A Phase 3b, Open-label Study to Evaluate the Non-inferiority of the Immune Response and to Evaluate the Safety of the RSVPreF3 OA Investigational Vaccine in Adults 18-49 Years of Age at Increased Risk for Respiratory Syncytial Virus Disease, Compared to Older Adults >=60 Years of Age
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

CONFIDENTIAL 
222253 (RSV OA=ADJ-025) 
Protocol Amendment 1 Final 
03 May 2024 
1 
 
CLINICAL STUDY PROTOCOL 
Primary Study Intervention 
GSK’s investigational respiratory syncytial virus 
(RSV) vaccine BIO RSV OA=ADJ (GSK3844766A) 
Study Identifier 
222253 (RSV OA=ADJ-025) 
EU CT Number  
2023-510190-34-00 
Approval Date 
03 May 2024 
Title 
A Phase 3b, open-label study to evaluate the non-
inferiority of the immune response and to evaluate 
the safety of the RSVPreF3 OA investigational 
vaccine in adults 18-49 years of age at increased risk 
for respiratory syncytial virus disease, compared to 
older adults ≥60 years of age. 
Brief Title 
A study on the immune response and safety of 
vaccine against respiratory syncytial virus given to 
adults 18 to 49 years of age at increased risk for 
respiratory syncytial virus disease, compared to older 
adults 60 years of age and above. 
Sponsor 
GlaxoSmithKline Biologicals S.A.  
Rue De L'Institut 89 
1330 Rixensart 
Belgium 
Sponsor signatory 
Veronica Hulstrøm, MD, PhD 
Clinical Project Lead 
RSV Older Adults 
Medical monitor name and contact can be found in local study contact 
information document 
©2024 GSK group of companies or its licensor. 

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Protocol Amendment 1 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments, with the terms of the clinical trial agreement and with any other study 
conduct procedures and/or study conduct documents provided by GSK. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of and will comply with GCP and all applicable regulatory 
requirements.  
• 
That I will comply with the terms of the site agreement. 
• 
To comply with local bio-safety legislation. 
• 
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 study-related duties 
and functions conducted at the study site. 
• 
To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained on-site or 
elsewhere without the approval of GSK and the express physical informed consent of 
the participant and/or the participant’s LAR.  
• 
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 and data management 
processes of the study with respect to data entry and resolution of queries about the 
data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the study. 
• 
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 study intervention(s), and more generally about their financial 
ties with the sponsor. GSK will use and disclose the information solely for the 
purpose of complying with regulatory requirements. 

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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. 

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Study identifier 
222253 (RSV OA=ADJ-025) 
EU CT number 
2023-510190-34-00 
Approval date 
03 May 2024 
Title 
A Phase 3b, open-label study to evaluate the non-
inferiority of the immune response and to evaluate 
the safety of the RSVPreF3 OA investigational 
vaccine in adults 18-49 years of age at increased risk 
for respiratory syncytial virus disease, compared to 
older adults ≥60 years of age. 
Investigator name 
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 
 
 

CONFIDENTIAL 
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Protocol Amendment 1 Final 
03 May 2024 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 1 
03 May 2024 
Original Protocol 
18 December 2023 
Amendment 1 (03 May 2024) 
Overall rationale for the current Amendment: 
The purpose of this amendment is to implement a new Cohort 3 as a Part B of this study 
to collect safety information in an extended sample size to better characterize the safety 
profile of the RSVPreF3 OA investigational vaccine in a population of individuals at 
increased risk for RSV disease 18-49 years of age. It is planned to include an extra 
~600 adults 18-49 years of age at increased risk for RSV disease, who will be monitored 
for reactogenicity and safety for a period of 6 months following the administration of one 
dose of RSVPreF3 OA investigational vaccine at Visit 1. The same inclusion and 
exclusion criteria as well as enrolment rules as for participants of Cohort 1 will apply for 
Cohort 3.  
Minor editorial changes for consistency and clarity have also been made and 
typographical errors have been corrected. 
Other updates made to the protocol are described in the table below. 

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LIST OF MAIN CHANGES IN THE PROTOCOL AND THEIR RATIONALE: 
Section # and 
title 
Description of change 
Brief rationale 
1.2 Schema 
Included the study design overview for Part B  
The study population has been 
extended to include a cohort of 
AIR participants 18-49 YOA to 
better characterize the safety 
profile of the RSVPreF3 OA 
investigational vaccine in this 
population. 
 
1.3 Schedule of 
activities 
A separate table for Part B schedule of activities 
and intervals between study visits has been added. 
3 Objectives, 
endpoints and 
estimands 
Differentiated the objectives, endpoints and 
estimands that are specific to Part A and Part B 
4.1 Overall design 
Study design details for Part B (Cohort 3) have 
been included. 
5.1 Inclusion criteria 
Numbering has been added for each inclusion 
criterion. 
This change has been made to 
align with latest protocol template 
5.2 Exclusion criteria 
Numbering has been added for each exclusion 
criterion. 
This change has been made to 
align with latest protocol template 
6.3.3 Intervention 
allocation to the 
participant 
Participants enrolment in Part B has been included 
The study population has been 
extended to include a cohort of 
AIR participants 18-49 YOA to 
better characterize the safety 
profile of the RSVPreF3 OA 
investigational vaccine in this 
population. 
9 Statistical 
considerations 
Additional details for Cohort 3 has been provided 
where applicable. 
10.5. Appendix 5: 
Country-specific 
requirements 
Added South Africa specific requirements for HIV 
participants 
This change has been made to 
align with local requirements. 
10.6 Appendix 6: 
Grading scaled for 
chronic diseases in 
scope of the AIR 
population 
Added Appendix 6: Grading scales for chronic 
diseases in scope of the AIR population 
This was added to clarify the 
grading of medical conditions 
mentioned in Section 5.1.1. 
Throughout protocol 
Administrative and editorial changes were made to 
align table numbers, formatting, and cross 
references. 
To maintain consistency with 
template guidance. 
 

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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 5 
List of main changes in the protocol and their rationale: ........................................... 6 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................ 14 
1. 
PROTOCOL SUMMARY ........................................................................................ 24 
1.1. 
Synopsis ..................................................................................................... 24 
1.2. 
Schema ...................................................................................................... 24 
1.3. 
Schedule of activities (SoA) ........................................................................ 27 
2. 
INTRODUCTION .................................................................................................... 33 
2.1. 
Study rationale ............................................................................................ 33 
2.2. 
Background ................................................................................................ 33 
2.3. 
Benefit/risk assessment .............................................................................. 34 
2.3.1. 
Risk assessment .......................................................................... 34 
2.3.2. 
Benefit assessment ..................................................................... 37 
2.3.3. 
Overall benefit-risk conclusion ..................................................... 37 
3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS .................................................... 37 
4. 
STUDY DESIGN .................................................................................................... 41 
4.1. 
Overall design ............................................................................................. 41 
4.2. 
Scientific rationale for study design ............................................................. 42 
4.2.1. 
Participant input into design ......................................................... 43 
4.3. 
Justification for dose ................................................................................... 43 
4.4. 
End-of-study definition ................................................................................ 43 
5. 
STUDY POPULATION ........................................................................................... 43 
5.1. 
Inclusion criteria .......................................................................................... 43 
5.1.1. 
Specific inclusion criteria for all participants in Cohort 1 
and Cohort 3 ................................................................................ 44 
5.1.2. 
Specific inclusion criteria for all participants in Cohort 2 ............... 45 
5.2. 
Exclusion criteria ......................................................................................... 46 
5.2.1. 
Medical conditions ....................................................................... 46 
5.2.2. 
Prior/Concomitant therapy ........................................................... 47 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 47 
5.2.4. 
Other exclusions .......................................................................... 47 
5.2.4.1. 
Other exclusions for all participants ............................ 47 
5.2.4.2. 
Other exclusions for Cohort 1 and Cohort 3 ................ 48 
5.3. 
Lifestyle considerations ............................................................................... 48 
5.4. 
Screen failures ............................................................................................ 48 
5.5. 
Criteria for temporarily delaying enrollment/ administration of study 
intervention ................................................................................................. 48 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 49 
6.1. 
Study intervention(s) administered .............................................................. 49 
6.1.1. 
Medical devices ........................................................................... 50 
6.2. 
Preparation, handling, storage, and accountability ...................................... 50 
6.3. 
Assignment to study intervention ................................................................ 51 

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6.3.1. 
Participant identification ............................................................... 51 
6.3.2. 
Randomization to study intervention ............................................ 51 
6.3.3. 
Intervention allocation to the participant ....................................... 51 
6.3.4. 
Allocation of participants to 
 in Part A ............. 52 
6.4. 
Blinding ....................................................................................................... 52 
6.5. 
Study intervention compliance .................................................................... 52 
6.6. 
Dose modification ....................................................................................... 52 
6.7. 
Continued access to study intervention after the end of the study ............... 52 
6.8. 
Treatment of overdose ................................................................................ 53 
6.9. 
Prior and concomitant therapy .................................................................... 53 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 55 
7.1. 
Discontinuation of study intervention ........................................................... 55 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 55 
7.3. 
Lost to follow-up.......................................................................................... 56 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 57 
8.1. 
Administrative baseline procedures ............................................................ 58 
8.1.1. 
Collection of demographic data .................................................... 58 
8.1.2. 
Medical/vaccination history .......................................................... 58 
8.1.3. 
Measure height and weight .......................................................... 59 
8.1.4. 
Smoking status and smoking exposure history ............................ 59 
8.2. 
Immunogenicity assessments ..................................................................... 59 
8.2.1. 
Biological samples ....................................................................... 59 
8.2.2. 
Laboratory assays ....................................................................... 60 
8.2.3. 
Immunological read-outs .............................................................. 61 
8.2.4. 
Immunological correlates of protection ......................................... 61 
8.3. 
Safety assessments .................................................................................... 61 
8.3.1. 
Pre-study intervention administration procedures ........................ 61 
8.3.1.1. 
Physical examination .................................................. 61 
8.3.1.2. 
Vital signs ................................................................... 62 
8.3.1.3. 
Pregnancy testing ....................................................... 62 
8.3.2. 
Post-study intervention administration procedures ....................... 62 
8.3.2.1. 
Physical examination .................................................. 62 
8.3.3. 
Warnings and precautions to administration of study 
intervention .................................................................................. 62 
8.3.4. 
Safety monitoring and Committee ................................................ 63 
8.4. 
Adverse Events (AEs), serious adverse events (SAEs), and other 
safety reporting ........................................................................................... 63 
8.4.1. 
Time period and frequency for collecting AE, SAE, and 
other safety information ............................................................... 63 
8.4.2. 
Method of detecting AEs and SAEs ............................................. 65 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 65 
8.4.4. 
AESIs .......................................................................................... 65 
8.4.4.1. 
Potential immune-mediated diseases ......................... 65 
8.4.4.2. 
Atrial fibrillation (AF) ................................................... 70 
8.4.5. 
Regulatory reporting requirements for 
SAEs/pregnancies/AESIs ............................................................ 70 
8.4.6. 
Pregnancy ................................................................................... 71 
8.4.7. 
Contact information for reporting SAEs, AESIs and 
pregnancies. ................................................................................ 72 
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8.4.8. 
Participant card ............................................................................ 72 
8.5. 
Pharmacokinetics ....................................................................................... 72 
8.6. 
Pharmacodynamics .................................................................................... 72 
8.7. 
Genetics ..................................................................................................... 72 
8.8. 
Biomarkers ................................................................................................. 72 
8.9. 
Immunogenicity assessments ..................................................................... 72 
8.10. 
Health economics or medical resource utilization and health 
economics .................................................................................................. 72 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 73 
9.1. 
Statistical hypotheses ................................................................................. 73 
9.2. 
Analysis sets ............................................................................................... 73 
9.2.1. 
Criteria for elimination from analyses ........................................... 74 
9.3. 
Statistical analyses ..................................................................................... 74 
9.3.1. 
Primary endpoints/estimands analysis (Part A) ............................ 74 
9.3.1.1. 
Success criteria for non-inferiority and testing 
sequence .................................................................... 74 
9.3.2. 
Secondary endpoints/estimands analyses ................................... 75 
9.4. 
Interim analyses .......................................................................................... 76 
9.4.1. 
Sequence of analysis ................................................................... 76 
9.5. 
Pre-dose sample size determination ........................................................... 76 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 77 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 77 
10.1.1. 
Regulatory and ethical considerations ......................................... 77 
10.1.2. 
Financial disclosure ..................................................................... 78 
10.1.3. 
Informed consent process ............................................................ 78 
10.1.4. 
Recruitment strategy .................................................................... 79 
10.1.5. 
Data protection ............................................................................ 80 
10.1.6. 
Committees structure ................................................................... 80 
10.1.7. 
Dissemination of Clinical Study Data ........................................... 80 
10.1.8. 
Data quality assurance ................................................................ 81 
10.1.9. 
Source documents ....................................................................... 82 
10.1.10. Study and site start and closure ................................................... 83 
10.1.11. Publication policy ......................................................................... 83 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 84 
10.2.1. 
RSV-A and RSV-B neutralization assays ..................................... 84 
10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 85 
10.3.1. 
Definition of AE ............................................................................ 85 
10.3.2. 
Definition of SAE .......................................................................... 86 
10.3.3. 
Solicited events............................................................................ 87 
10.3.4. 
Unsolicited AE ............................................................................. 88 
10.3.5. 
Recording, assessment and follow-up of AE, SAE, AESIs 
and pregnancies .......................................................................... 88 
10.3.5.1. AE and SAE recording ................................................ 88 
10.3.5.2. Assessment of intensity .............................................. 90 
10.3.5.3. Assessment of causality ............................................. 91 
10.3.5.4. Assessment of outcomes............................................ 92 
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10.3.5.5. Follow-up of AEs, SAEs, AESIs, pregnancies 
or any other events of interest .................................... 92 
10.3.5.6. Updating of SAE, AESI and pregnancy 
information after removal of write access to the 
participant’s eCRF ...................................................... 93 
10.3.5.7. Reporting of SAEs, AESIs and pregnancies ............... 93 
10.4. 
Appendix 4: Contraceptive and barrier guidance ......................................... 94 
10.4.1. 
Definitions .................................................................................... 94 
10.4.1.1. WOCBP Definition ...................................................... 94 
10.4.1.2. Woman of Nonchildbearing Potential 
(WONCBP) ................................................................. 95 
10.4.2. 
Contraception guidance ............................................................... 95 
10.5. 
Appendix 5: Country-specific requirements ................................................. 97 
10.5.1. 
Germany ...................................................................................... 97 
10.5.2. 
Japan ........................................................................................... 97 
10.5.3. 
South Africa ................................................................................. 97 
10.6. 
Appendix 6: Grading scales for chronic diseases in scope of the AIR 
population ................................................................................................... 98 
10.6.1. 
GOLD classification ..................................................................... 98 
10.6.2. 
New York Heart Association Classification of heart failure ........... 98 
10.6.3. 
Chronic kidney disease classification ........................................... 99 
11. REFERENCES ..................................................................................................... 100 
 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities (Part A) ................................................................ 27 
Table 2 
Schedule of Activities (Part B) ................................................................ 30 
Table 3 
Intervals between study visits (Part A) .................................................... 33 
Table 4 
Intervals between study visits (Part B) .................................................... 33 
Table 5 
Risk Assessment .................................................................................... 35 
Table 6 
Objectives and Endpoints ....................................................................... 37 
Table 7 
Primary estimands (Part A) .................................................................... 39 
Table 8 
Secondary estimands for safety (Part A and Part B) .............................. 40 
Table 9 
Study Intervention administered ............................................................. 49 
Table 10 
Prohibited medications and washout period ........................................... 54 
Table 11 
Timing of collection of concomitant medication to be recorded ............... 54 
Table 12 
Biological samples (Part A) .................................................................... 60 
Table 13 
Laboratory assays (Part A) ..................................................................... 60 
Table 14 
Immunological read-outs (Part A) ........................................................... 61 
Table 15 
Collection and reporting of safety information ......................................... 64 
Table 16 
List of potential immune-mediated diseases (pIMDs) ............................. 66 
Table 17 
Timeframes for submitting SAE, pregnancy and pIMDs to GSK ............. 71 
Table 18 
Study objectives and null hypothesis ...................................................... 73 
Table 19 
Analysis sets .......................................................................................... 73 
Table 20 
Power for primary objectives of non-inferiority of the humoral 
immune response after RSVPreF3 OA vaccine between the 
RSV-A-AIR (18-49 YOA) Cohort 1 to RSV-OA (≥ 60 YOA) Cohort 
2 for 361 evaluable participants per group.............................................. 77 
Table 21 
Solicited administration site .................................................................... 87 
Table 22 
Solicited systemic events ....................................................................... 87 
Table 23 
Intensity scale for solicited events .......................................................... 90 

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Table 24 
Intensity scale of administration site redness 
(Erythema)/swelling, and fever ............................................................... 91 
Table 25 
Highly effective contraceptive methods .................................................. 95 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview (Part A) .............................................................. 25 
Figure 2 
Study design overview (Part B) .............................................................. 26 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation Definition 
AAION 
Arteritic Anterior Ischemic Optic Neuropathy 
ACTM 
Acute Complete Transverse Myelitis 
ADE 
Adverse device effect 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AF 
Atrial fibrillation 
AHEI 
Acute Hemorrhagic Edema of Infancy 
AIR 
At Increased Risk 
AMSAN 
Acute Motor and Sensory Axonal Neuropathy 
ANCA 
Anti-Neutrophil Cytoplasmic Antibody 
APTM 
Acute Partial Transverse Myelitis 
AS01 
Adjuvant System 01 
ATCC 
American Type Culture Collection 
BYOD 
Bring Your Own e-Device 
CA 
Competent authority 
CAD 
Coronary Artery Disease  
CHF 
Congestive Heart Failure 
CI 
Confidence Interval  
CIAP 
Chronic Idiopathic Axonal Polyneuropathy 
CIDP 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 
CIOMS 
Council for International Organizations of Medical Sciences 
CIS 
Clinically Isolated Syndrome 
CCI

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Abbreviation Definition 
CONSORT 
Consolidated Standards of Reporting Trials 
COPD 
Chronic obstructive pulmonary disease 
COVID-19 
Coronavirus Disease 2019 
CREST 
Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, 
Sclerodactyly, and Telangiectasia 
CRO 
Clinical Research Organization 
CSR 
Clinical study report 
DLP 
Data lock point 
DRE 
Disease-related event 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eDiary 
Electronic Diary 
EOS 
End-of-study 
ERD 
Enhanced Respiratory Disease 
ES 
Exposed Set 
EU 
European Union 
EUA 
Emergency use authorization 
FSFV 
First subject first visit 
FSH 
Follicle Stimulating Hormone 
GCP 
Good clinical practices 
GMT 
Geometric Mean Titer 
GOLD 
Global Initiative for Chronic Disease Obstructive Lung Disease 
GSK 
GlaxoSmithKline Biologicals SA  
HHS 
Home healthcare services 

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Abbreviation Definition 
HIPAA 
Health Insurance Portability and Accountability Act 
HLT 
High Level Term 
HRT 
Hormonal Replacement Therapy 
IAF 
Informed assent form 
IB  
Investigator Brochure 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
ICSR 
Individual case safety reports 
IDMC 
Independent data monitoring committee 
IEC 
Independent ethics committee 
IgG 
Immunoglobulin 
IM 
Intramuscular 
IMP 
Investigational medicinal product 
IRB 
Institutional review board 
ITP 
Idiopathic thrombocytopenic purpura 
LABD 
Linear IgA-mediated Bullous Dermatosis 
LAR 
Legally acceptable representative 
LRTD 
Lower Respiratory Tract Disease 
LSLV 
Last Subject Last Visit 
MART 
Maintenance and Reliever Therapy 
MGI 
Mean Geometric Increase 
MIS-A 
Multisystem Inflammatory Syndrome in Adults 

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Abbreviation Definition 
MIS-C 
Multisystem Inflammatory Syndrome in Children 
MMN 
Multifocal Motor Neuropathy 
MS 
Multiple Sclerosis 
NI 
Non-inferiority 
OA 
Older Adults 
PI 
Principal Investigator 
pIMD 
Potential immune-mediated disease 
PPFE 
Pleuroparenchymal fibroelastosis 
PPS 
Per-Protocol Set 
QS-21 
Quillaja saponaria Molina, fraction 21 
QTL 
Quality tolerance limit 
RS 
Reynolds Syndrome 
RSV 
Respiratory Syncytial Virus 
RTI 
Respiratory Tract Infections 
RTSM 
Randomization and Trial Supply Management 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SAR 
Serious adverse reaction 
SJS 
Stevens-Johnson Syndrome 
SLS 
Shrinking Lung Syndrome 
SmPC 
Summary of product characteristics 
SoA 
Schedule of activities 
SOC 
System Organ Class 

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Abbreviation Definition 
SRR 
Seroresponse rate 
SRT 
Safety Review Team 
SUSAR 
Suspected unexpected serious adverse reaction 
TED 
Thyroid Eye Disease 
TEN 
Toxic Epidermal Necrolysis 
TNF 
Tumor Necrosis Factor 
TTS 
Thrombosis with thrombocytopenia syndrome 
UK 
United Kingdom 
US/USA 
United States of America 
USADE 
Unanticipated serious adverse device effect 
VAED 
Vaccine Associated Enhanced Disease 
VAERD 
Vaccine Associated Enhanced Respiratory Disease 
VMED 
Vaccine-Mediated Enhanced Disease 
Vx CL&AP 
Vaccines Clinical Laboratory and Assay Portfolio 
WOCBP 
Woman of childbearing potential 
WONCBP 
Woman of nonchildbearing potential 
YOA 
Years of Age 
Definition of Terms  
Term 
Definition 
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 unfavorable and unintended 
sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product. For 

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Term 
Definition 
marketed medicinal products, this also includes failure 
to produce expected benefits (i.e., lack of efficacy), 
abuse or misuse. 
Adverse event of special 
interest 
An adverse event of special interest (serious or non-
serious) is one of scientific and medical concern specific 
to the sponsor’s product or program, for which ongoing 
monitoring and rapid communication by the investigator 
to the sponsor can be appropriate. Such an event might 
warrant further investigation in order to characterize and 
understand it. Depending on the nature of the event, 
rapid communication by the trial sponsor to other parties 
(e.g., regulators) might also be warranted. 
Blinding: 
A procedure in which 1 or more parties to the study 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 
study, and only when the data are cleaned to an 
acceptable level of quality will appropriate personnel be 
unblinded or when required in case of a SAE.  
In an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned.  
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 their 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. 
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. 

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Term 
Definition 
Co-administered 
(concomitant) products 
A product given to clinical trial participants as required 
in the protocol as part of their standard care for a 
condition which is not the indication for which the IMP 
is being tested and is therefore not part of the objective 
of the study. 
Current smoker 
A person who is currently smoking or who has stopped 
smoking within 6 months before study start. 
eDiary 
Electronically registered patient data and automated data 
entries on, for example, a handheld mobile device, tablet 
or computer. 
Eligible 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolled participant 
All participants who entered the study (who received 
study intervention administration or underwent a post-
screening study procedure). 
Note: screening failures (who never passed screening) 
and participants screened (met eligibility) but never 
enrolled into the study are excluded from the Enrolled 
analysis set as they did not enter the study. 
Refer to the Section 9.2 for the definition of ‘Enrolled 
Set’ applicable to the study. 
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced. 
Evaluable 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis. 
Former smoker 
A person who stopped smoking for at least 6 months at 
the time of study start.  
Home Healthcare Services  
Deployment of mobile health care professional(s) 
(nurses or phlebotomists) to perform study activities 
remotely. 
Intercurrent medical 
condition 
A condition that has the capability of altering the 
immune response to the study vaccine or is confirmed to 
have an alteration of the participant’s initial immune 
status. 

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Term 
Definition 
Intervention number 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Investigational product 
A pharmaceutical form of an active substance or placebo 
being tested or used as a reference in a clinical trial, 
including products already with a marketing 
authorization but used or assembled (formulated or 
packaged) in a way different from the authorised form, 
or when used for an unauthorised indication, or when 
used to gain further information about the authorised 
form. 
Investigator 
A person responsible for the conduct of the clinical 
study at a study site. If a study is conducted by a team of 
individuals at a study site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate study-related duties and 
functions conducted at the study site to qualified 
individual or party to perform those study-related duties 
and functions. 
Legally acceptable 
representative 
An individual, judicial or other body authorized under 
applicable law to consent on behalf of a prospective 
participant to the participant's participation in the 
clinical study. 
The terms legal representative or legally authorized 
representative are used in some settings. 
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. 
Primary Completion Date 
The date on which the last participant in a clinical study 
was examined or received an intervention to collect final 
data for the primary outcome measure. 
Whether the clinical study ended according to 
the protocol or was terminated does not affect this date. 

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Term 
Definition 
For clinical studies with more than one primary outcome 
measure with different completion dates, this term refers 
to the date on which data collection is completed for all 
the primary outcome measures.  
Randomization 
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. 
Screened participant 
All participants who were screened for eligibility. 
Self-contained study 
Study with objectives not linked to the data of another 
study. 
Serious Adverse Reaction 
All noxious and unintended responses to an IMP related 
to any dose administered that result in death, are life-
threatening, require patient hospitalization or 
prolongation of existing hospitalization, result in 
persistent or significant disability or incapacity, or are a 
congenital anomaly or birth defect. 
Solicited adverse 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 study necessary for the 
reconstruction and evaluation of the study. 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 study). 

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Term 
Definition 
Study completion date 
The date on which the last participant in a clinical study 
was examined or received an intervention/treatment to 
collect final data for the primary outcome 
measures, secondary outcome measures, and AEs (that 
is, the last participant's last visit or LSLV). 
Study 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. 
Note: “Study intervention” and “study treatment” are 
used interchangeably unless otherwise specified. 
Study monitor 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction; in a 
clinical trial, a serious adverse reaction that is 
considered unexpected, i.e., the nature or severity of 
which is not consistent with the reference safety 
information (e.g., Investigator's Brochure for an 
unapproved investigational medicinal product). All 
adverse drug reactions (ADRs) that are both serious and 
unexpected are subject to expedited reporting. 
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. 
Virtual visit 
This term refers to study visits conducted using 
multimedia or technological platforms. 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 3b, open-label study to evaluate the non-inferiority of the 
immune response and to evaluate the safety of the RSVPreF3 OA investigational vaccine 
in adults 18-49 years of age at increased risk for respiratory syncytial virus disease, 
compared to older adults ≥60 years of age. 
Brief Title: A study on the immune response and safety of vaccine against respiratory 
syncytial virus given to adults 18 to 49 years of age at increased risk for respiratory 
syncytial virus disease, compared to older adults 60 years of age and above. 
Rationale: Refer to Section 2.1. 
Objectives, Endpoints, and Estimands: Refer to Section 3. 
Overall Design: Refer to Section 4.1. 
Number of Participants: Refer to Section 9.5. 
Data Monitoring/Other Committee: Refer to Section 10.1.6. 
1.2. 
Schema 
The study design overview for Part A and Part B is presented in Figure 1 and Figure 2, 
respectively. 
 

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Figure 1 
Study design overview (Part A) 
 
A= Adults; AE=Adverse event; AESI=Adverse events of special interest; AIR=At increased risk; 
; N=Number of participants; OA=Older adults; 
pIMD=Potential immune-mediated disease; RSV=Respiratory syncytial virus; SAE=Serious adverse event; YOA=Years of age. 
*Participants with underlying medical conditions such as chronic pulmonary and cardiovascular diseases, diabetes mellitus types 1 and 2, chronic liver and renal diseases, and 
neurologic or neuromuscular conditions. 
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Figure 2 
Study design overview (Part B) 
 
A= Adults; AE=Adverse event; AESI=Adverse events of special interest; AIR=At increased risk; 
; N=Number of participants; pIMD=Potential 
immune-mediated disease; RSV=Respiratory syncytial virus; SAE=Serious adverse event; YOA=Years of age. 
*Participants with underlying medical conditions such as chronic pulmonary and cardiovascular diseases, diabetes mellitus types 1 and 2, chronic liver and renal diseases, and 
neurologic or neuromuscular conditions. 
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1.3. 
Schedule of activities (SoA)  
Table 1 
Schedule of Activities (Part A) 
Type of contact 
Visit 1 
Visit 2 
Visit 3 
Notes 
Timepoints 
Day 1 
Day 31 
Month 6 
Informed consent/Informed assent 
● 
 
 
See Section 10.1.3 for details 
Inclusion and exclusion criteria 
● 
 
 
See Sections 5.1 and 5.2 for 
details 
Distribution of ‘participant card’ 
○ 
 
 
See Section 8.4.8 for more details 
Check with participants if he/she will appoint a caregiver, and distribute information letter to caregiver, when 
applicable  
○ 
○ 
○ 
 
Baseline and demography assessments 
Collect demographic data 
● 
 
 
See Section 8.1.1 for more 
information 
Measure height and weight 
● 
 
 
See Section 8.1.3 for more 
information 
Record medical and vaccination history  
● 
 
 
See Section 8.1.2 for more details 
Physical examination/vital signs 
● 
○1 
○1 
See Section 8.3.1.2 for more 
information.  
Record smoking status and smoking exposure history (including electronic smoking devices) 
● 
 
 
See Section 8.1.4 for more details 
Screening conclusion 
● 
 
 
 
Clinical specimen for laboratory assessment 
 
Blood sampling for humoral immune response assessment (~15 mL) 
●2,a 
●a 
●a 
See Section 8.2.1 for more 
information 
Urine pregnancy test (only for women of childbearing potential in Cohort 1)3 
● 
 
 
See Section 8.3.1.3 for more 
details 
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Type of contact 
Visit 1 
Visit 2 
Visit 3 
Notes 
Timepoints 
Day 1 
Day 31 
Month 6 
Study intervention 
Check contraindications, warnings and precautions to vaccination 
○ 
 
 
See Section 8.3.3 for details 
Check criteria for temporary delay for enrolment and/or study intervention administration 
○ 
 
 
See Section 5.5 for more 
information 
Record body temperature before study intervention administration 
● 
 
 
The route for measuring 
temperature can be oral or 
axillary. Fever is defined as 
temperature  38.0°C/100.4°F, 
regardless of the location of 
measurement 
Study intervention number allocation 
● 
 
 
 
Study intervention administration (including 30-minutes post-study intervention administration observation) 
● 
 
 
 
Record administered study intervention number 
● 
 
 
 
Safety assessments 
Set-up of eDiary and/or distribute eDiary device 
○ 
 
 
See Section 10.3.5.1 for more 
details 
Training on use of eDiary 
○ 
 
 
See Section 10.3.5.1 for more 
details 
Record solicited administration site and systemic events (Days 1–4 post-dose) 
○a 
 
 
See Section 8.4.1 for more 
information 
Review eDiary 
 
○4 
 
 
Collect eDiary or assist participant to delete application 
 
○ 
 
 
Record unsolicited AEs (Days 1-30 post-study intervention administration) 
● 
● 
 
See Section 10.3.5 for more 
details 
Record concomitant medications/vaccinations 
● 
● 
● 
See Section 6.9 for more 
information 
Record any intercurrent medical conditions  
● 
● 
● 
 
Record all SAEs, AESI (including pIMDs and AF5) and pregnancy 
● 
● 
● 
See Section 10.3.5 for more 
details 

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Type of contact 
Visit 1 
Visit 2 
Visit 3 
Notes 
Timepoints 
Day 1 
Day 31 
Month 6 
Record AE/SAEs leading to withdrawal from the study 
● 
● 
● 
See Section 10.3.5.1 for more 
details 
Record SAEs related to study participation, or to a concurrent GSK medication/vaccine6 
● 
● 
● 
See Section 10.3.5 for more 
details 
Study conclusion 
 
 
● 
See Section 4.4 for more details 
Note: The double-line border indicates the analyses which will be performed on all data (i.e., data that are as clean as possible) obtained up to these timepoints. See Section 9.4.1 for 
more details. 
AE=Adverse event; AESI=Adverse event of specific interest; AF=Atrial fibrillation; eCRF=electronic case report form; pIMD=Potential immune-mediated diseases; SAE=Serious 
adverse event. 
● 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. 
○a Is used to indicate a study procedure recorded in eDiary by participants. 
●a Is used to indicate a study procedure that requires documentation in Site2Test app 
1 If deemed necessary by the investigator.  
2 Blood sampling at Visit 1 should be performed prior to study intervention administration. If the study intervention administration is delayed by any reason, blood sampling needs to be 
repeated on the day of study intervention administration. 
3 The urine sample for pregnancy test must be taken on the same day, prior to study intervention administration. If the study intervention administration is delayed by any reason, urine 
pregnancy test needs to be repeated on the day of study intervention administration. 
4 Designated site staff must review the responses in the eDiary frequently in the portal during the active event collection period to assess participant compliance and monitor reported 
events to ensure correct data is provided. 
5 AF will be considered as AESI in this study and will be additionally reported in the AF follow-up questionnaire (electronic or paper) in eCRF. AF reporting will follow the same reporting 
periods as for AEs and SAEs. The reporting of non-serious AF will be performed according to the unsolicited AE reporting period. The reporting of AF meeting the SAE definition 
(serious AF) will be performed according to the SAE reporting period. 
6 SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to study vaccine administration) up to 
study end. 
Return of the eDiary device is not applicable if the participant has a “Bring Your Own” e-device. 
Visit 3 should preferably be done on-site but in case of exceptional circumstances where the participant cannot come to the site, this study visit can be replaced by a home visit 
conducted by authorized staff. Any information from the participant required according to study procedures and not collected during the home visit can be obtained by multiple 
formats (e.g., email, text, message, fax or phone call) conducted by the site staff. 
 
 
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Table 2 
Schedule of Activities (Part B) 
Type of contact 
Visit 1 
Visit 2 
Contact 
Notes 
Timepoints 
Day 1 
Day 31 
Month 6 
Informed consent/Informed assent 
● 
 
 
See Section 10.1.3 for details 
Inclusion and exclusion criteria 
● 
 
 
See Sections 5.1 and 5.2 for 
details 
Distribution of ‘participant card’ 
○ 
 
 
See Section 8.4.8 for more details 
Check with participants if he/she will appoint a caregiver, and distribute information letter to caregiver, when 
applicable 
○ 
○ 
○ 
 
Baseline and demography assessments 
Collect demographic data 
● 
 
 
See Section 8.1.1 for more 
information 
Measure height and weight 
● 
 
 
See Section 8.1.3 for more 
information 
Record medical and vaccination history  
● 
 
 
See Section 8.1.2 for more details 
Physical examination/vital signs 
● 
○1 
 
See Section 8.3.1.2 for more 
information.  
Record smoking status and smoking exposure history (including electronic smoking devices) 
● 
 
 
See Section 8.1.4 for more details 
Screening conclusion 
● 
 
 
 
Clinical specimen for laboratory assessment 
 
Urine pregnancy test (only for women of childbearing potential)2 
● 
 
 
See Section 8.3.1.3 for more 
details 
Study intervention 
Check contraindications, warnings and precautions to vaccination 
○ 
 
 
See Section 8.3.3 for details 
Check criteria for temporary delay for enrolment and/or study intervention administration 
○ 
 
 
See Section 5.5 for more 
information 
Record body temperature before study intervention administration 
● 
 
 
The route for measuring 
temperature can be oral or 
axillary. Fever is defined as 
temperature  38.0°C/100.4°F, 
regardless of the location of 
measurement 
Study intervention number allocation 
● 
 
 
 

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Type of contact 
Visit 1 
Visit 2 
Contact 
Notes 
Timepoints 
Day 1 
Day 31 
Month 6 
Study intervention administration (including 30-minutes post-study intervention administration observation) 
● 
 
 
 
Record administered study intervention number 
● 
 
 
 
Safety assessments 
Set-up of eDiary and/or distribute eDiary device 
○ 
 
 
See Section 10.3.5.1 for more 
details 
Training on use of eDiary 
○ 
 
 
See Section 10.3.5.1 for more 
details 
Record solicited administration site and systemic events (Days 1–4 post-dose) 
○a 
 
 
See Section 8.4.1 for more 
information 
Review eDiary 
 
○3 
 
 
Collect eDiary or assist participant to delete application 
 
○ 
 
 
Record unsolicited AEs (Days 1-30 post-study intervention administration) 
● 
● 
 
See Section 10.3.5 for more 
details 
Record concomitant medications/vaccinations 
● 
● 
● 
See Section 6.9 for more 
information 
Record any intercurrent medical conditions  
● 
● 
● 
 
Record all SAEs, AESI (including pIMDs and AF4) and pregnancy 
● 
● 
● 
See Section 10.3.5 for more 
details 
Record AE/SAEs leading to withdrawal from the study 
● 
● 
● 
See Section 10.3.5.1 for more 
details 
Record SAEs related to study participation, or to a concurrent GSK medication/vaccine5 
● 
● 
● 
See Section 10.3.5 for more 
details 
Study conclusion 
 
 
● 
See Section 4.4 for more details 
Note: The double-line border indicates the analyses which will be performed on all data (i.e., data that are as clean as possible) obtained up to these timepoints. See Section 9.4.1 for 
more details 
AE=Adverse event; AESI=Adverse event of specific interest; AF=Atrial fibrillation; eCRF=electronic case report form; pIMD=Potential immune-mediated diseases; SAE=Serious 
adverse event. 
● 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. 
○a Is used to indicate a study procedure recorded in eDiary by participants. 
1 If deemed necessary by the investigator.  
2 The urine sample for pregnancy test must be taken on the same day, prior to study intervention administration. If the study intervention administration is delayed by any reason, urine 
pregnancy test needs to be repeated on the day of study intervention administration. 

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3 Designated site staff must review the response in the eDiary in the portal frequently during the active event collection period to assess participant compliance and monitor reported 
events to ensure correct data is provided. 
4 AF will be considered as AESI in this study and will be additionally reported in the AF follow-up questionnaire (electronic or paper) in eCRF. AF reporting will follow the same reporting 
periods as for AEs and SAEs. The reporting of non-serious AF will be performed according to the unsolicited AE reporting period. The reporting of AF meeting the SAE definition 
(serious AF) will be performed according to the SAE reporting period. 
5 SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to study vaccine administration) up to 
study end. 
Return of the eDiary device is not applicable if the participant has a “Bring Your Own” e-device. 
Visit 2 should preferably be done on-site but in case of exceptional circumstances where the participant cannot come to the site, this study visit can be replaced by a home visit 
conducted by authorized staff. Any information from the participant required according to study procedures and not collected during the home visit can be obtained by multiple 
formats (e.g., email, text, message, fax or phone call) conducted by the site staff. 

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Table 3 
Intervals between study visits (Part A) 
Interval 
Planned visit interval  
Allowed interval range 
Visit 1→Visit 2 
30 days 
30-42 days 
Visit 1→Visit 3 
180 days 
180-210 days 
If the study intervention date is different from the ICF signature date, the study intervention date needs to be taken as a 
reference for calculating intervals relative to subsequent visits. 
Interval is computed as the difference between 2 dates. 
Table 4 
Intervals between study visits (Part B) 
Interval 
Planned visit interval  
Allowed interval range 
Visit 1→Visit 2 
30 days 
30-42 days 
Visit 1→ Contact (Month 6) 
180 days 
180-210 days 
If the study intervention date is different from the ICF signature date, the study intervention date needs to be taken as a 
reference for calculating intervals relative to subsequent visits. 
Interval is computed as the difference between 2 dates. 
2. 
INTRODUCTION 
2.1. 
Study rationale 
GSK has developed an RSV PreFusion protein F3 Older Adult (referred to as RSVPreF3 
OA vaccine throughout this document) which consists of 120 µg of the RSVPreF3 
recombinant antigen and the AS01E adjuvant system administered as a single dose, to 
address the unmet medical need for prevention of RSV-LRTD in older adults. The 
vaccine was approved for use in adults ≥60 YOA in the US on 03 May 2023, under the 
tradename Arexvy. To date, the vaccine is also approved in the EU, UK, Canada, Japan 
Hongkong, Australia and other countries. However, some younger patient groups also 
have an increased risk for RSV disease. The aim of this open-label study is to 
demonstrate the NI of the immune response and to evaluate safety of the RSVPreF3 OA 
investigational vaccine in adults 18-49 YOA, who are AIR for RSV disease, versus adults 
≥60 YOA, where vaccine efficacy against RSV disease has been assessed in another 
clinical study (RSV OA=ADJ-006). 
2.2. 
Background 
RSV is a ribonucleic acid virus of which 2 antigenically distinct subtypes exist, referred 
to as RSV-A and RSV-B [Borchers, 2013]. RSV causes respiratory tract infections (RTI) 
in people of all ages. RSV can cause severe disease in infants, OA and adults AIR due to 
presence of chronic diseases. Currently, there are 2 vaccines available for prevention of 
RSV infection in adults ≥60 YOA; Arexvy (manufactured by GSK) and Abrysvo 
(manufactured by Pfizer Inc). 
RSV is recognized as an important cause of hospitalization for severe respiratory illness 
in OA and those with underlying medical conditions [Branche, 2022a; Jain, 2015]. RSV 

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infections are increasingly recognized as a cause of serious illness in high-risk, non-
immunocompromised adults, including those with chronic lung and heart disease, 
diabetes mellitus, chronic renal and liver disease, and neurologic disease [Melgar, 2023]. 
In a prospective cohort study over 4 RSV seasons in healthy elderly patients (≥65 YOA) 
and high-risk adults (≥21 YOA) with chronic heart or lung disease, RSV infection 
developed annually in 3% to 7% of healthy elderly patients and in 4% to 10% of high-
risk adults [Falsey, 2005; Shi, 2021]. 
In patient populations with chronic diseases, both the prevalence and incidence of RSV 
infections is increased, leading to an increased need for medical care and hospitalization 
in high income countries. In a major study in the United States (US), the incidence 
among chronic pulmonary disease patients ranged between 1.47 to 4.68 per 
10 000 patients aged 18-49 years. Among patients with diabetes, the incidence of RSV-
hospitalizations ranged between 6.54 to 8.34 per 10 000 patients aged 18-49 years. For 
patients with congestive heart failure (CHF), the incidence ranged between 11.5 to 29.52 
per 10 000 patients aged 20-39 years and 23.16 to 48.59 per 10 000 patients aged 
40-59 years [Branche, 2022b]. 
The RSVPreF3 OA vaccine induces humoral and cellular immune responses to both 
RSV-A and RSV-B at 1-month post-vaccination in adults 50-59 YOA, including adults 
AIR for RSV disease. The results observed in adults 50-59 YOA are consistent with the 
robust immunogenicity data observed in the pivotal Phase 3 study RSV OA=ADJ-004 
and study RSV OA=ADJ-006, where overall vaccine efficacy of 82.6% (96.95% CI, 
57.9-94.1) against RSV-LRTD up to 6 months post-vaccination was demonstrated. Based 
on these results, licensure of the RSV OA vaccine was received in different countries 
[Papi, 2023; Leroux-Roels, 2023]. Currently, studies in participants ˂ 60 YOA who are 
more vulnerable to severe disease as result of RSV infection are ongoing, among which is 
the RSV OA=ADJ-018-NI study in patients with chronic diseases AIR for RSV-LRTD in 
50-59 YOA and RSV OA=ADJ-023- evaluating the immune response and safety of the 
vaccine in renal and lung SOT patients ≥ 18 YOA. 
The aim of this study is to demonstrate the NI of the immune response and evaluate 
safety of RSVPreF3 OA investigational vaccine in non-immunocompromised adults 
18-49 YOA, who are AIR for RSV disease, versus adults ≥60 YOA, where vaccine 
efficacy against RSV disease has been demonstrated. 
Please refer to the IB for information regarding pre-clinical studies, and clinical studies of 
RSVPreF3 OA investigational vaccine. 
2.3. 
Benefit/risk assessment 
2.3.1. 
Risk assessment 
Detailed information about the known and expected benefits, potential risks, and 
reasonably expected AEs of RSVPreF3 OA investigational vaccine can be found in the 
IB/PI. 

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Table 5 
Risk Assessment  
Potential Risk 
of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
RSVPreF3 OA investigational vaccine 
pIMDs 
pIMDs are considered a 
theoretical risk, as for all vaccines 
containing an adjuvant system. 
Refer to Section 8.4.4 for details. 
Hypersensitivity 
reactions 
(including 
anaphylaxis)  
Previous exposure to components 
of the vaccine might have induced 
an immune response that results 
in an exaggerated or inappropriate 
reaction. 
All participants will remain under observation at the clinical 
center for at least 30 minutes after study intervention 
administration or longer if deemed necessary by site 
personnel. 
Appropriate medical care must be readily available during 
this period. 
Participants with a history of hypersensitivity or severe 
allergic reaction to any component of the vaccine are 
excluded from study enrollment. 
Syncope 
(fainting)  
Syncope (fainting) can occur 
following or even before study 
intervention administration as a 
psychogenic response to the 
needle insertion. 
Participants who mention experiencing previous episodes 
of fainting or dizziness before, during or after vaccination, 
will be asked to lie down during the intervention and remain 
under observation at the clinical center for at least 30 
minutes after study intervention administration or longer if 
deemed necessary by site personnel. 
Appropriate medical care must be readily available during 
this period. 
Study procedures 
Local reactions 
at the injection 
site 
Intramuscular vaccination 
commonly precipitates a transient 
and self-limiting local inflammatory 
reaction. This may typically 
include pain at injection site, 
erythema/redness, and swelling. 
Physician can implement the measures that they consider 
necessary. 
Solicited local AE will be collected and reviewed up to Day 
4 following vaccination. 
Local reactions 
at site of blood 
draw 
Pain, redness/erythema, irritation, 
and bruising may occur at the site 
where blood is drawn. 
Physician can implement the measures that they consider 
necessary. 
Syncope 
(fainting)  
Syncope (fainting) can occur 
following or even before any blood 
draw as a psychogenic response 
to the needle insertion. 
Participants who mention experiencing previous episodes 
of fainting or dizziness before, during or after a blood draw, 
will be asked to lie down during the intervention and remain 
under observation at the clinical center for at least 30 
minutes after blood draw or longer if deemed necessary by 
site personnel. 
Appropriate medical care must be readily available during 
this period. 
pIMD: Potential immune-mediated disease; AE-Adverse event 
For details of study procedures, dose, and study design justification, refer to Section 1.3 
and Section 4.2. 
In parallel with the RSVPreF3 OA clinical development program, another RSV vaccine 
development program was initiated by GSK. GSK developed an investigational RSV 
vaccine for administration to pregnant women, with the aim of preventing medically 
assessed, RSV-associated LRTIs in their infants up to 6 months of age, by transfer of 
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In 2020, GSK initiated a Phase 3, double-blind, 2:1-randomized, placebo-controlled study 
(RSV MAT-009; NCT04605159) in 24 countries to assess the safety and efficacy of the 
maternal vaccine candidate (RSVPreF3 Mat) administered to 18–49-year-old women in 
the late second or third trimester of pregnancy. 
In February 2022, GSK decided to stop enrollment and vaccination in RSV maternal 
vaccine studies involving pregnant women. This decision was taken because of an 
observed imbalance in the proportions of both preterm births and neonatal deaths (death 
of an infant within the first 28 days of life) in the treatment group vs. the placebo group 
in the RSV MAT-009 study. Subsequently, the enrollment and vaccination in all studies 
of the RSV maternal vaccine candidate involving women of childbearing potential were 
also stopped. 
Following the Day 43 post-birth interim analysis (DLP 04 October 2022) of the RSV 
MAT-009 study, GSK concluded that preterm birth is an identified risk for the pregnant 
women population, for the RSV maternal vaccine candidate. The observed numerical 
imbalance in neonatal deaths is not an independent safety signal but a consequence of the 
imbalance in preterm births. GSK has discontinued the further development of this RSV 
maternal vaccine candidate. 
The safety concern is specific to women who received the RSV maternal vaccine 
candidate during the late second or third trimester of pregnancy [Dieussaert, 2024]. 
Analyses of the available safety data have not established what caused the observed 
imbalance in preterm births. The overall incidence of preterm birth in the study was low 
in both treatment groups and remained below the preterm birth background rates for the 
majority of the participating countries. The imbalance in preterm births was observed 
more in low and middle-income countries (relative risk 1.57 [95% CI: 1.17 - 2.10) than 
high-income countries (relative risk 1.04 [95% CI: 0.68 - 1.58]). 
The vaccine candidate for OA (RSV PreF3 OA vaccine), contains the same RSV antigen 
as the RSV maternal vaccine candidate but the RSVPreF3 OA vaccine is combined with 
GSK’s established AS01E adjuvant to boost the immune response in the OA population. 
After further consideration of the preterm birth safety signal observed in the RSV 
Maternal study and recommendations by external experts, GSK has assessed that 
WOCBP can be included in this study. As a precautionary measure, no pregnant women 
will be included and all WOCBP will be required to use adequate contraception and have 
a negative pregnancy test prior to each vaccination in this study (see Section 5.1.1). Study 
participants will be adequately informed of the risks associated with pregnancy as the 
informed consent contains specific information regarding the RSV Maternal study. 
The RSVPreF3 OA vaccine clinical trials are closely monitored for safety with all 
available safety data reviewed by the sponsor. In addition, the Phase 3 RSV OA=ADJ-
006 clinical study is monitored by an IDMC on an ongoing basis. The IDMC has not 
raised any concern for safety in the OA population. The RSVPreF3 OA vaccine has not 
been studied in pregnant women to date. 

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2.3.2. 
Benefit assessment 
The participants may or may not benefit directly from participating in this study. By 
receiving the RSVPreF3 OA vaccine, the participant may have the benefit of being 
protected against RSV-LRTD. In a pre-specified efficacy interim analysis of an ongoing 
Phase 3 trial (RSV OA=ADJ-006) in participants ≥ 60 YOA, for those receiving a single 
dose of the RSVPreF3 OA investigational vaccine, the primary endpoint was met with 
82.6% vaccine efficacy (96.95% CI, 57.9-94.1) [Papi, 2023] during the first RSV season 
and no unexpected safety concerns observed (refer to IB). A study in adults 50-59 YOA, 
in which half of the population was AIR for RSV disease, showed that the immune 
response was not lower in adults 50-59 YOA-AIR for RSV compared to older adults 
≥ 60 YOA. 
An indirect benefit is that the information obtained in this study will further aid the 
development of the RSV OA vaccine, which is intended to prevent disease associated 
with RSV infection in OA and adults at increased risk for RSV disease. 
Another benefit for all study participants may include gaining information about their 
general health status through the medical evaluations/assessments associated with this 
study (i.e., physical examination). 
2.3.3. 
Overall benefit-risk conclusion 
The RSVPreF3 OA vaccine’s marketing authorization has been initially granted for use 
in adults ≥ 60 YOA. The clinical development of the RSVPreF3 PA investigational 
vaccine in other populations is ongoing. Considering the measures taken to minimize the 
risk to participants in this study, the potential risks are justified by the potential benefits 
linked to the development of this vaccine. 
3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS 
Table 6 
Objectives and Endpoints 
Objective 
Endpoint 
Primary* (Part A) 
• 
To demonstrate the NI** of the humoral immune 
response in participants 18-49 YOA at increased 
risk for RSV disease compared to OA (≥60 YOA) 
for the RSV-A strain after RSVPreF3 OA 
investigational vaccine administration. 
• 
RSV-A neutralizing titers expressed as GMT ratio 
(RSV-OA over RSV-A-AIR) at 1 month (Day 31) 
after study intervention administration***. 
• 
Seroresponse in RSV-A neutralizing titers from Day 
1 to Day 31***. 
• 
To demonstrate the NI** of the humoral immune 
response in participants 18-49 YOA at increased 
risk for RSV disease compared to OA (≥60 YOA) 
for the RSV-B strain after RSVPreF3 OA 
investigational vaccine administration. 
• 
RSV-B neutralizing titers expressed as GMT ratio 
(RSV-OA over RSV-A-AID) at 1 month (Day 31) 
after study intervention administration***. 
• 
Seroresponse in RSV-B neutralizing titers from Day 
1 to Day 31***. 
Secondary Safety (Part A and Part B) 
• 
To evaluate the safety and reactogenicity after the 
RSVPreF3 OA investigational vaccine 
administration. 
• 
Occurrence of each solicited administration site 
event with onset within 4 days after dosing (i.e., the 
day of study intervention administration and 
3 subsequent days). 

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Objective 
Endpoint 
• 
Occurrence of each solicited systemic event with 
onset within 4 days after study intervention 
administration (i.e., the day of study intervention 
administration and 3 subsequent days). 
• 
Occurrence of unsolicited AEs within 30 days after 
study intervention administration (i.e., the day of 
study intervention administration and 
29 subsequent days). 
• 
Occurrence of all SAEs (including fatal and related 
SAEs) and AESIs after study intervention 
administration (Day 1) up to study end (Month 6). 
Secondary Immunogenicity (Part A) 
• 
To evaluate the humoral immune response to the 
RSVPreF3 OA investigational vaccine until 6 
months after study vaccination for both 
populations. 
• 
RSV-A and RSV-B neutralizing titers, at pre-study 
intervention administration and 1 month and 6 
months after study intervention administration.  
Tertiary Immunogenicity (Part A) 
AE=Adverse event; AESI=Adverse event of special interest; AIR=At increased risk; 
 
; 
; GMT=Geometric mean titer; NI=Non-inferiority; OA=Older 
adults; RSV=Respiratory syncytial virus; SAE=Serious adverse event; YOA=Years of age. 
* Refer to Section 9.3.1 for the testing sequence of primary objectives. 
** NI criteria are defined in Section 9.3.1.1. 
*** Co-primary endpoints. Refer to Section 9.1 for statistical hypotheses. 
Primary estimands (for Part A) 
The primary question of interest is to evaluate the NI of the humoral immune response after 
RSVPreF3 OA investigational study intervention in RSV-A-AIR group (18-49 YOA), 
vaccinated as per protocol when compared to RSV-OA (≥60 YOA) group. 
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Table 7 
Primary estimands (Part A) 
Attributes 
Summary measure 
Treatment 
Population 
Endpoint (variable) 
Intercurrent events (ICEs) 
Description 
Handling strategy 
RSVPreF3 OA 
investigational vaccine at 
Day 1. 
Non-
immunocompromised 
adults at increased risk 
for RSV disease with 18-
49 YOA. 
OA with ≥60 YOA. 
• 
RSV-A neutralizing titers (expressed in 
ED60) measured at 1 month (Day 31) 
after study intervention administration. 
• 
Seroresponse in RSV-A neutralizing titers 
(expressed in ED60) from Day 1 to 
Day 31. 
• 
RSV-B neutralizing titers (expressed in 
ED60) measured at 1 month (Day 31) 
after study intervention administration. 
• 
Seroresponse in RSV-B neutralizing titers 
(expressed in ED60) from Day 1 to 
Day 31. 
Taking prohibited 
medication 
/vaccine or intercurrent 
medical condition prior to 
Day 31. 
 
Data collected after 
ICEs will be 
excluded from the 
analysis at Day 31 
(Hypothetical 
strategy) 
Rationale: To 
evaluate the 
immunogenicity 
parameters in the 
absence of ICE 
Ratio of GMTs with 
95% CI and 
difference in 
seroresponse rate 
(SRR) with 95% CI 
for RSV-A and RSV-
B neutralizing titers 
(ED60) at Day 31 
between the RSV-
OA group 
(≥60 YOA) and the 
RSV-A-AIR group 
(18-49 YOA) 
SRR is defined as the proportion of participants having a fold increase in neutralizing titers (1-month post-study intervention administration over pre-study intervention administration) 
≥4. 
AIR=At increased risk; CI=Confidence interval; ED60= Estimated dilution 60; GMT=Geometric mean titer; OA=Older adults; YOA=Years of age 
Rationale for estimand:  
The primary estimands address the objective of demonstrating the NI of the humoral immune response in non-immunocompromised 
adults aged 18-49 YOA AIR for RSV disease, when compared to older adults aged ≥ 60 YOA after administration of a single dose of 
RSVPreF3 OA investigational vaccine. This is done by estimating the true effect of the vaccine without any confounding of other 
medications/vaccinations/medical condition(s) on the target population since the impact of developing medical condition(s) forbidden by 
protocol and use of forbidden medications and vaccinations is anticipated to modify the vaccine effect. 

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Table 8 
Secondary estimands for safety (Part A and Part B) 
Attributes 
Summary measure 
Treatment 
Population 
Endpoint (Variable) 
Intercurrent events (ICEs) 
Description 
Handling strategy 
RSVPreF3 OA 
investigational vaccine 
at Day 1. 
Non-immunocompromised 
adults at increased risk for 
RSV disease with 18-49 
YOA. 
OA with ≥60 YOA. 
• 
Occurrence of each solicited 
administration site event with onset 
within 4 days after study intervention 
administration. 
• 
Occurrence of each solicited systemic 
event with onset within 4 days after 
study intervention administration. 
• 
Occurrence of unsolicited AEs within 
30 days after study intervention 
administration. 
• 
Occurrence of SAEs (including fatal 
and related SAEs) and AESIs after 
study intervention administration (Day 
1) up to study end (Month 6). 
Taking prohibited 
medication 
/vaccine or intercurrent 
medical condition 
during respective 
duration. 
 
All the data collected for 
the variable of interest 
are used regardless of 
whether the intercurrent 
event occurs (treatment 
policy). 
The percentage of 
participants by 
group who report 
each of the 
endpoints. 
AE=Adverse event; AESI=Adverse event of special interest; RSV=Respiratory syncytial virus; SAE=Serious adverse event; YOA=Years of age. 

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4. 
STUDY DESIGN 
4.1. 
Overall design 
• 
Type of study: Self-contained. 
• 
Experimental design: Phase 3b, open-label, uncontrolled (as there is no 
comparative intervention), non-randomized study. The study will be conducted in 
2 Parts - Part A and Part B. Part A will include 2 parallel cohorts (Cohort 1 and 
Cohort 2) (See Figure 1) and Part B will include 1 Cohort (Cohort 3) (see Figure 2) 
− 
Enrollment rules will be applied to ensure adequate representation by sex 
category within Part A (Cohort 1 and 2) and Part B (Cohort 3): 
o 
Approximately 35% of male participants per cohort. 
o 
Approximately 35% of female participants per cohort. 
o 
The remaining 30% can be distributed freely across the 2 categories. 
Part A: 
− 
Cohort 1: approximately 425 adults (A)18-49 YOA AIR for RSV disease (RSV-
A-AIR Group) will receive 1 dose of RSVPreF3 OA investigational vaccine at 
Visit 1 (Day 1). 
− 
Enrollment rules for disease categories within Cohort 1: 
o 
At least ~25% of participants with cardiopulmonary conditions. 
o 
At least ~25% of participants with diabetes mellitus. 
o 
The remaining ~50% can be distributed freely across the above 2 disease 
categories as well as include participants with chronic renal or liver disease 
or neurological or neuromuscular disease. 
− 
Cohort 2: approximately 425 adults ≥60 YOA (RSV-OA Group) will receive 
1 dose of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1). 
− 
Enrollment rules will be applied to ensure adequate representation by age 
category within Cohort 2: 
o 
Approximately 40% of participants 60-69 YOA. 
o 
Approximately 30% of participants 70 YOA or above. 
o 
The remaining 30% can be distributed freely across the 2 age categories. 
Part B: 
− 
Cohort 3: Approximately 600 adults (A)18-49 YOA AIR for RSV disease 
(RSV-A-AIR Group) will receive 1 dose of RSVPreF3 OA investigational 
vaccine at Visit 1 (Day 1). 
− 
Enrollment rules for disease categories within Cohort 3: 
o 
At least ~25% of participants with cardiopulmonary conditions. 

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o 
At least ~25% of participants with diabetes mellitus. 
o 
The remaining ~50% can be distributed freely across the above 2 disease 
categories as well as include participants with chronic renal or liver disease 
or neurological or neuromuscular disease. 
• 
Duration of the study: Approximately 6 months for all participants.  
• 
Sampling schedule: Three blood samples (approximately 15 mL each) will be 
collected from all participants in Part A (Cohort 1 and Cohort 2) to evaluate humoral 
immune response to the investigational RSVPreF3 OA vaccine on Visit 1 (pre-
intervention), Visit 2 (Day 31, post-study intervention) and Visit 3 (Month 6, post-
study intervention). 
 
 
. No blood samples will be collected 
from participants in Part B (Cohort 3). 
• 
Primary completion date: Completion of last Visit 2 at Day 31 after the study 
intervention for participants in Part A. 
• 
Blinding: Open-label, all participants will receive the RSVPreF3 OA investigational 
vaccine. 
• 
Data collection: A standardized electronic case report form (eCRF) will be used. 
Solicited events will be collected by the participant using an eDiary. Unsolicited AEs 
and new concomitant medications/vaccinations will be collected in source 
documents by the PI or delegated study team member prior to entering them in the 
eCRF and this until study end. 
• 
Safety monitoring: The study will be conducted with oversight by the project SRT.  
• 
Dosing schedule: Participants will receive a single dose of the investigational study 
intervention (RSVPreF3 OA) at Visit 1 (Day 1). 
Refer to the SoA in Section 1.3 for additional details. 
4.2. 
Scientific rationale for study design 
RSV is a respiratory infection which may lead to an increased risk for RSV disease in OA 
and adults AIR for RSV disease. The efficacy of a single dose of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV disease in OA ≥60 YOA has been 
established in the Phase 3 clinical study RSV OA=ADJ-006 (refer to IB). 
The immune response of AIR patients has been shown to be non-inferior in patients aged 
50-59 compared to the OA population as of 60 YOA. Part A of this study aims to 
continue exploring the immune response of patients considered AIR between the ages of 
18-49. By including a cohort of OA with the same inclusion and exclusion criteria as in 
the pivotal RSV OA=ADJ-006 efficacy study in this study, vaccine efficacy can 
potentially be inferred based on NI of the immune response.  
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Lastly, safety of the RSVPreF3 OA investigational vaccine will be evaluated in Part A 
and Part B of the study. By including Part B, safety will be evaluated in a larger sample 
size of adults AIR aged between 18-49, which will allow better characterization of the 
safety profile of the RSVPreF3 OA investigational vaccine in this population.  
4.2.1. 
Participant input into design 
Not applicable. 
4.3. 
Justification for dose 
A single dose (0.5 mL) of the licensed formulation (120 μg RSVPreF3/AS01E) will be 
used in this study. 
4.4. 
End-of-study definition 
A participant is considered to have completed the study if the participant has completed 
visits of the study including the last visit or the last scheduled procedure shown in the 
SoA. 
EOS: LSLV (Visit 3/contact) or Date of the last testing/reading released of the Human 
Biological Samples, related to primary and secondary endpoints, whichever occurs later. 
EOS must be achieved no later than 8 months after LSLV. EOS cannot be before LSLV. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
• 
Participants and/or participant’s parent(s)/LAR who, in the opinion of the 
investigator, can and will comply with the requirements of the protocol (e.g., 
completion of the eDiary, attend study site visits, ability to access and utilize a phone 
or other electronic communications). INC#1 
Note: for participants in case of physical incapacity that would preclude the 
self-completion of the eDiary, either (i) site staff can assist the participant (for 
activities performed during site visits) (ii) or the participant may assign a caregiver 
to assist him/her with this activity (for activities performed at home). However, at no 
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time will the site staff or caregiver evaluate the participant’s health status while 
completing eDiaries or make decisions on behalf of the participant. 
• 
Written or witnessed informed consent obtained from the participant/participant’s 
parent(s)/LAR(s) (participant must be able to understand the informed consent) prior 
to performance of any study-specific procedure. INC#2 
Written informed assent obtained from the participant (participant must be able to 
understand the informed assent) if he/she is less than the legal age* prior to 
performance of any study-specific procedure. 
*The legal age is determined according to local regulations in each participating 
country. In case the legal age is achieved during the conduct of the study, an 
additional written informed consent from the participant should be obtained at the 
time of the legal age. 
5.1.1. 
Specific inclusion criteria for all participants in Cohort 1 and 
Cohort 3 
• 
A male or female participant 18-49 YOA at the time of the study intervention 
administration. INC#3 
• 
Participants should be diagnosed with at least 1 of the following medical conditions 
if considered medically stable* by the investigator: INC#4 
*A stable condition is defined as a disease not requiring significant change (based 
on the investigator’s opinion) in therapy or worsening during the 3 months before 
enrollment. 
- 
Chronic cardiopulmonary disease resulting in activity restricting symptoms or 
use of long‑term medication: 
o 
Chronic obstructive pulmonary disease (COPD) 
• 
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 
Grade 2-4 
o 
Asthma 
• 
Patient on Maintenance and Reliever Therapy (MART) OR with at 
least one rescue treatment per week (excluding exercise asthma)  
o 
Cystic fibrosis 
o 
Other chronic respiratory diseases: lung fibrosis, restrictive lung disease, 
interstitial lung disease, emphysema or bronchiectasis 
o 
Chronic heart failure: 
• 
A minimum of class II symptoms according to New York Heart 
Association classification of heart failure 
o 
Pre-existing CAD (CAD not otherwise specified) 

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• 
Physician diagnosis of CAD based on electrocardiogram, exercise 
stress test, nuclear stress test, cardiac computed tomography scan or 
cardiac angiogram (more than the presence of hypercholesterolemia) 
o 
Cardiac arrhythmia 
• 
Patient diagnosed with a cardiac arrythmia that require medical support 
either pharmacologically or with a medical device 
- 
Diabetes mellitus: types 1 or 2 with active treatment for the past 6 months 
- 
Other diseases at increased risk for RSV disease 
o 
Chronic kidney disease 
• 
G2-G3 disease (Glomerular Filtration Rate between 30 and 
90 ml/min/1.73 m2) 
o 
Chronic moderate to severe liver disease 
o 
Neurologic or neuromuscular conditions (for specific exclusion criteria, see 
Section 5.2.1) 
• 
Female participants of non-childbearing potential may be enrolled in the study. 
Nonchildbearing potential is defined as premenarche, hysterectomy, bilateral 
oophorectomy, bilateral salpingectomy or post-menopause. INC#5 
• 
Female participants of childbearing potential may be enrolled in the study, if the 
participant: 
- 
has practiced adequate contraception from 1 month prior to study intervention 
administration, and 
- 
has a negative pregnancy test on the day of study prior to intervention 
administration, and 
- 
has agreed to continue adequate contraception for at least 1 month after 
completion of the study intervention administration. INC#6 
Refer to Section 10.4.1 for definitions of woman of childbearing potential and non-
childbearing potential, and Section 10.4.2 on adequate contraception. 
5.1.2. 
Specific inclusion criteria for all participants in Cohort 2 
• 
A male or female participant 60 YOA at the time of the study intervention 
administration. INC#7 
• 
Participants with chronic stable medical conditions with or without specific 
treatment, such as diabetes, hypertension or cardiac disease are allowed to participate 
in this study if considered medically stable* by the investigator. INC#8 
*A stable condition is defined as disease not requiring significant change (based on 
the Investigator's opinion) in therapy or worsening disease during the 3 months 
before enrollment. 

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• 
Participants living in the general community or in an assisted-living facility that 
provides minimal assistance, such that the participant is primarily responsible for 
self-care and activities of daily living. INC#9 
5.2. 
Exclusion criteria  
Participants are excluded from the study if any of the following criteria apply: 
5.2.1. 
Medical conditions 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition 
resulting from disease (e.g., current malignancy, human immunodeficiency virus) or 
immunosuppressive/cytotoxic therapy (e.g., medication used during cancer 
chemotherapy, organ transplantation, or to treat autoimmune disorders), based on 
medical history and physical examination (no laboratory testing required). EXC#1 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study intervention (For details on components of study 
intervention administered, refer to Arexvy SmPC/Prescribing Information [Arexvy 
Summary of Product Characteristics, 2023; Arexvy Prescribing Information, 2023] 
and Table 9 in Section 6.1). EXC#2 
• 
Unstable* chronic illness. EXC#3 
*Unstable condition is defined as a disease that does not fall under the definition of 
stable disease in Section 5.1.1. 
• 
Any history of dementia or any medical condition that moderately or severely 
impairs cognition. EXC#4 
Note: If deemed necessary for clinical evaluation, the investigator can use tools such 
as Mini-Mental State Exam, Mini-Cog or Montreal Cognitive Assessment (to 
determine cognition levels of the participant). 
• 
Recurrent or uncontrolled neurological disorders or seizures. Participants with 
medically controlled active or chronic neurological diseases can be enrolled in the 
study as per investigator assessment, provided that their condition will allow them to 
comply with the requirements of the protocol (e.g., completion of the diary cards, 
attend study site visits). Study participants may decide to assign a caregiver to help 
them complete the study procedures. EXC#5 
• 
Significant underlying illness that in the opinion of the investigator would be 
expected to prevent completion of the study (e.g., life-threatening disease). EXC#6 
• 
Any medical condition that in the judgment of the investigator would make 
intramuscular injection unsafe. EXC#7 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study. EXC#8 

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5.2.2. 
Prior/Concomitant therapy 
• 
Use of any investigational or non-registered product (drug, vaccine, or medical 
device) other than the study intervention during the period beginning 30 days before 
the dose of study intervention (Day -29 to Day 1), or planned use during the study 
period (up to Visit 3/ contact, Month 6). EXC#9 
• 
Planned or actual administration of a vaccine not foreseen by the study protocol in 
the period starting 30 days before and ending 30 days after the dose of study 
intervention administration*, with the exception of inactivated, subunit and split 
influenza vaccines or COVID-19 vaccines which can be administered up to 14 days 
before or from 14 days after the study intervention administration. EXC#10 
Note: In case an emergency mass vaccination for an unforeseen public health threat 
(e.g., a pandemic) is recommended and/or organized by the public health authorities, 
outside the routine immunization program, the time period described above can be 
reduced if necessary for that vaccine provided it is used according to the local 
governmental recommendations and that the Sponsor is notified accordingly. 
• 
Previous vaccination with any RSV vaccine, including investigational RSV vaccines. 
EXC#11 
• 
Chronic administration of immune-modifying drugs (defined as more than 
14 consecutive days in total) and/or administration of long-acting immune-modifying 
treatments or planned administration at any time up to the EOS. EXC#12 
− 
Up to 3 months prior to the study intervention administration: 
o 
For corticosteroids, this will mean prednisone 20 mg/day, or equivalent. 
Inhaled, topical and intra-articular steroids are allowed. 
o 
Administration of immunoglobulins and/or any blood products or plasma 
derivatives 
− 
Up to 6 months prior to study intervention administration: long-acting immune-
modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), 
monoclonal antibodies, antitumoral medication. 
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 or invasive medical device). EXC#13 
5.2.4. 
Other exclusions 
5.2.4.1. 
Other exclusions for all participants 
• 
History of chronic alcohol consumption and/or drug abuse as deemed by the 
investigator to render the potential participant unable/unlikely to provide accurate 
safety reports or comply with study procedures. EXC#14 
• 
Bedridden participants. EXC#15 

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• 
Planned move during the study period that will prohibit participating in the study 
until study end. EXC#16 
• 
Participation of any study personnel or their immediate dependents, family, or 
household members. EXC#17 
5.2.4.2. 
Other exclusions for Cohort 1 and Cohort 3 
• 
Pregnant or lactating female participant. EXC#18 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions within 1 month after study intervention administration. EXC#19 
5.3. 
Lifestyle considerations 
No restrictions are required. 
5.4. 
Screen failures 
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently entered in the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to 
meet the CONSORT publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility 
criteria, and any SAEs related to study procedures/concurrent GSK medication. 
5.5. 
Criteria for temporarily delaying enrollment/ administration 
of study intervention 
Enrollment/study intervention administration may be postponed until transient conditions 
cited below are resolved, and prior to the end of the study enrollment period: 
• 
Acute disease and/or fever at the time of enrollment and/or study intervention 
administration. Refer to the SoA in Section 1.3 and Section 8.3.1.2 for definition of 
fever and preferred location for measuring temperature in this study. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be enrolled and/or dosed at the discretion of the 
investigator.  
• 
Participants with symptoms suggestive of active COVID-19 infection (e.g., fever, 
cough, etc.). The return of the participant to the site will follow the specific guidance 
from local public health and other competent authorities (e.g., free of symptoms, 
COVID-19 negative testing, etc.). 
• 
Participants with known COVID-19 positive contacts may be dosed at least 14 days 
after the exposure, provided that the participant remains symptom-free, and at the 
discretion of the investigator. 
• 
In case of administration of inactivated and subunit influenza vaccines and COVID-
19 vaccines: postponement of study intervention administration within given 
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respect of at least 14 days interval between flu/COVID-19 vaccination and study 
intervention administration. 
• 
In case of administration of any other vaccines, postponement of study intervention 
administration within given protocol timelines and prior to the end of the study 
enrollment period, to allow respect of at least 30 days interval between other 
vaccination and study intervention administration. 
All efforts should be made so that blood sample is taken on the same date as vaccination.  
The following procedures must be repeated prior to the delayed study intervention 
administration: 
• 
Blood sampling (applicable for Part A only) 
• 
Urine for pregnancy testing 
• 
Body temperature and vital signs 
• 
Physical examination 
• 
Re-check contradictions, warnings, and precautions to study intervention 
• 
Re-check inclusion/exclusion criteria 
Visit window for Visit 2 starts from day of first study administration. 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
The definition of study intervention is provided in the Definition of Terms. 
6.1. 
Study intervention(s) administered 
Study intervention administered is mentioned in Table 9 below. Refer to Section 4.1 for 
study intervention administration schedule. 
Table 9 
Study Intervention administered 
Study intervention name: 
RSVPreF3 OA Investigational Vaccine 
Study intervention formulation: 
RSVPreF3 (120 µg) 
AS01E: QS-21* (25 µg), MPL 
(25 µg), liposomes; Water for 
injections 
Presentation: 
Powder for suspension for 
injection; Vial 
Suspension for suspension for 
injection; Vial 
Type: 
Investigational 
Product category: 
Biologic 
Route of administration:  
IM 
Administration site: 
• 
Location 
Deltoid 
• 
Directionality 
Upper 
• 
Laterality ** 
Non-Dominant 
Number of doses to be administered: 
1 
Volume to be administered by dose ***: 
0.5 mL 
Packaging and labeling: 
Refer to the pharmacy manual for more details 
Manufacturer: 
GSK 
 GSK=GlaxoSmithKline Biologicals SA; IM=Intramuscular; MPL=Monophosphoryl lipid A; OA=Older adults 

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* QS-21: Quillaja saponaria Molina, fraction 21 (Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation)  
** The non-dominant arm is the preferred 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. 
*** Refer to the pharmacy manual for the volume after re-constitution. 
Study participants must be observed closely for at least 30 minutes after the 
administration of the study intervention. Appropriate medical treatment and equipment 
must be readily available during the observation period in case of anaphylaxis or 
syncope. 
6.1.1. 
Medical devices 
• 
There are no GSK manufactured medical devices (or devices manufactured for GSK 
by a third party) provided for use in this study. Other medical devices (not 
manufactured by or for GSK) provided for use in this study are thermometer for 
body temperature measurement, ruler for skin reaction measurement, materials for 
study intervention administration, syringes, blood collection kits, and cup for urine 
collection. 
• 
Instructions for medical device use are provided in Laboratory Manual and 
Pharmacy Manual. 
• 
Complaints related to medical devices should be reported to GSK as detailed in the 
Pharmacy Manual. 
6.2. 
Preparation, handling, storage, and accountability 
• 
The investigator or designee must confirm appropriate conditions (e.g., temperature) 
have been maintained during transit for all study intervention received, and any 
discrepancies are reported and resolved before use of the study intervention. 
• 
Only participants enrolled in the study may receive study intervention, and only 
authorized site staff may supply, prepare, or administer study intervention. 
• 
All study intervention must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. 
• 
The investigator, institution, the head of the medical institution (where applicable), 
or authorized site staff is responsible for study intervention accountability, 
reconciliation, and record maintenance (i.e., receipt, reconciliation, and final 
disposition records). 
• 
Further guidance and information for the final disposition of unused study 
interventions are provided in the pharmacy manual. 

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6.3. 
Assignment to study intervention 
6.3.1. 
Participant identification 
Participant identification numbers will be assigned sequentially to the individuals who 
have consented to participate in the study. Each study center will be allocated a range of 
participant identification numbers. 
6.3.2. 
Randomization to study intervention 
All participants will receive 1 dose of the RSVPreF3 OA investigational vaccine at 
Visit 1 (Day 1). 
The assignment of clinical trial supplies will be performed using a GSK RTSM system. 
6.3.3. 
Intervention allocation to the participant 
The subject level study intervention assignment activity is conducted using a GSK RTSM 
system. 
Participants in Part A will be enrolled into 2 different cohorts. 
• 
Participants 18-49 YOA at increased risk for RSV disease will be enrolled into 
Cohort 1 in 3 disease categories (cardiopulmonary conditions, diabetes mellitus and 
other disease categories), with approximately 25% of participants with 
cardiopulmonary conditions and approximately 25% of participants with diabetes 
mellitus. The remaining approximately 50% can be distributed freely across the 
above 2 disease categories as well as include participants with chronic renal or liver 
disease or neurological or neuromuscular disease. In terms of the sex as well 
approximately 35% of male participants, approximately 35% of female participants 
and remaining 30% can be distributed freely across the 2 categories will be enrolled 
to Cohort 1. 
• 
Participants in Cohort 2 will be enrolled in 2 age categories (60-69 YOA and 
≥ 70 YOA), with approximately 40% of participants 60-69 YOA and approximately 
30% of participants ≥ 70 YOA. The remaining 30% can be distributed freely across 
the 2 age categories. In terms of the sex as well approximately 35% of male 
participants, approximately 35% of female participants and remaining 30% can be 
distributed freely across the 2 categories will be enrolled to Cohort 2. 
Participants in Part B will be enrolled into 1 cohort. 
• 
Participants 18-49 YOA at increased risk for RSV disease (Cohort 3) will be enrolled 
in 3 disease categories (cardiopulmonary conditions, diabetes mellitus and other 
disease categories), with approximately 25% of participants with cardiopulmonary 
conditions and approximately 25% of participants with diabetes mellitus. The 
remaining approximately 50% can be distributed freely across the above 2 disease 
categories as well as include participants with chronic renal or liver disease or 
neurological or neuromuscular disease. In terms of the sex approximately 35% of 

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male participants, approximately 35% of female participants and remaining 30% can 
be distributed freely across the 2 categories. 
The RTSM system will assign the study intervention number. Recruitment caps are 
managed by the RTSM system. 
When RTSM system is not available, please refer to the Pharmacy Manual for 
instructions. 
Refer to the Pharmacy Manual for additional information about the study intervention 
number allocation. 
6.4. 
Blinding 
This is an open-label study. 
6.5. 
Study intervention compliance 
When participants are dosed at the site, they will receive study intervention directly from 
the investigator or designee, under medical supervision. The date of the dose as well as 
kit number administered in the clinic will be recorded in the source documents.  
A record of the quantity of RSVPreF3 OA investigational vaccine administered to each 
participant must be maintained and reconciled with study intervention and compliance 
records. 
6.6. 
Dose modification 
Not applicable. 
6.7. 
Continued access to study intervention after the end of the 
study 
There is no plan to provide continued access to the study intervention following the end 
of study. 
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During the study conclusion visit, the investigator will ask each participant/participant’s 
parent(s)/LAR(s) if they are interested in participating/allowing the participant to join any 
potential booster or long-term evaluation studies. If a participant/participant’s 
parent(s)/LAR(s) are not interested in joining any potential booster or long-term 
evaluation studies the reason for refusal will be documented, when available, in the 
participant’s eCRF. 
6.8. 
Treatment of overdose 
Not applicable. 
6.9. 
Prior and concomitant therapy 
At each study visit, the investigator(s) or their delegate(s) 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 medication including vaccines/products, except vitamins and dietary 
supplements, administered during the 30-day period after the dose of study 
intervention (Day 1 to Day 30). 
• 
All concomitant medication leading to elimination from the analysis, including 
products/vaccines. Please refer to the Section 5.2.2 for further details. 
• 
All concomitant medication which may explain/cause/be used to treat an 
SAE/pIMD/AESI including vaccines/products, as defined in Section 8.4.1 and 
Section 10.3.5. These must also be recorded in the Expedited AE Report (as 
applicable). 
− 
For all AF AESIs (including serious and non-serious), concomitant drugs which 
could be associated with development or worsening of AF must be reported in 
the AF follow-up questionnaire. 
• 
Any prophylactic medication (e.g., analgesics, antipyretics) administered in the 
absence of ANY symptom and in anticipation of a reaction to the study intervention 
administration. 
• 
Any medication or vaccine (including over-the-counter or prescription medicines, 
recreational drugs, vitamins, and/or herbal supplements) or other specific categories 
of interest that the participant is receiving at the time of enrolment or receives during 
the study must be recorded along with: 
− 
Reason for use 
− 
Dates of administration including start and end dates 
− 
Dosage information including dose and frequency 
• 
Any antipyretic administered in the period starting 6 hours before vaccination and 
ending 12 hours after vaccination needs to be recorded on the eCRF. 

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The Medical monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Medications that are contraindicated for use in this study are stipulated in the exclusion 
criteria in Section 5.2.2. 
Table 10 describes prohibited medications (that could impact evaluation of participants 
baseline status, safety and efficacy assessments) and the required washout period prior to 
study intervention administration. Generally, these medications are prohibited until after 
study end (Visit 3/contact, Month 6), unless otherwise stated below. 
Medications that are not stipulated in the exclusion criteria or listed in Table 10 may be 
used based on the discretion of the investigator (after careful evaluation whether or not 
the medication could impact evaluation of the clinical trial objective or the safety of the 
participant). 
Table 10 
Prohibited medications and washout period  
Prohibited medications 
Washout period 
Investigational or non-registered product 
30 days prior to first dose until Visit 3 (Part A) and 
contact (Part B) 
Vaccine 
30 days prior to first dose until 30 days after study 
administration (Visit 1)1 
Immune-modifying drugs >14 consecutive days in total 
3 months prior to first dose until Visit 3 (Part 
A)/Contact (Part B)2 
Long-acting immune-modifying treatments (e.g., 
immunotherapy (e.g., TNF-inhibitors), monoclonal 
antibodies, antitumoral medication) 
6 months prior to first dose until Visit 3 (Part A)/ 
Contact (Part B) 
Immunoglobulins and/or any blood products or plasma 
derivatives2 
3 months prior to first dose until Visit 3 (Part A)/ 
Contact (Part B) 
1 Any vaccine. However, for COVID-19 and inactivated/subunit/split influenza vaccines (fully licensed or with EUA), this 
time window can be decreased to 14 days before and after each dose. If emergency mass vaccination for an 
unforeseen public health threat (e.g., a pandemic) is recommended and/or organized by the public health 
authorities outside the routine immunization program, the time period of 30 days 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.  
2For corticosteroids, this will mean prednisone equivalent ≥20 mg/day, or equivalent. Please note: Inhaled, topical and 
intra-articular steroids are allowed. 
Refer to Table 11 for an overview of the timing for recording of concomitant medication 
during the study. 
Table 11 
Timing of collection of concomitant medication to be recorded  
 
Dose 1 
Study conclusion 
(Visit 3/ contact at 
Month 6) 
 
Day 1 
Day 30 
All concomitant medication including vaccines/products, except 
vitamins and dietary supplements 
 
 
 
All concomitant medication including products/vaccines leading 
to elimination from the analysis 
 
 
 
All concomitant medication including vaccines/products which 
may explain/cause/be used to treat an SAE/AESI (pIMD and 
AF*) 
 
 
 
Any prophylactic medication 
 
 
 

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AESI: Adverse event of special interest; AF=Atrial Fibrillation; pIMD=Potential immune-mediated disease; 
SAE=Serious adverse event. 
Note: The collection period for the concomitant medications to be recorded in eCRF is indicated in gray. 
* For all AF AESIs (including serious and non-serious), concomitant drugs which could be associated with development 
or worsening of AF must be reported in the AF follow-up questionnaire. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
Not applicable to this study. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant may withdraw from the study at any time at the participant’s own request 
for any reason (or without providing any reason). 
A participant may be withdrawn at any time at the discretion of the investigator for 
safety, behavioral, or compliance reasons. 
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. If the participant withdraws 
consent for disclosure of future information, the sponsor may retain and continue to use 
any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, the participant may request destruction of 
samples taken and not tested, and the investigator must document this in the site study 
records. Local regulations may also require that any samples taken and not yet tested at 
the time a participant withdraws from the study are destroyed. 
A participant can also request for the destruction of their samples any time during the 
study. The investigator must document the request in the site study records.  
The primary reason for participant discontinuation/ withdrawal from the study will be 
documented in the eCRF based on the list below: 
Reasons 
Additional items/Sub-reasons 
AE 
Unsolicited AE 
Solicited event 
SAEs/AESIs 
Lost to follow-up 
Unknown 
Other, Specify 
Protocol deviation 
 

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Reasons 
Additional items/Sub-reasons 
Investigator Decision 
Specify 
Pregnancy 
  
Site Terminated by Sponsor 
  
Study Terminated by Sponsor 
  
Withdrawal by Participant 
Burden of Procedure  
Participant Relocated  
Pandemic  
Other, Specify 
Death 
 
Other 
Specify 
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/AESI until the 
event is resolved, stabilized, otherwise exaplained, or the participant is lost to follow up 
(see Section 10.3.5.5). 
7.3. 
Lost to follow-up 
A participant will be considered lost to follow-up if the participant repeatedly fails to 
return for scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls, and if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• 
Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study.  
• 
Site personnel will attempt to collect the vital status of the participant within legal 
and ethical boundaries for all participants randomized, including those who did not 
get study intervention. Public sources may be searched for vital status information. If 
vital status of the participant is determined as deceased, this will be documented, and 
the participant will not be considered lost to follow-up. Sponsor personnel will not 
be involved in any attempts to collect vital status information. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA in Section 1.3. 
Protocol waivers or exemptions are not allowed. 
• 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
Immediate safety concerns should be discussed with the sponsor as soon as they 
occur or when the study team becomes aware of them. In case of doubts of 
immediate safety concerns regarding the inclusion of a possible participant, inclusion 
should be postponed until a decision can be made. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria prior to study intervention administration. 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. Participants who have signed informed consent but 
are not eligible to proceed should be recorded in the eCRF with a status of ‘screen 
failure’. 
• 
If allowed by country regulation/ethics, study visits may be conducted remotely (by a 
HHS professional or site’s own staff) and/or virtually (secure video conferences, 
phone calls, or a web portal and/or mobile application), as per the SoA. 
• 
In the event of a significant study-continuity issue (e.g., caused by a pandemic), 
alternate strategies for participant visits, assessments, study intervention distribution 
and monitoring may be implemented by the sponsor or the investigator, as per local 
health authority/ethics requirements. 
• 
The maximum amount of blood collected from each participant in Part A (Cohort 1 
and 2) over the duration of the study, related to procedures in this study, will not 
exceed 45 mL and 
 
 Repeat or unscheduled samples may be taken once at every 
timepoint for technical issues with the samples. 
• 
Study participants may decide to assign a caregiver to help them fulfill the study 
procedures. 
• 
It is preferred to have all visits on-site. However, during special circumstances (e.g.,  
pandemic, patients for whom the transfer to the clinic has become very difficult), the 
specific guidance from local public health, if applicable, and other competent 
authorities regarding the protection of individuals’ welfare must be applied and 
consulted with the sponsor. For the duration of such special circumstances, the 
following measures may be implemented for enrolled participants: 
− 
For Part A, Visit 3 may be conducted at the participant’s home (by the site 
staff), if appropriate. Biological sample at Visit 3 may be collected at 
participant’s home. Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use. 
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− 
For Parts A and B, if the eDiary device has been provided by GSK it may be 
transmitted from and to the site by courier service if allowed by local regulations 
and or collected at home. 
• 
Impact of visits performed outside of the site’s location on the PPS for 
immunogenicity will be determined on a case-by-case basis. 
8.1. 
Administrative baseline procedures 
8.1.1. 
Collection of demographic data 
Record demographic data such as year of birth, sex, race*, and ethnicity in the 
participant’s eCRF.  
Collection of sex, race and ethnicity data is necessary to assess and monitor the diversity 
of the trial participants, and to determine if the trial participants are truly representative of 
the impacted population. 
*Differences in the safety and efficacy of certain medical products, including vaccines 
[Haralambieva, 2013; Pérez-Losada, 2009; Kollmann, 2013] have been observed in 
racially and ethnically distinct subgroups. These differences may be attributable to 
intrinsic factors (e.g., genetics, metabolism, elimination), extrinsic factors (e.g., diet, 
environmental exposure, sociocultural issues), or interactions between these factors. 
Therefore, both geographic ancestry (race) and ethnicity will be collected for all study 
participants. 
Year of birth is collected to stratify the population and determine the impact of the study 
intervention by age.  
8.1.2. 
Medical/vaccination history 
Obtain the participant’s medical/vaccination history by interviewing the 
participant/parent(s)/LAR(s) and/or review of the participant’s medical records. Record 
any relevant pre-existing conditions, signs and/or symptoms present prior to the study 
intervention/study start in the eCRF. 
Any vaccine administered up to 1 year before study vaccine administration should be 
recorded in the eCRF with date of vaccination. For history of influenza vaccination, 
information about the vaccine formulation (e.g., adjuvanted or non-adjuvanted or 
high-dose) should be recorded. 
Administration of Shingrix and any COVID-19 vaccine/vaccines (if multiple 
doses/administrations) at any timepoint (even if longer than 1 year before the study 
vaccine administration) should be recorded in the eCRF. The date of vaccinations should 
be collected and recorded in the eCRF. 
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8.1.3. 
Measure height and weight 
Measure the participant’s height and weight and record the values in the eCRF.  
8.1.4. 
Smoking status and smoking exposure history 
The smoking status will be collected in the eCRF, differentiating tobacco use (cigarettes, 
cigars, cigarillos, pipes, etc.) and use of electronic smoking devices (e-cigarettes). Refer 
to Definition of Terms for the definitions of current and former smoker. 
Smoking exposure history should be recorded as number of years for both current and 
former smokers. When applicable, the number of years of exposure should be collected 
separately for tobacco and electronic smoking devices. 
All data will be recorded in the participant’s eCRF. 
8.2. 
Immunogenicity assessments 
Planned timepoints for all immunogenicity assessments are provided in the SoA. 
Immunogenicty assessments will be performed for participants in Part A only (Cohort 1 
and Cohort 2). 
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/participant’s parent(s)/LAR(s). 
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. 
8.2.1. 
Biological samples 
An overall volume of 45 mL (approximately 15 mL at each visit) will be collected from 
all study participants in Part A (Cohort 1 and Cohort 2) during the entire study period. 

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Refer to SoA in Section 1.3 for information on volumes collected for different 
assessments. 
 
 
Table 12 
Biological samples (Part A)  
Sample type 
Quantity 
Unit 
Timepoint 
Subset name* 
Blood for humoral 
response 
~15 
mL 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
Visit 3 (Month 6) 
All participants (Part A) 
. 
* Refer to Section 6.3 for subset description. 
Blood sample at Visit 1 (Day 1) should be collected prior to study intervention administration. 
8.2.2. 
Laboratory assays 
All clinical testing will be performed at GSK laboratory or in a laboratory designated by 
GSK. 
Table 13 
Laboratory assays (Part A) 
Test Classification 
System 
Component 
Challenge 
Method 
Laboratory 
Humoral immunity 
(antibody determination) 
Serum 
RSV-A 
neutralizing 
titer 
Neutralization 
GSK* 
Serum 
RSV-B 
neutralizing 
titer 
Neutralization 
GSK* 
GSK* 
; GSK=GlaxoSmithKline Biologicals 
SA; ICS=Intracellular cytokine staining; 
 
RSV=Respiratory syncytial virus; 
;
. 
 
 
 
Please refer to 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 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. 
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8.2.3. 
Immunological read-outs 
Immunological read-outs are described in Table 14. 
Table 14 
Immunological read-outs (Part A) 
Blood sampling time point 
Subset name 
No. of 
participants 
Component 
Type of contact and 
time point 
Sampling time 
point 
Humoral immunity (on serum samples) 
Visit 1 (Day 1) 
Pre-Adm 
All 
participants 
~850 
RSV-A neutralizing titer 
RSV-B neutralizing titer 
Visit 2 (Day 31) 
Day 31 
All 
participants 
~850 
RSV-A neutralizing titer 
RSV-B neutralizing titer 
Visit 3 (Month 6) 
Month 6 
All 
participants 
~850 
RSV-A neutralizing titer 
RSV-B neutralizing titer 
 
 
Pre-Adm=Pre-study intervention administration; RSV=Respiratory syncytial virus; 
 
 
 
 
 
8.2.4. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen used in the RSVPreF3 OA investigational vaccine. 
8.3. 
Safety assessments 
Planned timepoints for all safety assessments are provided in the SoA. 
8.3.1. 
Pre-study intervention administration procedures 
8.3.1.1. 
Physical examination 
History directed physical examination will be performed for each participant. 
If the investigator determines that the participant’s health on the day of study intervention 
administration temporarily precludes dosing, the visit will be rescheduled. Refer to the 
Section 5.5 for the list of criteria for temporary delay of study intervention 
administration. Treatment of any abnormality observed during this examination has to be 
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performed according to local medical practice outside this study or by referral to an 
appropriate health care provider. 
8.3.1.2. 
Vital signs 
At a minimum, oral or axillary temperature, pulse rate, respiratory rate, and blood 
pressure will be recorded. 
The body temperature of each participant needs to be measured prior to study 
intervention administration and recorded in the eCRF. The location for measuring 
temperature will be oral or axillary. If the participant has fever (defined as temperature 
≥38.0°C/100.4°F regardless of the location of measurement) on the day of study 
intervention administration, the visit will be rescheduled (refer to Section 5.5 for details). 
Vital signs are to be taken after at least 10 minutes of rest and before blood collection for 
laboratory tests and will consist of systolic/diastolic blood pressure, heart rate and 
respiratory rate by counting the number of breaths for 1 minute. 
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
Collected information needs to be recorderd in the eCRF. 
8.3.1.3. 
Pregnancy testing 
Female participants of childbearing potential must perform 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 Section 8.4.6 for the information on study continuation for participants who 
become pregnant during the study.  
8.3.2. 
Post-study intervention administration procedures 
8.3.2.1. 
Physical examination 
Physical examination at each study visit after the study intervention administration will 
be performed only if the participant/participant’s parent/LAR(s) indicates during 
questioning that there might be some underlying pathology(ies) or if deemed necessary 
by the investigator or delegate. Should there be an underlying condition or illness that is 
diagnosed in any of these visits, this will be adequatly recorded in eCRF. 
8.3.3. 
Warnings and precautions to administration of study intervention 
Refer to Arexvy SmPC/Prescribing Information [Arexvy Summary of Product 
Characteristics, 2023; Arexvy Prescribing Information, 2023]. 

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Warnings and precautions to administration of study intervention must be checked at 
Visit 1 (Day 1) as specified in SoA. 
8.3.4. 
Safety monitoring and Committee 
• 
Participant safety will be continuously monitored by the Medical Monitor, 
designated Safety Lead (or delegate) and SRT, throughout the study. Pertinent 
findings and conclusions are shared with the product’s SRT for review of the overall 
benefit-risk profile of the product. 
8.4. 
Adverse Events (AEs), serious adverse events (SAEs), and 
other safety reporting 
For definitions relating to safety information see Section 10.3 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording events that meet the definition of an AE or SAE or pIMD and other safety 
information and remain responsible for following up all AEs (see Section 7). This 
includes events reported by the participant (or, when appropriate, by a caregiver, or the 
participant’s legally authorized representative). 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.1. 
Time period and frequency for collecting AE, SAE, and other 
safety information 
All AEs and SAEs will be collected at time points specified in the SoA (Section 1.3). 
AF reporting will follow the same reporting periods as for AEs and SAEs. Non-serious 
AF with an onset during the 30-day period following each study vaccine administration 
will be collected. The reporting of AF meeting the SAE definition (serious AF) will be 
performed according to the SAE reporting period. 
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 (non-IMP) will 
be recorded from the time a participant consents to participate in the study. 
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded as medical history/current medical conditions, not as 
AEs. 

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Table 15 
Collection and reporting of safety information  
Event 
Pre-adm* 
Day 1 
Adm 
6 months post-
intervention and 
study conclusion 
Day 1 
Day 4# 
Day 30 
Month 6 
Solicited administration 
site and systemic solicited 
AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs† 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SAEs and AESIs 
(including pIMDs and AF†) 
and fatal SAEs† 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation**  
or concurrent GSK 
medication/ vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intercurrent medical 
conditions*** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AF=Atrial fibrillation; Pre-adm=pre-study intervention administration; Adm=study intervention administration; 
AE=Adverse event; SAE=Serious adverse event; pIMD=Potential immune-mediated disease. 
* Corresponds to the day when informed consent/informed assent is obtained (Day 1, prior to study intervention 
administration). 
** Any SAE assessed as related to study participation (e.g., protocol-mandated procedures, invasive tests) or related to 
a GSK product will be recorded from the time a participant consents to participate in the study. 
*** A condition that has the capability of altering the immune response to the study vaccine or is confirmed to have an 
alteration of the participant’s initial immune status. 
†Atrial fibrillation will be considered as AESI in this study and will be additionally reported in the AF follow-up 
questionnaire in (electronic or paper) in eCRF. The collection of AF will be performed following the AE/SAE 
reporting periods. The reporting of non-serious AF will be performed according to the unsolicited AE reporting 
period. The reporting of AF meeting the SAE definition (serious AF) will be performed according to the SAE 
reporting period. 
# Day 4 is not a visit/contact at site. 
The shaded region in the table indicates time period of data collection. 
All SAEs will be recorded and reported to the sponsor or designee immediately and under 
no circumstance should this exceed 24 hours, as indicated in Section 10.3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
A poststudy AE/SAE is defined as any event that occurs outside of the AE/SAE reporting 
period defined in Section 8.4.1. 

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Investigators are not obligated to actively seek information on AEs or SAEs after 
conclusion of the study participation. However, if the investigator learns of any SAE, 
including a death, after a participant has been discharged from the study, the investigator 
must record it in the medical records. If the investigator considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor. 
8.4.2. 
Method of detecting AEs and SAEs  
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
nonleading verbal questioning of the participant/participants’ parent(s)/LAR(s) is the 
preferred method to inquire about AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and AESIs [and AEs of special 
interest (as defined in Section 8.4.4)] will be followed until resolution, stabilization, the 
event is otherwise explained, or the participant is lost to follow-up (as defined in Section 
7.3). For AF cases, the investigator will provide any new or updated relevant information 
on previously reported AF during the study to GSK using a paper/electronic Expedited 
AEs Report and the AF follow-up questionnaire as applicable. Further information on 
follow-up procedures is provided in Section 10.3.5.5. 
8.4.4. 
AESIs  
pIMDs and AF are the AESIs collected during the study. 
Collecting and reporting timeframes for AESIs: 
• 
pIMDs: To be reported from Day 1 (after administration of study intervention) up to 
study end (6 months after administration of study intervention). 
• 
Atrial fibrillation: 
− 
AF Non-serious AEs: to be reported from Day 1 (after administration of study 
intervention) up to Day 30. 
− 
AF SAEs: to be reported from Day 1 (after administration of study intervention) 
up to study end (6 months after administration of study intervention). 
8.4.4.1. 
Potential immune-mediated diseases 
pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory 
and/or neurologic disorders of interest which may or may not have an autoimmune 
etiology. AEs that need to be recorded and reported as pIMDs include those listed in the 
Table 16. 

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In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire and a list of preferred terms (PTs) and PT codes corresponding to the below 
diagnoses will be available to investigators at study start. 
The investigator(s) must exercise their medical/scientific judgment to determine whether 
other diseases have an autoimmune origin (i.e., pathophysiology involving systemic or 
organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. In 
addition, the investigator should categorize each pIMD either as a new onset condition (if 
it started following vaccination) or as an exacerbation of a preexisting chronic condition 
(if it exacerbated following vaccination) in the eCRF. 
Table 16 
List of potential immune-mediated diseases (pIMDs) 
Blood disorders and 
coagulopathies 
Cardio-pulmonary inflammatory 
disorders 
Endocrine disorders 
• 
Antiphospholipid syndrome 
• 
Autoimmune aplastic anemia 
• 
Autoimmune hemolytic 
anemia, including: 
− 
Warm antibody 
hemolytic anemia 
− 
Cold antibody hemolytic 
anemia 
• 
Autoimmune 
lymphoproliferative syndrome 
(ALPS) 
• 
Autoimmune neutropenia  
• 
Autoimmune pancytopenia 
• 
Autoimmune 
thrombocytopenia 
− 
Frequently used related 
terms include: 
“autoimmune 
thrombocytopenic 
purpura”, “idiopathic 
thrombocytopenic 
purpura (ITP)”, 
“idiopathic immune 
thrombocytopenia”, 
“primary immune 
thrombocytopenia”. 
• 
Evans syndrome 
• 
Pernicious anemia 
• 
Thrombosis with 
thrombocytopenia syndrome 
(TTS) 
• 
Thrombotic thrombocytopenic 
purpura 
− 
Also known as 
“Moschcowitz-
syndrome” or 
“microangiopathic 
hemolytic anemia” 
• 
Idiopathic Myocarditis/Pericarditis, 
including: 
− 
Autoimmune / 
Immune-mediated myocarditis 
− 
Autoimmune / Immune-
mediated pericarditis 
− 
Giant cell myocarditis 
• 
Idiopathic pulmonary fibrosis, 
including: 
− 
Idiopathic interstitial pneumonia 
(Interstitial lung disease, 
Pulmonary fibrosis, 
Immune-mediated pneumonitis) 
− 
Pleuroparenchymal 
fibroelastosis (PPFE) 
• 
Pulmonary alveolar proteinosis (PAP) 
− 
Frequently used related terms 
include: “pulmonary alveolar 
lipoproteinosis”, 
“phospholipidosis” 
• 
Addison’s disease 
• 
Autoimmune / Immune-
mediated thyroiditis, 
including: 
− 
Hashimoto 
thyroiditis 
(autoimmune 
hypothyroidism, 
lymphocytic 
thyroiditis) 
− 
Atrophic thyroiditis  
− 
Silent thyroiditis  
− 
Thyrotoxicosis 
• 
Autoimmune diseases of 
the testis and ovary, 
including: 
− 
Autoimmune 
oophoritis 
− 
Autoimmune 
ovarian failure 
− 
Autoimmune orchitis 
• 
Autoimmune 
hyperlipidemia 
• 
Autoimmune hypophysitis 
• 
Diabetes mellitus type I 
• 
Graves’ or Basedow’s 
disease, including: 
− 
Marine Lenhart 
syndrome 
− 
Graves' 
ophthalmopathy, 
also known as 
thyroid eye disease 
(TED) or endocrine 
ophthalmopathy 
• 
Insulin autoimmune 
syndrome 

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• 
Polyglandular 
autoimmune syndrome, 
including: 
− 
Polyglandular 
autoimmune 
syndrome type I, 
II and III 
Eye disorders 
Gastrointestinal disorders 
Hepatobiliary disorders 
• 
Ocular Autoimmune / 
Immune-mediated disorders, 
including: 
− 
Acute macular 
neuroretinopathy (also 
known as acute macular 
outer retinopathy) 
− 
Autoimmune/Immune-m
ediated retinopathy  
− 
Autoimmune/Immune-m
ediated uveitis, 
including idiopathic 
uveitis and sympathetic 
ophthalmia  
− 
Cogan's syndrome: an 
oculo-audiovestibular 
disease 
− 
Ocular pemphigoid 
− 
Ulcerative keratitis 
− 
Vogt-Koyanagi-Harada 
disease 
• 
Autoimmune / Immune-mediated 
pancreatitis 
• 
Celiac disease 
• 
Inflammatory Bowel disease, 
including: 
− 
Crohn’s disease  
− 
Microscopic colitis  
− 
Terminal ileitis 
− 
Ulcerative colitis  
− 
Ulcerative proctitis 
• 
Autoimmune cholangitis 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing 
cholangitis 
Musculoskeletal and connective 
tissue disorders 
Neuroinflammatory/neuromuscular 
disorders 
Renal disorders 
• 
Gout, including: 
− 
Gouty arthritis 
• 
Idiopathic inflammatory 
myopathies, including: 
− 
Dermatomyositis 
− 
Inclusion body myositis 
− 
Immune-mediated 
necrotizing myopathy 
− 
Polymyositis 
• 
Mixed connective tissue 
disorder 
• 
Polymyalgia rheumatica 
(PMR) 
• 
Psoriatic arthritis (PsA) 
• 
Relapsing polychondritis 
• 
Rheumatoid arthritis, 
including: 
− 
Rheumatoid arthritis 
associated conditions 
− 
Juvenile idiopathic 
arthritis 
− 
Palindromic rheumatism 
− 
Still's disease 
− 
Felty’s syndrome 
• 
Acute disseminated 
encephalomyelitis (ADEM) and other 
inflammatory-demyelinating variants, 
including:  
− 
Acute necrotising myelitis 
− 
Bickerstaff's brainstem 
encephalitis  
− 
Disseminated necrotizing 
leukoencephalopathy (also 
known as Weston-Hurst 
syndrome, acute hemorrhagic 
leuko-encephalitis, or acute 
necrotizing hemorrhagic 
encephalomyelitis)  
− 
Myelin oligodendrocyte 
glycoprotein 
antibody-associated disease 
− 
Neuromyelitis optica (also 
known as Devic’s disease) 
− 
Noninfective encephalitis/ 
encephalomyelitis / myelitis 
− 
Postimmunization 
encephalomyelitis 
• 
Guillain-Barré syndrome (GBS)*, 
including: 
• 
Autoimmune/Immune-me
diated glomerulonephritis, 
including: 
− 
IgA nephropathy 
− 
IgM nephropathy 
− 
C1q nephropathy 
− 
Fibrillary 
glomerulonephritis 
− 
Glomerulonephritis 
rapidly progressive 
− 
Membranoproliferati
ve 
glomerulonephritis 
− 
Membranous 
glomerulonephritis 
− 
Mesangioproliferativ
e glomerulonephritis 
− 
Tubulointerstitial 
nephritis and uveitis 
syndrome 

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• 
Sjogren’s syndrome 
• 
Spondyloarthritis, including: 
− 
Ankylosing spondylitis 
− 
Juvenile 
spondyloarthritis 
− 
Keratoderma 
blenorrhagica 
− 
Psoriatic spondylitis  
− 
Reactive Arthritis 
− 
Undifferentiated 
spondyloarthritis 
• 
Systemic Lupus 
Erythematosus, including: 
− 
Lupus associated 
conditions (e.g., 
Cutaneous lupus 
erythematosus, Lupus 
nephritis, etc.) 
− 
Complications such as 
shrinking lung syndrome 
(SLS) 
• 
Systemic Scleroderma 
(Systemic Sclerosis), 
including: 
− 
Raynaud’s syndrome 
− 
Systemic sclerosis with 
diffuse scleroderma 
− 
Systemic sclerosis with 
limited scleroderma 
(also known as CREST 
syndrome) 
− 
Variants such as Miller Fisher 
syndrome and the acute motor 
and sensory axonal neuropathy 
(AMSAN) 
• 
Idiopathic cranial nerve 
palsies/paresis and inflammations 
(neuritis), including: 
− 
Cranial nerve neuritis (e.g., 
Optic neuritis) 
− 
Idiopathic nerve palsies/paresis 
(e.g., Bell’s palsy) 
− 
Melkersson-Rosenthal 
syndrome 
− 
Multiple cranial nerve 
palsies/paresis 
• 
Multiple Sclerosis (MS), including: 
− 
Clinically isolated syndrome 
(CIS)  
− 
Malignant MS (the Marburg 
type of MS)  
− 
Primary-progressive MS 
(PPMS) 
− 
Radiologically isolated 
syndrome (RIS) 
− 
Relapsing-remitting MS 
(RRMS) 
− 
Secondary-progressive MS 
(SPMS) 
− 
Uhthoff's phenomenon 
• 
Myasthenia gravis, including: 
− 
Ocular myasthenia 
− 
Lambert-Eaton myasthenic 
syndrome 
• 
Narcolepsy (with or without presence 
of unambiguous cataplexy) 
• 
Peripheral inflammatory 
demyelinating neuropathies and 
plexopathies, including 
− 
Acute Brachial Radiculitis (also 
known as Parsonage-Turner 
Syndrome or neuralgic 
amyotrophy) 
− 
Antibody-mediated 
demyelinating neuropathy 
− 
Chronic idiopathic axonal 
polyneuropathy (CIAP) 
− 
Chronic Inflammatory 
Demyelinating 
Polyradiculoneuropathy (CIDP), 
including atypical CIDP variants 
(e.g., multifocal acquired 
demyelinating sensory and 
motor neuropathy also known 
as Lewis-Sumner syndrome) 
− 
Multifocal motor neuropathy 
(MMN) 

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• 
Transverse myelitis (TM), including: 
− 
Acute partial transverse myelitis 
(APTM) 
− 
Acute complete transverse 
myelitis (ACTM) 
Skin and subcutaneous tissue 
disorders 
Vasculitis 
Other (including 
multisystemic) 
• 
Alopecia areata 
• 
Autoimmune / Immune-
mediated blistering 
dermatoses, including: 
− 
Bullous Dermatitis 
− 
Bullous Pemphigoid  
− 
Dermatitis herpetiformis  
− 
Epidermolysis bullosa 
acquisita (EBA)  
− 
Linear IgA-mediated 
bullous dermatosis 
(LABD), also known as 
Linear IgA disease 
− 
Pemphigus 
• 
Erythema multiforme 
• 
Erythema nodosum 
• 
Lichen planus, including: 
− 
Liquen planopilaris 
• 
Localised Scleroderma 
(Morphoea) 
− 
Eosinophilic fasciitis 
(also called Shulman 
syndrome) 
• 
Psoriasis 
• 
Pyoderma gangrenosum 
• 
Reactive granulomatous 
dermatitis, including: 
− 
Interstitial 
granulomatous 
dermatitis 
− 
Palisaded neutrophilic 
granulomatous 
dermatitis 
• 
Stevens-Johnson Syndrome 
(SJS), including: 
− 
Toxic Epidermal 
Necrolysis (TEN)  
− 
SJS-TEN overlap 
• 
Sweet’s syndrome, including: 
− 
Acute febrile 
neutrophilic dermatosis 
• 
Vitiligo 
• 
Large vessels vasculitis*, including: 
− 
Arteritic anterior ischemic optic 
neuropathy (AAION or arteritic 
AION) 
− 
Giant cell arteritis (also called 
temporal arteritis)  
− 
Takayasu's arteritis 
• 
Medium sized and/or small vessels 
vasculitis*, including: 
− 
Anti-neutrophil cytoplasmic 
antibody (ANCA) positive 
vasculitis (type unspecified)  
− 
Behcet's syndrome  
− 
Buerger’s disease 
(thromboangiitis obliterans) 
− 
Churg–Strauss syndrome 
(allergic granulomatous angiitis)  
− 
Erythema induratum (also 
known as nodular vasculitis) 
− 
Henoch-Schonlein purpura 
(also known as IgA vasculitis) 
− 
Microscopic polyangiitis 
− 
Necrotizing vasculitis 
− 
Polyarteritis nodosa 
− 
Single organ cutaneous 
vasculitis, including 
leukocytoclastic vasculitis, 
hypersensitivity vasculitis and 
acute hemorrhagic edema of 
infancy (AHEI) 
− 
Granulomatosis with 
polyangiitis  
• 
Anti-synthetase syndrome 
• 
Capillary leak syndrome 
− 
Frequently used 
related terms 
include: “systemic 
capillary leak 
syndrome (SCLS)” 
or “Clarkson's 
Syndrome” 
• 
Goodpasture syndrome 
− 
Frequently used 
related terms 
include: “pulmonary 
renal syndrome” 
and 
“anti-Glomerular 
Basement 
Membrane disease 
(anti-GBM disease)” 
• 
Immune-mediated 
enhancement of disease, 
including: 
− 
Vaccine associated 
enhanced disease 
(VAED and 
VAERD). Frequently 
used related terms 
include “vaccine-
mediated enhanced 
disease (VMED)”, 
“enhanced 
respiratory disease 
(ERD)”, “vaccine-
induced 
enhancement of 
infection”, “disease 
enhancement”, 
“immune 
enhancement”, and 
“antibody-
dependent 
enhancement (ADE) 
• 
Immunoglobulin G4 
related disease 
• 
Langerhans' cell 
histiocytosis 

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• 
Multisystem inflammatory 
syndromes, including: 
− 
Kawasaki’s disease 
− 
Multisystem 
inflammatory 
syndrome in adults 
(MIS-A) 
− 
Multisystem 
inflammatory 
syndrome in 
children (MIS-C) 
• 
Overlap syndrome 
• 
Raynaud’s phenomenon 
• 
Sarcoidosis, including: 
− 
Loefgren syndrome 
• 
Susac's syndrome 
8.4.4.2. 
Atrial fibrillation (AF) 
AEs of AF are considered as AESI in this study. 
In the efficacy study (RSV OA=ADJ-006), at the time of safety analysis DLP of 30 April 
2022, a numerical imbalance in events of AF was observed within 30 days post-
vaccination, with 10 events of AF (among which 7 [0.1%] were serious) in the RSVPreF3 
group versus 4 (among which 1 [<0.1%] was serious) in the placebo group. No imbalance 
was observed for serious events of AF reported within 6 months post-vaccination. To 
further characterize events of AF, AF will be considered as an AESI. 
When there is enough evidence to make the above diagnosis, the AE must be reported as 
AESI. Symptoms, signs or conditions which might (or might not) represent AF, should be 
recorded and reported as AEs but not as AESI until the final or definitive diagnosis has 
been determined, and alternative diagnoses have been eliminated or shown to be less 
likely. 
For each case of AF reported as AE or SAE in the eCRF, additional information will be 
collected in a specific ‘AF follow-up questionnaire’ eCRF screen. 
8.4.5. 
Regulatory reporting requirements for SAEs/pregnancies/AESIs  
• 
Prompt notification by the investigator to the sponsor of an SAE/pregnancy/AESI is 
essential so that legal obligations and ethical responsibilities toward the safety of 
participants and the safety of a study intervention under clinical investigation are 
met. See Section 8.4.1 for reporting timeframes. 
• 
For SAEs/AESIs, the investigator must always provide an assessment of causality at 
the time of the initial report, as defined in the Section 10.3.5.3. 
• 
An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (e.g., summary or listing of SAEs) from the sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if 
appropriate according to local requirements. 

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Table 17 
Timeframes for submitting SAE, pregnancy and pIMDs to GSK  
Type of event 
Initial reports 
Follow-up of relevant information on a 
previous report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours*  
electronic AEs Report 
24 hours* 
electronic AEs Report 
Pregnancies 
24 hours* 
electronic pregnancy report  24 hours * 
electronic pregnancy report  
pIMDs 
24 hours**  
electronic AEs Report 
24 hours* 
electronic AEs Report 
Serious AF*** 
24 hours** 
Electronic AEs Report + AF 
follow-up questionnaire  
24 hours* 
Electronic AEs Report + AF 
follow-up questionnaire 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
** Timeframe allowed once the investigator determines that the event meets the protocol definition of an AESI. 
*** Only AF meeting SAE definition will be reported in electronic Expedited AEs Report and in the specific AF follow-up 
questionnaire. Non-serious AF will be reported as non-serious adverse event eCRF screen and in the AF follow-
up questionnaire. 
8.4.6. 
Pregnancy 
Female participants who become pregnant after administration of the study intervention 
may continue the study at the discretion of the investigator.  
• 
Details of all pregnancies in female participants will be collected after the start of 
study intervention and until EOS. 
• 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the 
female participant pregnancy. 
• 
Any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• 
The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant/pregnant female 
partner and the neonate and the information will be forwarded to the sponsor. See 
Table 17 for reporting timeframes. 
• 
Any poststudy pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.4.5. While the investigator is not obligated to actively seek this information 
in former study participants/pregnant female partner, he or she may learn of an SAE 
through spontaneous reporting. 
• 
Any female participant who becomes pregnant while participating in the study will 
continue to be monitored after study intervention.  

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8.4.7. 
Contact information for reporting SAEs, AESIs and pregnancies. 
Study contact for questions regarding SAEs, AESIs, pregnancies and SAEs linked 
to device deficiencies 
Contact GSK’s local and/or medical contacts 
Contacts for reporting SAEs, AESIs, pregnancies and SAEs linked to device 
deficiencies 
Available 24/24 hours and 7/7 days 
ogm28723@gsk.com  
8.4.8. 
Participant card 
The investigator (or designee) must provide the participant/participant’s parent(s)/LAR(s) 
with a “participant card” containing information about the clinical study. The 
participant/participant’s parent(s)/LAR(s) must be instructed to always keep the 
participant card in their possession for the duration of the study. In an emergency, this 
card serves to inform the responsible attending physician/LAR/caregiver/family member 
that the participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator(s) or their back up. 
8.5. 
Pharmacokinetics 
Not applicable to this study. 
8.6. 
Pharmacodynamics 
Pharmacodynamics are not evaluated in this study. 
8.7. 
Genetics 
Genetics are not evaluated in this study. 
8.8. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.9. 
Immunogenicity assessments 
Immunogenicity is described in Section 8.2. 
8.10. 
Health economics or medical resource utilization and health 
economics 
Not applicable in this study. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
Statistical hypotheses are associated to the confirmatory primary NI objectives, which 
will be tested according to the hierarchical testing procedure described in Section 9.3.1. 
Global type I error is controlled at 2.5% (1-sided). 
Table 18 
Study objectives and null hypothesis  
Objectives 
Null hypothesis 
Primary (Part A) 
• 
To demonstrate the NI of the humoral immune 
response in participants 18-49 YOA at increased 
risk for RSV disease compared to OA (60 YOA) for 
the RSV-A strain after RSVPreF3 OA investigational 
vaccine administration. 
• 
Null hypothesis 1 (H1):  
The anti-RSV-A GMT ratio RSV-OA (60 YOA) over 
RSV-A-AIR (18-49 YOA) is >1.5 or the SRR 
difference (RSV-OA [60 YOA] minus RSV-A-AIR 
[18-49 YOA]) is >10% at 1 month post RSVPreF3 
OA vaccine administration. This must be rejected in 
favor of the alternative hypothesis that the GMT ratio 
is ≤1.5 and the SRR difference is ≤10%. 
• 
To demonstrate the NI of the humoral immune 
response in participants 18-49 YOA at increased 
risk for RSV disease compared to OA (60 YOA) for 
the RSV-B strain after RSVPreF3 OA investigational 
vaccine administration. 
• 
Null hypothesis 2 (H2):  
The anti-RSV-B GMT ratio RSV-OA (60 YOA) over 
RSV-A-AIR (18-49 YOA) is >1.5 or the SRR 
difference (RSV-OA [60 YO]) minus RSV-A-AIR 
[18-49 YOA]) is >10% at 1 month post RSVPreF3 
OA vaccine administration. This must be rejected in 
favor of the alternative hypothesis that the GMT ratio 
is ≤1.5 and the SRR difference is ≤10%. 
A=Adults; AIR=At increased risk; GMT=Geometric mean titer; H1=Null hypothesis 1; H2=Null hypothesis 2; NI=Non-
inferiority; OA=Older adults; RSV=Respiratory syncytial virus; SRR=Seroresponse rate; YOA=Years of age. 
9.2. 
Analysis sets 
Table 19 
Analysis sets 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened Set 
All participants who were screened for eligibility.  
Study Population  
Enrolled Set 
All participants who entered the study (who were allocated a 
treatment number or received study intervention or 
underwent a post screening study procedure). 
Note: screening failures (who never passed screening) and 
participants screened (met eligibility) but never enrolled into 
the study are excluded from the Enrolled analysis set as they 
did not enter the study. 
Study Population  
Exposed Set (ES) 
All participants who received the study intervention. Analysis 
per group is based on the administered intervention. 
Study population, 
Reactogenicity, Safety  
Per-Protocol Set 
(PPS)* 
All eligible participants who received the study intervention as 
per protocol, had immunogenicity results pre- and post-dose, 
complied with blood draw intervals, without intercurrent 
conditions that may interfere with immunogenicity and without 
prohibited concomitant medication/vaccination. Analysis per 
group is based on the administered intervention. 
Immunogenicity  
*Contribution of participants to PPS will be defined by timepoint 

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9.2.1. 
Criteria for elimination from analyses 
If a participant meets one of the criteria mentioned in the Section 5.2.1 (medical 
conditions) or Section 5.2.2 (concomitant therapy), they may be eliminated from per-
protocol analysis. 
Participants may be eliminated from the PPS for immunogenicity if, during the study, 
they incur a condition that has the capability of altering their immune response 
(intercurrent medical condition) or are confirmed to have an alteration of their initial 
immune status. Refer to Definition of Terms for the definition of intercurrent medical 
conditions. 
9.3. 
Statistical analyses 
SAP will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of 
the primary and secondary endpoints. Supportive analyses and demography summaries 
will be described in the SAP. 
9.3.1. 
Primary endpoints/estimands analysis (Part A) 
Primary estimand analysis will be performed on the Per-Protocol Set (PPS) for 
participants in Part A. 
RSV-A and RSV-B neutralizing group GMT ratio at 1 month after the RSVPreF3 OA 
vaccine administration will be computed for RSV-OA (60 YOA) cohort over RSV-A-
AIR (18-49 YOA) cohort, with 95% CI, using an 
 on log10-transformed 
titers for each neutralization assay. The model will include the group RSV-OA 
(60 YOA) and RSV-A-AIR (18-49 YOA) and the baseline log10-transformed titer as 
covariate. 
RSV-A and RSV-B neutralizing group SRR differences at 1 month after the RSVPreF3 
OA vaccine administration will be computed for RSV-OA (60 YOA) cohort minus 
RSV-A-AIR (18-49 YOA) cohort, with 95% CI. The 95% CI will be derived using the 
method of 
1985. SRR is defined as the proportion of participants having a fold 
increase in neutralizing titers (post-study intervention administration over pre-study 
intervention administration) 4. 
Missing data will not be imputed. 
9.3.1.1. 
Success criteria for non-inferiority and testing sequence 
In order to control the global type I error at 2.5% (1-sided), the primary objective will be 
assessed using a hierarchical testing. NI will be first tested for RSV-A strain and, only if 
NI has been demonstrated, will the NI be tested for RSV-B strain. 
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NI for RSV-A strain will be claimed to be successful if the upper limit of the 95% CI for 
the RSV-A neutralizing group GMT ratio will be ≤1.5 and the upper limit of 95% CI for 
the RSV-A neutralizing group SRR difference will be ≤10%. 
NI for RSV-B strain will be claimed to be successful if NI has been demonstrated for 
RSV-A strain and if the upper limit of the 95% CI for the RSV-B neutralizing group 
GMT ratio will be ≤1.5 and the upper limit of 95% CI for the RSV-B neutralizing group 
SRR difference will be ≤10%. 
9.3.2. 
Secondary endpoints/estimands analyses 
The estimand analysis for immunogenicity will be performed on the PPS, for participants 
in Part A.  
For each timepoint with blood sample collection for humoral immune response and for 
RSV-A/B neutralizing titers, the following analysis will be performed by group: 
• 
Percentage of participants with neutralizing titers equal to or above the technical 
assay cut-off and their exact 95% CI will be tabulated. 
• 
GMTs and their 95% CI will be tabulated and represented graphically.  
• 
Distribution of neutralizing titers will be displayed using reverse cumulative curves. 
• 
MGI, i.e., geometric mean of ratios of neutralizing titers of post vaccination time 
point over pre-vaccination (Day 1), will be tabulated with 95% CI.  
• 
SRR and 95% CI will be tabulated.  
The estimand analysis for safety will be performed on the ES, for participants in Parts A 
and Part B. Descriptive analysis by group will be summarized as follows: 
• 
Percentage of participants reporting each solicited administration site event (any 
grade, Grade 3 and resulting in medically attended visit) with onset within 4 days 
after study intervention administration (i.e., the day of study intervention 
administration and 3 subsequent days). 
• 
Percentage of participants reporting each solicited systemic event (any grade, 
Grade 3 and resulting in medically attended visit) with onset within 4 days after 
study intervention administration (i.e., the day of study intervention administration 
and 3 subsequent days). 
• 
Percentage of participants reporting unsolicited AEs within 30 days after study 
intervention administration (i.e., the day of study intervention administration and 
29 subsequent days) by MedDRA Primary System Organ Class (SOC), High Level 
Term (HLT) and Preferred Term (PT). Similar tabulation will be done for Grade 3 
unsolicited AEs, for any causally related unsolicited AEs, for Grade 3 causally 
related unsolicited AEs and for unsolicited AEs resulting in a medically attended 
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• 
Percentage of participants reporting SAEs and AESIs (including pIMDs and AF) 
after study intervention administration (Day 1) up to study end (6 months after study 
intervention administration) by MedDRA Primary SOC, HLT and PT.  
• 
Percentage of participants reporting SAEs and AESIs (including pIMDs and AF) 
related to study intervention administration after study intervention administration 
(Day 1) up to study end (6 months after study intervention administration) by 
MedDRA Primary SOC, HLT and PT. 
• 
Percentage of participants reporting any fatal SAEs after study intervention 
administration (Day 1) up to study end (6 months after study intervention 
administration). 
9.4. 
Interim analyses 
9.4.1. 
Sequence of analysis 
The analyses will be performed stepwise: 
• 
Day 31 (Part A): A first analysis will be performed on all immunogenicity, 
reactogenicity and safety data available and as clean as possible, when data for at 
least primary and secondary endpoints up to Visit 2 (Day 31) are available for all 
participants in Part A. This analysis will be considered as final for the primary 
endpoints. 
• 
Month 6 (Part A): If required, a safety analysis can be performed when safety data 
up to Month 6 are available and as clean as possible, for all participants in Part A.  
• 
Day 31 (Part B): If required, a safety analysis can be performed when safety data up 
to Visit 2 (Day 31) are available and as clean as possible, for all participants in Part 
B. This analysis may be combined with Month 6 safety analysis for Part A. 
Month 6 (Part A): If required an immunogenicity analysis can be performed when 
all data for secondary endpoints up to study conclusion (Visit 3, Month 6) are 
available and as clean as possible, for all participants in Part A. 
• 
An EOS analysis will be performed when all immunogenicity and safety data up to 
study conclusion (Visit 3/Contact, Month 6) will be available for all participants in 
Part A and Part B. 
• 
If the data of different analyses become available around the same timepoint, these 
analyses can be combined into one analysis.  
9.5. 
Pre-dose sample size determination 
The target sample size for the study is approximately 850 participants for Part A: 
425 participants in Cohort 1 (RSV-A-AIR [18-49 YOA group]) and 425 participants in 
Cohort 2 (RSV-OA [60 YOA group]), to obtain at least 722 evaluable participants 
(361 participants in the RSV-A-AIR [18-49 YOA] cohort and 361 participants in the 
RSV-OA [60 YOA] cohort) for the evaluation of the primary objectives, assuming that 
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Participants who withdraw from the study will not be replaced. 
The power to demonstrate the primary NI objectives following the hierarchical testing 
procedure described in Section 9.3.1 is presented in Table 20. 
Table 20 
Power for primary objectives of non-inferiority of the humoral 
immune response after RSVPreF3 OA vaccine between the RSV-A-
AIR (18-49 YOA) Cohort 1 to RSV-OA (≥ 60 YOA) Cohort 2 for 
361 evaluable participants per group  
Objective 
Standard deviation (SD) of 
log10 titers / SRR (%) 
Non-
inferiority 
margin 
Type II Error 
Power1 
NI for RSV-A strain 
 
 
 
 
GMT RSV-A  
SD=0.45 
 
1.5 
0.05 
99.95% 
SRR RSV-A  
SRR=81.6%2 
 
10% 
6.92 
93.08% 
Global power for 
RSV-A strain 
 
 
 
93% 
NI for RSV-B strain 
 
 
 
 
GMT RSV-B 
SD=0.45 
1.5 
0.05 
99.95% 
SRR RSV-B 
SRR=78.7%2 
10% 
9.56 
90.44% 
If non-inferiority 
is demonstrated 
for RSV-A, global 
power for RSV-B 
strain 
 
 
 
90% 
NI=Non-inferiority; SRR=Seroresponse rate; GMT=Geometric mean titer; RSV=Respiratory syncytial virus 
1Pass 2019 1-sided alpha=2.5% for each endpoint (GMT ratio and SRR difference), two-Sample T-Tests for Non-
Inferiority assuming equal variance for group GMT ratios and 
 for Non-Inferiority tests for 
group SRR difference, Non-inferiority limit=0.176 (=log10(1.5)) for group GMT ratios 
2Reference from RSV OA=ADJ-006 
For the evaluation of reactogenicity and safety, the sample size of 1025 participants in 
combined Cohorts 1 and 3 (RSV-A-AIR group) has 64% and 87% probability of 
observing at least one vaccinated participant with AE if the true AE incidence rate is 
0.1% and 0.2% respectively. This probability increases to at least 95% for true AE 
incidence rates ≥0.3%. 
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 the following: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS international ethical guidelines 
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− 
Applicable ICH GCP guidelines 
− 
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 and reviewed 
and approved by the IRB/IEC before the study is initiated.  
• 
Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants.  
• 
Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
The investigator will be responsible for the following, as applicable: 
− 
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/IEC 
− 
Notifying the IRB/IEC of SAEs 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 will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
• 
The investigator or the investigator’s representative will explain the nature of the 
study, including the risks and benefits, to the participants/participants’ 
parent(s)/LAR(s) and answer all questions regarding the study. 
• 
Potential participants/participants’ parent(s)/LAR(s) must be informed that their 
participation is voluntary. They or their LARs will be required to physically sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, HIPAA requirements, privacy and data protection 
requirements, where applicable, and the IRB/IEC or study center. 
• 
The investigator must obtain assent from the minor participant in addition to the 
consent provided by the participants’ parent(s)/LAR(s) when a minor can assent to 
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capacity to assent to participation in a research study according to the local laws and 
regulations. 
• 
In accordance with local laws and regulations, participants who become legally 
emancipated during the study, i.e., reach the legal age of consent, must be 
reconsented. 
• 
The medical record must include a statement that physical informed consent was 
obtained before the participant was enrolled in the study and the date the physical 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• 
Participants/participant’s parent(s)/LAR(s) must be reconsented to the most current 
version of the ICF(s)/IAF during their participation in the study. 
• 
A physical copy of the ICF(s)/IAF must be provided to the participant/participant’s 
parent(s) or their LAR. 
• 
In accordance with local laws and regulations, participants who become legally 
emancipated during the study, i.e., reach the legal age of consent, must be 
reconsented.  
• 
The participant/participant’s parent(s)/LAR(s) must provide consent by signing an 
ICF/IAF, which summarizes the study, includes a consent statement and provides 
documentation that the participant agrees to continue participating in the study.  
The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research. The investigator or authorized designee will 
explain to each participant the objectives of the exploratory research. Participants will be 
told that they are free to refuse to participate and may withdraw their consent at any time 
and for any reason during the storage period 
In case of unexpected pregnancy, participant must be informed that PI such as date of 
birth, sex of the baby will be collected as part of safety follow-up. Consent for the baby 
may be obtained from the participant and/or their partner as per local regulations. 
10.1.4. 
Recruitment strategy 
• 
The study is planned to be conducted at sites in multiple countries. The recruitment 
plan will be defined by each participating site. Recruitment will be tracked using 
RTSM system. 
• 
The recruitment plan may be adapted based on the actual number of participants 
enrolled in each country. In case a site would fall behind in participant recruitment, a 
redistribution of the enrollment target in the participating sites across participant 
countries may be made. This would allow the other participating sites to enroll 
additional participants to ensure full and timely enrollment of the overall targeted 
number of participants specified in this protocol. 
• 
When the target number of participants is reached in each cohort, further enrollment 
of participants in that cohort will be stopped. If needed, the maximum number of 
participants in a particular cohort may be adapted during the study. 

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• 
The procedures for participants identification/recruitment (e.g., referral letters, 
advertisements etc.) must be approved by the IRB/IEC together with the material 
intended for participants identification/recruitment and participants use. 
10.1.5. 
Data protection 
• 
Participants will be assigned a unique identifier by the investigator. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable 
will not be transferred. 
• 
GSK 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. 
• 
The participant/participants’ parent(s)/LAR(s) must be informed that their/the minor 
participants’s personal study-related data will be used by the sponsor in accordance 
with local data protection law. The level of disclosure must also be explained to the 
participant/participants’ parent(s)/LAR(s), that their/the minor partcipant’sdata will 
be used as described in the informed consent/assent. 
• 
The participant/participants’ parent(s)/LAR(s) must be informed that their/the minor 
participant’s medical records may be examined by Clinical Quality Assurance 
auditors or other authorized personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
• 
The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure 
or access.  GSK and/or trusted third parties working on behalf of GSK and/or 
institutions working with GSK for the purposes of this study are contractually bound 
to protect participant coded data. GSK will protect participant coded data and will 
only share it as described in the ICF. 
10.1.6. 
Committees structure 
A SRT is in place for each GSK product. It comprises of a global cross-functional team 
responsible for the ongoing assessment of benefit-risk for a product. The SRT contribute 
to the continual assessment of incoming new efficacy and safety information. 
10.1.7. 
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 
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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 study 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, including a summary of trial results 
understandable to laypersons. The investigator is encouraged to share the plain 
language summary with the study participants, as appropriate. The full study report 
will be made available upon request, after decision on marketing authorization by 
regulatory authorities.   
• 
GSK will provide the investigator with the Treatment Code and participant-level line 
listings for their site only after completion of the full statistical analysis. 
• 
GSK intends to make anonymized participant-level data from this study 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 study participants are used to maximum effect in the creation of 
knowledge and understanding. 
10.1.8. 
Data quality assurance 
• 
All participant data relating to the study will be recorded on eCRFs unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
lectronically signing the CRF. 
• 
Guidance on completion of eCRFs will be provided in eCRF completion guidelines. 
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents. 
• 
QTLs will be predefined in the quality plan to identify systematic issues that can 
impact participant right, safety and/or reliability of study results. These predefined 
parameters will be monitored during the study, and important deviations from the 
QTLs and remedial actions taken will be summarized in the CSR. 
• 
Monitoring details describing strategy, including definition of study critical data 
items and processes (e.g., risk-based initiatives in operations and quality such as risk 
management and mitigation strategies and analytical risk-based monitoring, 
involvement of central reading mechanism) methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the monitoring 
plan. 
• 
The sponsor or designee is responsible for the data management of this study, 
including quality checking of the data. 

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• 
The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• 
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years rom the issue of the final CSR/ 
equivalent summary unless local regulations or institutional policies require a 
different 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.  
• 
When copies of source documents are shared externally for review by a central 
reader mechanism (e.g., endpoint adjudication committee; expert reader), documents 
are stored by the external body for 25 years. 
10.1.9. 
Source documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the eCRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must 
be explained. The investigator may need to request previous medical records or 
transfer records, depending on the study. Also, current medical records must be 
available. 
• 
Definition of what constitutes source data and its origin can be found in the 
Definition of Terms. 
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• 
The sponsor or designee will perform monitoring to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and 
that the study is being conducted in accordance with the currently approved protocol 
and any other study agreements, ICH GCP, and all applicable regulatory 
requirements. 
• 
Copies of documents are shared with external third parties contracted by GSK for 
review by a central reader mechanism (e.g., endpoint adjudication committee; expert 
reader). The non-exhaustive list of documents shared to inform the central reader 
may include, discharge summaries, imaging reports, ECG reports etc. Participant 
names or any information which would make the participant identifiable or is not 
essential for the central reader mechanism will be redacted by the investigator sites 
prior to transfer.  Details of the list of documents and the redaction procedure are 
provided in the site manual or equivalent. These documents will be used by the third 
party solely for the purpose indicated within this protocol. 

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10.1.10. 
Study and site start and closure 
Start of study and first act of recruitment 
The start of study and the first act of recruitment are defined as FSFV at a country-level. 
Study/Site Termination 
GSK or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• 
Discontinuation of further study intervention development 
For site termination: 
• 
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 or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or temporarily suspended, the sponsor shall 
promptly inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
temporary 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. 
10.1.11. 
Publication policy 
The results of this study may be published in peer reviewed scientific literature and/or 
presented at scientific meetings. The sponsor will comply with the requirements for 
publication of study results in accordance with standard editorial and ethical practice and 
as per the sponsor’s internal policy. Authorship will be determined by mutual agreement 
and in line with ICMJE authorship requirements. 

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10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
RSV-A and RSV-B neutralization assays 
The serum neutralization assay is a functional assay that measures the ability of serum 
antibodies to neutralize RSV entry and replication in a host cell line. 
Virus neutralization is performed by incubating a fixed amount of RSV-A strain (Long, 
ATCC No. VR-26) or RSV-B strain (18537, ATCC No. VR-1580) with serial dilutions of 
the test serum. The serum-virus mixture is then transferred onto a layer of Vero cells 
(African Green Monkey, kidney, Cercopitheus aethiops, ATCC CCL 81) and incubated 
for 2 days to allow infection of the Vero cells by non-neutralized virus and the formation 
of plaques in the cell layer. Following a fixation step, RSV-infected cells are detected 
using a primary antibody directed against RSV (Polyclonal anti-RSV-A/B IgG) and a 
secondary antibody conjugated to horse-radish peroxidase, allowing the visualization of 
plaques after coloration with TrueBlue peroxidase substrate. Viral plaques are counted 
using an automated microscope coupled to an image analyzer (Scanlab system with a 
Reading software or equivalent). For each serum dilution, a ratio, expressed as a 
percentage, is calculated between the number of plaques at each serum dilution and the 
number of plaques in the virus control wells (no serum added). The serum neutralizing 
titer is expressed in Estimated Dilution 60 and corresponds to the inverse of the 
interpolated serum dilution that yields a 60% reduction in the number of plaques 
compared to the virus control wells, as described by others [Barbas, 1992; Bates, 
2014]. Secondary standards calibrated against the international reference (NIBSC 16/284) 
[McDonald, 2018; McDonald, 2020] are included in every run to allow conversion into 
international units per milliliter. 
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10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting 
10.3.1. 
Definition of AE 
AE definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study intervention. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
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an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• 
Events that occur as a result of protocol-mandated procedures (i.e. invasive 
procedures, modification of participant’s previous therapeutic regimen). 
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (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 
diseases will be recorded in the medical history section of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
• 
Results in death 
• 
Is life threatening 
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. 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
• 
Results in persistent or significant disability/incapacity 

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• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
• 
Is a congenital anomaly/birth defect in the offspring of a study participant 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) 
• 
Is a suspected transmission of any infectious agent via an authorized medicinal 
product 
• 
Other situations: 
• 
Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as significant 
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
− 
Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions, or 
development of intervention dependency or intervention abuse. 
10.3.3. 
Solicited events  
• 
Definition of solicited event 
• 
Solicited events are predefined events administration site events and systemic 
events for which the participant/ participant’s parent(s) /LAR(s) is specifically 
questioned, and which are noted by the participant/ participant’s parent(s) /LAR(s) 
in their eDiary. 
Table 21 
Solicited administration site  
Pain at administration site 
Redness (Erythema) at administration site 
Swelling at administration site 
Table 22 
Solicited systemic events  
Fever 
Myalgia (muscle pain) 
Arthralgia (joint pain) 
Headache 
Fatigue (tiredness) 
Note: Participants/participants’ parent(s)/LAR(s) will be instructed to measure and 
record the oral/axillary temperature in the evening. If additional temperature 

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measurements are taken at other times of the day, participants/participants’ 
parent(s)/LAR(s) will be instructed to record the highest temperature in the eDiary. 
10.3.4. 
Unsolicited AE  
• 
Definition of unsolicited AE 
• 
An unsolicited AE is an AE 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 communicated by participants/ participant’s parent(s)/LAR(s) who has 
signed the informed consent. Unsolicited AEs include both serious and nonserious 
AEs. 
• 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare 
provider). The participants/ participant’s parent(s)/LAR(s) 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/ participant’s 
parent(s) /LAR(s) 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 nor perceived as a concern by the 
participant/participant’s parent(s)/LAR(s) will be collected during an interview 
with the participants/participant’s parent(s)/LAR(s) and by review of available 
medical records at the next visit. 
10.3.5. 
Recording, assessment and follow-up of AE, SAE, AESIs and 
pregnancies 
10.3.5.1. 
AE and SAE recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE information. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the eCRF /required form. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 

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• 
An eDiary will be used in this study to capture solicited administration site or 
systemic events. The participant/participant’s parent(s)/LAR(s) should be trained on 
how and when to complete the eDiary.  
• 
Anyone who measures administration site or systemic events and who will record the 
event in the eDiary, e.g., the study caregiver, should have received a caregiver 
information letter explaining the role of the caregiver prior to completing the eDiary. 
This training must be documented in the participant’s source record. 
• 
For each solicited and unsolicited AE the participant experiences, the participant/ 
participant’s parent(s)/LAR(s) will be asked if they/their child received medical 
attention (defined as unscheduled visit to or from medical personnel for any reason, 
including emergency room visits). This information will be recorded in the 
participant’s eDiary and in the participant’s eCRF as part of normal AE reporting 
(for solicited and unsolicited AEs). If the collection of solicited AEs was not possible 
for any reasons via the eDiary and solicited AEs were reported to the investigator by 
the participant, then it would be possible for it to be reported directly to the site staff 
and submitted (e.g., via the eCRF). Medical attention received for SAEs/AESIs will 
have to be reported using the normal AE reporting process in the eCRF. 
• 
If any individual other than the participant/participant’s parent(s)/LAR(s) is making 
entries in the eDiary, their identity must be documented in the participant’s source 
record. 
• 
The completed eDiary will be collected and verified during discussions with the 
participant/participant’s caregiver(s) on Visit 2.  
• 
All solicited events that occur during the four days following administration of the 
dose of the study intervention (Day 1 to Day 4) must be recorded into the eDiary, 
irrespective of intensity. An automatic reminder to complete the eDiary will be sent 
to the participants during this time frame. Daily eDiary compliance will be checked 
by the investigator or delegate on the eDiary portal. In case of non-compliance, the 
investigator should contact the participant to remind the importance of daily entries. 
All other AEs occurring within this time frame should be recorded into the 
appropriate section of the eCRF, irrespective of their intensity or whether or not they 
are considered related to the study intervention. 
• 
After review and verbal discussion of the eDiary entries with the 
participant/participant’s parent(s)/LAR(s), if there are clear eDiary errors the 
investigator will complete his/her own assessment in the relevant sections of the 
eCRF. 
• 
Note: eDiary may be completed by a minor participant under the supervision of the 
participant’s parent(s)/LAR(s) provided the minor is capable of assessing and 
reporting the information to be recorded on eDiary. The ultimate accountability for 
completion of the eDiary remains with the participant’s parent(s)/LAR(s). The 
investigator should discuss this accountability with the participant’s 
parent(s)/LAR(s). 
• 
The investigator or delegate should verify the reported information during a 
discussion with the minor participant preferably in the presence of their 
parent(s)/LAR(s). 

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• 
Return of the eDiary device is not applicable if the participant has BYOD but 
verification of the recorded data should always take place. 
• 
Any unreturned eDiary will be sought from the participant/participant’s 
parent(s)/LAR(s) through telephone call(s) or any other convenient procedure. 
• 
Data on solicited events reported in the eDiary will be electronically transferred to 
the eDiary vendor, where it can be monitored by appropriately qualified site staff and 
sponsor staff through a web-based portal.  
• 
Refer to the eDiary Manual for more information regarding the use of eDiary. 
10.3.5.2. 
Assessment of intensity 
The investigator will make an assessment of intensity for each AE, AESI, SAE reported 
during the study and assign it to one of the following categories:  
• 
Mild: 
A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities 
of daily living. 
• 
Moderate:  
A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
• 
Severe:  
A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention.   
The intensity of the following solicited AEs will be assessed as described: 
Table 23 
Intensity scale for solicited events  
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 (Erythema) at 
administration site 
See Table 
Greatest surface diameter in mm 
Swelling at administration site 
See Table 
Greatest surface diameter in mm 
Temperature* 
See Table 
Temperature in °C/°F 
Headache 
0 
None/Normal** 
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 
None/Normal** 

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Event 
Intensity grade 
Parameter 
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/Normal** 
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/Normal** 
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. 
**For participants already experiencing some of the solicited systemic events prior to vaccine administration, 
‘None/Normal’ corresponds to ‘similar to baseline’ and only discomfort above baseline is to be reported as ≥1. 
The maximum intensity of administration site redness (Erythema)/swelling, and fever 
will be scored at GSK as follows: 
Table 24 
Intensity scale of administration site redness (Erythema)/swelling, 
and fever  
Intensity 
grade 
Redness (Erythema)/Swelling 
Fever 
0 
≤20 mm 
<38.0°C (100.4°F) 
1 
>20 - ≤50 mm 
≥38.0°C (100.4°F) - ≤38.5°C (101.3°F) 
2 
>50 - ≤100 mm 
>38.5°C (101.3°F) - ≤39.0°C (102.2°F) 
3 
>100 mm 
>39.0°C (102.2°F) 
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 judgment. 
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. 
10.3.5.3. 
Assessment of causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. 
• 
A reasonable possibility of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 

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• 
For causality assessment, the investigator will also consult the IB and/or product 
information, for marketed products. 
• 
The investigator must review and provide an assessment of causality for each 
AE/SAE and document this in the medical notes There may be situations in which an 
SAE has occurred and the investigator has minimal information to include in the 
initial report to GSK. However, it is very important that the investigator always make 
an assessment of causality for every event before the initial transmission of the SAE 
data to GSK. 
• 
The investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
10.3.5.4. 
Assessment of outcomes 
The investigator will assess the outcome of all serious and nonserious unsolicited AEs 
recorded during the study as: 
• 
Recovered/resolved 
• 
Recovering/resolving 
• 
Not recovered/not resolved 
• 
Recovered with sequelae/resolved with sequelae 
• 
Fatal (SAEs only). 
10.3.5.5. 
Follow-up of AEs, SAEs, AESIs, pregnancies or any other events of 
interest 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other health care professionals. 
• 
New or updated information will be recorded in the originally submitted documents. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
• 
After the initial AE/SAE/AESI/pregnancy or any other event of interest, the 
investigator is required to proactively follow each participant at subsequent 
visits/contacts. All SAEs, and nonserious AESI (as defined in the Section 8.4.4), will 
be followed until the event is resolved, stabilized, otherwise explained, or the 
participant is lost to follow-up. 
• 
Other nonserious AEs must be followed until EOS or until the participant is lost to 
follow-up. 

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Follow-up during the study 
AEs/AESIs documented at a previous visit/contact and defined as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until EOS. 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available postmortem findings, including 
histopathology. 
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 paper pregnancy follow-up 
report/electronic pregnancy report and the AE 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, the investigator must report any SAE occurring as a result of a poststudy 
pregnancy that is considered by the investigator to be reasonably related to the study 
intervention, to GSK as described in the Section 10.3.5.7. 
10.3.5.6. 
Updating of SAE, AESI and pregnancy information after removal of 
write access to the participant’s eCRF 
When additional SAE, AESI 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 sent to the Study contact for reporting SAEs (refer to Section 
8.4.7). 
10.3.5.7. 
Reporting of SAEs, AESIs and pregnancies  
SAE Reporting to GSK via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool will be 
taken offline to prevent the entry of new data or changes to existing data. 

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• 
If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken offline, then the site can report this information on a paper SAE form (see next 
section) or to the GSK/medical monitor by telephone. 
• 
If the site during the course of the study or poststudy becomes aware of any serious, 
nonserious AEs, pregnancy exposure, related to any GSK non-IMP they will report 
these events to GSK or to the concerned competent authority via the national 
spontaneous reporting system.  These will be classified as spontaneous ICSRs. 
• 
Contacts for SAE reporting can be found in Section 8.4.7.  
SAE Reporting to GSK via Paper Data Collection Tool 
• 
Email/facsimile transmission of the SAE paper data collection tool is the preferred 
method to transmit this information to the GSK/medical monitor. 
• 
In rare circumstances and in the absence of email/facsimile equipment, notification 
by telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting 
timeframes. 
• 
Contacts for SAE reporting can be found in Section 8.4.7. 
10.4. 
Appendix 4: Contraceptive and barrier guidance 
10.4.1. 
Definitions 
10.4.1.1. 
WOCBP Definition 
Women in the following categories are considered WOCBP (fertile): 
• 
Adolescents of childbearing potential: Tanner stage ≥2 (post-thelarche) irrespective 
of the occurrence of menarche or following menarche. 
• 
From the time of menarche until becoming postmenopausal unless permanently 
sterile (see below) 
• 
Note: 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.  

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10.4.1.2. 
Woman of Nonchildbearing Potential (WONCBP) 
Women in the following categories are considered WONCBP: 
• 
Premenarchal: Tanner stage 1 (prepubertal) 
Permanently sterile due to one of the following procedures: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For permanently sterile individuals due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
investigator discretion should be applied to determining study entry. If reproductive 
status is questionable, additional evaluation should be considered. 
Note: Documentation can come from the site personnel’s review of the 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, confirmation with more than one FSH measurement is required. 
• 
Females on HRT and whose menopausal status is in doubt must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment. 
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 
25). 
Table 25 
Highly effective contraceptive methods  
Highly Effective Contraceptive Methods That Are User Dependenta 
Failure rate of <1% per year when used consistently and correctly 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• 
Oralb 
• 
Intravaginal  
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 

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• 
Injectable 
• 
Oralb  
Highly Effective Methods That Are User Independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion/ligation 
Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.)  
Male partner sterilization prior to the female 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.)  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with 
local regulations regarding the use of contraceptive methods for subjects in clinical studies. 
b For WOCBP taking hormonal contraception, an additional barrier contraception method is recommended if they are 
concomitantly taking drugs that interact and reduce effectiveness of hormonal contraception. The investigator 
should check the list of drugs that could reduce hormonal contraceptive effectiveness (Potent drug enzyme 
inducers). 

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10.5. 
Appendix 5: Country-specific requirements 
10.5.1. 
Germany 
Explanatory statement concerning Gender Distribution (Article 7, paragraph 2 (12) 
of the German GCP ORDER). 
For this study, there is no intention to conduct specific analyses investigating the 
relationship between gender and the safety, immunogenicity and efficacy of the 
investigational RSVPreF3 OA vaccine. Recruitment will include both males and females. 
To not expose pregnant women and their fetuses/children to an investigational vaccine, 
females enrolled in this study will either be of nonchildbearing potential (i.e., 
hysterectomy, bilateral oophorectomy, bilateral salpingectomy or post-menopause), or if 
she is of childbearing potential, she must have a negative pregnancy test and use 
appropriate methods of contraception for the study duration (refer to the study protocol, 
Section 5.1  “Inclusion criteria” and Section 5.2 “Exclusion criteria”). Women who are 
pregnant, planning to become pregnant or breastfeeding are excluded from this study. 
10.5.2. 
Japan 
Regulatory and ethical considerations 
The study will be conducted in accordance with “the Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (MHW Notification 
No.28 dated 27 March 1997)” and Pharmaceuticals and Medical Devices Act. 
The statement “To assume responsibility for the proper conduct of the study at this site.” 
on the Protocol Investigator Agreement Page means the investigator’s responsibility 
defined by Japanese GCP. 
GSK will submit the clinical trial notification to the regulatory authorities in accordance 
with Pharmaceuticals and Medical Devices Act before conclusion of any contract for the 
conduct of the study with study sites. 
Study period 
Study Period is included in Exhibit. 
Study administrative structure 
Sponsor information, List of Medical Institutions and Investigators are included in 
Exhibit. 
10.5.3. 
South Africa 
As per regulatory requirement and due to high prevalence of HIV infection, all 
participants from South Africa with unknown HIV status (unknown or previously tested 
negative) will be counselled and tested for HIV infection, using the South African Health 

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Products Regulatory Authority (SAHPRA) approved test kits prior to enrolment. If HIV 
result is positive, these participants will be excluded as per Section 5.2.1 Medical 
Conditions exclusion criterion 1. 
10.6. 
Appendix 6: Grading scales for chronic diseases in scope of 
the AIR population 
10.6.1. 
GOLD classification 
Stages of COPD quantify the severity of the disease. COPD is classified into 4 classes 
[GOLD, 2020]. 
GOLD Class 
Intensity 
Definition 
GOLD 1 
Mild 
FEV1 ≥ 80% predicted 
GOLD 2 
Moderate 
50% ≤ FEV1 <80% 
GOLD 3 
Severe 
30% ≤ FEV1 <50% 
GOLD 4 
Very severe 
FEV1 < 30% predicted 
10.6.2. 
New York Heart Association Classification of heart failure 
Stages of chronic heart failure quantify the severity of the disease. CHF is classified into 
4 classes [NYHA]. 
NYHA Class 
Definition 
Limitation 
Example 
I 
Ordinary physical activity does 
not cause undue fatigue, 
dyspnoea, or palpitations. 
None 
Can complete any activity requiring ≤7 MET: 
• 
Carry 11 kg up 8 steps 
• 
Carry objects weighing 36 kg 
• 
Shovel snow 
• 
Spade soil 
• 
Ski 
• 
Play squash, handball, or basketball 
• 
Jog or walk 8 km/hour. 
II 
Ordinary physical activity 
causes fatigue, dyspnoea, 
palpitations, or angina. 
Mild 
Can complete any activity requiring ≤5 MET: 
• 
Sexual intercourse without stopping 
• 
Garden 
• 
Roller skate 
• 
Walk 7 km/hour on level ground 
• 
Climb one flight of stairs at a normal pace 
without symptoms. 
III 
Comfortable at rest; less than 
ordinary physical activity 
causes fatigue, dyspnoea, 
palpitations, or angina. 
Moderate 
Can complete any activity requiring ≤2 MET: 
• 
Shower or dress without stopping 
• 
Strip and make a bed 
• 
Clean windows 
• 
Play golf 
• 
Walk 4 km/hour. 
IV 
Symptoms occur at rest; any 
physical activity increases 
discomfort. 
Severe 
Cannot do or cannot complete any activity 
requiring ≥2 MET; cannot do any of the above 
activities. 
MET = Metabolic equivalent of task, a measure of how much energy is expended compared to remaining at rest. 

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10.6.3. 
Chronic kidney disease classification 
Stages of CKD quantify the severity of the disease. CKD is classified into 5 stages 
[CKD, 2021]. 
• 
Stage 1 (G1): Normal GFR (≥90 mL/min/1.73 m2) plus either persistent albuminuria 
or known structural or hereditary renal disease. 
• 
Stage 2 (G2): GFR 60 to 89 mL/min/1.73 m2 
• 
Stage 3a (G3a): 45 to 59 mL/min/1.73 m2 
• 
Stage 3b (G3b): 30 to 44 mL/min/1.73 m2 
• 
Stage 4 (G4): GFR 15 to 29 mL/min/1.73 m2 
• 
Stage 5 (G5): GFR < 15 mL/min/1.73 m2 
GFR (in mL/min/1.73 m2) in CKD can be estimated by the CKD-EPI creatinine equation: 
141 × (serum creatinine) -1.209× 0.993 age. The result is multiplied by 1.018 if the 
patient is female, and by 1.159 if the patient is African American. For female African 
Americans, the result is multiplied by 1.018 × 1.159 (1.1799). Alternatively, GFR can be 
estimated using timed (most commonly 24 hours) urine creatinine clearance using 
measured serum and urine creatinine; this equation tends to overestimate GFR by 10 to 
20%. It is used when serum creatinine assessment may not be as accurate (e.g., in patients 
who are sedentary, very obese, or very thin). Serum cystatin C is an alternative 
endogenous GFR marker used as a confirmatory test in people with nonrenal factors 
affecting serum creatinine level (e.g., extremely high, or low muscle mass, exogenous 
creatine intake, amputations or neuromuscular diseases, and high protein or exclusively 
plant-based diets). GFR is calculated using CKD-EPI cystatin C equation. 
The CKD-EPI formula is more accurate than the MDRD and Cockcroft-Gault formulas, 
particularly for patients with a GFR near normal values. The CKD-EPI equation yields 
fewer falsely positive results indicating chronic kidney disease and predicts outcome 
better than the other formulas. 

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11. 
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