A Phase 3, Open-label, Randomized, Controlled Study to Evaluate the Immune Response, Safety and Reactogenicity of RSVPreF3 OA Investigational Vaccine When Co-Administered With a COVID-19 mRNA Vaccine (Omicron XBB.1.5) in Adults Aged 50 Years and Above
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

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CLINICAL STUDY PROTOCOL 
Primary Study Intervention 
GlaxoSmithKline Biologicals S.A. (GSK)’s 
investigational respiratory syncytial virus (RSV) 
vaccine BIO RSV OA=ADJ (GSK3844766A) 
Other Study Intervention 
Comirnaty Omicron XBB.1.5 COVID-19 mRNA 
vaccine 
Study Identifier 
217848 (RSV OA=ADJ-013) 
EU CT Number 
2023-510196-59-00 
Approval Date 
09 Jan 2024 
Title 
A Phase 3, open-label, randomized, controlled study 
to evaluate the immune response, safety and 
reactogenicity of RSVPreF3 OA investigational 
vaccine when co-administered with a COVID-19 
mRNA vaccine (Omicron XBB.1.5) in adults aged 
50 years and above. 
Brief Title 
A study on the immune response and safety of a 
vaccine against respiratory syncytial virus (RSV) 
when given alone and together with a vaccine against 
SARS-CoV-2 in adults aged 50 years and above. 
Sponsor 
GlaxoSmithKline Biologicals S.A. 
Rue De L'Institut 89 
1330 Rixensart 
Belgium 
Sponsor signatory 
Nadia Meyer, MD 
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 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. 
• 
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 
217848 (RSV OA=ADJ-013) 
EU CT Number 
2023-510196-59-00 
Approval date 
09 Jan 2024 
Title 
A Phase 3, open-label, randomized, controlled study 
to evaluate the immune response, safety and 
reactogenicity of RSVPreF3 OA investigational 
vaccine when co-administered with a COVID-19 
mRNA vaccine (Omicron XBB.1.5) in adults aged 
50 years and above. 
Investigator name 
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 
 
 
 

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TABLE OF CONTENTS 
PAGE 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................ 11 
1. 
PROTOCOL SUMMARY ........................................................................................ 19 
1.1. 
Synopsis ..................................................................................................... 19 
1.2. 
Schema ...................................................................................................... 19 
1.3. 
Schedule of activities (SoA) ........................................................................ 20 
2. 
INTRODUCTION .................................................................................................... 24 
2.1. 
Study rationale ............................................................................................ 24 
2.2. 
Background ................................................................................................ 24 
2.3. 
Benefit/risk assessment .............................................................................. 26 
2.3.1. 
Risk assessment .......................................................................... 26 
2.3.2. 
Benefit assessment ..................................................................... 28 
2.3.3. 
Overall benefit-risk conclusion ..................................................... 28 
3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS .................................................... 29 
3.1. 
Objectives and endpoints ............................................................................ 29 
3.2. 
Estimands ................................................................................................... 31 
3.2.1. 
Immunogenicity Objectives .......................................................... 31 
3.2.2. 
Safety Objectives ......................................................................... 35 
4. 
STUDY DESIGN .................................................................................................... 36 
4.1. 
Overall design ............................................................................................. 36 
4.2. 
Scientific rationale for study design ............................................................. 37 
4.2.1. 
Participant input into design ......................................................... 37 
4.3. 
Justification for dose ................................................................................... 38 
4.4. 
End-of-study definition ................................................................................ 38 
5. 
STUDY POPULATION ........................................................................................... 38 
5.1. 
Inclusion criteria .......................................................................................... 38 
5.2. 
Exclusion criteria ......................................................................................... 39 
5.2.1. 
Medical Conditions ...................................................................... 39 
5.2.2. 
Prior/Concomitant Therapy .......................................................... 40 
5.2.3. 
Prior/Concurrent Clinical Study Experience ................................. 41 
5.2.4. 
Other Exclusion Criteria ............................................................... 41 
5.3. 
Lifestyle considerations ............................................................................... 41 
5.4. 
Screen failures ............................................................................................ 42 
5.5. 
Criteria for temporarily delaying enrollment/ administration of study 
intervention ................................................................................................. 42 
6. 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY ................................ 43 
6.1. 
Study interventions administered ................................................................ 43 
6.1.1. 
Medical devices ........................................................................... 44 
6.2. 
Preparation, handling, storage, and accountability ...................................... 44 
6.3. 
Assignment to study intervention ................................................................ 44 
6.3.1. 
Participant identification ............................................................... 44 
6.3.2. 
Randomization to study intervention ............................................ 45 
6.3.3. 
Intervention allocation to the participant ....................................... 45 
6.4. 
Blinding ....................................................................................................... 45 

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6.5. 
Study intervention compliance .................................................................... 46 
6.6. 
Dose modification ....................................................................................... 46 
6.7. 
Continued access to study intervention after the end of the study ............... 46 
6.8. 
Treatment of overdose ................................................................................ 46 
6.9. 
Prior and concomitant therapy .................................................................... 46 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 47 
7.1. 
Discontinuation of study intervention ........................................................... 47 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration .............................................................................. 48 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 48 
7.3. 
Lost to follow-up.......................................................................................... 50 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 50 
8.1. 
Administrative and baseline procedures ..................................................... 51 
8.1.1. 
Collection of demographic data .................................................... 51 
8.1.2. 
Medical/vaccination history .......................................................... 52 
8.1.3. 
Pre-vaccination body temperature ............................................... 52 
8.2. 
Immunogenicity assessments ..................................................................... 52 
8.2.1. 
Biological samples ....................................................................... 53 
8.2.2. 
Laboratory assays ....................................................................... 53 
8.2.3. 
Immunological read-outs .............................................................. 54 
8.2.4. 
Cytology ...................................................................................... 54 
8.2.5. 
Immunological correlates of protection ......................................... 54 
8.3. 
Safety assessments .................................................................................... 54 
8.3.1. 
History directed physical examination .......................................... 54 
8.3.2. 
Clinical safety laboratory tests ..................................................... 55 
8.3.3. 
Pregnancy testing ........................................................................ 55 
8.3.4. 
Safety monitoring AND Committee .............................................. 55 
8.3.5. 
Post-vaccination procedures ........................................................ 55 
8.3.5.1. 
Safety contact at 6 months post-last 
vaccination ................................................................. 55 
8.4. 
Adverse Events (AEs), serious adverse events (SAEs), and other 
safety reporting ........................................................................................... 56 
8.4.1. 
Time period and frequency for collecting AE, SAE, and 
other safety information ............................................................... 56 
8.4.2. 
Method of detecting AEs and SAEs ............................................. 58 
8.4.3. 
Follow-up of AEs and SAEs ......................................................... 58 
8.4.4. 
Adverse events of special interest................................................ 58 
8.4.4.1. 
Potential immune-mediated diseases ......................... 58 
8.4.4.2. 
Atrial fibrillation (AF) ................................................... 64 
8.4.5. 
Regulatory reporting requirements for SAEs/AESIs 
/pregnancies ................................................................................ 65 
8.4.6. 
Pregnancy ................................................................................... 66 
8.4.7. 
Contact information for reporting SAEs, AESIs, and 
pregnancies ................................................................................. 66 
8.4.8. 
Participant card ............................................................................ 66 
8.5. 
Pharmacokinetics ....................................................................................... 67 
8.6. 
Pharmacodynamics .................................................................................... 67 
8.7. 
Genetics ..................................................................................................... 67 
8.8. 
Biomarkers ................................................................................................. 67 

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8.9. 
Immunogenicity assessments ..................................................................... 67 
8.10. 
Health economics or medical resource utilization and health 
economics .................................................................................................. 67 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 68 
9.1. 
Statistical hypotheses ................................................................................. 68 
9.2. 
Analysis sets ............................................................................................... 69 
9.2.1. 
Criteria for elimination from analysis ............................................ 69 
9.3. 
Statistical analyses ..................................................................................... 70 
9.3.1. 
Primary endpoints/estimands analysis ......................................... 70 
9.3.2. 
Secondary endpoints/estimands analyses ................................... 71 
9.4. 
Interim analyses .......................................................................................... 71 
9.4.1. 
Sequence of analyses.................................................................. 71 
9.4.2. 
Statistical Considerations for Interim Analyses............................. 72 
9.5. 
Pre-dose sample size determination ........................................................... 72 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 73 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations .......... 73 
10.1.1. 
Regulatory and ethical considerations ......................................... 73 
10.1.2. 
Financial disclosure ..................................................................... 73 
10.1.3. 
Informed consent process ............................................................ 74 
10.1.4. 
Recruitment strategy .................................................................... 74 
10.1.5. 
Data protection ............................................................................ 75 
10.1.6. 
Committees structure ................................................................... 75 
10.1.7. 
Dissemination of Clinical Study Data ........................................... 75 
10.1.8. 
Data quality assurance ................................................................ 76 
10.1.9. 
Source documents ....................................................................... 77 
10.1.10. Study and site start and closure ................................................... 78 
10.1.11. Publication policy ......................................................................... 78 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 79 
10.3. 
Appendix 3: AEs and SAEs: Definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 80 
10.3.1. 
Definition of AE ............................................................................ 80 
10.3.2. 
Definition of SAE .......................................................................... 81 
10.3.3. 
Solicited events............................................................................ 82 
10.3.4. 
Unsolicited AE ............................................................................. 83 
10.3.5. 
Recording, assessment and follow-up of AEs, SAEs 
AESIs and pregnancies ............................................................... 83 
10.3.5.1. AE and SAE recording ................................................ 83 
10.3.5.2. Assessment of intensity .............................................. 84 
10.3.5.3. Assessment of causality ............................................. 86 
10.3.5.4. Assessment of outcomes............................................ 86 
10.3.5.5. Follow-up of AEs, SAEs, AESIs, and 
pregnancies ................................................................ 87 
10.3.5.6. Updating of SAE, AESI and pregancy 
information after removal of write access to the 
participant’s eCRF ...................................................... 88 
10.3.5.7. Reporting of SAEs, AESIs and pregnacies ................. 88 
10.4. 
Appendix 4: Guidance on Contraception, Women not considered as 
WOCBP and collection of pregnancy information ........................................ 89 
10.4.1. 
Definitions .................................................................................... 89 

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10.4.1.1. Woman of childbearing potential (WOCBP) ................ 89 
10.4.1.2. Woman of Nonchildbearing potential 
(WONCBP) ................................................................. 89 
10.4.2. 
Contraception guidance ............................................................... 90 
10.4.2.1. Woman of childbearing potential (WOCBP) ................ 90 
10.5. 
Appendix 5: Country-specific requirements ................................................. 90 
11. REFERENCES ....................................................................................................... 91 
 

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LIST OF TABLES 
PAGE 
Table 1 
SoA for Co-Ad group .............................................................................. 20 
Table 2 
SoA for Control group ............................................................................ 21 
Table 3 
Intervals between study visits (Co-Ad group) ......................................... 23 
Table 4 
Study objectives, endpoints and estimands ............................................ 29 
Table 5 
Study Intervention(s) Administered......................................................... 43 
Table 6 
Biological samples ................................................................................. 53 
Table 7 
Laboratory assays .................................................................................. 53 
Table 8 
Immunological read-outs ........................................................................ 54 
Table 9 
Timeframes for collecting and reporting of safety information ................. 57 
Table 10 
List of potential immune-mediated diseases (pIMDs) ............................. 59 
Table 11 
Timeframes for submitting SAEs, pregnancies and pIMDs to 
GSK ....................................................................................................... 65 
Table 12 
Contact information for reporting SAEs, AESIs, and pregnancies .......... 66 
Table 13 
Study Objectives and Null Hypothesis .................................................... 68 
Table 14 
Analysis sets .......................................................................................... 69 
Table 15 
Power to demonstrate non-inferiority of the Co-Ad group 
compared to the Control group in terms of GMT with 361 
evaluable participants per group. ........................................................... 72 
Table 16 
Solicited administration site events......................................................... 82 
Table 17 
Solicited systemic events ....................................................................... 82 
Table 18 
Intensity scales for solicited events in participants ≥50 YOA .................. 85 
Table 19 
Intensity scales of administration site erythema/swelling, and 
fever ....................................................................................................... 85 
Table 20 
Highly effective contraceptive methods .................................................. 90 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 19 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
List of Abbreviations 
Abbreviation 
Definition 
AAION 
Arteritic anterior ischemic optic neuropathy 
Ab 
Antibody 
ADEM 
Acute disseminated encephalomyelitis 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AF 
Atrial fibrillation 
ANCA 
Anti-neutrophil cytoplasmic antibody 
ANCOVA 
Analysis of Covariance 
Anti-S 
Anti-Spike 
APTM 
Acute partial transverse myelitis 
ARI 
Acute Respiratory Infection 
AS01E 
Adjuvant System containing MPL, QS-21 and liposome (25 µg 
MPL and 25 µg QS-21) 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CIDP 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy 
CIOMS 
Council for International Organizations of Medical Sciences 
CIS 
Clinically isolated syndrome 
CLS 
Clinical Laboratory Sciences 
CONSORT 
Consolidated Standards of Reporting Trials 
CoP 
Correlates of protection 
COPD 
Chronic obstructive pulmonary disease 
COVID-19 
Coronavirus Disease 2019 
CSR 
Clinical Study Report 
DNA 
Deoxyribonucleic Acid 
EBA 
Epidermolysis Bullosa Acquisita 
ECL 
Electrochemiluminescence 
eCRF 
electronic Case Report Form 
EMA 
European Medicines Agency 

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Abbreviation 
Definition 
EoS 
End of study 
ES 
Exposed Set 
FDA 
Food and Drug Administration 
FSFV 
First subject first visit 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
GMC 
Geometric Mean Concentration 
GMC 
Geometric Mean Concentration 
GMT 
Geometric Mean Titer 
GSK 
GlaxoSmithKline Biologicals SA 
HCP 
Healthcare Professional 
HIPAA 
Health Insurance Portability and Accountability Act 
HRP 
Horseradish peroxidase 
HRT 
Hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
ICU 
Intensive Care Unit 
IDMC 
Independent data monitoring committee 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IMP 
Investigational medicinal product 
IRB 
Institutional Review Board 
LABD 
Linear IgA-mediated bullous dermatosis 
LLOQ 
Lower Limit of Quantification 
LNP 
Lipid Nanoparticle 
LRTD 
Lower Respiratory Tract Disease 
LSLV 
Last subject last visit 
MGI 
Mean Geometric Increase 
MMSE 
Mini-Mental State Examination 

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Abbreviation 
Definition 
MoCA 
Mini-Cog or Montreal Cognitive Assessment 
MPL 
Monophosphoryl Lipid A 
mRNA 
Messenger Ribonucleic Acid 
MS 
Multiple sclerosis 
MSD 
Meso Scale Discovery (Rockville, US) 
NAAT 
Nucleic acid amplification test 
Nab 
Neutralizing Antibody 
NI 
Non-inferiority 
OA 
Older Adults 
Omi 
Omicron 
pIMD 
Potential Immune-Mediated Disease 
PPS 
Per Protocol Set 
PT 
Preferred terms 
QTL 
Quality Tolerance Limit 
RLU 
Relative light units 
RNA 
Ribonucleic Acid 
RSV 
Respiratory Syncytial Virus 
RTI 
Respiratory Tract Infection 
RTSM 
Registration and Medication Ordering System 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAR 
Serious adverse reaction 
SAS 
Statistical Analysis System 
SCLS 
Systemic capillary leak syndrome 
SD 
Standard Deviation 
SoA 
Schedule of activities 
SRR 
Seroresponse Rate 
SRT 
Safety Review Team 
SUSAR 
Suspected unexpected serious adverse reaction 
TED 
Thyroid eye disease 
TM 
Transverse myelitis 
TPA 
Tripropylamine 

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Abbreviation 
Definition 
ULOQ 
Upper Limit Of Quantification 
US 
United States 
VAED 
Vaccine associated enhanced disease 
VAERD 
Vaccine associated enhanced respiratory disease 
VSV 
Vesicular Stomatitis Virus 
WOCBP 
Woman of childbearing 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 adverse event (AE) can therefore be any unfavourable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal product. 
For marketed medicinal products, this also includes failure 
to produce expected benefits (i.e. lack of efficacy), abuse or 
misuse. 
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 

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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. 
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. 
Comparator 
Any product used as a reference (including placebo, 
marketed product, GSK or non-GSK) for an investigational 
product being tested in a clinical trial. This is any product 
that is being used to assess the safety, efficacy, or other 
measurable value against the test product (IMP). 
Eligible 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolled participant 
‘Enrolled’ means a participant’s agreement to participate in 
a clinical study following completion of the informed 
consent process. Potential participants who are screened for 
determining eligibility for the study, but do not participate in 
the study, are not considered enrolled, unless otherwise 
specified by the protocol. 
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. 
Immunological 
correlate of protection 
A correlate of risk that has been validated to predict a certain 
level of protection from the targeted endpoint. 

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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. 
Intervention number 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Invasive medical device EEC Directive 93/42/EEC defines an invasive medical 
device as ‘A device which, in whole or in part, penetrates 
inside the body, either through a body orifice or through the 
surface of the body’. 
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 
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. 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.  

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Protocol amendment 
The International Council on Harmonisation (ICH) defines a 
protocol amendment as: ‘A written description of a 
change(s) to or formal clarification of a protocol.’ GSK 
further details this to include a change to an approved 
protocol that affects the safety of participants, scope of the 
investigation, study design, or scientific integrity of the 
study. 
Protocol administrative 
change 
A protocol administrative change addresses changes to only 
logistical or administrative aspects of the study.  
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. 
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 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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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 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 monitor 
An individual assigned by the sponsor and responsible for 
assuring proper conduct of clinical studies at 1 or more 
investigational sites. 
Suspected Unexpected 
Serious Adverse 
Reaction 
A Suspected Unexpected Serious Adverse Reaction is a 
Serious Adverse Reaction whose nature, severity or outcome 
is not consistent with the reference safety information. 
Unsolicited adverse 
event 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse event. 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: 
A Phase 3, open-label, randomized, controlled study to evaluate the immune response, 
safety and reactogenicity of RSVPreF3 OA investigational vaccine when co-administered 
with a COVID-19 mRNA vaccine (Omicron XBB.1.5) in adults aged 50 years and above. 
Brief Title: 
A study on the immune response and safety of a vaccine against respiratory syncytial 
virus (RSV) when given alone and together with a vaccine against SARS-CoV-2 in adults 
aged 50 years and above. 
Rationale: Refer to Section 2.1. 
Objectives, Endpoints, and Estimands: Refer to Section 3. 
Overall Design: Refer to Section 1.2 and Section 4.1. 
Number of Participants: Refer to Section 9.5. 
Data Monitoring/Other Committee: Refer to Section 10.1.6. 
1.2. 
Schema 
Figure 1 
Study design overview 
 

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1.3. 
Schedule of activities (SoA) 
Table 1 
SoA for Co-Ad group 
Type of contact 
Visit 1 
Visit 2** 
Contact 
Notes 
Timepoints 
Day 1 
Day 31 
Month 61 
Baseline and demography assessments 
Informed consent 
●2 
 
 
See Section 10.1.3 
Distribution of participant card 
○ 
 
 
See Section 8.4.8 
Inclusion and exclusion criteria 
● 
 
 
See Section 5.1 and Section 
5.2 for Inclusion and Exclusion 
criteria 
Check with participant if he/she will appoint a 
caregiver and distribute caregiver information 
letter, when applicable 
○ 
○ 
 
See Sections 8 for details 
Demography 
● 
 
 
See Section 8.1.1 
Medical and vaccination history 
● 
 
 
See Sections 8.1.2 
History directed physical examination 
○ 
 
 
See Section 8.3.1 
Screening conclusion 
● 
 
 
See Section 5.4 
Laboratory assessment 
Urine pregnancy test (only for women of 
childbearing potential) 
●3 
 
 
See Section 8.3.3 
Blood sampling from all participants for 
humoral response assessment (~15 mL) 
●4 
●5 
 
See Section 8.2.2 
Study Intervention administration 
Check contraindications, warnings and 
precautions to vaccination 
○ 
 
 
See Sections 7.1.1 
Check criteria for temporary delay for 
enrollment and/or study intervention 
administration* 
○ 
 
 
See Section 5.5 
Randomization, study group and intervention 
number allocation 
○ 
 
 
See Section 6.3.2 and Section 
6.3.3 
Body temperature before study interventions 
administration 
● 
 
 
The preferred location for 
measuring temperature will be 
oral cavity/axilla (see Section 
8.1.3). Fever is defined as 
temperature ≥38.0°C/100.4°F, 
regardless of the location of 
measurement. 
Study interventions administration (COVID-19 
mRNA vaccine + RSVPreF3 OA 
investigational vaccine on separate arms) 
(including 30-minute post-vaccination 
observation) 
● 
 
 
See Section 6.1 
Recording of administered study interventions 
numbers 
● 
 
 
See Section 6.3.3 
Safety assessment 
Distribution of diary cards for solicited events 
and unsolicited AEs 
○ 
 
 
See Section 10.3.5 
Record concomitant medications/vaccinations 
● 
● 
● 
See Section 6.9 
Recording of intercurrent medical conditions  
● 
● 
● 
See Section 9.2.1 and Table 9 
Recording of solicited events (Days 1–4 after 
study intervention administration)  
● 
 
 
See Section 10.3.5 
Recording of unsolicited AEs (Days 1-30 after 
study intervention administration)6 
● 
● 
 
See Sections 10.3.5 
Recording of all SAEs and pIMDs6 
● 
● 
● 
See Section 10.3.5. 

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Type of contact 
Visit 1 
Visit 2** 
Contact 
Notes 
Timepoints 
Day 1 
Day 31 
Month 61 
Recording of pregnancy 
● 
● 
● 
See Section 10.3.5 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine7 
● 
● 
● 
See Section 10.3.5 
Return of diary cards  
 
○ 
 
See Section 10.3.5.1 
Diary card review and transcription by 
investigator/delegate 
 
● 
 
See Section 10.3.5.1 
Recording of AEs/SAEs leading to withdrawal 
from the study 
● 
● 
● 
See Section 10.3.5 
Phone contact for safety follow-up 
 
 
● 
See Sections 10.3.5.5 
Study Conclusion 
 
 
● 
See Section 4.4 
Note: The double-line borders following Day 31 and Month 6 indicates analyses which will be performed on all data 
obtained up to these time points. 
AE = adverse event; AESI = Adverse event of special interest, AF = Atrial fibrillation, pIMDs = potential immune-
mediated diseases; SAE = Serious Adverse Event; eCRF = electronic case report form. 
● 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. 
* Visit 1 procedures should preferably be done on the same day. If not, all the visit procedures must be repeated prior 
to the study interventions administration and recorded in the eCRF when required, excluding the informed 
consent, the collection of demographic data. All efforts should be made to collect the blood sample on the day of 
study intervention administration, however if the blood sampling was previously taken for this visit, the blood 
sample does not need to be retaken. 
** Visit 2 should preferably be done on site but if local regulations allow and quality of study procedures is maintained, 
participant(s) can be offered remote visits (e.g., home visits) conducted by an authorized staff. Any further 
information from the participant, not collected during the home visit, can be obtained by means of a phone call 
conducted by the site staff. 
1. 
Month 6 = 6 months after last study intervention administration. For this contact, multiple formats can be 
proposed by the study site (refer to Section 8.3.5.1 for details). 
2. 
Freely given and written informed consent must be obtained from each study participant at Visit 1. 
3. 
The urine sample for pregnancy test (only for women of childbearing potential) should be taken prior to study 
intervention administration. If the study intervention administration is delayed by any reason, the sample will need 
to be collected again on the day of study intervention administration. 
4. 
Sample collected at Day 1 will be used as baseline for both COVID-19 mRNA and RSVPreF3 OA investigational 
vaccine-related testing. 
5. 
Sample collected at Day 31 will be used for the post-vaccination testing related to both COVID-19 mRNA and 
RSVPreF3 OA investigational vaccine-related testing. 
6. 
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. 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. 
7. 
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. 
Table 2 
SoA for Control group 
Type of contact 
Visit 1 
Visit 2 
Visit 3** Contact Notes 
Timepoints 
Day 1 
Day 31 
Day 61 
Month 71 
Baseline and demography assessments 
Informed consent 
●2 
 
 
 
See Section 10.1.3 
Distribution of participant card 
○ 
 
 
 
See Section 8.4.8 
Inclusion and exclusion criteria 
● 
 
 
 
See Sections 5.1 and 
Section 5.2 for Inclusion 
and Exclusion criteria 
Check with participant if he/she will appoint a 
caregiver and distribute caregiver information 
letter, when applicable 
○ 
○ 
○ 
 
See Sections 8 for details 

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Type of contact 
Visit 1 
Visit 2 
Visit 3** Contact Notes 
Timepoints 
Day 1 
Day 31 
Day 61 
Month 71 
Demography 
● 
 
 
 
See Section 8.1.1 
Medical and vaccination history 
● 
 
 
 
See Section 8.1.2 
History directed physical examination  
○ 
 
 
 
See Section 8.3.1 
Screening conclusion 
● 
 
 
 
See Section 5.4 
Laboratory assessment 
Urine pregnancy test (only for women of 
childbearing potential) 
●3 
●3 
 
 
See Section 8.3.3 
Blood sampling from all participants for 
humoral response assessment (~15 mL) 
●4 
●5 
●6 
 
See Section 8.2.2 
Study Intervention Administration 
Check contraindications, warnings and 
precautions to study intervention 
administration 
○ 
○ 
 
 
See Sections 7.1.1 
Check criteria for temporary delay of study 
intervention administration* 
○ 
○ 
 
 
See Section 5.5 
Randomization, study group and intervention 
number allocation 
○ 
 
 
 
See Section 6.3.2 and 
Section 6.3.3 
Body temperature before study intervention 
administration 
● 
● 
 
 
The preferred location for 
measuring temperature 
will be oral cavity/axilla 
(see Section 8.1.3). Fever 
is defined as temperature 
≥38.0°C/100.4°F, 
regardless of the location 
of measurement. 
Study intervention administration: COVID-19 
mRNA vaccine (including 30-minute post-
vaccination observation) 
● 
 
 
 
See Section 6.1 
Study intervention administration: RSVPreF3 
OA investigational vaccine (including 30-
minute post-vaccination observation) 
 
● 
 
 
See Section 6.1 
Recording of administered study intervention 
number 
● 
● 
 
 
See Section 6.3.3 
Safety assessment 
Distribution of diary cards for solicited events 
and unsolicited AEs 
○ 
○ 
 
 
See Section 10.3.5 
Record concomitant 
medications/vaccinations 
● 
● 
● 
● 
See Section 6.9 
Recording of intercurrent medical conditions  
● 
● 
● 
● 
See Section 9.2.1 and 
Table 9 
Recording of solicited events (Days 1–4 after 
study intervention administration)  
● 
● 
 
 
See Section 10.3.5 
Recording of unsolicited events (Days 1-30 
after study intervention administration)7 
● 
● 
● 
 
See Sections 10.3.5 
Recording of SAEs and pIMDs7 
● 
● 
● 
● 
See Section 10.3.5 
Recording of pregnancy 
● 
● 
● 
● 
See Section 10.3.5 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine8 
● 
● 
● 
● 
See Section 10.3.5 
Return of diary cards  
 
○ 
○ 
 
See Section 10.3.5.1 
Diary card review and transcription by 
investigator/delegate 
 
● 
● 
 
See Section 10.3.5.1 
Recording of Aes/SAEs leading to withdrawal 
from the study 
● 
● 
● 
● 
See Section 10.3.5 

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Type of contact 
Visit 1 
Visit 2 
Visit 3** Contact Notes 
Timepoints 
Day 1 
Day 31 
Day 61 
Month 71 
Phone contact for safety follow-up  
 
 
 
● 
See Sections 10.3.5.5 
Study Conclusion 
 
 
 
● 
See Section 4.4 
Note: The double-line borders following Day 61 indicate analyses which will be performed on all data obtained up to 
these time points. 
AE = adverse event; AESI = Adverse event of special interest; AF = Atrial fibrillation, pIMDs = potential immune-
mediated diseases; SAE = Serious Adverse Event; eCRF = electronic case report form. 
● 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 
* Visit 1 procedures should preferably be done on the same day. If not, all the visit procedures must be repeated prior 
to the study intervention administration and recorded in the eCRF when required, excluding the informed consent, 
the collection of demographic data. All efforts should be made to collect the blood sample on the day of study 
intervention administration, however if the blood sampling was previously taken for this visit, the blood sample 
does not need to be retaken.  
If during Visit 2 the study intervention administration is postponed, all the visit procedures must be repeated prior to the 
study intervention administration and recorded in the eCRF when required, excluding blood sampling if previously 
taken for this visit. 
** Visit 3 should preferably be done on site but if local regulations allow and quality of study procedures is maintained, 
participant(s) can be offered remote visits (e.g. home visits) conducted by authorized staff. Any further information 
from the participant, not collected during the home visit, can be obtained by means of a phone call conducted by 
the site staff. 
1. 
Month 7 = 6 months after last administration of RSVPreF3 OA investigational vaccine. For this contact, multiple 
formats can be proposed by the study site (refer to Section 8.3.5.1 for details). 
2. 
Freely given and written informed consent must be obtained from each study participant at Visit 1. 
3  
The urine samples for pregnancy test (only for women of childbearing potential) should be taken on the same day, 
prior to study intervention administration of any dose. If the study intervention administration is delayed by any 
reason, the samples will need to be collected again on the day of study intervention administration. 
4. 
Sample collected at Day 1 will be used as baseline for the COVID-19 mRNA vaccine-related testing. 
5. 
Sample collected at Day 31 will be used as baseline for the RSVPreF3 OA investigational and for the post-
vaccination COVID-19 mRNA vaccine-related testing. 
6. 
Sample collected at Day 61 will be used for the post-vaccination RSVPreF3 OA investigational vaccine-related 
testing. 
7. 
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. 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. 
8. 
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. 
Table 3 
Intervals between study visits (Co-Ad group) 
Interval 
Planned visit interval  
Allowed interval range 
Visit 1 → Visit 2 
30 days 
30-42 days 
Visit 1 → Contact 
180 days 
180-210 days 
Table 4 
Intervals between study visits (Control group) 
Interval 
Planned visit interval  
Allowed interval range 
Visit 1 → Visit 2 
30 days 
30-42 days 
Visit 2 → Visit 3 
30 days 
30-42 days 
Visit 2 → Contact 
180 days 
180-210 days 

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2. 
INTRODUCTION 
2.1. 
Study rationale 
GSK has developed a new RSVPreF3 OA vaccine against RSV-associated (subtypes A 
and B) disease in adults ≥ 60 YOA at an increased risk of RSV-LRTD. The RSVPreF3 
OA vaccine was approved for protection against LRTD caused by RSV in adults 
≥ 60 YOA in the US on 3 May 2023, under the trade name Arexvy. To date the vaccine is 
also approved in the EU and in other countries. 
GSK is aiming to expand the label indication to include a population of 50 to 59 years of 
age with comorbidities that place them at increased risk for RSV-LRTD. A study to 
evaluate immune response and safety of RSVPreF3 OA investigational vaccine in adults 
50 to 59 YOA, versus adults ≥60 YOA is ongoing. 
The current study will assess the immunogenicity, safety and reactogenicity of the 
RSVPreF3 OA investigational vaccine when co-administered with a COVID-19 mRNA 
vaccine (Omicron XBB.1.5) in adults ≥ 50 YOA. 
Note: In some sections of this protocol, for readability, the COVID-19 mRNA vaccine 
(Omicron XBB.1.5) is referred as “COVID-19 mRNA vaccine”. 
2.2. 
Background 
RSV is an RNA virus of which 2 antigenically distinct subtypes exist, referred to as 
RSV A and RSV B [Borchers, 2013]. RSV causes RTI in people of all ages. RSV can 
cause severe lower respiratory tract infection in OA and adults with chronic medical 
conditions including cardiopulmonary and immunocompromising conditions. 
Based on epidemiological data collected prospectively in 2008-2010 in 14 countries 
worldwide (including North America, Europe, and East Asia), the average percentage of 
documented RSV infections in OA with influenza-like illness is 7.4%, with values 
between 0% and 17.1% across countries [Falsey, 2014]. In 2015, an estimated 1.5 million 
episodes of RSV related acute respiratory illness occurred in OA in industrialized 
countries; approximately 14.5% of these episodes involved a hospital admission [Nam, 
2019]. 
Currently, there are two vaccines available for prevention of RSV infections in 
adults ≥ 60 YOA; Arexvy (manufactured by GSK) and Abrysvo (manufactured by Pfizer 
Inc). 
Recent in-house results from a Phase 3 clinical trial in OA (RSV OA=ADJ-004) 
demonstrated that one dose of the RSV OA investigational vaccine-induced strong 
humoral and cell-mediated immune responses, which remained above pre-vaccination 
levels up to at least the 13 months post-vaccination readout timepoint. In another large 
Phase 3 vaccine clinical trial (RSV OA=ADJ-006) in adults aged 60 years and above, the 
vaccine candidate demonstrated an overall vaccine efficacy of 82.6% (96.95% CI, 

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57.9-94.1) against RSV-LRTD up to 6 months post-vaccination. The vaccine was well 
tolerated with a favorable safety profile [Papi, 2023]. 
Please refer to the current IB for information regarding the pre-clinical and clinical 
studies of the RSVPreF3 OA investigational vaccine. 
The COVID-19 mRNA vaccine which will be used in this study contains 30 micrograms 
of raxtozinameran embedded in lipid nanoparticles. Raxtozinameran is a single-stranded, 
5’-capped mRNA produced using a cell-free in vitro transcription from the corresponding 
DNA templates encoding the viral spike (S) protein of SARS-CoV-2 (Omicron 
XBB.1.5). 
The US FDA and the EMA have authorized the Comirnaty Omicron XBB.1.5 
30 micrograms/dose dispersion as a single dose injection as active immunisation to 
prevent COVID-19 caused by the SARS-CoV-2, in individuals 12 years of age and older 
[Comirnaty product information package insert, EMA, 2023; US FDA, 2023].  
Although a consistent and anticipated pattern of COVID-19 seasonality is yet to be 
determined, the analysis of severe COVID-19 outcomes (such as hospitalizations, ICU 
admissions, and COVID-19 deaths) since the start of the pandemic revealed that the 
disease has had a more significant impact during the time frame that aligns with the 
conventional influenza and RSV seasons [Stockholm, 2023].  
Since both vaccines will be indicated for use in individuals within similar age groups, 
evaluation of the co-administration of the RSVPreF3 OA vaccine and COVID-19 mRNA 
vaccine is of interest.  

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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 the RSVPreF3 OA investigational vaccine can be found in 
the IB and/or package insert. 
Potential Risk of 
Clinical Significance 
Rationale for Risk 
Mitigation Strategy 
RSV investigational vaccine 
pIMDs 
pIMDs are considered a theoretical 
risk, as for all vaccines containing an 
adjuvant system. 
Refer to Section 8.4.4.1 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. 
Participants with a history of hypersensitivity 
or severe allergic reaction to any component 
of the vaccine are excluded from study 
enrollment. 
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. 
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. 
As a mitigation strategy, physicians can 
implement the measures that they consider 
necessary. 
Local reactions at site of 
blood draw 
Pain, redness, irritation, and bruising 
may occur at the site where blood is 
drawn. 
Physicians 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. 

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For expected adverse reactions associated with the COVID-19 mRNA vaccine, please 
refer to the Prescribing Information. 
For details of study procedures, dose, and study design justification, refer to Sections 1.3 
and 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 
maternal antibodies.  
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 pregnant 
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 Day 43 post-birth interim analysis (DLP 04 October 2022) of 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. To date, 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 older adults (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. 
For women in the 50-59 YoA age group, the incidence of spontaneous pregnancy is about 
4 in 100000 women [Salihu, 2003]. As a precautionary measure, no pregnant women will 
be included and all WOCBP will be required to use adequate contraception and have a 

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negative pregnancy test prior to each vaccination in this study. 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. 
2.3.2. 
Benefit assessment 
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 a high vaccine 
efficacy during the first RSV season and no safety concerns were observed (refer to IB). 
By receiving the RSVPreF3 OA vaccine the participant may have the benefit of being 
protected against RSV-associated disease. All participants will receive a COVID-19 
mRNA vaccine as part of the study. By receiving this vaccine as part of standard medical 
care, the participant may have the benefit of continued protection against COVID-19. 
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 
Considering the measures taken to minimize the risk to participants participating in this 
study, the potential or recognized risks identified in association with the study vaccines 
(RSVPreF3 OA investigational vaccine and COVID-19 mRNA vaccine) and study 
procedures are justified by the potential benefits that may be afforded to the participants 
receiving these vaccines and by the value of information to be gained. 

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3. 
OBJECTIVES, ENDPOINTS AND ESTIMANDS 
3.1. 
Objectives and endpoints 
Table 4 
Study objectives, endpoints and estimands 
Objectives 
Endpoints and Estimands 
Primary 
• 
To demonstrate non-inferiority* of humoral 
immune response to RSVPreF3 OA 
investigational vaccine when co-administered 
with a COVID-19 mRNA vaccine compared to 
RSVPreF3 OA investigational vaccine 
administered alone. 
• 
RSV-A neutralization titers expressed as group GMT ratio 
1 month after the RSVPreF3 OA investigational vaccine 
dose. 
• 
RSV-B neutralization titers expressed as group GMT ratio 
1 month after the RSVPreF3 OA investigational vaccine 
dose. 
• 
To demonstrate non-inferiority* of humoral 
immune response to a COVID-19 mRNA 
vaccine when co-administered with the 
RSVPreF3 OA investigational vaccine 
compared to COVID-19 mRNA vaccine 
administered alone. 
• 
SARS-CoV-2 Omicron XBB.1.5 neutralization titers 
against pseudovirus bearing S protein expressed as group 
GMT ratio 1 month after the COVID-19 mRNA vaccine. 
Secondary 
• 
To evaluate the humoral immune response to 
RSVPreF3 OA investigational vaccine when 
co-administered with a COVID-19 mRNA 
vaccine or administered alone. 
• 
RSV-A neutralization titers expressed as GMT, MGI and 
SRR at 1 month after the RSVPreF3 OA investigational 
vaccine dose. 
• 
Percentage of participants having RSV-A neutralizing titers 
≥ assay cut-off (i.e., LLOQ) at pre-vaccination and 
1 month after the RSVPreF3 OA investigational vaccine 
dose. 
• 
RSV-B neutralization titers expressed as GMT, MGI and 
SRR at 1 month after the RSVPreF3 OA investigational 
vaccine dose. 
• 
Percentage of participants having RSV-B neutralizing titers 
≥ assay cut-off (i.e., LLOQ) at pre-vaccination and 
1 month after the RSVPreF3 OA investigational vaccine 
dose. 
• 
To evaluate the humoral immune response to 
a COVID-19 mRNA vaccine when co-
administered with the RSVPreF3 OA 
investigational vaccine or administered alone. 
• 
SARS-CoV-2 Omicron XBB.1.5 neutralization titers 
against pseudovirus bearing S protein expressed as GMT 
and MGI at 1 month after the COVID-19 mRNA vaccine.  
• 
Percentage of participants having SARS-CoV-2 Omicron 
XBB.1.5 neutralization titers ≥ assay cut-off (i.e., LLOQ) at 
pre-vaccination and 1 month after the COVID-19 mRNA 
vaccine dose. 

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Objectives 
Endpoints and Estimands 
• 
To evaluate the safety and reactogenicity 
following administration of the RSVPreF3 OA 
investigational vaccine and a COVID-19 
mRNA vaccine, co-administered or 
administered alone. 
• 
Percentage of participants reporting each solicited 
administration site event and systemic event within 4 days 
post study intervention administration (i.e., the day of 
vaccination and 3 subsequent days). 
• 
Percentage of participants reporting unsolicited AEs within 
30 days post study intervention administration (i.e., the 
day of vaccination and 29 subsequent days). 
• 
Percentage of participants reporting SAEs after study 
intervention administration (Day 1) up to study end 
(6 months after last study intervention administration). 
• 
Percentage of participants reporting pIMDs after study 
intervention administration (Day 1) up to study end (6 
months after last study intervention administration). 
AE: adverse event; GMC: Geometric Mean Concentration; GMT: Geometric Mean Titer; MGI: Mean Geometric 
Increase; pIMD: potential immune mediated disease; SAE: serious adverse event, SRR: Seroreponse rate. MGI and 
SRR are defined in Section 9.3.2. 
* Non-inferiority criteria are defined in Section 9.3.1. 
 

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3.2. 
Estimands 
3.2.1. 
Immunogenicity Objectives  
Primary objective: 
The primary question of interest is to demonstrate the non-inferiority of the humoral 
immune response after RSVPreF3 OA investigational vaccine is co-administered with a 
dose of COVID-19 mRNA vaccine when compared to RSVPreF3 OA investigational 
vaccine administered alone and COVID-19 mRNA vaccine administered alone, in adults 
aged 50 years vaccinated as per protocol. 
The secondary objectives are the following: 
• 
To evaluate the humoral immune response to RSVPreF3 OA investigational vaccine 
when co-administered with a dose of COVID-19 mRNA vaccine or when 
administered alone. 
To evaluate the humoral immune response to a dose of COVID-19 mRNA vaccine when 
co-administered with the RSVPreF3 OA investigational vaccine or when administered 
alone.

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Attributes 
Summary measure 
Objectives 
Treatment 
Population 
Endpoint (Variable) 
Intercurrent events (ICEs) 
Description 
Handling strategy 
Primary 
Co-ad group: COVID-19 
mRNA vaccine at Day 1 
and RSVPreF3 OA 
investigational vaccine 
at Day 1 
 
Control group: COVID-
19 mRNA vaccine at 
Day 1 and RSVPreF3 
OA investigational 
vaccine at Day 31 
Adults ≥ 50 
years at the 
time of first 
vaccination 
• 
RSV-A and RSV-B neutralizing 
titers measured at 1 month (at 
Day 61 for Control group, at Day 
31 for Co-ad group) after 
RSVPreF3 OA investigational 
vaccine administration). 
• 
SARS-CoV-2 Omicron XBB.1.5 
neutralization titers measured at 
1 month (at Day 31 for both 
groups) after COVID-19 mRNA 
vaccine administration. 
1. 
Study 
vaccination 
not 
administered 
as per 
protocol. 
2. 
Prohibited 
medication, 
vaccination 
or 
intercurrent 
medical 
condition 
prior to the 
blood 
sample. 
Data collected after 
ICEs will be 
excluded from the 
analysis.  
(Hypothetical 
strategy) 
Rationale: To 
evaluate the 
immunogenicity 
parameters in the 
absence of ICE 
• 
Ratio of GMTs with 95% CI 
for RSV-A and RSV-B 
neutralizing titers 1 month 
after RSVPreF3 OA 
investigational vaccine 
administration between the 
Control group versus Co-ad 
group. 
• 
Ratio of GMTs with 95% CI 
for SARS-CoV-2 Omicron 
XBB.1.5 titers 1 month after 
COVID-19 mRNA vaccine 
administration between the 
Control group versus Co-ad 
group. 

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Attributes 
Summary measure 
Objectives 
Treatment 
Population 
Endpoint (Variable) 
Intercurrent events (ICEs) 
Description 
Handling strategy 
Secondary 
Co-ad group: COVID-19 
mRNA vaccine at Day 1 
and RSVPreF3 OA 
investigational vaccine 
at Day 1 
 
Control group: COVID-
19 mRNA vaccine at 
Day 1 and RSVPreF3 
OA investigational 
vaccine at Day 31 
Adults ≥ 50 
years at the 
time of first 
vaccination 
• 
RSV-A and RSV-B neutralizing 
titers measured at pre-
vaccination (at Day 1 for Co-ad 
group and at Day 31 for Control 
group) and at 1 month (at Day 
31 for Co-ad group and at Day 
61 for Control group) after 
RSVPreF3 OA investigational 
vaccine administration. 
• 
Fold increase in RSV-A and 
RSV-B neutralizing titers from 
pre-vaccination to 1-Month post 
RSVPreF3-OA investigational 
vaccine administration. 
• 
RSV-A and RSV-B neutralizing 
titers ≥ assay cut-off at pre-
vaccination and 1 month after 
the RSVPreF3 OA 
investigational vaccine dose 
administration. 
• 
Seroresponse in RSV-A and 
RSV-B, defined as a fold 
increase in neutralizing titers 
from pre-vaccination to 1-Month 
post RSVPreF3-OA 
investigational vaccine 
administration ≥4. 
1. 
Study 
vaccination 
not 
administered 
as per 
protocol. 
2. 
Prohibited 
medication, 
vaccination 
or 
intercurrent 
medical 
condition 
prior to the 
blood 
sample. 
Data collected after 
ICEs will be 
excluded from the 
analysis.  
(Hypothetical 
strategy) 
Rationale: To 
evaluate the 
immunogenicity 
parameters in the 
absence of ICE 
• 
GMTs with 95% CI for RSV-
A and RSV-B neutralizing 
titers at pre-vaccination and 
at 1 month after RSVPreF3 
OA investigational vaccine 
dose administration. 
• 
MGI with 95% CI for RSV-A 
and RSV-B neutralizing titers 
at 1 month after RSVPreF3 
OA investigational vaccine 
dose administration 
• 
Percentage of participants 
having RSV-A and RSV-B 
neutralizing titers ≥ cut-off 
and 95% CI at pre-
vaccination and 1 month 
after the RSVPreF3 OA 
investigational vaccine dose 
administration. 
• 
Seroresponse rate (SRR) 
with 95% CIs for RSV-A and 
RSV-B, defined as the 
proportion of participants 
having a fold increase in 
neutralizing titers from pre-
vaccination to 1-Month post 
RSVPreF3-OA 
investigational vaccine 
administration ≥4. 

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Attributes 
Summary measure 
Objectives 
Treatment 
Population 
Endpoint (Variable) 
Intercurrent events (ICEs) 
Description 
Handling strategy 
Secondary  
Co-ad group: COVID-19 
mRNA vaccine at Day 1 
and RSVPreF3 OA 
investigational vaccine 
at Day 1 
 
Control group: COVID-
19 mRNA vaccine at 
Day 1 and RSVPreF3 
OA investigational 
vaccine at Day 31 
Adults ≥ 50 
years at the 
time of first 
vaccination 
• 
SARS-CoV-2 Omicron XBB.1.5 
neutralization titers measured at 
pre-vaccination (at Day 1) and at 
1 month (at Day 31) after 
COVID-19 mRNA vaccine 
administration. 
• 
Fold increase in SARS-CoV-2 
Omicron XBB.1.5 neutralization 
titers from pre-vaccination to 1-
Month post COVID-19 mRNA 
vaccine administration. 
• 
SARS-CoV-2 Omicron XBB.1.5 
neutralizing titers ≥ assay cut-off 
at pre-vaccination and 1 month 
after the COVID-19 mRNA 
vaccine vaccine dose 
administration. 
1. 
Study 
vaccination 
not 
administered 
as per 
protocol. 
2. 
Prohibited 
medication, 
vaccination 
or 
intercurrent 
medical 
condition 
prior to the 
blood 
sample. 
Data collected after 
ICEs will be 
excluded from the 
analysis.  
(Hypothetical 
strategy) 
Rationale: To 
evaluate the 
immunogenicity 
parameters in the 
absence of ICE 
• 
GMTs with 95% CI for 
SARS-CoV-2 Omicron 
XBB.1.5 neutralizing titers at 
pre-vaccination and at 1 
month after COVID-19 
mRNA vaccine dose 
administration. 
• 
MGI with 95% CI for SARS-
CoV-2 Omicron XBB.1.5 
neutralizing titers at 1 month 
after COVID-19 mRNA 
vaccine dose administration. 
• 
Percentage of participants 
having SARS-CoV-2 
Omicron XBB.1.5 
neutralizing titers ≥ cut-off 
and 95% CI at pre-
vaccination and 1 month 
after the COVID-19 mRNA 
vaccine dose administration. 

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3.2.2. 
Safety Objectives 
The secondary question of interest is to evaluate the safety and reactogenicity following administration of the RSVPreF3 OA 
investigational vaccine and a dose of COVID-19 mRNA vaccine, co-administered or administered alone. 
Attributes 
Summary measure 
Treatment 
Population 
Endpoint (Variable) 
Intercurrent events (ICEs) 
Description 
Handling strategy 
Co-ad group: COVID-
19 mRNA vaccine at 
Day 1 and RSVPreF3 
OA investigational 
vaccine at Day 1 
 
Control group: 
COVID-19 mRNA 
vaccine at Day 1 and 
RSVPreF3 OA 
investigational 
vaccine at Day 31 
Adults ≥50 years at 
the time of first 
vaccination 
• 
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 after study intervention 
administration (Day 1) up to study end (6 months 
after last study intervention administration). 
• 
Occurrence of pIMDs after study intervention 
administration (Day 1) up to study end (6 months 
after last study intervention administration). 
1. 
Study vaccination 
not administered as 
per protocol. 
2. 
Prohibited 
medication, 
vaccination or 
intercurrent medical 
condition prior to the 
blood sample. 
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 
endpoint. 

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4. 
STUDY DESIGN 
4.1. 
Overall design 
The study design overview is presented in Figure 1. 
• 
Type of study: Self-contained. 
• 
Experimental design: Phase 3, randomized, open-label study with 2 parallel groups 
(see Figure 1). 
• 
Study groups and randomization: Approximately 830 eligible participants will be 
randomly assigned (1:1) to the following 2 groups: Co-Ad group and Control group 
at Visit 1 (Day 1). Each group will include approximately include 415 participants. 
• 
Vaccination schedule: 
− 
Co-Ad group: Participants will receive a single dose of COVID-19 mRNA 
vaccine and a single dose of RSVPreF3 OA investigational vaccine at Visit 1 
(Day 1). 
− 
Control group: Participants will receive a single dose of COVID-19 mRNA 
vaccine at Visit 1 (Day 1), followed by a single dose of the RSVPreF3 OA 
investigational vaccine at Visit 2 (Day 31). 
• 
Primary completion date: Day 61 (1 month after the RSVPreF3 OA investigational 
vaccine dose in Control group). 
• 
Duration of the study: ~ 6 months for participants in Co-Ad group; ~ 7 months for 
participants in Control group. 
• 
Control: Active comparator, i.e., staggered administration of licensed COVID-19 
mRNA vaccine and RSVPreF3 OA investigational vaccine. 
• 
Blinding: Open-label. Refer to Section 6.4 for details. 
• 
Data collection: Standardized eCRF. Solicited events and unsolicited AEs will be 
collected using a participant Diary card (paper Diary card). 
• 
Safety monitoring: The study will be conducted with oversight by the project SRT. 
Please refer to Section 10.1.6 for the SRT structure. 
• 
Enrollment rules: 
Overall, participants will be enrolled in 3 age categories reflecting an approximate age 
distribution in the general population with a balance between males and females. It is 
therefore intended to enroll: 
• 
Approximately 30% of participants 50-59 YOA, approximately 30% of participants 
60-69 YOA and approximately 25% of participants ≥ 70 YOA. The remaining 15% 
can be distributed freely across the 3 age categories. The enrollment of participants 
as per the age categories, and percentage of participants in each age category, if any, 
will be guided by the feasibility assessment. 

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• 
Approximately 40% of participants from each sex; the remaining 20% can be 
distributed freely between the two sexes. 
4.2. 
Scientific rationale for study design 
Vaccination programs with SARS-CoV-2 mRNA vaccines have been implemented in 
many countries worldwide. SARS-CoV-2 mRNA vaccines are administered throughout 
the year and may thus be administered around the same time when the RSVPreF3 OA 
investigational vaccine may potentially be recommended for immunization against RSV 
infection. To date, there is no data available on the safety and immunogenicity of the 
RSVPreF3 OA investigational vaccine when it is co-administered with a SARS-CoV-2 
mRNA vaccine. 
RSV is associated with serious illness in OA and high-risk adults, including those with 
chronic lung and heart disease or other co-morbidities that may lead to increased risk of 
RSV-LRTD. A large US prospective, population-based study reported the overall annual 
estimated incidence of RSV infection during 3 seasons among different age groups, in 
two different settings (New York City and Rochester). The specific estimated incidence 
ranged from 7.7–11.9/100 000 population, 33.5–57.5/100 000, and 136.9–255.6/100 000 
in patients 18–49, 50–64, and ≥65 YOA, respectively. Moreover, the incidence of RSV 
infection in hospitalized adults of 50–64 and ≥65 YOA was approximately 5 and 15 times 
higher, respectively, than incidence among patients 18–49 YOA [Branche, 2022]. In 
another prospective study it was determined that the hospitalization rates for RSV were 
similar to those associated with influenza in adults aged ≥50 YOA [Widmer, 2012]. 
The US FDA and the EMA have authorized the Comirnaty Omicron XBB.1.5 
30 micrograms/dose dispersion as a single dose for injection for active immunisation to 
prevent COVID-19 caused by the SARS-CoV-2, in individuals 12 years of age and older 
[Comirnaty product information package insert, EMA, 2023; US FDA, 2023].  
Both RSVPreF3 OA investigational vaccine and SARS-CoV-2 vaccines will be available 
for individuals within similar age groups. These data are expected to help public health 
authorities provide more evidence-based guidance and health care providers to make 
decisions on such vaccine co-administrations. 
The current study is therefore designed to assess the safety, reactogenicity and 
immunogenicity of the RSVPreF3 OA investigational vaccine when it is co-administered 
with a COVID-19 mRNA vaccine, compared to administration of the vaccines separately 
in adults aged 50 years and above. 
As the RSVPreF3 OA investigational vaccine is adjuvanted, all participants will be 
followed up for safety for 6 months post-RSV investigational vaccine administration. 
4.2.1. 
Participant input into design 
Not applicable. 

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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. 
In the current study, the authorized Comirnaty Omicron XBB.1.5 30 micrograms/dose 
dispersion for injection will be administered.  
4.4. 
End-of-study definition 
A participant is considered to have completed the study if the participant has completed 
all periods of the study including the last scheduled contact as described in the protocol. 
EoS: LSLV (contact at 6 months post-last dose) 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, who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g., completion of the diary cards, return for follow-up 
visits). INC#1 
Note: In case of physical incapacity that would preclude the self-completion of the 
diary cards, either site staff can assist the participant (for activities performed 
during site visits) or the participant may assign a caregiver to assist him/her with 
this activity (for activities performed at home). However, at no time will the site staff 
or caregiver evaluate the participant’s health status while answering diaries or make 
decisions on behalf of the participant. 
• 
Written or witnessed informed consent obtained from the participant (participant 
must be able to understand the informed consent) prior to performance of any study-
specific procedure. INC#2 
• 
A male/female of ≥50 YOA at the time of the first study intervention administration. 
INC#3 
• 
Participants who are medically stable in the opinion of the investigator at the time of 
first vaccination. Participants with chronic stable medical conditions with or without 

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specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to 
participate in this study if considered by the investigator as medically stable. INC#4 
A stable medical condition is defined as disease not requiring significant change in 
therapy or hospitalization for worsening disease during the 3 months before 
enrollment. 
• 
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#5 
• 
Participants who have received previously a SARS-CoV-2 vaccine, being 
administered at least 3 months prior to study vaccination. INC#6 
• 
Female participants of non-childbearing potential may be enrolled in the study. 
Non-childbearing potential is defined as hysterectomy, bilateral oophorectomy, 
bilateral salpingectomy, and post-menopause. INC#7 
• 
Female participants of childbearing potential may be enrolled in the study if the 
participant. INC#8 
− 
has practiced adequate contraception from 1 month prior to study intervention 
administration and agreed to continue adequate contraception for at least 1 
month after the last vaccination. 
− 
has a negative pregnancy test on the day of and prior to study intervention 
administration. 
Refer to Section 10.4.1 for definitions of women of childbearing potential, 
non-childbearing potential, menarche and menopause and section 10.4.2 on adequate 
contraception. 
5.2. 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria apply: 
5.2.1. 
Medical Conditions 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study interventions, including a known history of severe allergic 
reaction (e.g., anaphylaxis) (For details on components of study interventions 
administered, refer to Table 5, [Arexvy Prescribing Information package insert, 2023] 
[Arexvy Summary of Product Characteristics, 2023] and Comirnaty Omicron 
XBB.1.5 COVID-19 mRNA vaccine SmPC/Prescribing information). EXC#1 
• 
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#2 
• 
Any history of myocarditis or pericarditis. EXC#3 

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• 
Recurrent history 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 diary cards, 
attend regular phone calls/study site visits). EXC#4 
• 
Serious or unstable chronic illness. EXC#5 
• 
Any history of dementia or any medical condition that moderately or severely 
impairs cognition. EXC#6 
Note: If deemed necessary for clinical evaluation, the investigator can use tools such 
as Mini-Mental State Examination (MMSE), Mini-Cog or Montreal Cognitive 
Assessment (MoCA) to determine cognition levels of the participant. 
• 
Significant underlying illness that in the opinion of the investigator would be 
expected to prevent completion of the study (e.g., life-threatening disease likely to 
limit survival up to study end). EXC#7 
• 
Any medical condition that in the judgment of the investigator would make 
intramuscular injection unsafe. EXC#8 
• 
Any SAE attributed to a previous dose of the SARS-CoV-2 mRNA vaccine. EXC#9 
• 
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#10 
• 
Recent SARS-CoV-2 infection within 3 months prior to the COVID-19 vaccine dose 
administration. Timelines to be determined from symptoms onset or positive 
COVID-19 test (if infection was asymptomatic). EXC#11 
5.2.2. 
Prior/Concomitant Therapy 
• 
Use of any investigational or non-registered product (drug, vaccine or invasive 
medical device) other than the study interventions during the period beginning 
30 days before the first dose of study interventions and ending 30 days after the last 
vaccine administration, or their planned use during the study period. EXC#12 
Note: EEC directive 93/42/EEC defines an invasive medical device as ‘A device 
which, in whole or in part, penetrates inside the body, either through a body orifice 
or through the surface of the body’. 
• 
Planned administration of a vaccine in the period starting 30 days before the first 
dose and ending 30 days after the last dose of study intervention(s) administration*, 
with the exception of inactivated and subunit influenza vaccines which can be 
administered up to 14 days before or from 14 days after the study vaccination. 
EXC#13 
*If emergency mass vaccination for an unforeseen public health threat (e.g., a 
pandemic) is recommended and/or organized by 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 Sponsor is notified. 

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• 
Chronic administration of immune-modifying drugs (defined as more than 
14 consecutive days in total) and/or planned use of long-acting immune-modifying 
treatments at any time up to the last blood sampling visit. EXC#14 
− 
Up to 3 months prior to the study intervention administration: 
o 
For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. 
Inhaled and topical 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 and antitumoral medication. 
• 
Administration of any SARS-CoV-2 vaccine during the 3 months preceding the 
study COVID-19 mRNA vaccine administration. EXC#15 
• 
Previous vaccination with licensed or investigational RSV vaccine. EXC#16 
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 intervention (drug/invasive medical device). EXC#17 
5.2.4. 
Other Exclusion Criteria 
• 
Pregnant or lactating female participant. EXC#18 
• 
Female participant planning to become pregnant or planning to discontinue 
contraceptive precautions. EXC#19 
• 
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#20 
• 
Participation of any study personnel or their immediate dependents, family, or 
household members. EXC#21 
• 
Planned move during the study conduct that prohibits participation until study end. 
EXC#22 
• 
Bedridden participants. EXC#23 
5.3. 
Lifestyle considerations 
Not applicable for this study. 

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5.4. 
Screen failures 
A screen failure occurs when a participant who consents to participate in this study but is 
not entered in the study/randomized to a study intervention. 
For screen-failed participants, limited data for screen failures (including demography, 
medical and vaccination history, eligibility criteria, concomitant medication, reason for 
screen failure and any SAEs that occurred at the visit) will be collected and reported in 
the eCRF to meet the CONSORT publishing requirements and to respond to queries from 
regulatory authorities. 
5.5. 
Criteria for temporarily delaying enrollment/ administration 
of study intervention 
Study intervention administration may be postponed within the permitted time interval as 
deemed appropriate by the investigator until transient conditions cited below are 
resolved. Participants meeting these criteria at Visit 1 will be considered screen failures if 
enrollment has closed once the condition(s) has/have resolved: 
• 
Acute disease and/or fever at the time of study intervention administration. Refer to 
the SoA (Section 1.3) for definition of fever and preferred location for measuring 
temperature in this study. 
• 
Participants with a minor illness (such as mild 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.). Please refer to Exclusion criteria Section 5.2.1 for 
time interval for study COVID-19 vaccination after a recent COVID-19 infection. 
• 
In case of administration of inactivated, subunit or split influenza vaccines (fully 
licensed): 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 14 days interval between above mentioned influenza vaccination and study 
intervention administration.  
• 
Other issues (e.g., technical or administrative) preventing dose administration on day 
of visit. 
All efforts should be made so that blood sample is taken on the same date as vaccination. 
For Visit 1, if the planned study intervention administration is delayed, blood sampling 
does not need to be repeated if it was obtained during enrollment visit. The following 
procedures must be repeated prior to the delayed study intervention administration: 
• 
Urine pregnancy test 
• 
Body temperature 
• 
Re-check contraindications, warnings, and precautions to study intervention 

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• 
Re-check inclusion/exclusion criteria 
Visit window for Visit 2 starts from day of first study intervention administration. 
For delay in the study intervention administration during Visit 2 (control group) the 
following procedures must be repeated: 
• 
Urine pregnancy test 
• 
Body temperature 
• 
Re-check contraindications, warnings, precautions to study intervention 
• 
Re-check inclusion/exclusion criteria 
6. 
STUDY INTERVENTIONS AND CONCOMITANT 
THERAPY 
The definition of study intervention is provided in the table of Definition of terms. 
6.1. 
Study interventions administered 
Refer Section 4 for the study intervention administration schedule. 
Table 5 
Study Intervention(s) Administered 
Study intervention 
name: 
RSVPreF3 OA investigational vaccine 
Comirnaty Omicron XBB.1.5 
COVID-19 mRNA vaccine 
Study intervention 
formulation: 
RSVPreF3 (120 µg) 
AS01E: QS-21* (25 µg), 
MPL (25 µg), 
liposomes; Water for 
injections 
Raxtozinameran (30 µg) 
embedded in LNP; Water 
for injections 
Presentation: 
Powder for 
suspension for 
injection; in vial 
Suspension for 
suspension for injection; 
in vial 
Dispersion for injection; in 
vial 
Type: 
Investigational 
Comparator  
Product category: 
Biological 
Biological 
Route of 
administration:  
IM injection 
IM injection 
Administration site: 
• 
Location 
Deltoid 
Deltoid 
• 
Directionality 
Upper 
Upper 
• 
Laterality ** 
Co-ad group: Dominant 
Control group: Non-dominant 
Co-ad group: Non-dominant 
Control group: Non-dominant 
Number of doses to 
be administered: 
1 
1 
Volume to be 
administered by dose 
*** 
0.5 mL 
0.3 mL 
Packaging and 
labelling: 
Refer to the pharmacy manual for more 
details 
Refer to the pharmacy 
manual for more details 
Manufacturer: 
GSK Biologicals SA 
Pfizer-BioNTech 
IM: Intramuscular; LNP: Lipid nanoparticle; MPL: Monophosphoryl lipid A. 

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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 interventions. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis, 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, pregnancy kits and 
cup for urine collection. 
• 
All medical devices are CE marked and will be used for their intended use. 
Instructions for medical device use are provided in Laboratory Manual and 
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. 
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. 

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6.3.2. 
Randomization to study intervention 
Approximately 830 eligible participants ≥50 YOA will be randomly assigned (1:1) to the 
study groups (Co-Ad or Control). 
Participants will be assigned to study treatment in accordance with the randomization 
schedule. The randomization schedule, including stratification, will be generated using 
the GSK validated randomization software RANDALL NG. The randomization schedule 
is comprised of a series of blocks, with 1:1 treatment allocation within each block, which 
are shared across centers via central randomization. 
6.3.3. 
Intervention allocation to the participant 
An automated Internet-based system RTSM will be used for randomization and for 
identification of intervention material. The randomization algorithm will use a 
permutated block procedure, including age (50-59, 60-69 or ≥ 70 years) as stratification 
factor. 
Once a participant identification number is allocated, the randomization system will 
determine study group and will provide the study intervention number to be used for the 
first dose. The study intervention number(s) to be used for subsequent dosing will be 
provided by the same automated Internet-based system (RTSM). 
When RTSM is not available, please refer to the RTSM user guide or pharmacy manual 
for specific instructions. 
Refer to the pharmacy manual for additional information about the study intervention 
number allocation. 
6.4. 
Blinding 
This is an open-label study because of the difference in dosing schedules between the 
study groups. However, the specific study intervention to be taken by a participant will be 
assigned using randomization system on internet (RTSM). Study site personnel will be 
required to register participants using RTSM for assignment of a unique identifier 
(designating the participant’s randomization code and treatment sequence assignment) for 
each participant participating in the study 
The site will record the study intervention assignment on the applicable eCRF. Potential 
bias will be reduced by the following steps: [central randomization, adjudications]. 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no link between the study intervention groups and the identity of the participant. 

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6.5. 
Study intervention compliance 
The study intervention will be administered at the site, and participants will receive it 
directly from the investigator or designee, under medical supervision. The date and time 
of administration of each study intervention dose will be recorded in the source 
documents. 
6.6. 
Dose modification 
Not applicable. 
6.7. 
Continued access to study intervention after the end of the 
study 
Not applicable. 
6.8. 
Treatment of overdose 
Not applicable. 
6.9. 
Prior and concomitant therapy 
At each study visit/contact, the investigator or his/her delegate should question the 
participant about all medications/products taken, and vaccinations received by the 
participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All prior vaccines within 1 year before the first study vaccination administration, and 
all prior COVID-19 vaccines. 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines. Please refer to Section 
5.2.2 and Section 9.2.1 for further details. 
• 
All concomitant medication which may explain/cause/be used to treat an SAE/pIMD 
including vaccines/products, as defined in Sections 8.4 and Section 10.3.5.7. These 
must also be recorded in the Expedited Adverse Event report. 
• 
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 on the day 
of study vaccination (Day 1 in the Co-Ad group, Day 1 and Day 31 in the Control 
group) in the absence of any symptom and in anticipation of a reaction to the study 
intervention administration. 

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• 
All concomitant medication, including vaccines/products, except vitamins and 
dietary supplements, that the participant is receiving at the time of enrollment or up 
to 30-day post-last study intervention. 
− 
Reason for use 
− 
Dates of administration including start and end dates 
− 
Dosage information including dose and frequency 
The Local Medical Lead should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Any antipyretic administered in the period starting 6 hours before vaccination and ending 
12 hours after vaccination need to be recorded on the eCRF. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
Discontinuation of study intervention refers to any participant who has not received all 
planned doses of study intervention. In rare instances, it may be necessary for a 
participant to permanently discontinue study intervention. If study intervention is 
permanently discontinued, the participant should, if possible, continue other study 
procedures (e.g., safety or immunogenicity), planned in the study protocol at the 
discretion of the investigator. 
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF based on the list below: 
Reasons 
Additional items/Sub-reasons 
AE 
Unsolicited AE 
Solicited AE 
SAE/pIMDs 
Lost to follow-up 
 
Withdrawal by Participant 
Burden of Procedure 
Participant Relocated 
COVID-19 
Other, specify 
Investigator decision 
Specify 
Protocol Deviation 
Specify 
Site Terminated by Sponsor 
 
Study Terminated by Sponsor 
 
Pregnancy 
 
Death 
 
Other 
Specify 
AE= Adverse event; COVID-19= Coronavirus disease; pIMD= Potential immune-mediated disease; SAE= Serious 
adverse event. 

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7.1.1. 
Contraindications to subsequent study intervention(s) 
administration 
The eligibility for participants in the control group for subsequent study intervention 
administration must be confirmed before administering the RSVPreF3 OA investigational 
vaccine at Visit 2. 
Participants who meet any of the criteria listed below or criteria listed in Section 5.2.1 
and Section 5.2.2 should not receive the RSVPreF3 OA investigational vaccine at Visit 2. 
Such participants should be encouraged to continue other study procedures, at the 
investigator’s discretion. All relevant criteria for discontinuation of study intervention 
administration must be recorded in the eCRF. 
• 
Participants who experience any SAE judged to be possibly or probably related to 
the first study intervention (COVID-19 mRNA vaccine administered at Visit 1) or 
non-study concomitant vaccine/product, including hypersensitivity reactions and 
that, in the opinion of the investigator, may pose additional risk to the participant if 
he/she receives the second study intervention (RSVPreF3 OA investigational 
vaccine). 
• 
Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participants if they continue to 
participate in the study. 
• 
Anaphylaxis following the administration of study intervention(s). 
• 
Condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
• 
Pregnant and lactating female participant (Refer Section 8.4.6) and lactation. 
• 
Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the 
opinion of the investigator, expose the participant to unacceptable risk from 
subsequent vaccination. In such cases, the investigator should use their clinical 
judgment prior to administering the next dose of the study intervention(s). Refer to 
Section 8.4.4.1 for the definition of pIMD. 
• 
Occurrence of a new Adverse Event of Special Interest (AESI) or the exacerbation of 
an existing AESI that, in the opinion of the investigator, exposes the participant to 
unacceptable risk from subsequent doses of study intervention. Refer to Section 8.4.4 
for the definition of AESI. 
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. 

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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 any 
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 AE 
SAEs/pIMDs 
Lost to follow-up 
 
Withdrawal by Participant 
Burden of Procedure 
Participant Relocated 
COVID-19 
Other, specify 
Investigator decision 
Specify 
Protocol Deviation 
Specify 
Site Terminated by Sponsor 
 
Study Terminated by Sponsor 
 
Pregnancy 
 
Death 
 
Other 
Specify 
AE= Adverse event; COVID-19= Coronavirus disease; pIMD= Potential immune-mediated disease; SAE= Serious 
adverse event. 
Participants who are withdrawn from the study because of AEs/SAEs/AESIs 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 (see Section 10.3.5.5). 

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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 
(within the allowed interval) 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. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA (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. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. Subjects who have signed informed consent 
but are not eligible to proceed should be recorded in the eCRF with a status of 
‘screen failure’. 
• 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the timeframe defined in the SoA. 
• 
Study participants may decide to assign a caregiver to help them fulfilling the study 
procedures. Please refer to the Definition of terms for the definition of a caregiver. 
− 
A caregiver can be appointed by the participant at any time during the study, 
when the participant feels it is necessary. Each caregiver should receive the 
caregiver information letter before providing support to the study participant. 

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Ideally, a single caregiver should be appointed by the participant but, in some 
situations, it may happen that several caregivers will support a study participant 
throughout the conduct of the study. This should be recorded in the source 
documents. 
− 
Caregivers may help the study participants with performing some practical study 
procedures such as receiving or making phone calls to site staff, planning study 
visits, transcribing responses to diaries, transportation to and from the study site 
etc. However, at no time, the caregiver should evaluate the participant’s health 
status while answering diaries or make decisions on behalf of the participant. At 
the first study visit (Visit 1), the site staff should inform the participant of the 
possibility to appoint a caregiver. Then at subsequent study visit(s), the site staff 
should check again with the participant if he/she wishes to appoint a caregiver or 
if there were or will be changes of caregiver. 
• 
If allowed by country regulation/ethics, study assessments may be conducted 
remotely by a HHS professional and/or virtually (TM, secure video conferences, 
phone calls, or a web portal and/or mobile application); however, on-site visits are 
required as per the SoA (Section 1.3). 
• 
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 over the duration of 
the study, including any extra assessments that may be required, will not exceed 
30 mL Co-Ad group and 45 mL for Control group. Repeat or unscheduled samples 
may be taken for safety reasons or for technical issues with the samples. 
8.1. 
Administrative and 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. 

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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 
and/or review of the participant’s medical/vaccination records. Record any relevant pre-
existing conditions, signs and/or symptoms present prior to the study interveniton in the 
eCRF. History of previous SARS-CoV-2 infection(s) should also be recorded. 
History of following vaccine administration should be recorded in the eCRF. 
• 
Any vaccine administered up to 1 year before study vaccine administration (if 
possible, with date of vaccination). 
• 
COVID-19 vaccine administration (if possible, with the date of vaccination; this 
information should be collected even if administration was >1 year). 
8.1.3. 
Pre-vaccination body temperature 
The body temperature of each participant needs to be measured prior to any study 
intervention administration and recorded in the eCRF. The route for measuring 
temperature can be oral or axillary. If the participant has fever (fever is defined as 
temperature ≥38.0°C/100.4°F regardless the location of measurement) on the day of 
vaccination, the vaccination visit will be rescheduled within the allowed interval for this 
visit, refer to Table 4 for the Control group. 
8.2. 
Immunogenicity assessments 
Planned timepoints for all immunogenicity assessments are provided in the SoA (see 
Section 1.3). 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. 
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
IEC/IRB approval, if required by local legislation. 
Information on further research and its rationale can be obtained from GSK. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant. 
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 

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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 blood that will be collected per participant during the entire study 
period is as follows: 
• 
Co-Ad group: 2 x ~15 mL = ~30 mL 
• 
Control group: 3 x ~15 mL = ~45 mL 
Refer to Table 6 and SoA (Section 1.3) for information on volumes collected for different 
assessments. 
Table 6 
Biological samples 
Sample type 
Quantity 
Unit 
Timepoint 
Group 
Blood for humoral response 
~15 
mL 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
All participants in the Co-Ad group 
Blood for humoral response 
~15 
mL 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
Visit 3 (Day 61) 
All participants in the Control group 
8.2.2. 
Laboratory assays 
Table 7 
Laboratory assays 
Test Classification 
System 
Component 
Method 
Laboratory* 
RSV Humoral Immunity 
(functional capacity)  
Serum 
RSV A neutralization titer  
Neutralization 
GSK** 
RSV B neutralization titer 
Neutralization 
SARS-CoV-2 Humoral 
immunity (functional 
capacity)  
Serum 
 
SARS-CoV-2 Omicron XBB 
1.5 variant Neutralization 
titer 
 
Neutralization assay 
against pseudoviruses 
Nexelis  
* Refer to the list of clinical laboratories for details. 
** GSK laboratory refers to the Vaccines Clinical Laboratory and Assay Portfolio (Vx CL&AP) in Rixensart, Belgium; 
Wavre, Belgium. Vx CL&AP may delegate testing to GSK Research laboratories in Rixensart, Belgium; Rockville, 
USA; Siena, Italy or to a contracted CRO. 
† Other serological assays or methods may be used to characterize the antibody responses. 
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 
Table 8 
Immunological read-outs 
Blood sampling timepoint 
Subset name 
No. 
participants 
Component 
Type of contact and 
timepoint 
Sampling timepoint 
Co-Ad group 
Visit 1 (Day 1) 
Pre-dose 1 
All participants 
415 
RSV A neutralization titer 
RSV B neutralization titer 
 
 
 
 
SARS-CoV-2 Omicron XBB 1.5 
variant neutralization titer 
Visit 2 (Day 31) 
Post-dose 1 
All participants 
415 
RSV A neutralization titer 
RSV B neutralization titer 
 
 
 
 
SARS-CoV-2 Omicron XBB 1.5 
variant neutralization titer 
Control group 
Visit 1 (Day 1) 
Pre-SARS-CoV-2 
dose 
All participants 
415 
SARS-CoV-2 Omicron XBB 1.5 
variant neutralization titer 
Visit 2 (Day 31) 
Post-SARS-CoV-2 
dose 
All participants 
415 
SARS-CoV-2 Omicron XBB 1.5 
variant neutralization titer 
Pre-RSV dose 
All participants 
415 
RSV A neutralization titer 
RSV B neutralization titer 
Visit 3 (Day 61) 
Post-RSV dose 
All participants 
415 
RSV A neutralization titer 
RSV B neutralization titer 
8.2.4. 
Cytology 
Not applicable. 
8.2.5. 
Immunological correlates of protection 
No generally accepted immunological CoP has been demonstrated so far for the antigen 
used in the RSVPreF3 OA investigational vaccine or in the COVID-19 mRNA vaccine. 
8.3. 
Safety assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
History directed physical examination 
• 
History directed physical examination will be performed for each participant. At 
each subsequent visit, a targeted physical examination will be performed, as needed. 
• 
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 performed according to local medical practice outside this 
study or by referral to an appropriate health care provider. 

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• 
Physical examination at each study visit after the study intervention administration 
visit will be performed only if the participant indicates during questioning that there 
might be some underlying pathology(ies) or if deemed necessary by the investigator 
or delegate. 
8.3.2. 
Clinical safety laboratory tests 
No clinical safety laboratory tests are scheduled for this study. 
8.3.3. 
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. 
8.3.4. 
Safety monitoring AND Committee 
• 
Participant safety will be continuously monitored by the Medical Monitor, 
designated Safety Lead (or delegate) and Safety Review Team (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. 
8.3.5. 
Post-vaccination procedures 
8.3.5.1. 
Safety contact at 6 months post-last vaccination 
Six months after the last dose of study intervention (i.e., Month 6 for participants in the 
Co-Ad group and Month 7 for participants of the Control group), each participant should 
be contacted to check if he/she has experienced any SAEs or any AESIs since last study 
intervention administration, and to collect information on concomitant medications/ 
vaccinations. 
Multiple formats can be proposed by the site staff to organize these contacts. This contact 
may be done via email, text message, fax or phone call for example. The most 
appropriate format should be agreed between site staff and the study participant. 
Text messages, email and fax may be used as a screening to check if the participant has 
anything to report. If the participant answers "Yes" for at least one of the items of 
interest, a phone call must be done to get the details on the event(s). 
Data collected via phone calls and text messages will have to be recorded in source 
documents. E-mails and faxes can be archived in source documents. Receipt of the 
message must be confirmed by the participant or caregiver, as applicable. 

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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 and other safety 
information and remain responsible for following up all AEs or AEs that are serious, 
considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study (see Section 7). This includes events reported by the 
participant (or, when appropriate, by a caregiver). 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (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 the timepoints 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 9 
Timeframes for collecting and reporting of safety information 
Co-Ad group 
Event 
Pre-
dose* 
Vacc 
Co-Ad 
 
 
 
 
 
 
 
6 months post-
last dose** 
Study conclusion 
 
D1 
D4 
D31 
 
 
 
 
 
 
Solicited administration site 
and systemic events  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs*** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Control group 
Event 
Pre-
dose* 
Vacc 
SARS-
CoV-2 
 
 
 
Vacc 
RSV 
 
 
 
6 months post-
last dose** 
Study conclusion 
 
D1 
D4 
D31 
 
D31 D34 
D61 
 
 
Solicited administration site 
and systemic events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs*** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All participants 
All SAEs*** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All pIMDs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or concurrent 
GSK medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intercurrent medical 
conditions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D: day; AE: adverse event; AESI = Adverse event of special interest; AF = Atrial fibrillation; SAE: serious adverse 
event; pIMD: potential immune-mediated disease. 
* i.e., consent obtained on Day 1 (prior to vaccination). 
** Post-last dose= 6 months after Co-Ad study intervention administration (Co-Ad group) or 6 months after RSV study 
intervention administration (Control group). 
*** AF will be considered as AESI in this study and will be additionally reported in the AF follow-up questionnaire in 
eCRF. 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. 
Fatal AF and Serious AF judged as related to study vaccination will be reported according to the fatal SAE and 
related SAE reporting period, respectively. 
Note: COVID-19 cases will be collected during the same timeframes as those used for collecting and reporting the 
other safety information (unsolicited AEs/SAEs, etc.) 

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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 post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Section 8.4.1 and Table 9. 
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 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 ( 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. 
Adverse events of special interest 
pIMDs and Atrial Fibrillation are the AESIs collected during the study. 
8.4.4.1. 
Potential immune-mediated diseases 
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 10. 
In order to facilitate the documentation of pIMDs in the eCRF, a pIMD standard 
questionnaire and a list of preferred terms (PTs) and PT codes corresponding to the above 
diagnoses will be available to investigators at study start. 
The investigator(s) must exercise their medical/scientific judgment to determine whether 
other diseases have an autoimmune origin (i.e., pathophysiology involving systemic or 

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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 pre-existing chronic condition 
(if it exacerbated following vaccination) in the eCRF. 
Table 10 
List of potential immune-mediated diseases (pIMDs) 
Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid syndrome 
 
Autoimmune aplastic anemia 
 
Autoimmune hemolytic anemia 
• 
Includes warm antibody hemolytic anemia and 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” 
Cardio-pulmonary inflammatory disorders 
Idiopathic 
Myocarditis/Pericarditis 
Including but not limited to: 
• 
Autoimmune / Immune-mediated myocarditis 
• 
Autoimmune / Immune-mediated pericarditis 
• 
Giant cell myocarditis 
Idiopathic pulmonary fibrosis 
Including but not limited to: 
• 
Idiopathic interstitial pneumonia (frequently used related terms include 
“Interstitial lung disease”, “Pulmonary fibrosis”, “Immune-mediated 
pneumonitis”) 
• 
Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar proteinosis 
(PAP) 
• 
Frequently used related terms include: “pulmonary alveolar 
lipoproteinosis”, “phospholipidosis” 
Endocrine disorders 
Addison’s disease 
 
Autoimmune / Immune-mediated 
thyroiditis  
Including but not limited to: 
• 
Hashimoto thyroiditis (autoimmune hypothyroidism, lymphocytic 
thyroiditis) 

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Medical Concept 
Additional Notes 
• 
Atrophic thyroiditis  
• 
Silent thyroiditis  
• 
Thyrotoxicosis 
Autoimmune diseases of the 
testis and ovary 
• 
Includes autoimmune oophoritis, autoimmune ovarian failure and 
autoimmune orchitis 
Autoimmune hyperlipidemia 
 
Autoimmune hypophysitis 
 
Diabetes mellitus type I 
 
Graves’ or Basedow’s disease 
• 
Includes Marine Lenhart syndrome and Graves' ophthalmopathy, also 
known as thyroid eye disease (TED) or endocrine ophthalmopathy 
Insulin autoimmune syndrome 
 
Polyglandular autoimmune 
syndrome 
• 
Includes Polyglandular autoimmune syndrome type I, II and III 
Eye disorders 
Ocular Autoimmune / Immune-
mediated disorders 
Including but not limited to: 
• 
Acute macular neuroretinopathy (also known as acute macular outer 
retinopathy) 
• 
Autoimmune / Immune-mediated retinopathy  
• 
Autoimmune / Immune-mediated uveitis, including idiopathic uveitis and 
sympathetic ophthalmia  
• 
Cogan's syndrome: an oculo-audiovestibular disease 
• 
Ocular pemphigoid 
• 
Ulcerative keratitis 
• 
Vogt-Koyanagi-Harada disease 
Gastrointestinal disorders 
Autoimmune / Immune-mediated 
pancreatitis 
 
Celiac disease 
 
Inflammatory Bowel disease  
Including but not limited to:  
• 
Crohn’s disease  
• 
Microscopic colitis  
• 
Terminal ileitis 
• 
Ulcerative colitis  
• 
Ulcerative proctitis 
Hepatobiliary disorders 
Autoimmune cholangitis 
 
Autoimmune hepatitis 
 
Primary biliary cirrhosis 
 
Primary sclerosing cholangitis 
 

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Medical Concept 
Additional Notes 
Musculoskeletal and connective tissue disorders  
Gout 
• 
Includes gouty arthritis 
Idiopathic inflammatory 
myopathies 
Including but not limited to: 
• 
Dermatomyositis 
• 
Inclusion body myositis 
• 
Immune-mediated necrotizing myopathy 
• 
Polymyositis 
Mixed connective tissue disorder 
 
Polymyalgia rheumatica (PMR) 
 
Psoriatic arthritis (PsA) 
 
Relapsing polychondritis 
 
Rheumatoid arthritis  
Including but not limited to: 
• 
Rheumatoid arthritis associated conditions 
• 
Juvenile idiopathic arthritis 
• 
Palindromic rheumatism 
• 
Still's disease 
• 
Felty’s syndrome 
Sjögren’s syndrome 
 
Spondyloarthritis 
Including but not limited to:  
• 
Ankylosing spondylitis 
• 
Juvenile spondyloarthritis 
• 
Keratoderma blenorrhagica 
• 
Psoriatic spondylitis  
• 
Reactive Arthritis  
• 
Undifferentiated spondyloarthritis 
Systemic Lupus Erythematosus  
• 
Includes Lupus associated conditions (e.g. Cutaneous lupus 
erythematosus, Lupus nephritis, etc.) or complications such as 
shrinking lung syndrome (SLS) 
Systemic Scleroderma (Systemic 
Sclerosis) 
• 
Includes Raynaud’s syndrome, systemic sclerosis with diffuse 
scleroderma and systemic sclerosis with limited scleroderma (also 
known as CREST syndrome) 
Neuroinflammatory/neuromuscular disorders 
Acute disseminated 
encephalomyelitis (ADEM) and 
other inflammatory-
demyelinating variants  
Includes the following: 
• 
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) 

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Medical Concept 
Additional Notes 
• 
Noninfective encephalitis / encephalomyelitis / myelitis 
• 
Postimmunization encephalomyelitis  
Guillain-Barré syndrome (GBS) 
• 
Includes variants such as Miller Fisher syndrome and the acute motor 
and sensory axonal neuropathy (AMSAN) 
Idiopathic cranial nerve 
palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• 
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) 
Includes the following: 
• 
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 
• 
Includes ocular myasthenia and Lambert-Eaton myasthenic syndrome 
Narcolepsy 
• 
Includes narcolepsy with or without presence of unambiguous cataplexy 
Peripheral inflammatory 
demyelinating neuropathies and 
plexopathies 
Including but not limited to: 
• 
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)  
Transverse myelitis (TM) 
• 
Includes acute partial transverse myelitis (APTM) and acute complete 
transverse myelitis (ACTM) 
Renal disorders 
Autoimmune / Immune-mediated 
glomerulonephritis  
Including but not limited to: 
• 
IgA nephropathy 
• 
IgM nephropathy 
• 
C1q nephropathy 
• 
Fibrillary glomerulonephritis 
• 
Glomerulonephritis rapidly progressive 
• 
Membranoproliferative glomerulonephritis 

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Medical Concept 
Additional Notes 
• 
Membranous glomerulonephritis 
• 
Mesangioproliferative glomerulonephritis 
• 
Tubulointerstitial nephritis and uveitis syndrome 
Skin and subcutaneous tissue disorders 
Alopecia areata 
 
Autoimmune / Immune-mediated 
blistering dermatoses  
Including but not limited to:  
• 
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 
 
Reactive granulomatous 
dermatitis  
Including but not limited to 
• 
Interstitial granulomatous dermatitis 
• 
Palisaded neutrophilic granulomatous dermatitis 
Lichen planus 
• 
Includes liquen planopilaris 
Localised Scleroderma 
(Morphoea) 
• 
Includes Eosinophilic fasciitis (also called Shulman syndrome) 
Psoriasis 
 
Pyoderma gangrenosum 
 
Stevens-Johnson Syndrome 
(SJS) 
 
Including but not limited to:  
• 
Toxic Epidermal Necrolysis (TEN)  
• 
SJS-TEN overlap 
Sweet’s syndrome 
• 
Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• 
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 but not limited to: 
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis (type 
unspecified)  
• 
Behcet's syndrome  
• 
Buerger’s disease (thromboangiitis obliterans) 
• 
Churg–Strauss syndrome (allergic granulomatous angiitis)  

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Medical Concept 
Additional Notes 
• 
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   
Other (including multisystemic) 
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 
• 
Includes 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 
 
Multisystem inflammatory 
syndromes 
Including but not limited to: 
• 
Kawasaki’s disease 
• 
Multisystem inflammatory syndrome in adults (MIS-A) 
• 
Multisystem inflammatory syndrome in children (MIS-C)  
Overlap syndrome 
 
Raynaud’s phenomenon 
 
Sarcoidosis 
• 
Includes 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 (data lock point 
[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 

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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 in the AE or SAE section 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/AESIs /pregnancies 
• 
Prompt notification by the investigator to the sponsor of an SAE/AESI /pregnancies 
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. 
Table 11 
Timeframes for submitting SAEs, pregnancies 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 Adverse Events 
Report 
24 hours* 
electronic Adverse Events 
Report 
pIMDs 
24 hours**  
electronic Adverse Events 
Report 
24 hours* 
electronic Adverse Events 
Report 
Serious AF***  
24 hours** 
electronic AEs Report + AF 
follow-up questionnaire 
24 hours* 
electronic AEs Report + AF 
follow-up questionnaire 
Pregnancies 
24 hours*  
electronic pregnancy report 
24 hours* 
electronic pregnancy report 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
** 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 AEs Report and in the specific AF follow-up 
questionnaire. Non-serious AF will be reported in the non-serious adverse event eCRF screen and in the AF 
follow-up questionnaire. 

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8.4.6. 
Pregnancy 
Female participants who become pregnant after the first study intervention dose must not 
receive subsequent doses of the study intervention but may continue other study 
procedures at the discretion of the investigator. 
• 
Details of all pregnancies in female participants will be collected after the start of 
study intervention and until end of study (refer Section 5.1). 
• 
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 and the neonate and 
the information will be forwarded to the sponsor. See Table 11 for reporting 
timeframes. 
• 
Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will reported to the sponsor as described in 
Section 8.4.4. While the investigator is not obligated to actively seek this information 
in former study participants, he or she may learn of an SAE through spontaneous 
reporting. 
8.4.7. 
Contact information for reporting SAEs, AESIs, and pregnancies 
Table 12 
Contact information for reporting SAEs, AESIs, and pregnancies 
Study contact for questions regarding SAEs, AESIs and pregnancies 
Contact GSK’s local and/or medical contacts 
Contacts for reporting SAEs, AESIs and pregnancies 
Available 24/24 hours and 7/7 days 
ogm28723@gsk.com  
8.4.8. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending physician that the 
participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator or their back up. 

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8.5. 
Pharmacokinetics 
PK is not evaluated in this study. 
8.6. 
Pharmacodynamics 
PD is 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 for this study. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
Statistical hypotheses are associated to the confirmatory primary non-inferiority (NI) 
objectives, which will be tested to control overall Type I error. Global Type I error is 
controlled at 2.5% (1-sided). The study includes three confirmatory primary objectives. 
The NI margins associated to each objective are provided in Table 13. 
Table 13 
Study Objectives and Null Hypothesis 
Objectives 
Null hypothesis 
Success criteria 
Primary 
To demonstrate non-inferiority of 
humoral immune response to 
RSVPreF3 OA investigational 
vaccine when co-administered with 
a COVID-19 mRNA vaccine 
compared to RSVPreF3 OA 
investigational vaccine administered 
alone. 
• 
True Group GMT ratio 
between Control group (at 
Day 61) divided by Co-ad 
group (at Day 31) for RSV-A 
neutralization titers 1-month 
after the RSVPreF3 OA 
investigational vaccine dose is 
above 1.5. 
• 
True Group GMT ratio 
between Control group (at 
Day 61) divided by Co-ad 
group (at Day 31) in RSV-B 
neutralization titers 1-month 
after the RSVPreF3 OA 
investigational vaccine dose is 
above 1.5. 
• 
The upper limit of the 2 sided 
95% CI of the GMT ratio 
between the Control group (at 
Day 61) versus Co-ad group 
(at Day 31) for RSV-A 
neutralization titer 1-month 
after the RSVPreF3 OA 
investigational vaccine dose is 
≤1.5. 
• 
The upper limit of the 2 sided 
95% CI of the GMT ratio 
between the Control group (at 
Day 61) versus Co-ad group 
(at Day 31) for RSV-B 
neutralization titer 1-month 
after the RSVPreF3 OA 
investigational vaccine dose is 
≤1.5. 
To demonstrate non-inferiority of 
humoral immune response to a 
COVID-19 mRNA vaccine when co-
administered with the RSVPreF3 
OA investigational vaccine 
compared to a COVID-19 mRNA 
vaccine administered alone. 
• 
True Group GMT ratio 
between Control group (at 
Day 31) divided by Co-ad 
group (at Day 31) for SARS-
CoV-2 neutralization titers 1-
month after the COVID-19 
mRNA vaccine dose is above 
1.5. 
• 
The upper limit of the 2 sided 
95% CI of the GMT ratio 
between the Control group (at 
Day 31) versus Co-ad group 
(at Day 31) for SARS-CoV-2 
neutralization titers 1-month 
after the COVID-19 mRNA 
vaccine dose is ≤1.5. 
Abbreviations: Co-ad=co-administration group; CI=confidence interval, GMT=geometric mean titer, RSV-A=respiratory 
syncytial virus subtype A; RSV-B=respiratory syncytial virus subtype B; RSVPreF3-OA=respiratory syncytial virus 
prefusion protein 3 older adult investigational vaccine. 
Co-ad group: RSVPreF3 OA investigational vaccine when co-administered with the COVID-19 mRNA vaccine. 
Control group: Administration of COVID-19 mRNA vaccine, followed by RSVPreF3 OA investigational vaccine with one 
month difference. 

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9.2. 
Analysis sets 
Analysis sets are presented in Table 14. 
Table 14 
Analysis sets 
Analysis set 
Description 
Screened Set 
All participants who were screened for eligibility. 
Enrolled Set [1] 
All participants who entered the study (who were randomized or received study 
intervention or underwent a post-screening study procedure). 
Exposed Set 
All participants who received the study intervention. Analysis per group is based on 
the administered intervention. 
RSV PPS [2] 
All eligible participants: 
• 
Who received RSV vaccine as per-protocol in the control group and received 
all the study interventions in the Co-ad group 
• 
Who had immunogenicity results pre and post-dose for RSV neutralization 
titers 
• 
Who comply with the blood draw intervals for RSV samples 
• 
Without intercurrent medical conditions that may interfere with immunogenicity 
and without prohibited concomitant medication/vaccination up to blood sample 
post RSV vaccination 
• 
Who do not meet any of the criteria for elimination up to blood sample post 
RSV vaccination  
COVID-19 mRNA PPS [2] 
All eligible participants: 
• 
Who received a COVID-19 mRNA vaccine as per-protocol in the control group 
and received all the study interventions in the Co-ad group 
• 
Who had immunogenicity results pre and post-dose for SARS-CoV-2 
neutralization titers 
• 
Who comply with the blood draw intervals for SARS-CoV-2 samples 
• 
Without intercurrent medical conditions that may interfere with immunogenicity 
and without prohibited concomitant medication/vaccination up to blood sample 
post COVID-19 mRNA vaccination 
• 
Who do not meet any of the criteria for elimination up to blood sample post 
COVID-19 mRNA vaccination 
[1] Screen failures (who never passed screening) and participants screened but never enrolled into the study (met 
eligibility but not needed to reach the target enrollment) are excluded from the Enrolled Set as they did not enter 
the study. 
[2] Contribution of participants to PPS will be defined by timepoint. 
9.2.1. 
Criteria for elimination from analysis 
If the participant meets one of the criteria mentioned in Section 7.1.1 (contraindication to 
subsequent vaccination), Section 5.2.1 (medical conditions) or Section 5.2.2 (prior and 
concomitant therapy), he/she 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. 

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9.3. 
Statistical analyses 
The Statistical Analysis Plan (SAP) will be developed and finalized before first subject 
first visit. This section is a summary of the planned statistical analyses of the primary and 
secondary endpoints. Supportive analyses, safety and demography summaries will be 
described in the SAP. 
9.3.1. 
Primary endpoints/estimands analysis 
The co-primary endpoints are described in Table 4. The confirmatory analyses of non-
inferiority will be based on the PPS. 
If in any study group the percentage of vaccinated participants with serological results 
excluded from the PPS is more than 5%, a second analysis based on the ES will be 
performed to complement the PPS analysis. 
• 
Method for non-inferiority of RSV-A specific neutralization titer GMT ratio at 
1 month after the RSVPreF3 OA investigational vaccine dose (i.e., at Day 31 for the 
Co-Ad group and at Day 61 for the Control group): 
The 2-sided 95% CI for group GMT ratio between RSVPreF3 OA investigational 
vaccine administered alone (Control group) over RSVPreF3 OA investigational 
vaccine when co-administered with the COVID-19 mRNA vaccine (Co-Ad group) 
and derived from an analysis of covariance (ANCOVA) model on log10 transformed 
titer. The model will include the treatment group, the age category (age at 
vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-
transformed titer as covariate. Missing data will not be replaced. Titers below the 
assay lower limit of quantification (LLOQ) will be replaced by half the assay cut-off, 
titers above the upper limit of quantification (ULOQ) will be replaced by the ULOQ. 
• 
Method for non-inferiority of RSV-B specific neutralization titer GMT ratio at 
1 month after the RSVPreF3 OA investigational vaccine dose (i.e., at Day 31 for the 
Co-Ad group and at Day 61 for the Control group): 
The 2-sided 95% CI for group GMT ratio between RSVPreF3 OA investigational 
vaccine administered alone (Control group) over RSVPreF3 OA investigational 
vaccine when co-administered with the COVID-19 mRNA vaccine (Co-Ad group) 
and derived from an analysis of covariance (ANCOVA) model on log10 transformed 
titer. The model will include the treatment group, the age category (age at 
vaccination: 50-59, 60-69 or ≥70 years) as fixed effects, and the pre-dose log10-
transformed titer as covariate. Missing data will not be replaced. Titers below the 
assay LLOQ will be replaced by half the assay cut-off, titers above the ULOQ will 
be replaced by the ULOQ. 
• 
Method for non-inferiority of SARS-CoV-2 neutralization titers GMT ratio at 
1 month after the COVID-19 mRNA vaccine (i.e., at Day 31 for both groups): 
The 2-sided 95% CI for group GMT ratio between COVID-19 mRNA vaccine 
administered alone (Control group) over RSVPreF3 OA investigational vaccine 
when co-administered with the COVID-19 mRNA vaccine (Co-Ad group) and 
derived from an ANCOVA model on log10 transformed titer. The model will include 

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the treatment group and the age category (age at vaccination: 50-59, 60-69 or ≥70 
years) as fixed effects, and the pre-dose log10-transformed concentration as covariate. 
Missing data will not be replaced. Titers below the assay LLOQ will be replaced by 
half the assay cut-off, titers above ULOQ will be replaced by the ULOQ. 
Success criteria for non-inferiority: 
The upper limit of the 2 sided 95% CI of the GMT ratio between the Control group (at 
Day 61) versus Co-ad group (at Day 31) for RSV-A neutralization titer 1-month after the 
RSVPreF3 OA investigational vaccine dose is ≤1.5. 
AND 
The upper limit of the 2-sided 95% CI of the GMT ratio between the Control group (at 
Day 61) versus Co-ad group (at Day 31) for RSV-B neutralization titer 1-month after the 
RSVPreF3 OA investigational vaccine dose is ≤1.5. 
AND 
The upper limit of the 2 sided 95% CI of the GMT ratio between the Control group (at 
Day 61) versus Co-ad group (at Day 31) for SARS-CoV-2 neutralization titer 1-month 
after the COVID-19 mRNA vaccine dose is ≤1.5. 
9.3.2. 
Secondary endpoints/estimands analyses 
The secondary endpoints are described in Table 4. Descriptive analyses of demography, 
immunogenicity and safety will be detailed in the SAP. 
Mean geometric increase (MGI) is defined as the geometric mean of the within subject 
ratios of the post-dose titer over the pre-dose titer. 
The SRR is defined as the proportion of participants having a fold increase in 
neutralization titers (1 month post-study intervention administration over pre-study 
intervention administration) ≥4. 
9.4. 
Interim analyses 
No interim analysis will be performed. 
9.4.1. 
Sequence of analyses 
The analyses will be performed stepwise: 
• 
A first analysis will be performed on all immunogenicity, reactogenicity and safety 
data available and as clean as possible, when data are available for primary and 
secondary endpoints up to and including Visit 3 (Day 61) are available for all 
participants. This analysis will be considered as final for those endpoints. 
• 
An end of study (EoS) analysis will be performed when all data up to the contact 
6 months post-last dose will be available for all participants. 

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9.4.2. 
Statistical Considerations for Interim Analyses 
This section is not applicable. 
9.5. 
Pre-dose sample size determination 
Table 15 shows that the probability (global power) to reach the non-inferiority criterion 
with 722 evaluable participants (361 in Co-Ad and 361 in Control group) is at least 
90.1%, with a 1-sided alpha = 0.025. 
Table 15 
Power to demonstrate non-inferiority of the Co-Ad group compared 
to the Control group in terms of GMT with 361 evaluable participants 
per group. 
Endpoint 
Standard 
deviation of 
log10 
concentration 
Reference 
ratio 
Non 
inferiority 
margin 
Type II 
error 
Power 
RSVPreF3 OA investigational vaccine Non-inferiority* (1-sided test with alpha = 2.5%)  
GMT RSV-A 
neutralization titers 
0.45 
1.05 
1.5 
0.4% 
99.6% 
GMT RSV-B 
neutralization titers 
0.45 
1.05 
1.5 
0.4% 
99.6% 
COVID-19 mRNA vaccine Non-inferiority* (1-sided test with alpha=2.5%) 
GMT SARS-CoV-2 
neutralization titer 
0.63 
1.05 
1.5 
9.1% 
90.9% 
Global Power and Global Type II error 
9.9% 
90.1% 
GMT: geometric mean titer 
Non-inferiority limit = 0.176 (=log10[1.5]). 
Reference Ratio = 0.0212 (=log10[1.05]) 
Pass 2022 (Non-Inferiority test of 2 independent means). Power = 100-the Type II error (Beta). The Type II error (Beta) 
has been adjusted using Bonferroni’s method (overall Type II error = sum of the individual Type II errors). 
The primary objective analysis will be performed on the PPS. Assuming about 13% 
non-evaluable rate among enrolled participants up to 2-month post-vaccination 
(participants dropped-out or excluded from the PPS), a total of 830 participants (415 per 
group) will have to be vaccinated in order to reach 361 participants evaluable for the 
primary objective. 

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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 
− 
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. 
• 
Substantial 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. 

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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 and answer all questions 
regarding the study. 
• 
Potential participants must be informed that their participation is voluntary. They 
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 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 must be reconsented to the most current version of the ICF(s) during 
their participation in the study. 
• 
A physical copy of the ICF(s) must be provided to the participant. 
• 
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 Personal 
Information 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 
No screening visit is planned for this study. The recruitment plan will be defined by each 
participating site. 
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 per site in the participating 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. 

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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 must be informed that their 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, that their data will be used as described in 
the informed consent. 
• 
The participant must be informed that their 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 
prior to study start and target results summaries submission within 12 months of 
primary/ study completion date. Where external regulations require earlier 
disclosure, GSK will follow those timelines. 
• 
Where required by regulation, summaries will also be posted on applicable national 
or regional clinical study registers. 

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• 
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 randomization codes 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 printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (e.g., laboratory 
data). The investigator is responsible for verifying that data entries are accurate and 
correct by physically or electronically signing the CRF. 
• 
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. 
• 
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 from the issue of the final CSR/ 
equivalent summary unless local regulations or institutional policies require a 

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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 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 (first ICF signature 
date) 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 
RSV A/B neutralization assay 
The neutralization assay is a functional assay that measures the ability of serum 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 horseradish peroxidase (HRP), 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). 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 neutralization 
titer is expressed in ED60 (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]. 
Titers will also be expressed in International Units per milliliter (IU/mL). Secondary 
standard calibrated against the international reference (NIBSC 16/284 [McDonald, 2018; 
McDonald, 2020]) will be included in the runs. 
Pseudotyped Virus Neutralization Assay (PNA) 
The SARS-CoV-2 PNA evaluates the level of SARS-CoV-2 neutralization titers present 
in the human serum samples. Pseudotyped virus particles are made from a modified 
Vesicular Stomatitis Virus (VSVΔG) backbone and bear the spike glycoprotein of the 
SARS-CoV-2 variant of interest. In addition, the pseudoparticles contain a luciferase 
reporter gene to allow detection and quantification of VSVΔG internalized by the target 
cells. The intensity of luminescence is quantified in relative luminescence units (RLU) 
and is inversely proportional to the neutralization titer. The neutralizing titer of a serum 
sample is calculated as the reciprocal serum dilution corresponding to the 50% signal 
reduction (NT50) for that sample. 

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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 
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). 

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• 
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 
− 
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 

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• 
Other situations: 
− 
Possible Hy’s Law case: ALT ≥ 3x ULN AND total bilirubin ≥ 2x ULN 
(>35% direct bilirubin) or INR >1.5 must be reported as SAE 
− 
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 
Solicited events are predefined events administration site events and systemic events for 
which the participant is specifically questioned, and which are noted by the participant in 
their diary. 
Table 16 
Solicited administration site events 
Pain at administration site 
Redness at administration site 
Swelling at administration site 
Table 17 
Solicited systemic events 
Fever 
Headache 
Myalgia (muscle pain) 
Arthralgia (joint pain) 
Fatigue (tiredness) 
Note: Participants will be instructed to measure and record the axillary or oral 
temperature in the evening. If additional temperature measurements are taken at other 
times of the day, participants will be instructed to record the highest temperature in the 
diary card. 

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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 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 will be instructed to contact the site as soon as possible 
to report medically attended event(s), as well as any events that, though not 
medically attended, are of participant concern. Detailed information about reported 
unsolicited AEs will be collected by qualified site personnel and documented in 
the participant’s records. 
• 
Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during an interview with the participants and by 
review of available medical records at the next visit. 
10.3.5. 
Recording, assessment and follow-up of AEs, SAEs 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. 
• 
A diary card will be used in this study to capture solicited administration site or 
systemic events. The participant should be trained on how and when to complete the 
diary card. 
• 
Anyone who measures administration site or systemic events and who will record the 
event in the diary card should be trained on using the diary card. This training must 
be documented in the participant’s source record. 

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• 
For each solicited and unsolicited AE the participant experiences, the participant will 
be asked if they 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 diary (for solicited AEs) and in the 
participant’s eCRF as part of normal AE reporting (for unsolicited AEs). 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 is making entries in the paper Diary, their 
identity must be documented in the participant’s source record. 
• 
Collect and verify completed diary card during discussions with the participant on 
Visit 2 (from all participants) and Visit 3 (only from participants in the Control 
group). 
• 
Any unreturned diary card will be sought from the participant through telephone 
call(s) or any other convenient procedure. 
• 
The investigator or delegate will transcribe the required information into the eCRF in 
English. 
10.3.5.2. 
Assessment of intensity 
The investigator will make an assessment of intensity for each AE, AESIs, SAE and 
pegnancies 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: 

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Table 18 
Intensity scales for solicited events in participants ≥50 YOA 
Event 
Intensity grade 
Parameter 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal everyday activities. 
 
2 
Moderate: Painful when limb is moved and interferes with 
everyday activities. 
 
3 
Severe: Significant pain at rest. Prevents normal 
everyday activities. 
Redness at administration site 
See Table 16 
Greatest surface diameter in mm 
Swelling at administration site 
See Table 16 
Greatest surface diameter in mm  
Temperature* 
See Table 17 
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 
0 
None/Normal** 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Myalgia 
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 
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 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, ‘Normal’ corresponds to ‘similar to 
baseline’ and only discomfort above baseline is to be reported as ≥1. 
The maximum intensity of local injection site erythema/swelling and fever will be scored 
at GSK as follows: 
Table 19 
Intensity scales of administration site erythema/swelling, and fever 
 
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 judgement. 
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 pre-defined 
outcomes as described in the Section 10.3.2. 

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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. 
• 
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). 

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10.3.5.5. 
Follow-up of AEs, SAEs, AESIs, and pregnancies 
• 
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, will be followed until the event is resolved, stabilized, 
otherwise explained, or the participant is lost to follow-up. 
• 
Other non-serious AEs must be followed until end of the study or until the 
participant is lost to follow-up. 
Follow-up during the study 
AEs/AESI 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 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. 

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10.3.5.6. 
Updating of SAE, AESI and pregancy 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 
8.4.3). 
10.3.5.7. 
Reporting of SAEs, AESIs and pregnacies 
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. 
• 
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). 
• 
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/fax transmission of the SAE paper data collection tool is the preferred method 
to transmit this information. 
• 
In rare circumstances and in the absence of email/fax 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. 

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10.4. 
Appendix 4: Guidance on Contraception, Women not 
considered as WOCBP and collection of pregnancy 
information 
This section covers wording on the definition of what we consider to be a woman of 
childbearing potential as well as guidance on what is considered as adequate 
contraception. 
10.4.1. 
Definitions 
10.4.1.1. 
Woman of childbearing potential (WOCBP) 
A woman is considered WOCBP (fertile) 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. 
10.4.1.2. 
Woman of Nonchildbearing potential (WONCBP) 
Women in the following categories are considered WONCBP: 
• 
Premenopausal female 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 FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or 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. 

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10.4.2. 
Contraception guidance 
10.4.2.1. 
Woman of childbearing potential (WOCBP) 
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 20). 
Table 20 
Highly effective contraceptive methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation 
• 
Oralb 
• 
Intravaginal 
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Injectable 
• 
Oralb (only if allowed by local regulations or if part of standard medical practice in the country) 
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). 
10.5. 
Appendix 5: Country-specific requirements 
Not applicable. 

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11. 
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