participants who develop any new condition which, in the opinion of the 
Investigator, may pose additional risk to the participant if he/she continues to 
participate in the study. 
• 
Any condition that in the judgement of the Investigator would make intramuscular 
injection unsafe. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for him/her since the date 
of withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who did not 
return for the concluding Visit/Contact planned in the protocol.  
Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
42 
The primary reason for study withdrawal will be documented in the eCRF, based on the 
list below: 
• 
AEs requiring expedited reporting to GSK (refer to Section 10.3.10.1 for more 
details) 
• 
Unsolicited non-serious adverse events 
• 
Solicited adverse event 
• 
Withdrawal by participant, not due to an adverse event* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
*If a participant is withdrawn from the study because he/she has withdrawn consent and 
the reason for withdrawal was provided, the Investigator must document this reason in 
the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.8.2). 
7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if he/she fails to return for scheduled 
visits and cannot be contacted by the study site.  
Please refer to the IQVIA Lab Manual and Pharmacy Manual for a description of actions 
to be taken before considering the participant lost to follow-up. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted, when necessary, for the management 
of immediate safety concerns for the participant.  
Immediate safety concerns should be discussed with the Sponsor as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarised in the SoA (Section 1.3).  
All Screening evaluations must be completed, and the results reviewed before confirming 
that potential participants meet all eligibility criteria.  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
43 
The Investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for Screening failure will be mentioned in 
this Screening log. 
Procedures conducted as part of routine clinical management (e.g. haematologic profiles), 
and obtained before the participant signed the informed consent form (ICF), may be used 
for Screening and/or for establishing a clinical baseline (provided the procedure met 
protocol specified criteria and was performed within the time frame defined in the SoA) 
(Section 1.3). 
The SPM provides the Investigator and site personnel with detailed administrative and 
technical information that does not impact participant safety. 
During special circumstances (e.g., COVID-19 pandemic), if local regulations allow, and 
quality of study procedures is maintained, participant(s) can be offered remote visits (e.g., 
telemedicine, home visits) for the collection of biological samples and/or safety 
data/safety assessment(s)/study intervention administration. These remote visits must be 
performed by qualified study staff. Refer to the SoA for the timing of these visits. Details 
of how these visits will be conducted are outlined in the SPM.  
The following procedures can be performed remotely/virtually (refer to the Glossary of 
terms for the definitions of telemedicine, remote and virtual visits) for the duration of 
such special circumstances: 
• 
Safety follow-up may be performed by telemedicine, which will use secure video 
conferences, phone calls, and a web portal and/or mobile application as a way of 
communicating with the participant and monitoring the participant’s progress. In 
addition, qualified study staff may also identify AEs and report them to the 
Investigator for evaluation.  
• 
Biological samples may be collected by qualified study staff in a different location 
other than the study site or at participant’s home. Biological samples should be 
collected only if they can be processed in a timely manner and appropriately stored 
until the intended use.  
• 
Administration of study intervention can be performed in a different location other 
than the study site or at participant’s home by qualified study staff if appropriate 
storage conditions for the study intervention can be ensured. Furthermore, 
appropriate medical treatment must be readily available during 60 minutes after 
dosing in case of anaphylaxis or syncope. 
• 
If despite best efforts it is not possible to perform the visits within the interval 
predefined in the protocol (see Table 2), then the interval may be extended for the 
specified visits up to a maximum length of days as presented in Table 6. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
44 
Table 6 
Intervals between study visits under special circumstances (e.g., 
COVID-19 pandemic) 
Interval 
Planned Visit interval  
Allowed interval range 
Visit 1 → Visit 2 
7 days 
7 days – 10 days 
Visit 1 → Visit 3 
28 days 
28 days – 38 days 
Visit 1 → Visit 4 
168 days 
154 days – 182 days 
Visit 4 → Visit 5 
7 days 
7 days – 10 days 
Visit 4 → Visit 6 
28 days 
28 days – 38 days 
Visit 4 → Follow-up safety phone contact 
168 days 
154 days – 182 days 
8.1. 
Immunogenicity assessments 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol.  
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
IEC/IRB approval, if required by local legislation. 
Information on further research and its rationale can be obtained from GSK.  
Sample testing will be done in accordance with the recorded consent of the individual 
participant.  
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed, and agreed 
with GSK. 
8.1.1. 
Biological samples 
Table 7 summarises the collection of blood in the study. The maximum amount of blood 
to be collected in the study is ~140 mL per participant. 
Table 7 
Biological samples 
Sample type 
Quantity 
Unit 
Timepoint 
Participants 
sampled 
Blood for 
serum 
preparation 
~10 mL/Visit for antibody determination, ~15 mL for 
assay standard generation, ~20 mL for safety 
Screening laboratory assays, ~13.5 mL/Visit for 
pre/post-vaccination visits safety laboratory assays 
mL 
As scheduled 
(refer to Table 1 
and Figure 1)  
All participants 
in Step 1 and 
Step 2 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
45 
8.1.2. 
Laboratory assays 
Table 8 
Laboratory assays  
Assay type 
System 
Component 
Method 
Laboratory* 
Humoral 
Immunity 
(Antibody 
determination) 
Serum 
Anti-Vi antigen IgG (Salmonella Typhi) 
ELISA 
GVGH or 
GVGH-
delegated 
lab 
Anti-O antigen IgG (Salmonella Paratyphi A) 
*Refer to the list of clinical laboratories for details. 
ELISA=enzyme-linked immunoassay; GVGH=GSK Vaccines Institute for Global Health; IgG=Immunoglobulin G;
 
Exploratory systems serology analysis assays will be performed by the GVGH 
laboratory, or a laboratory designated by GVGH. 
Please refer to the Section 10.2 for a brief description of the assays performed in the 
study. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 
GSK clinical laboratories (GVGH) have established a Quality System supported by 
procedures. The activities of GSK clinical laboratories are audited regularly for quality 
assessment by an internal (Sponsor-dependent) but laboratory-independent Quality 
Department. 
8.1.3. 
Immunological read-outs  
Table 9 
Immunological read-outs 
Blood sampling timepoint 
No. 
participants 
Component 
Type of contact and 
timepoint 
Sampling 
timepoint 
Visit 1 (Day 1) 
Pre-1st vaccination 
96 
Anti-Vi antigen IgG 
Anti-O:2 IgG 
 
Visit 3 (Day 29) 
Post-1st 
vaccination 
96 
Anti-Vi antigen IgG 
Anti-O:2 IgG 
 
Visit 4 (Day 169) 
Pre-2nd vaccination 
96 
Anti-Vi antigen IgG 
Anti-O:2 IgG 
 
Visit 5 (Day 176) 
Post-2nd 
vaccination 1 
96 
Anti-Vi antigen IgG 
Anti-O:2 IgG 
 
Visit 6 (Day 197) 
Post-2nd 
vaccination 2 
96 
Anti-Vi antigen IgG 
Anti-O:2 IgG 
 
8.1.4. 
Cytology 
Not applicable 
CCI
CCI
CCI
CCI
CCI
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
46 
8.1.5. 
Clinical safety laboratory assessments 
Refer to the Section 10.2.1 for the list of clinical laboratory safety assessments required 
by the protocol. These assessments must be conducted according to the clinical 
laboratory manual and the SoA. 
8.1.6. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the typhoid or paratyphoid A component used in the candidate vaccine. 
No antigen measurement that can assess immunological correlates of protection are 
planned in this study for the comparator vaccines. An antigen threshold for anti-Vi IgG of 
>4.3 µg/mL (similar to the endpoint threshold used in this study) was defined as criteria 
of sustained protection for at least 4 years during licensing of TYPHIBEV [Kasi, 2021]. 
An anti-Vi IgG of >2.0 µg/mL was estimated to be predictive of short-term protection in 
a previous paediatric study [Szu, 2014]. 
8.2. 
Safety assessments 
The Investigator and his/her designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. This includes the assessment 
of COVID-19 cases as per the WHO definition [WHO, 2022]. The Investigator and 
designees are responsible for following up AEs that are serious, considered related to the 
study intervention or the study, or that caused the participant’s withdrawal from the study 
intervention or the study.  
The safety measures in this study have been planned considering the nature of the 
existing knowledge on the investigational vaccine components (Vi, O:2, CRM197, Alum). 
The Vi component is licensed in India and WHO-prequalified; it is similar to the Bharat 
Biotech Typbar-TCV vaccine and the Sanofi Pasteur TYPHIM VI, both of which have 
been administered to millions of people worldwide with an acceptable safety profile and 
without particular risks. CRM197 and Alum are well-known vaccine components with a 
well-characterised safety profile. 
8.2.1. 
Pre-vaccination procedures 
8.2.1.1. 
Collection of demographic data 
Record demographic data such as month and year of birth, sex, and race in the 
participant’s eCRF. 
8.2.1.2. 
Medical history 
Obtain the participant’s medical history by interviewing the participant and/or review of 
the participant’s medical records. Record any pre-existing conditions, signs and/or 
symptoms present in the last 3 years prior to the first study intervention in the eCRF. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
47 
8.2.1.3. 
Physical examination  
A complete physical examination will be performed at screening and on each vaccination 
visits (Day 1 and Day 169). The physical examination will be performed by the 
Investigator and clinically relevant findings should be recorded in the participant source 
documents and in eCRF (only for enrolled participants). Physical examination includes 
assessment of body temperature (axillary is preferred location) and resting vital signs 
(systolic/diastolic blood pressure, pulse rate, and respiratory rate). On days of 
vaccination, body temperature and vital signs will be measured immediately prior to 
(maximum 60 minutes before) and 60 minutes after vaccination. Height and weight 
measurements will be performed during screening only. If the Investigator determines 
that the participant’s health on the days of vaccination temporarily precludes vaccination, 
the visit will be rescheduled as possible by the study site. 
A symptom-directed physical examination will be performed on visits where no 
vaccination is administered. The nature of the physical examination will be driven by any 
specific symptoms identified by the Investigator. The symptom-directed physical 
examination will not be recorded in the eCRF. However, any abnormalities detected that 
meet the definition of AE (refer to Section 10.3) will be recorded as such in the eCRF. 
Treatment of any abnormalities observed during any physical examinations must be 
performed according to local medical practice outside this study or by referral to an 
appropriate health care provider. 
8.2.1.4. 
Pregnancy test 
Female participants of childbearing potential must take a blood pregnancy test at 
screening and a urine pregnancy test before the administration of any dose of study 
intervention. Pregnancy testing must be done even if the participant is menstruating at the 
time of the study visit. The study intervention may only be administered if the pregnancy 
test is negative.  
Refer to the Section 10.4.3.1 for the information on study continuation for participants 
who become pregnant during the study. 
8.2.1.5. 
Pre-vaccination body temperature 
The axillary temperature of each participant needs to be measured prior to (maximum 60 
minutes before) administration of any study vaccine. If the participant has fever [fever is 
defined as temperature ≥38.0°C regardless of the location of measurement] on the day of 
vaccination, the vaccination visit will be rescheduled within the allowed interval for this 
visit (refer to Table 2). 
8.2.1.6. 
Warnings and precautions to vaccination 
Warnings and precautions to administration of study intervention must be checked at 
each visit with planned administration of study intervention. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
48 
For contraindications to the administered marketed study vaccines, refer to their SmPC 
and/or Prescribing Information.  
8.2.2. 
Study holding rules and safety monitoring 
Study holding rules (refer to Table 11) are introduced to ensure careful exposure to the 
investigational candidate vaccine and to prevent participants from being exposed to any 
unnecessary safety risks. The holding rules will serve as criteria to point attention to 
potential safety concerns and indicate requirements for additional formal committee 
reviews that will decide whether additional participants can be exposed to the vaccine. If 
the Investigator becomes aware of a holding rule threshold being met, he/she must 
suspend administration of the study intervention and inform IQVIA immediately. Refer 
to the IQVIA study contact list for contact information and Section 8.2.2.3 for additional 
information. 
Safety during the study will be monitored on an ongoing basis by the Safety Review 
Team (SRT), a cross-functional internal GSK committee that will evaluate safety data in 
a blinded manner. In addition, a GSK project-independent internal Safety Review 
Committee (iSRC) will be established to monitor safety at predefined timepoints and, 
more specifically, to recommend continuation of vaccine administration based on the 
unblinded safety results (refer to Section 8.2.2.1). The iSRC Chair together with the SRT 
will also perform blinded reviews at predefined timepoints (refer to Section 8.2.2.1), 
which will assess the need for full committee unblinded reviews by iSRC based on 
assessment of safety signals/concerns. Ad hoc safety evaluations by the iSRC may be 
called at any time if there are any suspected safety concerns.  
The iSRC will also include an external expert (non-GSK employee); the organisation of 
the iSRC, the specific roles of its members, how reviews will be conducted, and how 
blinding will be maintained, will be outlined in the iSRC Charter.  
8.2.2.1. 
Staggered vaccination  
Participants will always be vaccinated sequentially. At Visit 1 (Day 1), sentinel 
participants should receive the first vaccination each 1 day apart and non-sentinel 
participants should receive it at least 60 minutes apart. At Visit 4 (Day 169), all 
participants, should receive the second vaccination at least 60 minutes apart. All 
participants will be closely observed for at least 60 minutes after vaccination. 
The Investigator is not permitted to begin dosing study participants in Step 1b or Step 2 
until the receipt of favourable written documentation of safety evaluations (iSRC/SRT). 
Screening procedures may continue, to facilitate the enrolment of remaining participants. 
Step 1a: 
A “Step 1a low dose without Alum” subgroup comprises 2 study groups (2:1 
randomisation [Step 1a low dose without Alum: Step 1a control]) will receive either 2 
vaccinations with the candidate low dose Vi-CRM197+O:2-CRM197 vaccine without Alum 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
49 
or 1 vaccination with the TYPHIM VI vaccine (as control for the first vaccination) and 1 
vaccination with the 
vaccine (as control for the second vaccination).  
First, 6 sentinel participants will receive, on consecutive days, either the low dose of the 
Vi-CRM197+O:2-CRM197 or the TYPHIM VI vaccine (2:1 randomisation). Each sentinel 
participant will be followed up with a safety phone call approximately 1 day after 
vaccination. If there are any safety concerns, the sentinel participant will be asked to visit 
the site to assess any potential SAEs or to assess if any holding rules have been met. If no 
holding rules have been met nor SAEs reported by any of the sentinel participants, 12 
additional participants will receive sequentially (at least 60 minutes apart) either the low 
dose of the Vi-CRM197+O:2-CRM197 or the TYPHIM VI vaccine, maintaining the 2:1 
randomisation.  
All available safety data (including laboratory test results) collected until 7 days after first 
vaccination in Step 1a will be reviewed blindly by the iSRC Chair together with the SRT 
(Safety evaluation #1; refer to Table 10). The iSRC Chair and SRT will decide whether 
an unblinded review by the full iSRC is needed, before initiating the first vaccination in 
Step 1b (administration of the low dose of the candidate vaccine with Alum or control 
vaccine to sentinel participants). A positive outcome will also allow the 18 participants in 
Step 1a to receive further vaccinations as per the SoA.  
All available safety data (including laboratory test results) collected until 7 days after 
second vaccination in Step 1a will be reviewed blindly by the iSRC Chair together with 
the SRT (Safety evaluation #4; refer to Table 10). The iSRC Chair and SRT will decide 
whether an unblinded review by the full iSRC is needed, before initiating the second 
vaccination in Step 1b (administration of the low dose of the candidate vaccine with 
Alum or control vaccine to sentinel participants).  
Step 1b 
A “Step 1b low dose with Alum” subgroup comprises 2 study groups (2:1 randomisation 
[Step 1b low dose with Alum: Step 1b control]) will receive either 2 vaccinations with 
the low dose Vi-CRM197+O:2-CRM197 vaccine with Alum or 1 vaccination with the 
TYPHIM VI vaccine (as control for the first vaccination) and 1 vaccination with the 
 vaccine (as control for the second vaccination).  
Upon approval from the iSRC/SRT (Safety evaluation #1), 6 sentinel participants will 
receive on consecutive days the first vaccination with either the low dose Vi-
CRM197+O:2-CRM197 vaccine with Alum or the TYPHIM VI vaccine (2:1 
randomisation). Each sentinel participant will be followed up with a safety phone call 
approximately 1 day after vaccination. If there are any safety concerns, the sentinel 
participant will be asked to visit the site to assess any potential SAEs or if any holding 
rules have been met. If no holding rules have been met nor SAEs reported by any of the 
sentinel participants, a further 12 participants will receive sequentially (at least 60 
minutes apart) either the low dose Vi-CRM197+O:2-CRM197 vaccine with Alum or the 
TYPHIM VI vaccine and 
 vaccine, maintaining the 2:1 randomisation ratio. 
All available safety data (including laboratory test results) collected until 7 days after first 
vaccination in Step 1b will be reviewed blindly by the iSRC Chair together with the SRT 
CCI
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
50 
(Safety evaluation #2; refer to Table 10). The iSRC Chair and SRT will decide whether 
unblinded data review by the full iSRC is needed, before initiating the first vaccination in 
Step 2 (administration of the full dose of the candidate vaccine with Alum, full dose of 
the candidate vaccine without Alum, or control vaccines to sentinel participants).  
Step 2: 
A “full dose with and without Alum” subgroup comprises 3 study groups (2:2:1 
randomisation [Step 2 full dose without Alum: Step 2 full dose with Alum: Step 2 
control]) will receive either 2 vaccinations with the full dose Vi-CRM197+O:2-CRM197 
vaccine without Alum or the full dose Vi-CRM197+O:2-CRM197 vaccine with Alum or 1 
vaccination with the TYPHIM VI vaccine (as control for the first vaccination) and 1 
vaccination with the 
 vaccine (as control for the second vaccination).  
Upon approval from the iSRC/SRT (Safety evaluation #2), 5 sentinel participants will 
receive on consecutive days the first vaccination with either the full dose Vi-
CRM197+O:2-CRM197 vaccine without Alum, the full dose Vi-CRM197+O:2-CRM197 
vaccine with Alum, or the TYPHIM VI vaccine (2:2:1 randomisation). Each sentinel 
participant will be followed up with a safety phone call approximately 1 day after 
vaccination. If there are any safety concerns, the sentinel participant will be asked to visit 
the site to assess any potential SAEs or if any holding rules have been met. If no holding 
rules have been met nor SAEs reported by any of the sentinel participants, a further 55 
participants will receive sequentially (at least 60 minutes apart) either the full dose Vi-
CRM197+O:2-CRM197 vaccine without Alum, the full dose Vi-CRM197+O:2-CRM197 
vaccine with Alum, or the TYPHIM VI vaccine, maintaining the 2:2:1 randomisation 
ratio. 
All available safety data (including laboratory test results) collected until 28 days after 
first vaccination in Step 2 will be reviewed in an unblinded manner by the iSRC (Safety 
evaluation #3). The iSRC will recommend whether to proceed with second vaccination in 
Step 2 and allow the participants in Step 2 to complete the study as per the SoA. 
Table 10 
Safety evaluation schedule  
Safety 
evaluation 
Safety data reviewed 
Approval to proceed to 
#1: Blinded*  
Up to 7 days after 1st vaccination in Step 1a 
Administration of 1st study intervention to sentinel 
participants in Step 1b and subsequent 
administrations to participants in Step 1a 
#2: Blinded* 
Up to 7 days after 1st vaccination in Step 1b 
Administration of 1st study intervention to sentinel 
participants in Step 2 
#3: Unblinded 
Up to 28 days after 1st vaccination in Step 2  Administration of 2nd vaccination in Step 2 
#4: Blinded* 
Up to 7 days after 2nd vaccination in Step 1a 
Administration of 2nd vaccination in Step 1b 
*During blinded safety evaluations, if there are any concerns that would require the evaluation of unblinded safety data, 
an iSRC evaluation will occur that will decide on the succeeding administration of the vaccine or to begin the next Step 
of the study. 
Notes: All available safety data will be cumulatively reviewed at each safety evaluation (e.g., safety data after the first 
vaccination will be reviewed before the administration of the second vaccination). In case the safety evaluations #3 and 
#4 could become scheduled to occur close together, they may be combined in a single unblinded iSRC evaluation. 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
51 
8.2.2.2. 
Outcome of safety evaluation 
• 
If no safety concern is observed during the blinded or unblinded data review, the 
favourable outcome of the safety evaluations will be documented and provided in 
writing, authorising the Investigator to start vaccination of participants with the 
subsequent dose as well as enrolment and vaccination of the remaining participants 
of the next step of the study. 
• 
In case the Investigator becomes aware of one or more holding rules (refer to Section 
8.2.2.3), he/she should immediately inform IQVIA of the event (refer to the IQVIA 
study contact list for contact information). 
• 
If a safety issue is observed during the unblinded data review or if any of the holding 
rules (e.g. 2a or 2b; Refer to Table 11) is met, the iSRC Chair (or his/her 
representative) is responsible for the urgent communication to the GVGH PP, 
including any rationale for a decision to put the vaccination on hold or not. The 
GVGH PP will be accountable for notifying all investigators (through IQVIA) of the 
decision whether to suspend, modify, or continue the conduct of the study on all 
groups or on selected groups.  
• 
If a safety issue is observed during the blinded data review or a holding rule 
threshold is met (not known in which study group events occurred), an ad hoc iSRC 
safety evaluation meeting will be called.  
8.2.2.3. 
Study holding rules 
Table 11 shows the holding rules to be implemented for this study. These holding rules 
have been written under the assumption that the safety data from all participants will be 
available. If the data from all participants are not available (e.g., in case a participant is 
lost to follow-up), then the holding rules will be assessed on a pro-rata basis.  
Holding rules 1a-d in all steps of the study and holding rule 2c in Step 1a and 1b will be 
monitored by the Investigator on a continuous basis (threshold ≥1, refer to Table 11). 
Meeting any of these holding rules will trigger a hold of study intervention administration 
irrespective of number of participants enrolled and/or timing of the event.  
For holding rules 2a-b in all steps of the study and holding rule 2c in Step 2, the 
Investigator will inform IQVIA immediately if a threshold is suspected to be met, without 
pausing administration of the study intervention (threshold ≥2-6, refer to Table 11). 
IQVIA will provide a report to the GVGH PP who will then confirm if the threshold has 
been met and advise whether to pause the study intervention administration. 
If the Investigator becomes aware that a holding rule threshold has been met (either 
directly or via IQVIA), the following communication sequence must be followed: 
• 
The concerned site staff must put study intervention administration on hold. 
• 
The concerned site staff must immediately inform IQVIA CRA and Medical Monitor 
(contact details will be provided in a separate document) via email and phone 
communication who will in-turn inform the GVGH Study Responsible Project 
Physician. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
52 
• 
All informed site staff will confirm to their local contact that action has been taken 
providing appropriate documentation to GVGH through the IQVIA CRA and 
Medical Monitor. 
• 
GSK will further evaluate the case with the iSRC and GSK Global Safety Board and 
will take the decision to stop or to restart the study intervention administration. 
GVGH Project Physician will inform the IQVIA project lead of the decision and the 
rationale for the decision and all site staff will be informed by IQVIA project lead. 
Table 11 
Study holding rules 
Holding 
rule 
Event 
Number of participants needed to 
pause vaccination in the study and 
trigger further evaluation by the iSRC 
Step 1a 
Step 1b 
Step 2 
1a 
Death or any life-threatening SAE regardless of causality  
≥1 
≥1 
≥1 
1b 
Any non-life-threatening SAE that cannot be reasonably 
attributed to a cause other than vaccination as per 
Investigator or Sponsor assessment 
≥1 
≥1 
≥1 
1c 
Any withdrawal from the study (by Investigator or 
participant request) following a Grade 3 AE 
≥1 
≥1 
≥1 
1d 
Any solicited administration-site event or solicited 
systemic event leading to hospitalisation, 
OR 
Necrosis at the injection site, 
Each with an event onset within the 7-day post-
vaccination period 
≥1 
≥1 
≥1 
2a 
Any Grade 3 solicited administration-site events (lasting 
48h or more as Grade 3), with an event onset within each 
7-day post-vaccination period 
≥3 
≥3 
≥6 
2b 
Any Grade 3 solicited systemic events (lasting 48h or 
more as Grade 3), with an event onset within each 7-day 
post-vaccination period 
≥2 
≥2 
≥3 
2c 
Any Grade 3 unsolicited AE, which can be reasonably 
attributed to the vaccination as per Investigator or 
Sponsor assessment, with an event onset within each 7-
day post-vaccination period  
OR 
Any Grade 3 or above abnormality* in pre-specified 
haematological or biochemical laboratory parameters 
collected at 7 days post-vaccination period 
≥1** 
≥1** 
≥2 
AE=adverse event, SAE=serious adverse event 
*Refer to Section 10.9 for the grading scales to the pre-specified laboratory parameters 
**The Investigator should inform IQVIA CRA and Medical Monitor immediately if an event occurs and should follow 
instruction as applicable to holding rules 1a-1d. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
53 
8.3. 
AEs, SAEs, and other safety reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE, and other 
safety information 
Table 12 
Timeframes for collecting and reporting of safety information 
 
SCR* 
D-21 to D-1 
 
VAC 1 
 
 
 
 
VAC 2 
 
 
SFU 
 
D1 
D8 
D29 
 
D169 
D176 D197 D337 
Administration-site and 
systemic solicited events 
 
 
 
 
 
 
 
 
 
 
 
 
 
D1 to D7 
 
 
 
 
D169 to 
D175 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
D1 to D28 
 
 
 
D169 to D196 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the 
study 
 
 
 
 
 
 
 
 
 
 
 
 
 
D1 to D337 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
D1 to D337 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to the 
study intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
D1 to D337 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/ vaccine*** 
 
 
 
 
 
 
 
 
 
 
 
D-21 to D337 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
D1 to D197 
 
 
 
 
 
 
 
 
 
 
 
 
Any other event of 
interest for the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
D1 to D197 
 
 
 
 
 
 
 
 
 
 
 
 
*Consent obtained 
**Unsolicited AEs/SAEs due to COVID-19 will be recorded according to the WHO case definition [WHO, 2022]. 
*** Any SAEs assessed as related to study participation (e.g., protocol-mandated procedures, invasive tests, or change 
in existing therapy) or related to a GSK product will be recorded from the time a participant consents to participate in 
the study.  
D=Day; SFU=safety follow-up; SCR=Screening; VAC=Vaccination 
The Investigator or designee will record and immediately report all SAEs in enrolled 
participants to the Sponsor or designee via the Expedited AE Reporting Form. Reporting 
should, under no circumstances, occur later than 24 hours after the Investigator becomes 
aware of an SAE, as indicated in Section 10.3.10. The Investigator will submit any 
updated SAE data to the Sponsor or designee within 24 hours of it being available. SAEs 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
54 
related to study participation or to a concurrent GSK medication/vaccine will be collected 
from the time consent is obtained until the participant is discharged from the study.  
During the extended safety follow-up period (Day 197 to Day 337), participants will be 
encouraged to inform the Investigator in a timely manner if they have any event meeting 
the description of an SAE. Any SAE reported during this period will qualify for 
expedited reporting according to Section 10.3.10. Any SAEs discovered retrospectively 
during the safety phone call on Day 337 will also be reported accordingly. 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting periods defined in Table 12. Investigators are not obligated to actively seek AEs 
or SAEs from former study participants. However, if the Investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
he/she considers the event to be reasonably related to the study intervention, the 
Investigator will promptly notify the study contact for reporting SAEs mentioned in the 
IQVIA study contact list. 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies, and other 
events 
Detection and recording of AE/SAE/pregnancies are detailed in Section 10.3.8.  
Assessment of AE/SAE intensity, causality and outcome are described in Section 10.3.9.  
Open-ended and non-leading verbal questioning of participants is the preferred method of 
acquiring information related to an AE/SAE/pregnancy. 
8.3.2.1. 
Clinically significant abnormal laboratory findings 
The Investigator must review the laboratory report, document that he/she did so, and 
record any clinically relevant changes occurring during the study in the AE section of the 
eCRF. Clinically significant abnormal laboratory findings are those which are not 
associated with an underlying disease, unless judged by the Investigator to be more 
severe than expected for the participant’s condition. 
• 
All laboratory tests with clinically significant abnormal values reported during the 
study should be repeated until the values return to normal/baseline, or until they are 
no longer considered significantly abnormal by the Investigator. Refer to Section 
10.3.6 for more information on clinically abnormal laboratory assessments that 
qualify as an AE or SAE. 
• 
In case abnormal values are not considered clinically significant by the Investigator, 
additional evaluations could be requested by the GVGH PP. 
• 
If abnormal values do not return to normal/baseline after an interval judged 
reasonable by the Investigator, the aetiology of the abnormal value should be 
identified, and the Sponsor notified. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
55 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies, and 
other events 
Once the Investigator or designee becomes aware that a study participant has experienced 
an SAE, they or designated study staff must report it to the Sponsor’s delegate 
immediately, no later than 24 hours of obtaining knowledge, using an electronic 
Expedited AE Report in the eCRF. The Investigator will provide an assessment of 
causality at the time of the initial report, as defined in the Section 10.3.9.2. New or 
updated information will be recorded on the originally completed form with all changes 
signed and dated by the Investigator and reported to IQVIA within 24 hours. This is 
essential for meeting GSK legal obligations and ethical responsibilities for the 
participant’s safety and the safety of a study intervention under clinical investigation.  
For COVID-19-related SAEs, reports should be submitted following routine procedures 
for SAEs. Local regulatory requirements and GSK’s policy for the preparation of an 
Investigator safety report for SUSARs must be followed. These reports will be forwarded 
to investigators, as necessary.  
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. 
GSK and IQVIA will comply with country-specific requirements related to safety 
reporting to the regulatory authority, IRB, and investigators.  
Refer to the IQVIA study contact list for the Medical Monitor’s name and contact 
information. 
Table 13 
Timeframes for submitting SAE and pregnancy reports 
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  
24 hours* 
electronic pregnancy report 
24 hours* 
electronic pregnancy report 
* Timeframe allowed after receipt or awareness of the information by the Investigator/site staff. 
‡ For each SAE, the Investigator(s) must document in the medical notes that they have reviewed the SAE and have 
provided an assessment of causality. 
8.3.4. 
Treatment of expedited AEs 
Any medication administered for the treatment of an SAE should be recorded in the 
Expedited Adverse Event Report of the participant’s eCRF screen (refer to the Section 
10.3.10.1).  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
56 
8.3.5. 
Participant card 
The Investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in his/her/their possession for the duration of the study. 
In an emergency, this card serves to inform the responsible attending physician that the 
participant is in a clinical study and that relevant information may be obtained by 
contacting the Investigator or his/her back up. 
8.3.6. 
Medical device deficiencies 
The comparator vaccines used in this study are combination products constituted of a 
biologic product in a medical device (pre-filled syringes). Refer to the Glossary of terms 
for the definition of combination product and medical device deficiency.  
8.3.6.1. 
Detection, follow-up, and prompt reporting of medical device 
deficiency 
The Investigator is responsible for the detection, documentation and prompt reporting of 
any medical device deficiency occurring during the study to GSK. This applies to any 
medical device provided for the conduct of the study.  
Device deficiencies will be reported to GSK within 24 hours after the Investigator 
determines that the event meets the protocol definition of a device deficiency. Refer to 
Section 10.6 for definitions and details on recording and reporting of these events.  
The Investigator will ensure that follow-up includes any additional investigations to 
elucidate the nature and/or related of the device deficiency to the incident. Follow-up 
applies to all participants, including those who discontinue study intervention or the 
study. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the Investigator and reported to GSK within 24 hours. 
Medical device deficiencies and any associated AE/SAE for Associated Person (i.e., 
spouse, caregiver, site staff) will also be collected. The Associated Person will be 
provided with a safety reporting information and authorisation letter. 
Follow-up applies to all participants, including those who discontinue study intervention 
or the study, and associated persons. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
57 
8.3.6.2. 
Regulatory reporting of medical device deficiency when used as 
combination product  
The Investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study to GSK. GSK has a legal responsibility to notify 
appropriate regulatory authorities and other entities about safety information linked to 
medical devices being used in clinical studies. Refer to section 10.6.3 for details of 
reporting. 
The Investigator, or responsible person according to local requirements (e.g., the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/IEC. 
8.4. 
Pharmacokinetics 
Not applicable 
8.5. 
Genetics and/or Pharmacogenomics  
Not applicable 
8.6. 
Biomarkers 
Not applicable 
8.7. 
Immunogenicity 
Not applicable 
8.8. 
Health outcomes 
Not applicable 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
No specific statistical hypotheses will be tested in this study. All analyses of safety and 
immunogenicity will be descriptive. Results of this study will inform the planning of 
subsequent studies and selection of candidate vaccine formulation. 
9.2. 
Sample size determination 
Approximately 96 participants will be randomised to achieve 82 evaluable participants. 
Participants who withdraw from the study will not be replaced.  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
58 
Since no confirmatory objectives are being evaluated in this study, the sample size 
selected for this study is not driven by statistical considerations. The sample size has been 
determined to allow an adequate assessment of the investigational doses and an 
evaluation of the holding rules as detailed in Section 8.2.2.3. 
9.2.1. 
Statistical consideration for safety assessment 
Table 14 shows the probability to observe at least one AE for different sample sizes and 
AE rate. In Steps 1a and 1b, a sample size of 12 participants receiving the investigational 
vaccine would provide a probability of at least 80% to observe at least one AE, if the true 
AE rate is equal to or greater than 15%. In Step 2, a sample size of 24 participants 
receiving the investigational vaccine would provide a probability of at least 80% to 
observe at least one AE, if the true AE rate is equal to or greater than 7.5%. 
Table 14 
Probability to observe at least 1 AE according to sample size and AE 
rate 
Number of participants receiving 
investigational vaccine 
True AE rate 
Probability to observe at least one AE 
12 
1.0% 
11.4% 
2.5% 
26.2% 
5.0% 
46.0% 
7.5% 
60.8% 
10.0% 
71.8% 
12.5% 
79.9% 
15.0% 
85.8% 
17.5% 
90.1% 
20.0% 
93.1% 
24 
1.0% 
21.4% 
2.5% 
45.5% 
5.0% 
70.8% 
7.5% 
84.6% 
10.0% 
92.0% 
12.5% 
95.9% 
15.0% 
98.0% 
17.5% 
99.0% 
20.0% 
99.5% 
Probability to observe at least one AE was estimated with the PROBBNML function from SAS 9.4 
9.2.2. 
Statistical considerations on immunogenicity assessment 
The percentage of participants with 4-fold increases among the O:2 component has been 
defined as a measure of a seroresponse. Results on both full dose groups (adjuvanted and 
not adjuvanted) will be used to make decisions for the planning of subsequent studies and 
the clinical development programme. Assuming a 12% participant dropout rate in 24 
participants from each of full dose group, 21 participants will be considered evaluable. 
Table 15 shows the precision in terms of 95% confidence interval on the 4-fold increase 
in these participants. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
59 
Table 15 
95% confidence intervals for seroresponse in participants receiving 
the full dose of the vaccine 
Number of participants with 4-fold increases 
in anti-O:2 IgG 
Percentage of participants with 4-
fold increases 
95% confidence 
interval 
10 
47.6% 
25.7% - 70.2% 
11 
52.4% 
29.8% - 74.3% 
12 
57.1% 
34% - 78.2% 
13 
61.9% 
38.4% - 81.9% 
14 
66.7% 
43% - 85.4% 
15 
71.4% 
47.8% - 88.7% 
16 
76.2% 
52.8% - 91.8% 
17 
81.0% 
58.1% - 94.6% 
18 
85.7% 
63.7% - 97% 
Estimated with PASS 2019, v19.0.1 Two-Sided Confidence Intervals for One Proportion with Exact Formula (Clopper-
Pearson)  
9.3. 
Analysis sets 
The first-line analysis population set for immunogenicity analysis will be the Per-
Protocol Set (PPS). If, in any study group at any timepoint, the percentage of vaccinated 
participants with serological results excluded from the PPS for analysis of 
immunogenicity is 10% or more of the Full Analysis Set (FAS), a second-line analysis 
based on the FAS for immunogenicity will be performed to complement the PPS 
analysis. 
For the purposes of this study, the following analysis sets will be defined: 
Table 16 
Analysis sets 
Analysis set 
Description 
Enrolled  
All participants who entered the study (who were randomised, or received study 
intervention, or underwent a post-Screening study procedure).  
Note: participants who never passed Screening even if rescreened (Screening failures) and 
participants screened but never enrolled into the study (met eligibility but not needed for the 
study) are excluded from the Enrolled analysis set.  
Exposed  
All participants who received at least 1 dose of the study intervention. The allocation in a 
group is based on the administered intervention. 
Full Analysis  
All participants who received at least 1 dose of the study intervention and have post-
vaccination immunogenicity data. The allocation in a group is done in function of the 
randomised intervention. The Full Analysis Set (FAS) for immunogenicity will be defined by 
time point. 
Per-Protocol  
All eligible participants who received each dose as per-protocol, had immunogenicity results 
post-dose, complied with dosing/blood draw intervals, without intercurrent conditions that 
may interfere with immunogenicity and without prohibited concomitant 
medication/vaccination. The Per-Protocol Set (PPS) for immunogenicity will be defined by 
time point. 
Unsolicited Safety  
All participants who received at least 1 dose of the study intervention (Exposed Set) that 
report unsolicited AEs/report not having unsolicited AEs. The allocation in a group is based 
on the administered intervention. 
Solicited Safety  
All participants who received at least 1 dose of the study intervention (Exposed Set) who 
have solicited safety data. The allocation in a group is based on the administered 
intervention. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
60 
9.3.1. 
Criteria for elimination from analysis 
If the participant meets one of the criteria mentioned below or ones listed in the Section 
7.1.1, he/she may be eliminated from per-protocol analysis. 
• 
Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine(s) used during the study period. 
• 
Use of immunosuppressants or other immune-modifying drugs administered 
chronically (i.e., more than 14 days in total) during the study period. For 
corticosteroids, this will mean prednisone 20 mg/day (for adult participants), or 
equivalent. Inhaled and topical steroids are allowed. 
• 
Use of any long-acting immune-modifying drugs (e.g., infliximab) administered at 
any time during the study period. 
• 
Use of any immunoglobulins and/or any blood products administered during the 
study period. 
• 
Use of any vaccine not foreseen by the Study Protocol administered during the entire 
period of participant’s study participation. 
• 
Use of foreseen vaccines outside the recommended time window. 
• 
Unblinding after any study intervention has been administered. 
Other criteria for elimination from analyses will be reported in the Statistical Analysis 
Plan (SAP) and in the Protocol Deviation Management Plan. 
9.3.1.1. 
Intercurrent medical conditions 
The following intercurrent medical conditions must be recorded in the eCRF and may 
lead to elimination from the per-protocol analysis: 
• 
Occurrence of a condition that has the capability of altering their immune response 
(i.e., varicella, COVID-19) or are confirmed to have an alteration of their initial 
immune status 
• 
Occurrence of a serious chronic or progressive disease according to judgement of the 
Investigator (e.g., neoplasm, insulin-dependent diabetes, cardiac, renal, or hepatic 
disease) 
• 
Occurrence of any malignancy or lymphoproliferative disorder 
• 
Occurrence of any confirmed or suspected immunosuppressive or immunodeficient 
condition, based on physical examination 
• 
Any drug and/or alcohol abuse 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
61 
9.4. 
Statistical analyses 
9.4.1. 
Primary endpoint(s) (Amended, 21 August 2023) 
Endpoint description 
Analysis set 
Statistical analysis methods 
• 
Percentage of participants with 
solicited administration-site events 
during 7 days after each 
vaccination, on the days of 
vaccination and the 6 subsequent 
days (study intervention 
administered on Day 1 and Day 
169), per study group 
Solicited Safety 
Set 
• 
Number and percentages of participants 
with at least one, any, and Grade 3 
administration-site solicited AEs 
• 
Percentage of participants with 
solicited systemic events during 7 
days after each vaccination, on the 
days of vaccination and the 6 
subsequent days (study 
intervention administered on Day 1 
and Day 169), per study group 
Solicited Safety 
Set 
• 
Number and percentages of participants 
with at least one, any, and Grade 3 
systemic solicited AEs 
• 
Percentage of participants with 
unsolicited AEs during 28 days 
after each vaccination, on the days 
of vaccination and 27 subsequent 
days (study intervention 
administered on Day 1 and Day 
169), per study group 
Unsolicited Safety 
Set 
• 
Number and percentages of participants 
with unsolicited AEs 
• 
Percentage of participants with any 
SAEs from first vaccination until 28 
days after second study 
intervention administration (Day 1 
to Day 197), per study group 
Exposed Set 
• 
Number and percentages of participants 
with SAEs 
• 
Percentage of participants with 
AEs leading to withdrawal from the 
study or withholding further study 
intervention administration, from 
first study intervention 
administration until 28 days after 
second study intervention 
administration (Day 1 to Day 197), 
per study group 
Exposed Set 
• 
Number and percentage of participants with 
AEs/SAEs leading to withdrawal from the 
study or withholding further study 
intervention administration 
• 
Percentage of participants with 
deviations from normal or 
baseline † values of 
haematological, renal, and hepatic 
panel test results at 7 days after 
each vaccination Day 8 and Day 
176 per study group* 
Exposed Set  
• 
Number and percentages of participants 
having haematological, renal, and hepatic 
abnormalities  
†Baseline for post-first vaccination at Day 8 is Day 1 (can also be screening blood draw, if performed within 3 
days of first vaccination), and baseline for post-second vaccination at Day 176 is Day 169. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
62 
9.4.2. 
Secondary endpoint(s) 
Endpoint description 
Analysis set 
Statistical analysis methods 
• 
Percentage of participants with any 
SAE from 28 days after second 
vaccination (Day 197) up to Day 
337, per study group 
Exposed Set 
• 
Number and percentages of participants 
with SAEs 
• 
Percentage of participants with 
AEs/SAEs leading to withdrawal 
from the study from 28 days after 
second vaccination (Day 197) up to 
Day 337, per study group 
Exposed Set 
• 
Number and percentage of participants with 
AEs/SAEs leading to withdrawal from the 
study 
• 
Anti-Vi antigen IgG antibody 
concentrations as measured by 
ELISA, at selected timepoints, per 
study group 
• 
Anti-O:2 IgG antibody 
concentrations, as measured by 
ELISA, at selected timepoints, per 
study group 
PPS, FAS (only if 
number of 
participants 
differs more than 
10%) 
• 
Geometric Mean Concentrations (with 95% 
CI) at Day 1, Day 29, Day 169, Day 176, 
and Day 197 
• 
Within-subject geometric mean ratios (with 
95% CI) at Day 29, Day 169, Day 176, and 
Day 197 versus Day 1 baseline, and at Day 
176 and Day 197 versus Day 169 baseline 
• 
Anti-Vi antigen IgG antibody 
concentrations ≥ 4.3 µg/mL, as 
measured by ELISA, per study 
group 
• 
 Anti-Vi antigen IgG antibody 
concentrations ≥ 2.0 µg/mL, as 
measured by ELISA, per study 
group 
• 
Within-subject increase of at least 
4-fold in Anti-O:2 IgG antibody 
concentrations, as measured by 
ELISA, per study group 
PPS, FAS (only if 
number of 
participants 
differs more than 
10%) 
• 
Number and percentage (with 95% CI) of 
participants with Anti-Vi antigen IgG 
antibody concentrations ≥ 4.3 µg/mL at Day 
1, Day 29, Day 169, Day 176, and Day 197 
• 
Number and percentage (with 95% CI) of 
participants with Anti-Vi antigen IgG 
antibody concentrations ≥ 2.0 µg/mL at Day 
1, Day 29, Day 169, Day 176, and Day 197 
• 
Number and percentage (with 95% CI) of 
participants with at least 4 fold Anti-O:2 IgG 
antibody concentrations at, Day 29, Day 
169, Day 176, and Day 197 compared to 
Day 1 baseline 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
63 
9.5. 
Interim analyses  
To accelerate evaluation of vaccine immunogenicity in the target population and facilitate 
planning of future studies, interim and final analyses will be performed as described in 
Section 9.5.1.  
9.5.1. 
Sequence of analyses 
A first interim analysis on safety and immunogenicity will be performed by a Sponsor’s 
delegate unblinded statistician on data collected from all participants until 28 days after 
the first vaccination in Step 2 (Visit 3, Day 29). An interim CSR will be produced but no 
individual listings will be generated. Results will not impact the continuation of the study 
itself but will inform further development of the candidate vaccine in other studies. Since 
some treatment groups of specific participants may be revealed during the interim 
analysis, the study will be considered single-blind from this point and onwards with the 
Investigator, site staff and participants remaining blinded up to EoS. 
A second interim analysis on safety and immunogenicity may be performed by a 
Sponsor’s delegate unblinded statistician on data collected from all participants until 28 
days after the second vaccination in Step 2 (Visit 6, Day 197). No individual listings will 
be generated. 
The final analysis will include all data for at least primary and secondary endpoints up to 
and including follow-up safety phone contact (Day 337). 
 
 A final CSR containing all available data will be written 
and made available to the investigators. 
9.5.2. 
Statistical consideration for interim analysis 
No statistical adjustment will be performed since analyses are descriptive without any 
confirmatory objectives. 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight 
considerations  
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences International Ethical Guidelines 
− 
Applicable International Council of Harmonisation (ICH) GCP Guidelines 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
64 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the Investigator for review and 
approval. These documents will be signed and dated by the Investigator before the 
study is initiated.  
• 
Any protocol amendments will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants.  
• 
GSK/IQVIA will provide full details of the above procedures to the Investigator, 
either verbally, in writing, or both. 
• 
The Investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators must provide the Sponsor with sufficient, accurate 
financial information, as requested, to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
The Investigator or his/her representative must fully explain the nature of the study to the 
participant and answer all questions regarding the study.  
Participants must be informed that their participation is voluntary.  
Freely given and written informed consent must be obtained from each participant, as 
appropriate, prior to participation in the study.  
The content of the ICF must meet the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act requirements, where 
applicable, and the IRB/IEC or study centre. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
65 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the consent was obtained. 
The authorised person obtaining the informed consent must also sign the ICF.  
Participants must be re-consented if a new version of the ICF(s) or an ICF addendum is 
released during their participation in the study.  
A copy of the signed and dated ICF(s) must be provided to the participants.  
Participants who are rescreened are required to sign a new ICF, only if there are changes 
to the original ICF. If there are no changes to the original ICF, participants should 
confirm that they still agree to be part of the study. This information should be captured 
in the participant source document. 
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the Sponsor or Sponsor’s delegate. 
Any participant records or datasets transferred to the Sponsor or Sponsor’s delegate will 
contain only the identifier. Name and any other information which would identify the 
participant will not be transferred.  
The participants must be informed that: 
• 
His/her personal study-related data will be used by the Sponsor in accordance with 
local data protection law.  
• 
His/her medical records may be examined by Clinical Quality Assurance auditors or 
other authorised personnel appointed by the Sponsor, by appropriate IRB/IEC 
members, and by inspectors from regulatory authorities. 
• 
Sponsor or Sponsor’s delegate will ensure protection of the personal data of the 
Investigator and site staff which is collected within the framework of and for the 
purpose of the study, in accordance with the Data Privacy Notice that will be sent to 
the site staff.  
The participants must be notified about their rights regarding the use of their personal 
data in accordance with the data privacy section of the ICF. 
10.1.5. 
Committee structure 
The iSRC will consist of study-independent GSK clinician, safety representative, 
statistician and at least 1 external (non-GSK employee) member with expertise in clinical 
trials. All members’ roles and responsibilities will be defined in the iSRC Charter. 
The SRT is a cross-functional internal GSK committee responsible for ongoing safety 
assessment of the entire project. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
66 
10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries prior to 
study start and target results summaries submission within 12 months of primary/study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines.  
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical trial registers. 
Where required by applicable regulatory requirements, an Investigator signatory will be 
identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the Investigator 
with the full summary of the study results. The Investigator is encouraged to share the 
summary results with the study participants, as appropriate. 
Sponsor or Sponsor’s delegate will provide the Investigator with the randomisation codes 
for their site only after completion of the full statistical analysis. 
GSK intends to make anonymised patient-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by trial 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.7. 
Data quality assurance 
The Sponsor must keep coded data from clinical studies for a minimum of 30 years after 
the end of the study to ensure the validity of the research. This will also be the case if a 
participant stopped study participation prematurely. The Sponsor will also keep coded 
data, where needed because of legal action or an investigation involving the Sponsor. 
The Investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents (see Glossary of terms for the exact definition of 
essential and source documents). The document storage system used during the trial and 
for archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g., source documents, case report form), the copy should 
fulfil the requirements for certified copies (see Glossary of terms for the exact definition 
of certified copies).  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
67 
All participant data related to the study will be recorded on printed or eCRF unless 
transmitted to the GSK/IQVIA electronically (e.g., laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the eCRF. 
The Investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial participants (see Glossary 
of terms for the exact definition of source documents) that supports information entered 
in the eCRF.  
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies for such review and inspection.  
IQVIA is responsible for the data management of this study including quality checking of 
the source data (see Glossary of terms for the exact definition of source data).  
Study monitors will perform ongoing source data verification to confirm that data entered 
in the eCRF by authorised site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g., via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Quality tolerance limits (QTLs) will be predefined in the Risk Management Plan Study 
Risk Register (GVGH Study Risk-Based Quality Assessment Template) to identify 
systematic issues that can impact participant safety and/or the reliability of study results. 
These predefined parameters will be monitored during the study. Important deviations 
from the QTLs and remedial actions taken will be summarised in the clinical study report 
(CSR). 
Trial records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the Investigator for 25 years from issuance of the final 
CSR/equivalent summary unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the Sponsor. No records may be transferred to another location or 
party without written notification to the Sponsor.  
10.1.8. 
Source documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The Investigator should maintain a record of 
the location(s) of their source documents.  
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
68 
Definitions of what constitutes source data and documents can be found in the Glossary 
of terms. 
10.1.9. 
Study and site start and closure 
First act of recruitment 
The first act of recruitment, defined by either the date of first contact with a potential 
study participant or date of publication of an advertisement for this specific study 
(whichever is earlier), will signify the official start of the study. 
Study/Site termination 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at its sole discretion, provided there is sufficient notice given to 
account for all participants safe exit from study.  
Regular closure of study sites will occur upon study completion. A study site is 
considered closed when all required data/documents and study supplies have been 
collected and a study site closure visit has been performed.  
The Investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include 
but are not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the Investigator 
• 
Discontinuation of further study intervention development 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, GSK/IQVIA shall promptly inform 
the investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organisation(s) used in the study of the reason for termination or suspension, as specified 
by the applicable regulatory requirements. The Investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up. 
At the end of the study, the Investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the Study Conclusion screen in the eCRF. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
69 
10.1.10. 
Publication policy 
GSK aims to submit the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the Last Subject Last Visit (safety phone 
contact, Day 337) for interventional studies and follows the guidance from the 
International Committee of Medical Journal Editors. 
10.2. 
Appendix 2: Clinical laboratory tests (Amended, 21 August 
2023) 
Anti-Vi antigen IgG determination from serum 
Anti-Vi specific IgG antibodies will be measured by a qualified, fit for purpose 
(Amended 21 August 2023), anti-Vi IgG ELISA assay. The assay setup, qualification, 
and serology testing will be performed in a laboratory designated by GVGH. 
Anti-O antigen IgG determination from serum 
Anti-O:2 IgG antibodies in serum will be measured by an ELISA assay, which uses a 
standard curve with an assigned value of ELISA units/mL. This assay, developed by 
GVGH, is based on a method previously reported [Launay, 2017] and will be performed 
in a laboratory designated by GVGH. The ELISA is performed using S. Paratyphi A O 
antigen as coating antigen. For this assay, a standard curve is run in duplicate on each 
plate. Results are expressed in ELISA units (EU)/mL of serum. One unit equals the 
reciprocal of the dilution to give an optical density of 1.  
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
70 
10.2.1. 
Protocol-required safety laboratory assessments 
Table 17 shows the protocol-required safety assays, which will be performed by the local 
laboratory.  
Table 17 
Protocol-required safety laboratory assessments 
Laboratory assessments 
Parameters 
Safety Screening laboratory assays 
Haematology 
• 
Leukocytes (white blood cells [WBC]) 
• 
Erythrocytes (red blood cells [RBC]) 
• 
Haemoglobin 
• 
Haematocrit 
• 
Platelets 
• 
Eosinophils 
• 
Basophils 
• 
Neutrophils 
• 
Monocytes 
• 
Lymphocytes 
Clinical chemistry 
• 
Total bilirubin 
• 
Aspartic aminotransferase (AST) 
• 
Alanine aminotransferase (ALT) 
• 
γ-Glutamyl transferase (γ-GT) 
• 
Lactic dehydrogenase (LDH) 
• 
Alkaline phosphatase (AP) 
• 
Total proteins 
• 
Glucose (random glucose) 
• 
Blood urea (BU)* 
• 
Creatinine 
• 
Sodium 
• 
Potassium 
Other Screening tests 
• 
Hepatitis B surface antigen antibodies 
• 
Hepatitis C virus antibodies 
• 
HIV antibodies 
• 
Prothrombin time 
• 
Blood human chorionic gonadotropin (hCG) pregnancy test 
(for women of childbearing potential) 
Pre/Post-vaccination safety laboratory assays (Visit 1, Visit 2, Visit 4, and Visit 5) 
Haematology 
• 
Leukocytes (WBC) 
• 
Erythrocytes (RBC) 
• 
Haemoglobin 
• 
Haematocrit 
• 
Platelets 
• 
Eosinophils 
• 
Basophils 
• 
Neutrophils 
• 
Monocytes 
• 
Lymphocytes 
Clinical chemistry 
• 
Creatinine 
• 
AST 
• 
ALT 
• 
BU* 
Other tests 
• 
Urine hCG pregnancy test (as needed for women of 
childbearing potential; required at Visit 1 and Visit 4) 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
71 
*BU will be converted to blood urea nitrogen for grading purposes. Refer to Section 10.9. 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BU=blood urea; hCG=human chorionic 
gonadotropin; RBC=red blood cell; SAE=serious adverse event; ULN=upper limit of normal; WBC=white blood cell 
NOTES: 
All haematology assay outputs should be reported in absolute values. 
All events of ALT ≥3 × upper limit of normal (ULN) and bilirubin ≥2 × ULN (>35% direct bilirubin) or ALT ≥3 × ULN, 
which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE. 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of 
AE 
10.3.1. 
Definition of an AE  
An AE is any untoward medical occurrence (an unfavourable/unintended sign – including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical 
study participant that is temporally associated with the study intervention. The AE may or 
may not be considered related to the study intervention. 
10.3.1.1. 
Events Meeting the AE Definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease, or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 
• 
Signs, symptoms that require medical attention (e.g., hospital stays, physician 
visits and emergency room visits). 
• 
Significant failure of an expected pharmacologic or biological action. 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated 
procedures (i.e., invasive procedures, modification of participant’s previous 
therapeutic regimen). 
• 
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. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
72 
• 
AEs to be recorded as solicited AEs are described in the Section 10.3.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
10.3.1.2. 
Events NOT Meeting the AE Definition 
• 
Situations where an untoward medical occurrence did not occur (e.g., social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
• 
Pre-existing conditions or signs and/or symptoms present in a participant before 
the first dose of study intervention. These events will be recorded in the medical 
history section of the eCRF.  
• 
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the participant’s condition. 
10.3.2. 
Definition of an SAE 
An SAE is any untoward medical occurrence that: 
a. 
Results in death. 
b. Is life threatening 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the participant was at risk of death at the time of the event. It does not refer 
to an event, which hypothetically might have caused death, had it been more 
severe. 
c. 
Requires hospitalisation or prolongation of existing hospitalisation 
Note: In general, hospitalisation signifies that the participant 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. The 
event will also be considered serious if a complication prolongs hospitalisation or 
fulfils any other serious criteria. When in doubt as to whether ‘hospitalisation’ 
occurred or was necessary, the AE should be considered serious. 
d. Results in disability/incapacity  
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. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
73 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant 
f. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) 
g. Other situations 
Medical or scientific judgement must be exercised in deciding whether reporting is 
appropriate in other situations. Important medical events that may not be 
immediately life threatening or result in death or hospitalisation but may 
jeopardise the participant or require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition should 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; and 
convulsions that do not result in hospitalisation. 
10.3.3. 
Solicited events 
a. Solicited administration-site events 
The following administration-site events will be solicited: 
Table 18 
Solicited administration-site events 
All participants 
Pain at administration site 
Redness at administration site 
Swelling at administration site 
b. Solicited systemic events 
The following systemic events will be solicited: 
Table 19 
Solicited systemic events 
All participants 
Fever 
Headache 
Myalgia (muscle pain) 
Arthralgia (joint pain) 
Fatigue (tiredness) 
Note: participants will be instructed to measure and record the axillary temperature in the 
evening. If additional temperature measurements are taken at other times of the day, 
participants will be instructed to record the highest temperature in the diary card. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
74 
10.3.4. 
Unsolicited AEs 
An unsolicited adverse event is an adverse event that was either not included in the list of 
solicited events or could be included in the list of solicited events but with an onset 
outside the specified period of follow-up for solicited events. Unsolicited AEs must have 
been spontaneously communicated by a participant who has signed the informed consent. 
Unsolicited AEs include both serious and non-serious AEs. 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalisation, or an emergency room visit, or visit to/by a health care 
provider). The participants will be instructed to contact the site as soon as possible to 
report medically attended event(s), as well as any events that, though not medically 
attended, are of participant concern. Detailed information about reported unsolicited AEs 
will be collected by qualified site personnel and documented in the participant’s records. 
Unsolicited AEs that are not medically attended or perceived as a concern by the 
participant will be collected during an interview with the participants and by review of 
available medical records at the next visit. 
10.3.5. 
Adverse events of special interest 
Not applicable 
10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs  
In the absence of a diagnosis, abnormal laboratory findings assessments (e.g. clinical 
chemistry, haematology, or other tests) or other abnormal results the Investigator 
considers clinically significant will be recorded as an AE or SAE, if they meet the 
definition of an AE or SAE (refer to the Sections 10.3.1 and 10.3.2).  
The Investigator must exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 
All events of ALT ≥3 × upper limit of normal (ULN) and bilirubin ≥2 × ULN (>35% 
direct bilirubin) or ALT ≥3 × ULN, which may indicate severe liver injury (possible Hy’s 
Law), must be reported as an SAE. 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs  
10.3.7.1. 
Pregnancy 
Female participants who become pregnant after the first study intervention dose must not 
receive subsequent doses of the study intervention but may continue other study 
procedures at the discretion of the Investigator. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
75 
While pregnancy itself is not considered an AE or SAE, any abnormal pregnancy 
outcome or complication or elective termination of a pregnancy for medical reasons will 
be recorded and reported as an SAE. Please refer to the Section 10.3.2 for definition of 
SAE.  
10.3.8. 
Recording and follow-up of AEs, SAEs, and pregnancies 
The participants will be instructed to contact the Investigator immediately should they 
experience any signs or symptoms they perceive as serious.  
When an AE/SAE occurs, it is the Investigator’s responsibility to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) related 
to the event. This includes the assessment of COVID-19 cases as per the WHO definition 
[WHO, 2022]. The Investigator will then record all relevant information regarding an 
AE/SAE on the eCRF. The Investigator may not send photocopies of the participant’s 
medical records to GSK instead of appropriately completing the eCRF.  
There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers will be blinded on copies of the medical 
records prior to submission to GSK. 
The Investigator will attempt to establish a diagnosis pertaining to the event, based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE instead of individual signs/symptoms. 
A pDiary, hereafter referred to as Participant Diary, will be used in this study to capture 
solicited administration-site or systemic events. The participant should be trained on how 
and when to complete the Participant Diary. 
Anyone who measures administration-site or systemic events and who will record the 
event in the Participant Diary should be trained on using the Diary. This training must be 
documented in the participant’s source record. If any individual other than the participant 
is making entries in the Participant Diary, their identity must be documented in the 
Participant Diary/participant’s source record. 
The Investigator or delegate will transcribe the required information into the eCRF in 
English.  
10.3.8.1. 
Time period for collecting and recording AEs, SAEs, and pregnancies 
All AEs that occur during the 28 days following administration of each dose of study 
intervention (Day 1 to Day 28 and Day 169 to Day 196) must be recorded onto the 
appropriate section of the eCRF, irrespective of their intensity or whether they are 
considered related to the study intervention. 
All SAEs and pregnancies will be collected as specified in Table 12 and Section 10.3.10. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
76 
10.3.8.2. 
Follow-up of AEs, SAEs, pregnancies, or any other events of interest  
After the initial AE/SAE/pregnancy or any other event of interest, the Investigator is 
required to proactively follow each participant at subsequent visits/contacts. All SAEs 
will be followed up until the event is resolved, stabilised, otherwise explained, or the 
participant is lost to follow-up. 
Other non-serious AEs must be followed until resolution or until the participant is lost to 
follow-up. 
10.3.8.2.1. Follow-up during the study 
AEs documented at a previous visit/contact and defined as not recovered/not resolved or 
recovering/resolving will be reviewed at subsequent visits/contacts until 30 days after the 
last vaccination. 
If a participant dies during their participation in the study or during a recognised follow-
up period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.8.2.2. Follow-up after the participant is discharged from the study 
The Investigator will provide any new or updated relevant information to GSK on a 
previously reported SAE using an electronic Expedited Adverse Events Report and/or 
pregnancy report as applicable. The Investigator is obliged to perform or arrange for the 
conduct of supplemental clinical examinations/tests and/or evaluations to elucidate the 
nature and/or causality of the SAE as fully as possible. 
10.3.8.2.3. Follow-up of pregnancies 
Pregnant participants will be followed to determine the outcome of the pregnancy. At the 
end of the pregnancy, whether full-term or premature, information on the status of the 
mother and child will be forwarded to GSK using the electronic pregnancy report and the 
Expedited Adverse Events Report if applicable. Generally, the follow-up period does not 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, if the Investigator becomes aware of any SAE occurring as a result of a 
post-study pregnancy AND it is considered by the Investigator to be reasonably related to 
the study intervention, he/she must report this information to Sponsor or Sponsor’s 
delegate as described in the Section 10.3.10. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
77 
10.3.8.3. 
Updating of SAE and pregnancy information after removal of write 
access to the participant’s eCRF 
When additional SAE or pregnancy information is received after write access to the 
participant’s eCRF is removed, 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 
IQVIA study contact list) within the defined reporting time frames specified in the Table 
13. 
10.3.9. 
Assessment of intensity and toxicity 
10.3.9.1. 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 20 
Intensity scales for solicited events in adults 
Adult 
Event 
Intensity grade 
Parameter 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal everyday activities. 
 
2 
Moderate: Painful when limb is moved and interferes with 
everyday activities. 
 
3 
Severe: Significant pain at rest. Prevents normal 
everyday activities. 
Redness at administration site 
Greatest surface diameter in mm 
Swelling at administration site 
Greatest surface diameter in mm  
Temperature* 
Temperature in °C 
Headache 
0 
None 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue (tiredness) 
0 
Normal 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Myalgia (muscle pain) 
0 
None 
 
1 
Mild: Myalgia present but does not interfere with activity 
 
2 
Moderate: Myalgia that interferes with normal activity 
 
3 
Severe: Myalgia that prevents normal activity 
Arthralgia (joint pain) 
0 
None 
 
1 
Mild: Arthralgia present but does not interfere with 
activity 
 
2 
Moderate: Arthralgia that interferes with normal activity 
 
3 
Severe: Arthralgia that prevents normal activity 
*Refer to the SoA (Section 1.3) for the definition of fever and the preferred location for temperature measurement. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
78 
The maximum intensity of administration site redness/swelling will be scored as follows 
(based on the US Food & Drug Administration [FDA] grading scale [U.S. Department of 
Health and Human Services, 2007]): 
Redness/Swelling  
Grade 0 
Absent 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
<25 mm 
≥25 – ≤50 mm 
>50 – ≤100 mm 
>100 mm 
The maximum intensity of fever will be scored as follows (based on the US FDA grading 
scale [U.S. Department of Health and Human Services, 2007]): 
Fever 
Grade 0 
Absent 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
<38.0°C 
≥38.0°C – <38.5°C 
≥38.5°C – <39.0°C 
≥39.0°C 
The Investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the Investigator’s clinical judgement. 
The intensity should be assigned to 1 of the following categories: 
1 (mild) 
 =  An AE which is easily tolerated by the participant, 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 an SAE. Grade 3 
is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets 1 of the predefined 
outcomes as described in the Section 10.3.2. 
10.3.9.2. 
Assessment of causality 
The Investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgement. Where several different 
interventions were administered, the Investigator should specify, when possible, if the 
unsolicited AE/SAE could be causally related to a specific intervention. When a causal 
relationship to a specific study intervention cannot be determined, the Investigator should 
indicate the unsolicited AE/SAE to be related to all interventions. 
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The Investigator will also consult 
the IB and/or SmPC and/or Prescribing Information for marketed products to assist in 
making his/her assessment. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
79 
Causality should be assessed by the Investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study intervention? 
YES 
: 
There is a reasonable possibility that the study intervention contributed 
to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study intervention. There are other more likely 
causes, and administration of the study intervention is not suspected to 
have contributed to the AE. 
If an event meets the criteria to be determined ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the Investigator 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 study intervention, if applicable. 
• 
An error in study intervention administration. 
• 
Other cause (specify).  
There may be situations when an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to Sponsor or designee. However, it is very 
important to record an assessment of causality for every event before submitting the 
Expedited Adverse Events Report to Sponsor or designee.  
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. The Investigator may change his/her opinion of causality after 
receiving additional information and update the SAE information accordingly. 
10.3.9.3. 
Medically attended visits 
For each solicited and unsolicited AE the participant experiences, the participant 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 pDiary/source documents and in the 
eCRF/Expedited Adverse Events Report as applicable.  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
80 
10.3.9.4. 
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). 
10.3.10. 
Reporting of SAEs, pregnancies, and other events 
10.3.10.1. Events requiring expedited reporting to Sponsor or designee 
Once an Investigator becomes aware that an SAE has occurred in an enrolled participant, 
the Investigator (or designee) must complete information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS, even if the Investigator does not have 
complete information on the SAE. It must be completed as thoroughly as possible, with 
all available details of the event. The report must be dated and signed by the Investigator 
(or designee).  
The SAE report must be updated WITHIN 24 HOURS of the receipt of updated 
information on the SAE. The Investigator will always provide an assessment of causality 
at the time of the initial report. 
Refer to the Table 13 for the details on timeframes for reporting of SAEs and 
pregnancies.  
Refer to the Section 10.3.10.2 for information on backup systems in case the electronic 
reporting system does not work. 
10.3.10.2. Backup system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the Investigator (or designee) must fax 
or email a completed, dated and signed paper Expedited Adverse Events Report to the 
study contact for reporting SAEs (refer to the Sponsor Information or IQVIA study 
contact list) within 24 hours of becoming aware of the SAE.  
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
within 24 hours after the electronic reporting system is working again. The information 
reported through the electronic SAE reporting system will be considered valid for 
regulatory reporting purposes. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
81 
10.4. 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
10.4.1. 
Definitions 
10.4.1.1. 
Woman of childbearing potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
10.4.1.1.1. Women not considered as women of childbearing potential 
• 
Premenarchal 
Menarche is the first onset of menses in a young female. Menarche is normally 
preceded by several changes associated with puberty including breast development 
and pubic hair growth.  
Additional evaluation should be considered if a participant’s fertility status is unclear 
(e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention. 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
− 
Current bilateral tubal ligation or occlusion 
Note: Documentation can come from the site personnel’s: review of participant’s medical 
records, medical examination, or medical history interview. 
• 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in women not 
using hormonal contraception or hormonal replacement therapy (HRT). However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use a 
non-hormonal, highly effective contraception method if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrolment. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
82 
10.4.2. 
Contraception guidance 
• 
Female participants of childbearing potential are eligible to participate if they agree 
to use a highly effective contraceptive method consistently and correctly according 
to the methods listed in GSK’s list of highly effective contraceptive methods (Table 
21).  
Table 21 
Highly effective contraceptive methods 
Highly effective contraceptive methods that are user dependent 
Failure rate of <1% per year when used consistently and correctly 
Combined (oestrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• 
Oral 
• 
Intravaginal  
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Injectable 
• 
Oral  
Highly effective methods that are user independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion 
Vasectomised partner  
(A vasectomised partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the WOCBP, and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.)  
Male partner sterilisation prior to the female participant’s entry into the study, and this male 
is the sole partner for that participant, 
(The information on the male sterility can come from the site personnel’s review of the 
participant’s medical records; medical examination and/or semen analysis, or medical history 
interview provided by her or her partner.) 
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.)  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
83 
10.4.3. 
Collection of pregnancy information 
10.4.3.1. 
Female participants who become pregnant 
Refer to the Sections 8.3.1, 8.3.2, 10.3.8.1 and 10.3.8.3 for further information on 
detection, recording, reporting and follow-up of pregnancies. 
Any female participant who becomes pregnant during the study will discontinue study 
intervention or be withdrawn from the study. 
10.5. 
Appendix 5: Genetics 
Not applicable 
10.6. 
Appendix 6: Definition of medical device AE, adverse device 
effect (ADE), serious adverse device effect (SADE) and 
unanticipated SADE (USADE) 
10.6.1. 
Definition of medical device AE and ADE 
• 
Medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether considered related to a medical device or not. 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 medical device. This definition includes events related to the 
medical device or comparator and events related to the procedures involved. 
• 
An ADE is an AE related to the use of a medical device. This definition includes any 
AE resulting from: 
− 
insufficient or inadequate instructions for use (i.e., user error), or 
− 
any malfunction of a medical device, or 
− 
intentional misuse of the medical device. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
84 
10.6.2. 
Definition of medical device SAE, SADE and USADE 
A medical device SAE is any serious adverse event that: 
a. 
Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
− 
A life-threatening illness or injury. The term “life-threatening” in the 
definition of “serious” refers to an event in which the participant was at risk of 
death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
− 
A permanent impairment of a body structure or a body function. 
− 
Inpatient or prolonged hospitalisation. Planned hospitalisation for a pre-
existing condition, or a procedure required by the protocol, without serious 
deterioration in health, is not considered an SAE. 
− 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
c. 
Led to foetal distress, foetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of any infectious agent via a medicinal product  
Serious Adverse Device Effect (SADE) definition 
• 
A SADE is defined as an ADE that has resulted in any of the consequences 
characteristic of a SAE. 
• 
Any device deficiency that might have led to an SAE if appropriate action had not 
been taken or circumstances had been less fortunate. 
Unanticipated SADE (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a 
serious adverse device effect that by its nature, incidence, severity, or outcome has 
not been identified in the current version of the IB. 
10.6.3. 
Recording and reporting of medical device AE, ADEs, SADEs and 
USADE 
• 
Any device deficiency must be reported to Sponsor or Sponsor’s delegate within 24 
hours after the Investigator determines that the event meets the definition of a device 
deficiency. 
• 
Email/Facsimile transmission of the paper ‘Medical device or combination product 
with device deficiency/incident report form’ is the preferred method to transmit this 
information to the Sponsor. 
• 
Contacts for reporting can be found in the IQVIA study contact list. 
• 
GSK will review all device deficiencies, determine and document in writing whether 
they could have led to an SAE. These device deficiencies will be reported to the 
regulatory authorities and IRBs/IECs as required by national regulations. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
85 
10.6.4. 
Reporting of medical device deficiencies for Associated Person 
If an Associated Person (i.e., e.g., spouse, caregiver, site staff) experiences a device 
deficiency, the medical device deficiency information, and any associated AE/SAE 
information will be reported to Sponsor or Sponsor’s delegate. The Associated Person 
will be provided with the safety reporting information and authorisation 
to contact physician letter. 
If follow-up information is required, authorisation to contact physician (or other licensed 
medical practitioner) must be signed to obtain consent. 
• 
Medical device deficiencies should be reported using the medical device deficiency 
report form. 
• 
GSK will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported to 
the regulatory authorities and IRBs/IECs as required by national regulations. 
• 
Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 
10.7. 
Appendix 7 Country-specific requirements 
Not applicable 
10.8. 
Appendix 8: List of Asian countries considered endemic for 
typhoid fever 
• 
Bangladesh 
• 
Cambodia  
• 
China 
• 
India 
• 
Lao People’s Democratic Republic 
• 
Myanmar 
• 
Nepal 
• 
Pakistan 
• 
Sri Lanka 
• 
Thailand  
• 
Vietnam 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
86 
10.9. 
Appendix 9: Toxicity grading scale for safety laboratory 
assessment 
Laboratory test 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
BUN – mg/dL 
<23 – 26 
>26 – 31 
>31 
Requires dialysis 
Creatinine – mg/dL 
(female) 
>1.1 – 1.7 
>1.7 – 2.0 
>2.0 – 2.5 
>2.5 or requires 
dialysis 
Creatinine – mg/dL 
(male) 
>1.3 – 1.7  
 
>1.7 – 2.0 
>2.0 – 2.5 
>2.5 or requires 
dialysis 
Eosinophils – cell/mm3 
>500 – 1500 
>1500 – 5000 
>5000 
Hypereosinophilic 
Haemoglobin (female) – 
gm/dL 
11.0 – <11.6 
9.5 – <11 
8.0 – <9.5 
<8.0 
Haemoglobin (female/male) 
– change from baseline 
value – gm/dL 
Any decrease – 
1.5 
>1.5 – 2.0 
>2.0 – 5.0 
>5.0 
Haemoglobin (male) – 
gm/dL 
12.5 – <12.9 
10.5 – <12.5 
8.5 – <10.5 
<8.5 
Liver function tests – ALT, 
AST increase by factor 
≥1.1 – 2.5 x ULN 
>2.5 – 5.0 x ULN 
>5.0 – 10 x ULN 
>10 x ULN 
Lymphocyte decrease – 
cell/mm3 
750 - <800 
500 - <750 
250 - <500 
<250 
Neutrophil decrease – 
cell/mm3 
1340 
1000 - <1340 
500 - <1000 
<500 
Platelet decrease – cell/mm3 
125 000 – 
<150 000 
100 000 – 
<125 000 
25 000 – 
<100 000 
<25 000 
WBC decrease – cell/mm3 
2500 – <3700 
1500 – <2500 
1000 – <1500 
<1000 
WBC Increase – cell/mm3 
>10 000 – 15 000 
>15 000 – 20 000 
>20 000 – 25 000 
>25 000 
Toxicity Grading scale for safety laboratory test results have been based on the US FDA Guidance for Industry [U.S. 
Department of Health and Human Services, 2007] and adjusted in consideration of local normal ranges provided by the 
site. Parameters not included in the FDA grading scales will not be graded; their assessment will be based on 
laboratory normal ranges and medical judgement. 
ALT=alanine aminotransferase; AST=aspartate aminotransferase, BUN=blood urea nitrogen; ULN=upper limit of 
normal, WBC=white blood cells 
10.10. 
Appendix 10: Abbreviations and Glossary of terms 
10.10.1. 
List of abbreviations  
ADE: 
adverse device effect 
AE: 
adverse event 
ALT: 
alanine aminotransferase 
ANOVA: 
analysis of variance 
AST: 
aspartate aminotransferase 
BioE: 
Biological E Ltd 
BU: 
blood urea 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
87 
BUN: 
blood urea nitrogen 
CI: 
confidence intervals 
CoP: 
Correlate of Protection) 
CRM197 
Cross- Reacting Material 197 
CSR 
Clinical Study Report 
eCRF: 
electronic Case Report Form 
EoS: 
End of Study 
FAS: 
Full Analysis Set 
FDA: 
Food and Drug Administration, United States of America 
FSFV: 
First Subject First Visit 
FTIH: 
first-time-in-human 
GCP: 
Good Clinical Practice 
GMC: 
geometric mean concentration 
GMR: 
geometric mean ratio 
GS: 
Global Safety (GSK) 
GSK: 
GlaxoSmithKline 
GVGH: 
GSK Vaccines Institute for Global Health 
HCP: 
healthcare professional 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
ICH: 
International Council on Harmonisation 
IEC: 
Independent Ethics Committee 
IND: 
Investigational New Drug 
IRB: 
Institutional Review Board 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
88 
iSRC: 
Internal Safety Review Committee 
LSLV: 
Last Subject Last Visit 
MedDRA: 
Medical Dictionary for Regulatory Activities 
PP: 
Project Physician 
PPS: 
Per-Protocol Set 
QTL: 
quality tolerance limit 
RBC: 
red blood cell 
SADE: 
serious adverse device effect 
SAE: 
serious adverse event 
SmPC: 
Summary of Product Characteristics 
SoA: 
Schedule of Activities 
SPM: 
Study Procedures Manual 
SRT: 
Safety Review Team 
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
ULN: 
upper limit of normal 
USADE: 
unanticipated serious adverse device effect 
WBC: 
white blood cell 
WHO: 
World Health Organization 
WOCBP 
woman of childbearing potential 
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
89 
10.10.2. 
Glossary of terms  
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, 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. 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the intervention 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 an SAE.  
In an observer-blind study, the participant, the site, and 
Sponsor personnel involved in the clinical evaluation of 
the participants are blinded while other study personnel 
may be aware of the treatment assignment.  
For this study, single-blind means the Sponsor will be 
aware of the study intervention assignment but the 
Investigator and/or his staff will not. 
Caregiver: 
A ‘caregiver’ is someone who  
• 
lives in the close surroundings of a participant and 
has a continuous caring role or 
• 
has substantial periods of contact with a participant 
and is engaged in his/her daily health care (e.g., a 
relative of the participant, a nurse who helps with 
daily activities in case of residence in a nursing 
home).  
In the context of a clinical study, a caregiver could 
include an individual appointed to oversee and support 
the participant’s compliance with protocol specified 
procedures. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
90 
Certified copy: 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e., by a dated 
signature or by generation through a validated process) 
to have the same information, including data that 
describe the context, content, and structure, as the 
original. 
Combination product 
Combination product comprises any combination of  
• 
drug  
• 
device  
• 
biological product  
Each drug, device and biological product included in a 
combination product is a constituent part.  
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolment: 
The process of registering a participant into a clinical 
study by assigning participant identification number 
after signing the ICF. 
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced. 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis. 
GSK Vaccines Institute 
for Global Health 
(GVGH): 
A GSK-owned company, part of the GSK Global Health 
Programme, committed to develop vaccines for major 
neglected diseases of impoverished communities. 
Immunological correlate 
of protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intervention: 
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 participant. 
Invasive medical device: 
A device which, in whole or in part, penetrates inside the 
body, either through a body orifice or through the 
surface of the body. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
91 
Investigational 
vaccine/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.  
Synonym: Investigational Medicinal Product 
Investigator: 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the Investigator is the 
responsible leader of the team and may be called the 
principal Investigator.  
The Investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
and functions. 
Legally acceptable 
representative: 
An individual, judicial or other body authorised under 
applicable law to consent on behalf of a prospective 
participant to the participant’s participation in the 
clinical trial. 
The terms legal representative or legally authorised 
representative are used in some settings. 
Medical device deficiency: A device deficiency is an inadequacy of a medical 
device with respect to its identity, quality, durability, 
reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors and information 
supplied by the manufacturer. 
Participant: 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject 
Participant number: 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Pharmacogenomics: 
The ICH E15 Guidance for Industry defines 
pharmacogenomics as the “Study of variation of DNA 
and RNA characteristics as related to drug or treatment 
response.”  

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
92 
Pharmacogenetics, 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 is not 
pharmacogenomics. 
Primary completion date: 
The date that the final participant 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 administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  
Protocol amendment: 
The ICH defines a protocol amendment as: ‘A written 
description of a change(s) to or formal clarification of a 
protocol.’ GSK further details this to include a change to 
an approved protocol that affects the safety of 
participants, scope of the investigation, study design, or 
scientific integrity of the study. 
Randomisation: 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Remote visit: 
This term refers to the visit conducted in the place other 
than the study site. 
Safety Review Team: 
This team led by GSK global safety is comprised of core 
representatives from GSK safety, clinical, epidemiology, 
regulatory, and statistics departments, who are also part 
of the study team.  
Self-contained study: 
Study with objectives not linked to the data of another 
study. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
93 
Site Monitor: 
An individual assigned by the Sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Solicited event: 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified follow-up period following study 
intervention administration. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data 
are contained in source documents (original records or 
certified copies). 
Source documents: 
Original legible documents, data, and records (e.g. 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participants’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data 
from automated instruments, copies or transcriptions 
certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, participant files, and records 
kept at the pharmacy, laboratories and at medico-
technical departments involved in the clinical trial). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Study monitor: 
An individual assigned by the Sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Telemedicine: 
Telemedicine refers to the use of information 
technologies and electronic communications to provide 
clinical services to patients virtually. The digital 
transmission of medical imaging, virtual medical 
diagnosis and evaluations, and video consultations with 
specialists are all examples of telemedicine. 
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. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
94 
Virtual visit: 
This term refers to study visits conducted using 
multimedia or technological platforms. 
10.11. 
Appendix 11: Protocol amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment 
is located directly before the Table of Contents. 
DOCUMENT HISTORY 
Document 
Date of Issue 
Protocol Final 
23 August 2022 
Protocol amendment 1 Final 
25 May 2023 
Protocol amendment 2 Final 
21 August 2023 
Amendments summary of changes table: 
Document 
Date of 
issue 
Section # and title 
Description of change 
Brief rationale 
Protocol 
amendment 
1 
25 May 
2023 
Section 1.1 
(Synopsis); Section 
1.3 (Schedule of 
activities), Table 1 
(Schedule of 
Activities); Section 
2.1 (Study 
rationale); Section 
2.2 (Background); 
Section 4.1 (Overall 
design) 
The first vaccination with 
the Typhoid and 
Paratyphoid A conjugate 
vaccine will be called a 
priming, whereas the 
second vaccination after 
6 months will be called a 
booster. 
The target vaccine profile has 
been updated to a single dose 
(priming dose). The second dose 
is being studied as a booster in 
case the single dose is not 
sufficient. 
 
 
Section 1.2 
(Schema); Section 
4.1 (Overall 
design), Figure 1 
(Study design 
overview); Section 
8.2.2.1 (Staggered 
vaccination) 
It is clarified that only at 
Visit 1 should sentinel 
participants receive 
vaccination 1 day apart. 
This is a clarification consistent 
with the initial safety strategy. 
Section 1.3 
(Schedule of 
Activities), Table 2 
(Intervals between 
study visits) 
An allowed interval 
range between Visit 4 
(2nd vaccination visit) 
and reminder phone call 
2 has been added. 
This is to provide flexibility to the 
study site so an earlier reminder 
can be provided to the participant. 
Section 4.1 (Overall 
design), Table 4 
(Study groups, 
intervention, and 
blinding); Section 
6.3.4 (Blinding and 
After the first interim 
analysis (planned after 
Visit 3), the study will be 
considered single-blind, 
with both Investigator 
and participants 
This is implemented because of 
the risk that members of the study 
team may become unblinded to 
the intervention of some 
participants during the interim 
analysis. Although 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
95 
Document 
Date of 
issue 
Section # and title 
Description of change 
Brief rationale 
 
 
unblinding); Section 
9.5.1 (Sequence of 
analyses); Section 
10.10.2 (Glossary 
of terms) 
remaining blinded, until 
the last Contact (Safety 
phone call). 
individual/randomisation listings 
are not foreseen for interim 
analysis, indirect unblinding could 
occur by a combination of 
information from unblinded safety 
group results and participant 
information accessible via other 
clinical trial documents/systems. 
For this Phase 1, non-pivotal, 
study, single-blinding is deemed 
sufficient to not compromise the 
quality of the data. 
Section 5.2.4 
(Other exclusions) 
A clarification to the 
exclusion criterion on 
travel to endemic areas 
has been added to 
mention that it covers 
also travel during the 
study duration. 
This clarification is a more 
specific instruction to the 
Investigator. 
Section 8.2.1.3 
(Physical 
examination); 
Section 8.2.1.5 
(Pre-vaccination 
body temperature)  
The maximum amount 
of time before 
vaccination to obtain 
body temperature and 
vital signs has been set 
to 60 minutes. 
This clarification is a more 
specific instruction to the 
Investigator. 
Section 8.2.2.1 
(Staggered 
vaccination), Table 
10 (Safety 
evaluation 
schedule) 
The possibility of 
combining safety 
evaluations #3 and #4 
has been added in case 
these may occur close 
together. 
The rationale is to improve 
efficiency for the study conduct. 
Section 9.3.1 
(Criteria for 
elimination from 
analysis) 
Criteria for elimination 
for analyses will be 
listed also in the 
Protocol Deviation 
Management Plan. 
This is consistent with the latest 
GSK Standard Operating 
Procedures and allows easy 
documentation and update of 
criteria for elimination for 
analyses. 
Section 9.5.1 
(Sequence of 
analyses) 
It has been specified 
that an interim clinical 
study report will be 
produced after the first 
interim. 
This is in alignment with the new 
project strategy to consider the 
asset as a 1-dose vaccine and 
allow regulatory submissions for 
the subsequent study. 
Detailed description of the current Protocol amendment 2: 
Section 1 (Synopsis) and Section 3 (Objectives and Endpoints), Table 3 (Study 
objectives and endpoints)  
In the primary objective sections, clarification regarding the baseline for each post-
vaccination laboratory estimation has been added. 
 
 
 
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
96 
Objectives 
Endpoints 
Primary 
Evaluate the safety profile of the Vi-
CRM197+O:2-CRM197 vaccine, with and without 
adjuvant. 
• 
Percentage of participants with solicited administration-
site events during 7 days after each vaccination, on the 
days of vaccination and the 6 subsequent days (study 
intervention administered on Day 1 and Day 169), per 
study group. 
• 
Percentage of participants with solicited systemic events 
during 7 days after each vaccination, on the days of 
vaccination and the 6 subsequent days (study 
intervention administered on Day 1 and Day 169), per 
study group. 
• 
Percentage of participants with unsolicited adverse 
events (AE) during 28 days after each vaccination, on the 
days of vaccination and 27 subsequent days (study 
intervention administered on Day 1 and Day 169), per 
study group. 
• 
Percentage of participants with any serious adverse 
event (SAE) from first vaccination until 28 days after 
second study intervention administration (Day 1 to Day 
197), per study group. 
• 
Percentage of participants with AEs/SAEs leading to 
withdrawal from the study or withholding further study 
intervention administration, from first study intervention 
administration until 28 days after second study 
intervention administration (Day 1 to Day 197), per study 
group. 
• 
Percentage of participants with deviations from normal or 
baseline† values of haematological, renal, and hepatic 
panel test results at 7 days after each vaccination (Day 8 
and Day 176), per study group. 
Secondary 
Evaluate the long-term safety profile of the Vi-
CRM197+O:2-CRM197 vaccine, with and without 
adjuvant. 
• 
Percentage of participants with any SAE from 28 days 
after second vaccination (Day 197) up to Day 337, per 
study group.  
• 
Percentage of participants with AEs/SAEs leading to 
withdrawal from the study from 28 days after second 
vaccination (Day 197) up to Day 337, per study group. 
Evaluate the immunogenicity profile of the 
typhoid and paratyphoid A components of the 
Vi-CRM197+O:2-CRM197 vaccine, with and 
without adjuvant, using enzyme-linked 
immunoassay (ELISA). 
• 
Geometric mean concentration (GMC) of anti-Vi antigen 
Immunoglobulin G (IgG) antibody concentrations as 
measured by ELISA, before first vaccination (Day 1), 28 
days after first vaccination (Day 29), before second 
vaccination (Day 169), 7 days after second vaccination 
(Day 176), and 28 days after second vaccination (Day 
197), per study group. 
• 
GMC of Anti-O:2 IgG antibody concentrations, as 
measured by ELISA, before first vaccination (Day 1), 28 
days after first vaccination (Day 29), before second 
vaccination (Day 169), 7 days after second vaccination 
(Day 176), and 28 days after second vaccination (Day 
197), per study group. 
Evaluate different seroresponse rates to the 
typhoid and paratyphoid A component of the Vi-
CRM197+O:2-CRM197 vaccine, with and without 
adjuvant. 
• 
Percentage of participants achieving anti-Vi antigen IgG 
antibody concentrations ≥4.3 µg/mL*, as measured by 
ELISA, before first vaccination (Day 1), 28 days after first 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
97 
Objectives 
Endpoints 
vaccination (Day 29), before second vaccination (Day 
169), 7 days after second vaccination (Day 176), and 28 
days after second vaccination (Day 197), per study 
group. 
• 
Percentage of participants achieving anti-Vi antigen IgG 
antibody concentrations ≥2.0 µg/mL**, as measured by 
ELISA, before first vaccination (Day 1), 28 days after first 
vaccination (Day 29), before second vaccination (Day 
169), 7 days after second vaccination (Day 176), and 28 
days after second vaccination (Day 197), per study 
group. 
• 
Percentage of participants achieving at least 4-fold*** 
increase in Anti-O:2 IgG antibody concentrations, as 
measured by ELISA, at 28 days after first vaccination 
(Day 29), before second vaccination (Day 169), 7 days 
after second vaccination (Day 176), and 28 days after 
second vaccination (Day 197) compared to first 
vaccination baseline (Day 1), per study group. 
*This threshold, estimated to be protective against typhoid 
fever, was established in previous studies [Szu, 2013; WHO, 
2020] and then used in the registration of Vi conjugated vaccine 
in India. 
**This threshold, estimated to be protective against typhoid 
fever, was defined as a short-term threshold in a previous study 
[Szu, 2014]. 
***This threshold is chosen as a clinically meaningful threshold 
that, in the absence of an established correlate of protection, 
could allow quantitative decisions to be made for further 
development of this component of the vaccine. 
†Baseline for post-first vaccination at Day 8 is Day 1 (Can also be screening blood draw, if performed within 3 
days of first vaccination) and baseline for post-second vaccination at Day 176 is Day 169. 
Section 9.4 (Statistical analyses), Section 9.4.1 (Primary endpoint) 
In Section 9.4.1, clarification regarding the baseline for each post-vaccination laboratory 
estimation has been added.  
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
98 
Endpoint description 
Analysis set 
Statistical analysis methods 
• 
Percentage of participants with 
solicited administration-site events 
during 7 days after each 
vaccination, on the days of 
vaccination and the 6 subsequent 
days (study intervention 
administered on Day 1 and Day 
169), per study group 
Solicited Safety 
Set 
• 
Number and percentages of participants 
with at least one, any, and Grade 3 
administration-site solicited AEs 
• 
Percentage of participants with 
solicited systemic events during 7 
days after each vaccination, on the 
days of vaccination and the 6 
subsequent days (study 
intervention administered on Day 1 
and Day 169), per study group 
Solicited Safety 
Set 
• 
Number and percentages of participants 
with at least one, any, and Grade 3 
systemic solicited AEs 
• 
Percentage of participants with 
unsolicited AEs during 28 days 
after each vaccination, on the days 
of vaccination and 27 subsequent 
days (study intervention 
administered on Day 1 and Day 
169), per study group 
Unsolicited Safety 
Set 
• 
Number and percentages of participants 
with unsolicited AEs 
• 
Percentage of participants with any 
SAEs from first vaccination until 28 
days after second study 
intervention administration (Day 1 
to Day 197), per study group 
Exposed Set 
• 
Number and percentages of participants 
with SAEs 
• 
Percentage of participants with 
AEs leading to withdrawal from the 
study or withholding further study 
intervention administration, from 
first study intervention 
administration until 28 days after 
second study intervention 
administration (Day 1 to Day 197), 
per study group 
Exposed Set 
• 
Number and Percentage of participants with 
AEs/SAEs leading to withdrawal from the 
study or withholding further study 
intervention administration 
• 
Percentage of participants with 
deviations from normal or 
baseline † values of 
haematological, renal, and hepatic 
panel test results at 7 days after 
each vaccination Day 8 and Day 
176 per study group 
Exposed Set  
• 
Number and percentages of participants 
having haematological, renal, and hepatic 
abnormalities  
†Baseline for post-first vaccination at Day 8 is Day 1 (can also be screening blood draw, if performed within 3 
days of first vaccination), and baseline for post-second vaccination at Day 176 is Day 169. 
Section 9.4 (Statistical analyses), Section 9.4.2 (Secondary endpoint) 
In Section 9.4.2, “Number” has been added in the statistical analysis methods column for 
completeness, for the last endpoint to calculate within-subject increase of at least 4-fold 
in Anti-O:2 IgG antibody concentrations, as measured by ELISA, per study group. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
99 
Section 9.4 (Statistical analyses), 
 
Endpoint description 
Analysis set 
Statistical analysis methods 
• 
Percentage of participants with any 
SAE from 28 days after second 
vaccination (Day 197) up to Day 
337, per study group 
Exposed Set 
• 
Number and percentages of participants 
with SAEs 
• 
Percentage of participants with 
AEs/SAEs leading to withdrawal 
from the study from 28 days after 
second vaccination (Day 197) up to 
Day 337, per study group 
Exposed Set 
• 
Number and percentage of participants with 
AEs/SAEs leading to withdrawal from the 
study 
• 
Anti-Vi antigen IgG antibody 
concentrations as measured by 
ELISA, at selected timepoints, per 
study group 
• 
Anti-O:2 IgG antibody 
concentrations, as measured by 
ELISA, at selected timepoints, per 
study group 
PPS, FAS (only if 
number of 
participants 
differs more than 
10%) 
• 
Geometric Mean Concentrations (with 95% 
CI) at Day 1, Day 29, Day 169, Day 176, 
and Day 197 
• 
Within-subject geometric mean ratios (with 
95% CI) at Day 29, Day 169, Day 176, and 
Day 197 versus Day 1 baseline, and at Day 
176 and Day 197 versus Day 169 baseline 
• 
Anti-Vi antigen IgG antibody 
concentrations ≥ 4.3 µg/mL, as 
measured by ELISA, per study 
group 
• 
 Anti-Vi antigen IgG antibody 
concentrations ≥ 2.0 µg/mL, as 
measured by ELISA, per study 
group 
• 
Within-subject increase of at least 
4-fold in Anti-O:2 IgG antibody 
concentrations, as measured by 
ELISA, per study group 
PPS, FAS (only if 
number of 
participants 
differs more than 
10%) 
• 
Number and percentage (with 95% CI) of 
participants with Anti-Vi antigen IgG 
antibody concentrations ≥ 4.3 µg/mL at Day 
1, Day 29, Day 169, Day 176, and Day 197 
• 
Number and percentage (with 95% CI) of 
participants with Anti-Vi antigen IgG 
antibody concentrations ≥ 2.0 µg/mL at Day 
1, Day 29, Day 169, Day 176, and Day 197 
• 
Number and percentage (with 95% CI) of 
participants with at least 4-fold in Anti-O:2 
IgG antibody concentrations at, Day 29, 
Day 169, Day 176, and Day 197 compared 
to Day 1 baseline 
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
100 
Section 10.2 (Appendix 2: Clinical laboratory tests) 
In Section 10.2, information regarding VaccZyme Human anti-Vi IgG kit was deleted 
and replaced with a general description of an IgG ELISA assay 
Anti-Vi antigen IgG determination from serum 
Anti-Vi specific IgG antibodies will be measured by a qualified, fit for purpose, anti-Vi 
IgG ELISA kit assay, developed by BioE based on the commercially available 
VaccZyme Human anti-Vi IgG kit (BindingSite, UK). The assay setup, qualifications, 
and serology testing will be performed in a laboratory designated by GVGH. 

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
101 
11. 
REFERENCES 
Barkume C, Date K, Saha SK, et al. Phase I of the surveillance for enteric fever in Asia 
Project (SEAP): an overview and lessons learned. JID. 2018;218:S188-94. 
Bhutta ZA, Capeding MR, Bavdekar A, et al. Immunogenicity and safety of the Vi-
CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south 
and southeast Asia: results from two randomized, observer-blind, age de-escalation, 
phase 2 trials. Lancet Infect Dis. 2014;14(2) 119-29. 
Chung AW, Kumar MP, Arnold KB, et al. Dissecting polyclonal vaccine-induced 
humoral immunity against HIM using Systems Serology. Cell. 2015;163: 988-98. 
GBD 2017 Typhoid and Paratyphoid Collaborators. The global burden of typhoid and 
paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. 
Lancet Infect Dis. 2019;19:369-81. 
John J, Van Aart CJC, Grassly NC, et al. The burden of typhoid and paratyphoid in India: 
systematic review and meta-analysis. PLOS Negl Trop Dis. 2016;10:e0004616. 
Kasi SG, Shivananda S, Marathe S, et al. Indian Academy of Pediatrics (IAP) Advisory 
Committee on Vaccines and Immunization Practices (ACVIP): Recommended 
Immunization Schedule (2020-21) and Update on Immunization for Children Aged 0 
Through 18 Years. Indian Pediatr. 2021;58:44-53. 
Launay O, Lewis DJM, Anemona A, et al. Safety profile and immunologic responses of a 
novel vaccine against Shigella sonnei administered intramuscularly, intradermally and 
intranasally: results from two parallel randomized phase 1 clinical studies in healthy adult 
volunteers in Europe. EBioMedicine. 2017;22:164-72. 
Micoli F, Rondini S, Gavini M, et al. O:2-CRM(197) conjugates against Salmonella 
Paratyphi A. PloS One. 2012;7(11):e47039.  
Micoli F, Bjarnarson SP, Arcuri M, et al. Short Vi-polysaccharide abrogates T-
independent immune response and hyporesponsiveness elicited by long Vi-CRM197 
conjugate vaccine. PNAS. 2020;117(39):24443-9.  
Owais A, Sultana S, Zaman U, et al. Incidence of typhoid bacteremia in infants and 
young children in southern coastal Pakistan. Pediatr Infect Dis J. 2010;29(11):1035-9. 
CCI
CCI

CONFIDENTIAL 
205480 (TYPH-PARATYPH A CONJ VI-CRM O2-CRM GVGH-001 (H02_01TP)) 
Protocol Amendment 2 Final 
21 August 2023 
102 
Saha S, Saha S, Das RC, et al. Enteric fever and related contextual factors in Bangladesh. 
Am J Trop Med Hyg. 2018;99:20-5. 
Szu S, Hunt S, Xie G, et al. A human IgG anti-Vi reference for Salmonella typhi with 
weight-based antibody units assigned. Vaccine. 2013;31(15):1970-4.  
Szu SC, Klugman KP, Hunt S. Re-examination of immune response and estimation of 
anti-Vi IgG protective threshold against typhoid fever-based on the efficacy trial of Vi 
conjugate in young children. Vaccine. 2014;32(20):2359-63. 
U.S. Department of Health and Human Services. Guidance for Industry-Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials 2007. Accessed 1 August 2022. 
https://www.fda.gov/media/73679/download 
van Damme P, Kafeja F, Anemona A, et al. Safety, immunogenicity and dose ranging of 
a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in 
healthy adults. PLoS One. 2011;6:e25398.  
World Health Organization (WHO). Recommendations to assure the quality, safety and 
efficacy of typhoid conjugate vaccines, Annex 2, TRS No 1030. 5 November 2020. 
Meeting Report. Accessed 1 August 2022. 
https://www.who.int/publications/m/item/tcv71-recommendations  
World Health Organization (WHO). WHO COVID-19: Case Definitions. Updated in 
Public health surveillance for COVID-19. Updated 22 July 2022. Accessed 1 August 
2022. https://www.who.int/publications/i/item/WHO-2019-nCoV-
Surveillance_Case_Definition-2022.1 
CCI

Signature Page for  205480 TMF-16430589 v1.0
Signature Page for TMF-16430589 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 25-Aug-2023 15:53:39 GMT+0000
PPD