A Phase 3, Randomized, Placebo-controlled, Observer-blind, Multi-country Study to Demonstrate the Efficacy of a Single Dose and Annual Revaccination Doses of GSK's RSVPreF3 OA Investigational Vaccine in Adults Aged 60 Years and Above
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut, 89 
1330 Rixensart, Belgium 
Primary Study vaccine 
GlaxoSmithKline Biologicals SA (GSK)’s 
investigational respiratory syncytial virus (RSV) vaccine 
BIO RSV OA=ADJ (GSK3844766A) 
Other Study vaccine 
Placebo: Saline solution 
eTrack study number and 
abbreviated title 
212494 (RSV OA=ADJ-006) 
EudraCT number 
2020-000753-28 
Date of protocol 
Final: 16 October 2020 
Date of protocol 
amendment 
Amendment 1 Final: 25 February 2021 
Amendment 2 Final: 6 October 2021 
Amendment 3 Final: 24 January 2022 
Amendment 4 Final: 23 March 2023 
Amendment 5 Final: 12 July 2023 
Title (Amended, 12 July 
2023) 
A Phase 3, randomized, placebo-controlled, observer 
blind, multi-country study to demonstrate the efficacy of 
a single dose and annual revaccination of GSK’s 
RSVPreF3 OA investigational vaccine in adults aged 60 
years and above.  
Short title 
Efficacy study of GSK’s investigational respiratory 
syncytial virus (RSV) vaccine in adults aged 60 years 
and above. 
Based on GSK Biologicals’ Protocol WS v17.0 
© 2020 GSK group of companies or its licensor. 

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Protocol Amendment 5 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
212494 (RSV OA=ADJ-006) 
EudraCT number 
2020-000753-28 
Date of protocol 
amendment 
Amendment 5 Final: 12 July 2023 
Title (Amended, 12 July 
2023) 
A Phase 3, randomized, placebo-controlled, observer 
blind, multi-country study to demonstrate the efficacy of 
a single dose and annual revaccination of GSK’s 
RSVPreF3 OA investigational vaccine in adults aged 60 
years and above.  
Sponsor signatory 
 
Marie Van Der Wielen, MD 
Clinical Project Lead 
RSV Older Adults 
(Amended, 12 July 2023) 
 
 
Signature 
 
 
 
Date 
 
 
 
Note: Not applicable if an alternative signature process (e.g., electronic signature or e-
mail approval) is used to get the sponsor approval. 

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Protocol Amendment 5 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals SA. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study vaccine and other study-related duties and functions as described in 
the protocol. 
• 
To supervise any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site. 
• 
To ensure that any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site are qualified to perform those trial-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained on site or 
elsewhere without the approval of GSK and the express written informed consent of 
the participant. 
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s). 
• 
To co-operate with a representatives of GSK Biologicals in the monitoring process 
of the study and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine, and more generally about his/her financial 
ties with the sponsor. GSK will use and disclose the information solely for the 
purpose of complying with regulatory requirements. 

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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
course of the study and for 1 year following completion of the study. 
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and other documents 
required by regulatory agencies for this study. 

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eTrack study number and 
Abbreviated Title 
212494 (RSV OA=ADJ-006) 
EudraCT number 
2020-000753-28 
Date of protocol 
amendment 
Amendment 5 Final: 12 July 2023 
Title (Amended, 12 July 
2023) 
A Phase 3, randomized, placebo-controlled, 
observer-blind, multi-country study to demonstrate the 
efficacy of a single dose and annual revaccination of 
GSK’s RSVPreF3 OA investigational vaccine in adults 
aged 60 years and above. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
 
 name, function and 
title 
 
 
 
Signature 
 
 
 
Date 
 
 
 
GSK Japan study 
representative name, 
function and title 
 
 
 
Signature 
 
 
 
Date 
 
PPD
PPD

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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA 
2. Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
3. Sponsor Study Monitor 
Refer to the local study contact information document. 
4. Sponsor Study Contact for Reporting of a Serious Adverse Event 
GSK Central Back-up Study Contact for Reporting SAEs: refer to the protocol section 
8.3.4. 
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
5. GSK Biologicals’ Helpdesk for Emergency Unblinding  
Refer to the protocol section 6.3.5.1. 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document history 
Document 
Date 
Amendment 5 
12 July 2023 
Amendment 4 
23 March 2023 
Amendment 3 
24 January 2022 
Amendment 2 
6 October 2021 
Amendment 1 
25 February 2021 
Original Protocol 
16 October 2020 
Amendment 5: 
This amendment is considered substantial based on the criteria defined in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because of significant changes in the conduct or management of the study. 
Overall rationale for the current Amendment:  
The purpose of this amendment is to remove Dose 3 administration before the start of 
Season 3 for participants in the NH and to add a blood sample at Visit 5NH for all 
participants who are not in the reactogenicity and immunogenicity subset.  
The results of VE Analysis 3 evaluating efficacy and safety of RSVPreF3 OA 
investigational vaccine up to the end of Season 2 in the NH, showed that a single dose of 
the RSVPreF3 OA investigational vaccine was efficacious against RSV-confirmed LRTD 
and severe LRTD over 2 RSV seasons. The VE against RSV-confirmed LRTD was 
67.18% [97.5% CI: 48.19, 80.04]. The VE against severe LRTD was 78.83% (95% CI: 
52.59, 91.96). 
The study also evaluated efficacy following an annual revaccination schedule. Over 
2 seasons, the VE in participants who received a second dose of the vaccine before 
Season 2 was similar to the VE in participants who had received a single dose of vaccine 
prior to Season 1 with VE of 67.12% (97.5% CI: 48.09, 80.00) against RSV-confirmed 
LRTD. These data suggest that a revaccination administered approximately 12 months 
after the first dose does not confer additional benefit for the overall population. The 
optimal timing for revaccination still needs to be determined. 
Safety and reactogenicity data post-Dose 2 were consistent with previous results from the 
Phase 3 program. Based on available reactogenicity and safety data up to the end of 
Season 2 in the NH (DLP 31 March 2023), with a median follow-up time from Dose 1 up 
to DLP of approximately 18.2 months, and from Dose 2 up to DLP of approximately 
6.7 months, the RSVPreF3 OA investigational vaccine showed a clinically acceptable 
safety profile in adults ≥ 60 YOA. The reactogenicity of the RSVPreF3 OA 
investigational vaccine was similar following each dose, with most of the solicited events 
being mild to moderate and of short duration. No safety concerns were identified with 
currently available data. 

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Based on these observations, the study design was modified to remove the next planned 
dose of the study intervention (Dose 3 pre-Season 3) in the NH. The clinical development 
program will continue to evaluate long-term follow-up and the optimal timing for 
revaccination.  
To evaluate further the correlation between humoral immune response and protection, an 
additional blood sample has been added at Visit 5NH for all participants who are not in 
the reactogenicity and immunogenicity subset. 
This amendment does not impact participants enrolled in the SH as they have completed 
the 2 doses of study intervention as per study design. 
Minor editorial changes for consistency and clarity have also been made and 
typographical errors have been corrected. 
Other updates are described in the table below:  
 

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List of main changes in the protocol and their rationale 
Section # and title 
Description of change 
Brief rationale 
Title page; sponsor approval page; 
investigator agreement page 
3. Objectives and endpoints 
7.1 Discontinuation of study 
intervention 
9.4.4.4 Quality of life 
‘Annual revaccination doses’ has been changed to ‘Annual revaccination’ and 
‘Annual revaccinations’ has been changed to ‘Annual revaccination’. 
As Dose 2 pre-Season 2 administered 12 months 
post-Dose 1 did not confer additional benefit in 
prevention of RSV-confirmed LRTD, the study 
design was modified to remove the next planned 
dose of the study vaccine (Dose 3 pre-Season 3). 
These sections were thus updated to reflect this 
change. 
1.1 Synopsis 
2.1 Study rationale 
2.2 Background 
4.2.2 Rationale for the use of Placebo 
Clinical development status of GSK’s RSVPreF3 OA investigational vaccine has 
been updated. 
Marketing authorization approval of the study vaccine has been added.  
As GSK’s RSVPreF3 OA investigational vaccine is 
now approved for use, the clinical development 
status of the study vaccine was modified from 
‘developing’ to ‘developed’ and the market 
authorization approval details have been added. 
1.3 Schedule of activities  
(Table 1, Table 2, Table 4 and 
Table 5) 
For Table 1, table title has been revised to indicate that activities listed in this table 
is applicable for participants in the NH who have their Visit 5NH before the approval 
of the current Protocol Amendment 5. 
A new table has been added for the schedule of activities for participants in the NH 
who will have their Visit 5NH after the approval of the current Protocol 
Amendment 5 (Table 2).  
Intervals between study visits/contact for participants in the NH have been modified. 
Corrections have been made in the table footnotes to align with the changes made 
in the tables.  
Section has been updated to reflect that a blood sample will be taken at Visit 5NH 
from all participants in the NH who have their Visit 5NH after the approval of the 
current Protocol Amendment 5. 
Option for use of paper questionnaire for atrial fibrillation has been removed. 
Corrections in the footnotes were made to algin with the changes made in the table. 
To align with the changes made to the study 
design with respect to removal of Dose 3 (pre-
Season 3) and study procedures related to Dose 3 
administration. 
Blood samples collection from all participants in the 
NH at Visit 5NH (pre-Season 3) was added to allow 
for further assessment of correlation between 
humoral immune response and protection. 
As only electronic questionnaires will be used for 
follow-up of atrial fibrillation, the option for paper 
questionnaire was removed. 
2.3 Benefit/Risk assessment 
2.3.2 Benefit assessment 
Updated to clarify the current status of VE assessment and clinical benefit provided 
to participants. 
Since initial protocol approval, VE data has 
become available at VE Analysis 3. This section 
was thus updated to reflect this information. 

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Section # and title 
Description of change 
Brief rationale 
3 Objectives and endpoints 
The secondary confirmatory objectives have been modified to indicate that efficacy 
would be assessed for only 1 annual revaccination before Season 2. 
The term ‘pre-Dose 3’ has been removed from the secondary and tertiary 
immunogenicity endpoints.  
To align with the changes made to the study 
design with respect to removal of Dose 3 (pre-
Season 3) and study procedures related to Dose 3 
administration. 
3 Objectives and endpoints 
Tertiary endpoint pertaining to assessment of correlate of protection has been 
modified in indicate that RSVPreF3 IgG-binding antibody concentration will also be 
assessed at pre-Season 3 for all participants in the NH. 
To allow for further assessment of correlation 
between humoral immune response and 
protection. 
4 Study design 
4.1 Overall study design (Figure 1) 
Study design has been updated to clarify that at Visit 5NH (pre-Season 3) 
participants who will have their Visit 5NH before the approval of Protocol 
Amendment 5 will receive the study intervention as planned according to their 
group allocation. Participants having their Visit 5NH after approval of the current 
Protocol Amendment 5 will not receive any study intervention at pre-Season 3 visit 
(Visit 5NH). 
Dose 3 at Visit 5NH (pre-Season 3), Visit 6NH and Contact 5 have been removed 
from the study design figure. 
To align with the changes made to the study 
design with respect to removal of Dose 3 (pre-
Season 3) and study procedures related to Dose 3 
administration. 
4.1 Overall study design  
8.1.3.2 Biological samples for 
immunogenicity assessment 
8.1.5 Immunological read-outs 
8.1.7 Immunological correlates of 
protection 
9.4.5.4.1 Correlate of protection 
This section have been updated to reflect that a blood sample will be collected from 
all participants in the NH at Visit 5NH (pre-Season 3). 
Volume of blood sample to be collected from participants in the NH has been 
added. 
To allow for further assessment of correlation 
between humoral immune response and 
protection. 
4.2 Scientific rationale for the study 
design 
Updated to include the rationale for removing Dose 3 administration from the study 
design. 
To support the changes made to the study design 
with respect to removal of Dose 3 and study 
procedures related to Dose 3 administration. 
6.1 Study intervention administered 
6.3.2 Randomization to study 
intervention 
6.3.4 Allocation of participants to 
assay subsets 
6.5 Concomitant therapy 
7.1.2 Contraindications to subsequent 
vaccine administration 
Updated to reflect that for participants in the NH who have their Visit 5NH after the 
approval of the current Protocol Amendment 5, administration of Dose 3 at 
Visit 5NH (pre-Season 3) as well as all study procedures related to Dose 3 
administration have been cancelled. 
As Dose 2 administered 12 months post-Dose 1 
did not confer additional benefit in prevention of 
RSV-confirmed LRTD, the study design was 
modified to remove the next planned dose of the 
study vaccine (Dose 3 pre-Season 3). 

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Section # and title 
Description of change 
Brief rationale 
8.2.1.7 Distribution of paper diary 
cards 
8.2.2.3 Lung auscultation 
10.3.8 Recording and follow-up of 
AEs, SAEs, AESIs (including pIMDs 
and AF) 
8.1.1.5 Scheduled site staff contacts 
Figure 2 and its corresponding footnote has been updated to correct typographical 
errors. Visit 5SH was erroneously indicated as Visit 4SH both in the Figure and 
footnote and Visit 7NH was erroneously indicated as Visit 6NH.  
To correct typographical error. 
8.3.1 Time period and frequency for 
collecting AE, SAE and other safety 
information 
Safety information related to Dose 3 administration, collected at Day 1 - 4, Day 30 
and Month 6 post-Dose 3 have been removed for participants in NH who have their 
Visit 5NH after the approval of the current Protocol Amendment 5 and will not 
receive any study intervention at pre-Season 3 visit (Visit 5NH). 
To align with changes in the study design related to 
removal of Dose 3 (pre-Season 3). 
9.1.2 Secondary objectives 
9.2.2 Secondary objectives 
9.4.4.1 Efficacy 
9.4.5.1 Efficacy 
The secondary confirmatory objectives, endpoints, and analyses have been 
modified to indicate that efficacy would be assessed for only 1 annual revaccination 
before Season 2. 
The term ‘pre-Dose 3’ has been removed from the secondary and tertiary 
immunogenicity endpoints. 
A note has been added to clarify that participants who received Dose 3 of the study 
vaccine will not be included in the evaluation of VE of the annual revaccination over 
3 season.  
The expected total number of RSV LRTD cases and the power for each analysis 
provided in Table 28 have been updated.  
The expected number of RSV-confirmed LRTD cases for the evaluation of VE of 
the annual revaccination for Season A3NH provided in Table 30 have been 
updated.  
This section has been updated to align with the 
changes made in the secondary confirmatory 
objectives. 
9.3 Populations for analyses 
The following note has been added: Exposed Set Dose 2 and Exposed Set Dose 3 
including all participants who received the 2nd and the 3rd dose, respectively, will 
also be used to report analysis on post-dose 2/3 data. 
To account for data collected from participants in 
the NH who will have their Visit 5NH before the 
approval of the Protocol Amendment 5 and will 
receive Dose 3 of the study interventions at pre-
Season 3 visit (Visit 5NH). 

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Section # and title 
Description of change 
Brief rationale 
A note has been added to clarify that participants who received Dose 3 of the study 
vaccine will not be included in the evaluation of VE of the annual revaccination over 
3 season.  
In addition, the section has been updated to align 
with the changes made in the secondary 
confirmatory objectives. 
9.5.1 Sequence of analyses 
Formatting error in the numbering of analyses steps has been corrected. 
To correct typographical error. 
10.5.1 List of Abbreviations 
Updated to change mg to µg. 
To correct typographical error. 
 

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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT 5 INVESTIGATOR AGREEMENT ....................................... 3 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
Document history ..................................................................................................... 7 
List of main changes in the protocol and their rationale ............................................ 9 
TABLE OF CONTENTS ................................................................................................ 13 
LIST OF TABLES .......................................................................................................... 19 
LIST OF FIGURES ........................................................................................................ 21 
1. 
PROTOCOL SUMMARY ........................................................................................ 22 
1.1. 
Synopsis (Amended, 12 July 2023)............................................................. 22 
1.2. 
Schema ...................................................................................................... 22 
1.3. 
Schedule of activities (Amended, 12 July 2023) .......................................... 22 
2. 
INTRODUCTION .................................................................................................... 38 
2.1. 
Study rationale (Amended, 12 July 2023) ................................................... 38 
2.2. 
Background (Amended, 12 July 2023) ........................................................ 38 
2.3. 
Benefit/Risk assessment ............................................................................. 40 
2.3.1. 
Risk assessment .......................................................................... 40 
2.3.2. 
Benefit assessment (Amended, 12 July 2023) ............................. 40 
2.3.3. 
Overall Benefit/Risk conclusion .................................................... 41 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 41 
4. 
STUDY DESIGN .................................................................................................... 47 
4.1. 
Overall design (Amended, 12 July 2023) .................................................... 47 
4.1.1. 
Overview of the recruitment plan ................................................. 51 
4.1.2. 
Enrollment rules ........................................................................... 52 
4.2. 
Scientific rationale for study design (Amended, 12 July 2023) .................... 52 
4.2.1. 
Case definitions for evaluation of vaccine efficacy ....................... 53 
4.2.2. 
Rationale for the use of placebo (Amended, 12 July 2023) .......... 55 
4.2.3. 
Rationale for study blinding .......................................................... 55 
4.3. 
Justification for dose ................................................................................... 55 
4.4. 
End of Study definition ................................................................................ 56 
5. 
STUDY POPULATION ........................................................................................... 56 
5.1. 
Inclusion criteria for enrollment ................................................................... 56 
5.2. 
Exclusion criteria for enrollment .................................................................. 57 
5.2.1. 
Medical conditions ....................................................................... 57 
5.2.2. 
Prior/Concomitant therapy ........................................................... 57 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 58 
5.2.4. 
Other exclusions .......................................................................... 58 
5.3. 
Caregiver support ....................................................................................... 59 

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5.4. 
Screen failures ............................................................................................ 59 
6. 
STUDY INTERVENTION ........................................................................................ 59 
6.1. 
Study interventions administered (Amended, 12 July 2023) ........................ 60 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 62 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 62 
6.3.1. 
Participant identification ............................................................... 62 
6.3.2. 
Randomization to study intervention (Amended, 12 July 
2023) ........................................................................................... 63 
6.3.3. 
Intervention allocation to the participant ....................................... 63 
6.3.4. 
Allocation of participants to assay subsets ................................... 64 
6.3.5. 
Blinding and unblinding ................................................................ 65 
6.3.5.1. 
Emergency unblinding ................................................ 66 
6.3.5.2. 
Emergency unblinding prior to regulatory 
reporting of SAEs ....................................................... 67 
6.4. 
Study intervention compliance .................................................................... 68 
6.5. 
Concomitant therapy (Amended, 12 July 2023) .......................................... 68 
6.6. 
Dose modification ....................................................................................... 70 
6.7. 
Intervention after the end of the study ......................................................... 70 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 70 
7.1. 
Discontinuation of study intervention (Amended, 12 July 2023) .................. 70 
7.1.1. 
Criteria for temporary delay for enrollment and/or 
vaccination ................................................................................... 70 
7.1.2. 
Contraindications to subsequent vaccine administration 
(Amended, 12 July 2023) ............................................................. 71 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 72 
7.3. 
Lost to follow-up.......................................................................................... 72 
8. 
STUDY ASSESSMENTS AND PROCEDURES (AMENDED, 12 JULY 
2023) ...................................................................................................................... 73 
8.1. 
Efficacy and immunogenicity assessments ................................................. 74 
8.1.1. 
Efficacy assessments .................................................................. 74 
8.1.1.1. 
ARI surveillance period and methods ......................... 74 
8.1.1.1.1. 
Nasal self-swab training with the 
study participant ..................................... 75 
8.1.1.2. 
Definitions for ARI surveillance ................................... 75 
8.1.1.3. 
ARI capture and follow-up .......................................... 76 
8.1.1.4. 
Spontaneous reporting by the participant ................... 76 
8.1.1.5. 
Scheduled site staff contacts (Amended, 12 
July 2023) ................................................................... 76 
8.1.1.6. 
ARI procedures .......................................................... 78 
8.1.1.6.1. 
Primary route to capture ARI 
episodes ................................................. 78 
8.1.1.6.2. 
Other routes to capture ARI 
episodes ................................................. 83 
8.1.1.6.3. 
Hospitalization during an ARI 
episode ................................................... 84 
8.1.2. 
Immunogenicity assessments ...................................................... 85 
8.1.3. 
Biological samples ....................................................................... 86 
8.1.3.1. 
Biological samples for efficacy assessment ................ 86 

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8.1.3.2. 
Biological samples for immunogenicity 
assessment (Amended, 12 July 2023) ........................ 86 
8.1.4. 
Laboratory assays ....................................................................... 87 
8.1.4.1. 
Laboratory assays for efficacy assessment ................ 87 
8.1.4.2. 
Laboratory assays for immunogenicity 
assessment ................................................................ 88 
8.1.5. 
Immunological read-outs (Amended, 12 July 2023) ..................... 89 
8.1.6. 
Molecular biology read-outs ......................................................... 90 
8.1.7. 
Immunological correlates of protection (Amended, 12 July 
2023) ........................................................................................... 90 
8.2. 
Safety assessments .................................................................................... 91 
8.2.1. 
Pre-vaccination procedures ......................................................... 91 
8.2.1.1. 
Collection of demographic data .................................. 91 
8.2.1.2. 
Measure/record height and weight .............................. 91 
8.2.1.3. 
Medical history ........................................................... 91 
8.2.1.4. 
Vaccination history ..................................................... 91 
8.2.1.5. 
Smoking status and smoking exposure history ........... 92 
8.2.1.6. 
Pre-vaccination body temperature .............................. 92 
8.2.1.7. 
Distribution of paper diary cards (Amended, 12 
July 2023) ................................................................... 92 
8.2.2. 
Procedures carried out at vaccination and non-vaccination 
visits ............................................................................................ 92 
8.2.2.1. 
Physical examination .................................................. 92 
8.2.2.2. 
Body temperature during ARI episode ........................ 93 
8.2.2.3. 
Lung auscultation (Amended, 12 July 2023) ............... 93 
8.2.2.4. 
Pulse oximetry ............................................................ 93 
8.2.2.5. 
Vital signs ................................................................... 93 
8.2.3. 
Safety monitoring ......................................................................... 94 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and other 
events of interest ........................................................................................ 94 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information (Amended, 12 July 2023) ....................... 94 
8.3.2. 
Method of detecting AEs and SAEs and other events .................. 98 
8.3.3. 
Regulatory reporting requirements for SAEs and other 
events .......................................................................................... 98 
8.3.4. 
Contact information for reporting of SAEs, AESIs 
(including pIMDs and AF) ............................................................ 99 
8.3.5. 
Treatment of adverse events ....................................................... 99 
8.3.6. 
Participant card .......................................................................... 100 
8.4. 
Frailty status assessment ......................................................................... 100 
8.5. 
Treatment of overdose .............................................................................. 100 
8.6. 
Pharmacokinetics ..................................................................................... 100 
8.7. 
Pharmacodynamics .................................................................................. 100 
8.8. 
Genetics ................................................................................................... 100 
8.9. 
Biomarkers ............................................................................................... 100 
8.10. 
Health outcomes ....................................................................................... 100 
8.10.1. 
Completion of HR-QoL questionnaires ....................................... 101 
8.10.2. 
HCRU ........................................................................................ 101 
9. 
STATISTICAL CONSIDERATIONS ...................................................................... 102 
9.1. 
Statistical hypotheses ............................................................................... 102 
9.1.1. 
Primary objective ....................................................................... 102 

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9.1.2. 
Secondary objectives (Amended, 12 July 2023) ........................ 103 
9.2. 
Sample size determination ........................................................................ 106 
9.2.1. 
Primary objective: Vaccine efficacy ............................................ 106 
9.2.2. 
Secondary objectives (Amended, 12 July 2023) ........................ 107 
9.2.2.1. 
Expected number of RSV-confirmed LRTD 
cases (Amended, 12 July 2023) ............................... 108 
9.2.3. 
Sample size re-assessment ....................................................... 109 
9.2.4. 
Reactogenicity subset ................................................................ 110 
9.3. 
Populations for analyses (Amended, 12 July 2023) .................................. 111 
9.3.1. 
Criteria for elimination from analysis .......................................... 112 
9.3.1.1. 
Intercurrent medical conditions and 
concomitant medications/products/vaccines 
that may lead to elimination of a participant 
from per protocol analyses ....................................... 112 
9.4. 
Statistical analyses ................................................................................... 112 
9.4.1. 
General considerations .............................................................. 112 
9.4.1.1. 
Demography ............................................................. 112 
9.4.1.2. 
Efficacy ..................................................................... 112 
9.4.1.3. 
Immunogenicity ........................................................ 113 
9.4.1.4. 
Reactogenicity/Safety ............................................... 114 
9.4.1.5. 
Quality of life............................................................. 114 
9.4.2. 
Demographics and participants disposition ................................ 115 
9.4.3. 
Primary endpoint ........................................................................ 116 
9.4.4. 
Secondary endpoints ................................................................. 116 
9.4.4.1. 
Efficacy (Amended, 12 July 2023) ............................ 116 
9.4.4.2. 
Immunogenicity ........................................................ 119 
9.4.4.3. 
Safety ....................................................................... 119 
9.4.4.4. 
Quality of life............................................................. 122 
9.4.5. 
Tertiary/exploratory endpoints .................................................... 122 
9.4.5.1. 
Efficacy (Amended, 12 July 2023) ............................ 122 
9.4.5.2. 
Analysis of HCRU ..................................................... 123 
9.4.5.3. 
Quality of life............................................................. 123 
9.4.5.4. 
Immunogenicity ........................................................ 124 
9.4.5.4.1. 
Correlate of protection (Amended, 
12 July 2023) ........................................ 124 
9.4.5.4.2. 
Within groups analysis .......................... 124 
9.4.5.5. 
Safety ....................................................................... 124 
9.5. 
Interim analyses ........................................................................................ 125 
9.5.1. 
Sequence of analyses (Amended, 12 July 2023) ....................... 125 
9.6. 
Independent Data Monitoring Committee (IDMC) (Amended) ................... 126 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 127 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations .......................................................................................... 127 
10.1.1. 
Regulatory and ethical considerations ....................................... 127 
10.1.2. 
Financial disclosure ................................................................... 128 
10.1.3. 
Informed consent process .......................................................... 128 
10.1.4. 
Data protection .......................................................................... 129 
10.1.5. 
Committees structure ................................................................. 129 
10.1.6. 
Dissemination of clinical study data ........................................... 129 
10.1.7. 
Data quality assurance .............................................................. 130 

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10.1.8. 
Source documents ..................................................................... 131 
10.1.9. 
Study and site closure................................................................ 131 
10.1.10. Publication policy ....................................................................... 131 
10.2. 
Appendix 2: Clinical laboratory tests ......................................................... 132 
10.2.1. 
Laboratory assays for immune response ................................... 132 
10.2.2. 
Laboratory assays for molecular biology .................................... 133 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting .......................................... 134 
10.3.1. 
Definition of an Adverse Event (AE) ........................................... 134 
10.3.1.1. Events meeting the AE definition .............................. 134 
10.3.1.2. Events NOT meeting the AE definition...................... 135 
10.3.2. 
Definition of a Serious Adverse Event (SAE) ............................. 135 
10.3.3. 
Solicited events.......................................................................... 136 
10.3.4. 
Unsolicited adverse events ........................................................ 136 
10.3.5. 
Adverse events of special interest (AESIs) ................................ 137 
10.3.5.1. Potential immune-mediated diseases ....................... 137 
10.3.5.2. Atrial fibrillation ......................................................... 141 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs .................................... 142 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs ................... 142 
10.3.7.1. Pregnancy ................................................................ 142 
10.3.8. 
Recording and follow-up of AEs, SAEs, AESIs (including 
pIMDs and AF) (Amended, 12 July 2023) .................................. 142 
10.3.8.1. Time period for collecting and recording AEs, 
SAEs, AESIs (including pIMDs and AF) .................... 143 
10.3.8.2. Follow-up of AEs, SAEs, AESIs (including 
pIMDs and AF) ......................................................... 144 
10.3.8.2.1. Follow-up during the study .................... 144 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study .................... 144 
10.3.8.3. Updating of SAE, AESI (including pIMD and 
AF) information after removal of write access to 
the participant’s eCRF .............................................. 144 
10.3.9. 
Assessment of intensity and toxicity ........................................... 145 
10.3.9.1. Assessment of intensity ............................................ 145 
10.3.9.2. Assessment of causality ........................................... 146 
10.3.9.3. Medically attended visits ........................................... 147 
10.3.9.4. Assessment of outcomes.......................................... 147 
10.3.10. Reporting of SAEs, AESIs (including pIMDs and AF) ................. 147 
10.3.10.1. Events requiring expedited reporting to GSK ............ 147 
10.3.10.2. Back-up system in case facsimile or electronic 
reporting system does not work ................................ 148 
10.4. 
Appendix 4: Country-specific requirements ............................................... 148 
10.4.1. 
Japan ......................................................................................... 148 
10.4.1.1. Regulatory and ethical considerations ...................... 148 
10.4.1.2. Informed consent ...................................................... 149 
10.4.1.3. Study administrative structure .................................. 149 
10.4.1.4. Unapproved medical device ..................................... 149 
10.4.2. 
Germany .................................................................................... 149 
10.4.2.1. Explanatory statement concerning gender 
distribution (Article 7, Paragraph 2 (12) of the 
German GCP order) ................................................. 149 

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10.4.2.2. Remote Monitoring and Source Data 
Verification ............................................................... 149 
10.4.3. 
Republic of Korea ...................................................................... 150 
10.4.3.1. Study participants exclusion criteria for 
enrollment ................................................................ 150 
10.4.3.2. Safety monitoring ..................................................... 150 
10.5. 
Appendix 5: Abbreviations and glossary of terms ...................................... 151 
10.5.1. 
List of abbreviations (Amended, 12 July 2023) .......................... 151 
10.5.2. 
Glossary of terms ....................................................................... 154 
10.5.3. 
List of trademarks ...................................................................... 159 
10.6. 
Appendix 6: Protocol Amendment history ................................................. 159 
11. REFERENCES ..................................................................................................... 195 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of activities for participants in Northern hemisphere 
that have their Visit 5NH BEFORE approval of this Protocol 
amendment 5 (Amended, 12 July 2023) ................................................. 23 
Table 2 
Schedule of activities for participants in Northern hemisphere 
that have their Visit 5NH AFTER the approval of this Protocol 
Amendment 5 (Amended, 12 July 2023) ................................................ 27 
Table 3 
Schedule of activities for all participants in Southern hemisphere 
(Amended, 12 July 2023) ....................................................................... 31 
Table 4 
Schedule of activities for ARI surveillance (Amended, 12 July 
2023) ...................................................................................................... 35 
Table 5 
Intervals between study visits/contacts for all participants in 
Northern hemisphere (Amended, 12 July 2023) ..................................... 37 
Table 6 
Intervals between study visits/contacts for all participants in 
Southern hemisphere ............................................................................. 37 
Table 7 
Intervals between study visits/contacts for ARI surveillance ................... 38 
Table 8 
Study objectives and endpoints (Amended, 12 July 2023) ..................... 41 
Table 9 
Study groups, intervention and blinding foreseen in the study 
(Amended, 12 July 2023) ....................................................................... 50 
Table 10 
Case definitions for evaluation of vaccine efficacy .................................. 53 
Table 11 
Study interventions administered for Dose 1 .......................................... 61 
Table 12 
Study interventions administered for annual revaccination 
(Amended, 12 July 2023) ....................................................................... 62 
Table 13 
Number of participants in reactogenicity and immunogenicity 
subset (Amended, 12 July 2023) ............................................................ 65 
Table 14 
Contact information for emergency unblinding ....................................... 67 
Table 15 
Timing of collection of concomitant medication to be recorded 
(Amended, 12 July 2023) ....................................................................... 69 
Table 16 
Intensity grading for ARI/LRTD episode ................................................. 81 
Table 17 
Biological samples for efficacy assessment ............................................ 86 
Table 18 
Biological samples for immunogenicity assessment (Amended, 
12 July 2023) ......................................................................................... 87 

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Table 19 
Laboratory assays for molecular biology (PCR tests) ............................. 88 
Table 20 
Laboratory assays for humoral immune response (antibody 
determination) ........................................................................................ 89 
Table 21 
Immunological read-outs (Amended, 12 July 2023) ................................ 89 
Table 22 
Molecular biology tests on swab samples............................................... 90 
Table 23 
Timeframes for collecting and reporting of safety information 
(Amended, 12 July 2023) ....................................................................... 95 
Table 24 
Timeframes for submitting serious adverse event and other 
events reports to GSK ............................................................................ 99 
Table 25 
Contact information for reporting of SAEs, AESIs (including 
pIMDs and AF) ....................................................................................... 99 
Table 26 
One-sided alpha levels for interim and final analyses using 
Wang-Tsiatis method, according to information accumulated at 
interim analysis .................................................................................... 103 
Table 27 
Total sample size to be enrolled in the NH to ensure at least 90% 
power to demonstrate the primary objective depending on attack 
rate, assuming a non-evaluable rate of 10% ........................................ 107 
Table 28 
Power to demonstrate secondary confirmatory objectives 
(Amended, 12 July 2023) ..................................................................... 108 
Table 29 
Expected number of RSV-confirmed LRTD cases for the 
evaluation of VE of the single dose ...................................................... 108 
Table 30 
Expected number of RSV-confirmed LRTD cases for the 
evaluation of VE of the annual revaccination (Amended, 12 July 
2023) .................................................................................................... 109 
Table 31 
Probability (%) to observe at least one event depending on AE 
incidence .............................................................................................. 110 
Table 32 
Populations for analyses ...................................................................... 111 
Table 33 
Solicited administration site events....................................................... 136 
Table 34 
Solicited systemic events ..................................................................... 136 
Table 35 
List of potential immune-mediated diseases (pIMDs) ........................... 137 
Table 36 
Intensity scales for solicited events in adults ........................................ 145 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview for (Amended, 12 July 2023) .............................. 47 
Figure 2 
ARI surveillance in Northern and Southern hemispheres 
(Amended, 12 July 2023) ....................................................................... 77 
Figure 3 
ARI capture and follow-up ...................................................................... 79 
Figure 4 
Sequential evaluation of primary and confirmatory secondary 
objectives (Amended, 12 July 2023) ..................................................... 105 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis (Amended, 12 July 2023) 
Rationale: 
GlaxoSmithKline Biologicals SA (GSK) has developed a new RSV PreFusion protein 
F3 Older Adult (RSVPreF3 OA) vaccine against RSV-associated (subtypes A and B) 
disease in adults ≥ 60 years of age (YOA).  
The purpose of this study is to demonstrate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of reverse-transcriptase polymerase chain 
reaction (RT-PCR)-confirmed lower respiratory tract disease (LRTD) caused by RSV A 
and/or B in adults ≥ 60 YOA, following a single dose of the RSVPreF3 OA vaccine and 
following annual revaccination doses. The vaccine cross-protection against RT-PCR-
confirmed LRTD caused by human metapneumovirus (hMPV) will also be evaluated. In 
addition, the safety and immunogenicity of the vaccine will be assessed after each dose. 
Surveillance for acute respiratory illness (ARI) will be carried out during the entire study 
via spontaneous reporting by the study participant (starting on the first vaccination day 
[Visit 1]) and via scheduled site staff contacts (as of Visit 2 onwards). 
Based on the first results obtained in the Phase 1/2 dose formulation selection study for 
the RSVPreF3 OA investigational vaccine (RSV OA=ADJ-002), RSVPreF3 recombinant 
antigen 120 µg adjuvanted with AS01E as a single dose was selected for further 
evaluation in the Phase 3 program. 
Objectives and endpoints: 
Refer to Table 8 in Section 3 for an overview of the study objectives and endpoints. 
1.2. 
Schema 
Refer to Figure 1 for an overview of the study design. 
1.3. 
Schedule of activities (Amended, 12 July 2023) 
For participants who will have the Visit 5NH (pre-Season 3 visit) taking place 
BEFORE the approval of this Protocol Amendment 5, the study procedures should be 
performed according to the previously approved protocol amendment version. Refer to 
Table 1 for details.  
For participants who will have the Visit 5NH (pre-Season 3 visit) taking place AFTER 
the approval of this Protocol Amendment 5, the study procedures should be performed 
according to the current Protocol Amendment 5: Dose 3 administration should be 
cancelled as well as other procedures related to Dose 3 administration. Visit 6NH and 
Contact 5 should be cancelled for these participants. Blood sample should be collected 
for all participants at Visit 5NH. Refer to Table 2 for details.  
Timeframe for Visit 5NH are defined in Table 5. 

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Table 1 
Schedule of activities for participants in Northern hemisphere that have their Visit 5NH BEFORE approval of this 
Protocol amendment 5 (Amended, 12 July 2023) 
Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH 
V6NH 
C52 
V7NH Notes for more information 
and details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 End S1 Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 Pre S3 
Dose 3 
Day 31 
Post-D3 
Month 6 
Post-D3 End S3 
Study participant informed consent 
●3 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.1.3 
Study participant informed consent for 
annual revaccinations4 
 
 
 
 
● 
 
 
 
 
 
 
 
 
Distribution of participant card 
○ 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.3.6 
Check inclusion/exclusion criteria 
● 
 
 
 
 
 
 
 
 
 
 
 
See Sections 5.1 and 5.2 
Check with participant if he/she will 
appoint a caregiver and distribute 
information letter(s) to caregiver, 
when applicable 
○ 
○ 
 
 
○ 
○ 
 
 
○ 
○ 
 
 
See Sections 5.3 and 10.1.3 
Baseline and demography 
assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 
Measure/record height and weight 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 
Record medical history 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.3 
Record history of vaccine 
administration5 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.4 
Physical examination/Vital signs 
● 
○6 
 
 
● 
○6 
 
 
● 
○6 
 
○6 
See Section 8.2.2 
Lung auscultation 
○ 
○6 
 
 
○ 
○6 
 
 
○ 
○6 
 
○6 
See Section 8.2.2.3  
Record oxygen saturation 
● 
 
 
 
● 
 
 
 
● 
 
 
 
See Section 8.2.2.4 
Record smoking status and smoking 
exposure history (including electronic 
smoking devices) 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.5. Refer to 
Section 10.5.2 for definitions 
of current and former 
smoker. 
Clinical specimens for laboratory 
assays 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling in all participants 
(~20 mL) 
●7 
● 
 
 
 
 
 
 
 
 
 
 
See Section 8.1.3.2 
Blood sampling in subset (~20 mL)8  
 
 
 
 
●7 
 
 
 
●7 
 
 
 
See Section 8.1.3.2 

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Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH 
V6NH 
C52 
V7NH Notes for more information 
and details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 End S1 Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 Pre S3 
Dose 3 
Day 31 
Post-D3 
Month 6 
Post-D3 End S3 
Vaccine(s) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check criteria for temporary delay for 
enrollment and/or vaccination 
○ 
 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 7.1.1 
Check contraindications to vaccination 
 
 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 7.1.2 
Study group and intervention 
number allocation 
○ 
 
 
 
○ 
 
 
 
○ 
 
 
 
See Sections 6.3.2 and 6.3.3 
Record pre-vaccination body 
temperature 
● 
 
 
 
● 
 
 
 
● 
 
 
 
The route for measuring 
temperature can be oral, 
axillary or tympanic (see 
Section 8.2.1.6). 
Vaccine administration (including 30-
minute post-vaccination observation) 
● 
 
 
 
● 
 
 
 
● 
 
 
 
See Section 6.1 
Safety assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Distribute paper diary cards9 
○ 
 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 8.2.1.7 
Return of paper diary cards 
 
○ 
 
 
 
○ 
 
 
 
○ 
 
 
See Section 10.3.8  
Record solicited administration site 
and systemic events (Days 1-4) in the 
reactogenicity subset 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
See Section 10.3.8 
Record unsolicited AEs (Days 1-30) in 
all participants11 
● 
● 
 
 
● 
● 
 
 
● 
● 
 
 
See Section 10.3.8 
Record concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Table 15 for specific 
collection period and Section 
6.5 
Record intercurrent medical 
conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 9.3.1.1 
Record all SAEs and pIMDs11 
● 
● 
● 
 
● 
● 
● 
 
● 
● 
● 
 
See Section 10.3.8 
Record fatal SAEs, SAEs related to 
study vaccination, COVID-19 cases 
and pIMDs related to study 
vaccination11 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 
Record AEs/SAEs leading to 
withdrawal from the study 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 

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Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH 
V6NH 
C52 
V7NH Notes for more information 
and details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 End S1 Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 Pre S3 
Dose 3 
Day 31 
Post-D3 
Month 6 
Post-D3 End S3 
Record SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine10 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 
ARI surveillance 
 
 
 
 
 
 
 
 
 
 
 
 
 
Instruct/remind participants of ARI 
surveillance 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
 
See Section 8.1.1 
Nasal self-swab training with the study 
participant 
 
○ 
 
 
 
 
 
 
 
 
 
 
See Section 8.1.1.1.1 
Distribute material for nasal self-swab 
collection (including instructions) 
 
○ 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 8.1.1 
Frailty status 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess frailty status with Gait Speed 
test 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.4 
HR-QoL questionnaires 
 
 
 
 
 
 
 
 
 
 
 
 
 
Distribute the daily health 
questionnaires for participants to 
complete at home in case of ARI 
 
○ 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 8.10.1 
Completion of daily health 
questionnaires by the participant 
 
● 
 
 
 
 
 
 
 
 
 
 
See Section 8.10.1 
Completion of EQ-5D and SF-12 
questionnaires by the participant 
● 
 
 
 
● 
 
 
 
● 
 
 
 
See Section 8.10.1 
Study conclusion for NH 
 
 
 
 
 
 
 
 
 
 
 
● 
See Section 4.4 
Note: The double-line borders indicate the analyses, which will be performed on data that are as clean as possible: VE Analysis 2 at the end of Season 1 in NH, Safety analysis when 
all safety data up to 6 months post-Dose 1 will be available for all participants in NH and SH, VE Analysis 3 after at least 2 seasons in NH and 1 season in SH, and VE Analysis 6 after 
3 seasons in NH and 2 seasons in SH (end of study). VE Analysis 1 will be case-driven. Additional analyses, not indicated in this table, will be performed as detailed in Section 
9.5.1. 
Note: If following the sample size re-assessment an additional cohort needs to be enrolled before the next season in NH (see Section 9.2.3), the participants enrolled in this cohort will 
follow the same schedule of activities as indicated in this table. 
ARI: acute respiratory illness; C: Contact; D: Dose; EQ-5D: EuroQol 5-dimension health questionnaire; HR-QoL: health-related quality of life; pIMDs: potential immune-mediated 
diseases; S: Season; SAE: serious adverse event; SF-12: Short Form 12-item health survey; Pre-S1: pre-Season 1; Pre-S2: pre-Season 2; Pre-S3: pre-Season 3; V: Visit 
● 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. 

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1. Study visits should preferably be done on site or in the LTCF. If deemed necessary, study visits can be done at home. For the study contacts, multiple formats can be proposed by 
the study site. These contacts may be done via e-mail, text message, fax or phone call for example, or via a visit for LTCF participants. The most appropriate format should be 
agreed between site staff and the study participant. Text messages, e-mail 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). Receipt of the message must be confirmed by the participant or 
caregiver, as applicable. 
2. Contacts 1, 3 and 5 must not be performed before the 6-month post-vaccination time point to allow collection of safety data up to at least 6 months after each vaccination for each 
participant. These contacts can be combined with another contact or visit. 
3. Freely given and written informed consent must be obtained from each study participant prior to participation in the study. The participant’s informed consent may be obtained prior 
to Visit 1. In addition, participants should sign the ICF addendum for revaccination (Protocol Amendment 3) at Visit 3. 
4. In case the participant does not agree to continue the study for the annual revaccination, the study conclusion page of the eCRF should be completed. 
5. Any vaccination administered up to 1 year before administration of the first study vaccine dose should be recorded in the eCRF. Administration of Shingrix at any timepoint (even if 
longer than 1 year before the first study vaccination) should be recorded in the eCRF. 
6. If deemed necessary by the investigator. 
7. The blood samples at Visits 1, 3 and 5NH should be taken prior to vaccine administration. 
8. These blood samples should only be taken from participants in the reactogenicity and immunogenicity subset. 
9. A paper diary will be distributed to all study participants on each vaccination day (at Visits 1, 3 and 5NH). All participants will record unsolicited AEs and concomitant 
medications/products on the day of each vaccination and for 29 subsequent days (Days 1-30). In addition, participants in the reactogenicity subset will be asked to record solicited 
events on the day of each vaccination and for 3 subsequent days (Days 1-4). 
10. SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to administration of the first study 
vaccine dose) up to study end. 
11. Atrial fibrillation (AF) will be considered as adverse events of special interest (AESI) in this study and will be additionally reported in the AF follow-up questionnaire (electronic) in 
eCRF. The collection of AF will be performed following the AE/SAE reporting periods. For AF that were reported before the implementation of the Protocol Amendment 4, additional 
available information should be encoded in the specific AF follow-up questionnaire retrospectively. 

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Table 2 
Schedule of activities for participants in Northern hemisphere that have their Visit 5NH AFTER the approval of 
this Protocol Amendment 5 (Amended, 12 July 2023) 
Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH V6NH11 
C511 
V7NH 
Notes for more information 
and details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 End S1 Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
Pre S3 
Dose 3 
 
Day 31 
Post-D3 
Month 6 
Post-D3 End 
S3 
Study participant informed consent 
●3 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.1.3 
Study participant informed consent for 
annual revaccination 
 
 
 
 
● 
 
 
 
 
 
 
 
 
Study participant informed consent 
addendum for Protocol 
Amendment 5 
 
 
 
 
 
 
 
 
● 
 
 
 
 
Distribution of participant card 
○ 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.3.6 
Check inclusion/exclusion criteria 
● 
 
 
 
 
 
 
 
 
 
 
 
See Sections 5.1 and 5.2 
Check with participant if he/she will 
appoint a caregiver and distribute 
information letter(s) to caregiver, 
when applicable 
○ 
○ 
 
 
○ 
○ 
 
 
○ 
 
 
 
See Sections 5.3 and 10.1.3 
Baseline and demography 
assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 
Measure/record height and weight 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 
Record medical history 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.3 
Record history of vaccine 
administration4 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.4 
Physical examination/Vital signs 
● 
○5 
 
 
● 
○5 
 
 
● 
 
 
○5 
See Section 8.2.2 
Lung auscultation 
○ 
○5 
 
 
○ 
○5 
 
 
○ 
 
 
○5 
See Section 8.2.2.3  
Record oxygen saturation 
● 
 
 
 
● 
 
 
 
● 
 
 
 
See Section 8.2.2.4 
Record smoking status and smoking 
exposure history (including electronic 
smoking devices) 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.5. Refer to 
Section 10.5.2 for definitions of 
current and former smoker. 

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Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH V6NH11 
C511 
V7NH 
Notes for more information 
and details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 End S1 Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
Pre S3 
Dose 3 
 
Day 31 
Post-D3 
Month 6 
Post-D3 End 
S3 
Clinical specimens for laboratory 
assays 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling in all participants 
(~20 mL) 
●6 
● 
 
 
 
 
 
 
●12 
 
 
 
See Section 8.1.3.2 
Blood sampling in subset (~20 mL)7 
 
 
 
 
●6 
 
 
 
 
 
 
 
See Section 8.1.3.2 
Vaccine(s) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check criteria for temporary delay for 
enrollment and/or vaccination 
○ 
 
 
 
○ 
 
 
 
 
 
 
 
See Section 7.1.1 
Check contraindications to vaccination 
 
 
 
 
○ 
 
 
 
 
 
 
 
See Section 7.1.2 
Study group and intervention number 
allocation 
○ 
 
 
 
○ 
 
 
 
 
 
 
 
See Sections 6.3.2 and 6.3.3 
Record pre-vaccination body 
temperature 
● 
 
 
 
● 
 
 
 
 
 
 
 
The route for measuring 
temperature can be oral, 
axillary or tympanic (see 
Section 8.2.1.6). 
Vaccine administration (including 30-
minute post-vaccination observation) 
● 
 
 
 
● 
 
 
 
 
 
 
 
See Section 6.1 
Safety assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Distribute paper diary cards8 
○ 
 
 
 
○ 
 
 
 
 
 
 
 
See Section 8.2.1.7 
Return of paper diary cards 
 
○ 
 
 
 
○ 
 
 
 
 
 
 
See Section 10.3.8  
Record solicited administration site 
and systemic events (Days 1-4) in the 
reactogenicity subset 
● 
● 
 
 
● 
● 
 
 
 
 
 
 
See Section 10.3.8 
Record unsolicited AEs (Days 1-30) in 
all participants10 
● 
● 
 
 
● 
● 
 
 
 
 
 
 
See Section 10.3.8 
Record concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Table 15 for specific 
collection period and Section 
6.5 
Record intercurrent medical 
conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 9.3.1.1 
Record all SAEs and pIMDs10 
● 
● 
● 
 
● 
● 
● 
 
 
 
 
 
See Section 10.3.8 

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Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH V6NH11 
C511 
V7NH 
Notes for more information 
and details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 End S1 Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
Pre S3 
Dose 3 
 
Day 31 
Post-D3 
Month 6 
Post-D3 End 
S3 
Record fatal SAEs, SAEs related to 
study vaccination, COVID-19 cases 
and pIMDs related to study 
vaccination10 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 10.3.8 
Record AEs/SAEs leading to 
withdrawal from the study 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 10.3.8 
Record SAEs related to study 
participation, or to a concurrent 
GSK medication/vaccine9 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 10.3.8 
ARI surveillance 
 
 
 
 
 
 
 
 
 
 
 
 
 
Instruct/remind participants of ARI 
surveillance 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
 
 
 
See Section 8.1.1 
Nasal self-swab training with the study 
participant 
 
○ 
 
 
 
 
 
 
 
 
 
 
See Section 8.1.1.1.1 
Distribute material for nasal self-swab 
collection (including instructions) 
 
○ 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 8.1.1 
Frailty status 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess frailty status with Gait Speed 
test 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.4 
HR-QoL questionnaires 
 
 
 
 
 
 
 
 
 
 
 
 
 
Distribute the daily health 
questionnaires for participants to 
complete at home in case of ARI 
 
○ 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 8.10.1 
Completion of daily health 
questionnaires by the participant 
 
● 
 
 
 
 
 
 
 
 
 
 
See Section 8.10.1 
Completion of EQ-5D and SF-12 
questionnaires by the participant 
● 
 
 
 
● 
 
 
 
● 
 
 
 
See Section 8.10.1 
Study conclusion for NH 
 
 
 
 
 
 
 
 
 
 
 
● 
See Section 4.4 
Note: The double-line borders indicate the analyses, which will be performed on data that are as clean as possible: VE Analysis 2 at the end of Season 1 in NH, Safety analysis when 
all safety data up to 6 months post-Dose 1 will be available for all participants in NH and SH, VE Analysis 3 after at least 2 seasons in NH and 1 season in SH, and VE Analysis 6 after 

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3 seasons in NH and 2 seasons in SH (end of study). VE Analysis 1 will be case-driven. Additional analyses, not indicated in this table, will be performed as detailed in Section 
9.5.1. 
Note: If following the sample size re-assessment an additional cohort needs to be enrolled before the next season in NH (see Section 9.2.3), the participants enrolled in this cohort will 
follow the same schedule of activities as indicated in this table. 
ARI: acute respiratory illness; C: Contact; D: Dose; EQ-5D: EuroQol 5-dimension health questionnaire; HR-QoL: health-related quality of life; pIMDs: potential immune-mediated 
diseases; S: Season; SAE: serious adverse event; SF-12: Short Form 12-item health survey; Pre-S1: pre-Season 1; Pre-S2: pre-Season 2; Pre-S3: pre-Season 3; V: Visit. 
● 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. 
1. Study visits should preferably be done on site or in the LTCF. If deemed necessary, study visits can be done at home. For the study contacts, multiple formats can be proposed by 
the study site. These contacts may be done via e-mail, text message, fax or phone call for example, or via a visit for LTCF participants. The most appropriate format should be 
agreed between site staff and the study participant. Text messages, e-mail 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). Receipt of the message must be confirmed by the participant or 
caregiver, as applicable. 
2. Contacts 1 and 3 must not be performed before the 6-month post-vaccination time point to allow collection of safety data up to at least 6 months after each vaccination for each 
participant. These contacts can be combined with another contact or visit. 
3. Freely given and written informed consent must be obtained from each study participant prior to participation in the study. The participant’s informed consent may be obtained prior 
to Visit 1. In addition, participants should sign the ICF addendum for revaccination (Protocol Amendment 3) at Visit 3 and ICF addendum for Protocol Amendment 5 at 
Visit 5NH. 
4. Any vaccination administered up to 1 year before administration of the first study vaccine dose should be recorded in the eCRF. Administration of Shingrix at any timepoint (even if 
longer than 1 year before the first study vaccination) should be recorded in the eCRF. 
5. If deemed necessary by the investigator. 
6. The blood samples at Visits 1 and 3 should be taken prior to vaccine administration. 
7. The blood samples at Visit 3 should only be taken from participants in the reactogenicity and immunogenicity subset. 
8. A paper diary will be distributed to all study participants on each vaccination day (at Visits 1 and 3). All participants will record unsolicited AEs and concomitant 
medications/products on the day of each vaccination and for 29 subsequent days (Days 1-30). In addition, participants in the reactogenicity subset will be asked to record solicited 
events on the day of each vaccination and for 3 subsequent days (Days 1-4). 
9. SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to administration of the first study 
vaccine dose) up to study end. 
10. Atrial fibrillation (AF) will be considered as adverse events of special interest (AESI) in this study and will be additionally reported in the AF follow-up questionnaire (electronic) in 
eCRF. The collection of AF will be performed following the AE/SAE reporting periods. For AF that were reported before the implementation of the Protocol Amendment 4, additional 
available information should be encoded in the specific AF follow-up questionnaire retrospectively. 
11. Visit 6NH and Contact 5 are not applicable for participants that did not receive the Dose 3 but are not removed from the schedule of activities table as these timepoints 
still appear in the eCRFs.  
12. At Visit 5NH, a blood sample of 20 mL should be taken from all participants including the participants of the immunogenicity and reactogenicity subset. 

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Table 3 
Schedule of activities for all participants in Southern hemisphere (Amended, 12 July 2023) 
Type of contact for SH1 
V1 
V2 
V2b2 
C13 
C2 
V3 
V4 
C33 
C4 
V5SH Notes for more information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 Pre S1 Month 6 
Post-D1 End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
End of 
study 
Study participant informed consent 
●4 
 
 
 
 
 
 
 
 
 
See Section 10.1.3 
Study participant informed consent for 
annual revaccination5 
 
 
 
 
 
● 
 
 
 
 
 
Distribution of participant card 
○ 
 
 
 
 
 
 
 
 
 
See Section 8.3.6  
Check inclusion/exclusion criteria 
● 
 
 
 
 
 
 
 
 
 
See Sections 5.1 and 5.2 
Check with participant if he/she will 
appoint a caregiver and distribute 
caregiver information letter(s), when 
applicable 
○ 
 
○ 
 
 
○ 
○ 
 
 
 
See Sections 5.3 and 10.1.3 
Baseline and demography 
assessments 
 
 
 
 
 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 
Measure/record height and weight 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 
Record medical history  
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.3 
Record history of vaccine administration5 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.4  
Physical examination/Vital signs 
● 
○7 
● 
 
 
● 
○7 
 
 
○7 
See Section 8.2.2 
Lung auscultation 
○ 
○7 
○ 
 
 
○ 
○7 
 
 
○7 
See Section 8.2.2.3 
Record oxygen saturation 
● 
 
● 
 
 
● 
 
 
 
 
See Section 8.2.2.4 
Record smoking status and smoking 
exposure history (including electronic 
smoking devices) 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.5. Refer to 
Section 10.5.2 for definitions of 
current and former smoker. 
Clinical specimens for laboratory 
assays 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling in all participants 
(~20 mL) 
●8 
● 
 
 
 
 
 
 
 
 
See Section 8.1.3.2 
Blood sampling in subset (~20 mL)9 
 
 
 
 
 
●8 
 
 
 
 
See Section 8.1.3.2 
Vaccine(s) 
 
 
 
 
 
 
 
 
 
 
 
Check criteria for temporary delay for 
enrollment and/or vaccination 
○ 
 
 
 
 
○ 
 
 
 
 
See Section 7.1.1 
Check contraindications to vaccination 
 
 
 
 
 
○ 
 
 
 
 
See Section 7.1.2 

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Type of contact for SH1 
V1 
V2 
V2b2 
C13 
C2 
V3 
V4 
C33 
C4 
V5SH Notes for more information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 Pre S1 Month 6 
Post-D1 End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
End of 
study 
Study group and intervention number 
allocation 
○ 
 
 
 
 
○ 
 
 
 
 
See Sections 6.3.2 and 6.3.3 
Record pre-vaccination body temperature 
● 
 
 
 
 
● 
 
 
 
 
The route for measuring 
temperature can be oral, axillary 
or tympanic (see Section 
8.2.1.6). 
Vaccine administration (including 30-
minute post-vaccination observation) 
● 
 
 
 
 
● 
 
 
 
 
See Section 6.1 
Safety assessments 
 
 
 
 
 
 
 
 
 
 
 
Distribute paper diary cards10 
○ 
 
 
 
 
○ 
 
 
 
 
See Section 8.2.1.7 
Return of paper diary cards 
 
○ 
 
 
 
 
○ 
 
 
 
See Section 10.3.8 
Record solicited administration site and 
systemic events (Days 1-4) in the 
reactogenicity subset 
● 
● 
 
 
 
● 
● 
 
 
 
See Section 10.3.8 
Record unsolicited AEs (Days 1-30) in all 
participants12 
● 
● 
 
 
 
● 
● 
 
 
 
See Section 10.3.8 
Record concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Table 15 for specific 
collection period and Section 6.5 
Record intercurrent medical conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 9.3.1.1 
Record all SAEs and pIMDs12 
● 
● 
● 
● 
 
● 
● 
● 
 
 
See Section 10.3.8 
Record fatal SAEs, SAEs related to study 
vaccination, COVID-19 cases and pIMDs 
related to study vaccination12 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 
Record AEs/SAEs leading to withdrawal 
from the study 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 
Record SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine11 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 

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Type of contact for SH1 
V1 
V2 
V2b2 
C13 
C2 
V3 
V4 
C33 
C4 
V5SH Notes for more information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 Pre S1 Month 6 
Post-D1 End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
End of 
study 
ARI surveillance 
 
 
 
 
 
 
 
 
 
 
 
Instruct/remind participants of ARI 
surveillance 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
 
See Section 8.1.1 
Nasal self-swab training with the study 
participant 
 
○ 
 
 
 
 
 
 
 
 
See Section 8.1.1.1.1 
Distribute material for nasal self-swab 
collection (including instructions) 
 
○ 
○ 
 
 
○ 
 
 
 
 
See Section 8.1.1 
Frailty status 
 
 
 
 
 
 
 
 
 
 
 
Assess frailty status with Gait Speed test 
● 
 
 
 
 
 
 
 
 
 
See Section 8.4 
HR-QoL questionnaires 
 
 
 
 
 
 
 
 
 
 
 
Distribute the daily health questionnaires 
for participants to complete at home in 
case of ARI 
 
○ 
 
 
 
○ 
 
 
 
 
See Section 8.10.1 
Completion of daily health questionnaires 
by the participant 
 
● 
 
 
 
 
 
 
 
 
See Section 8.10.1 
Completion of EQ-5D and SF-12 
questionnaires by the participant 
● 
 
 
 
 
● 
 
 
 
 
See Section 8.10.1 
Study conclusion for SH 
 
 
 
 
 
 
 
 
 
● 
See Section 4.4 
Note: The double-line borders indicate the analyses, which will be performed on data that are as clean as possible: Safety analysis when all safety data up to 6 months post-Dose 1 will 
be available for all participants in NH and SH, VE Analysis 3 after at least 2 seasons in NH and 1 season in SH and VE Analysis 4 after 3 seasons in NH and 2 seasons in SH (end of 
study). VE Analysis 1 will be case-driven and VE Analysis 2 will be performed at the end of Season 1 in NH. Refer to Section 9.5.1 for details.  
ARI: acute respiratory illness; C: Contact; D: Dose; EQ-5D: EuroQol 5-dimension health questionnaire HR-QoL: health-related quality of life; pIMDs: potential immune-mediated 
diseases; S: Season; SAE: serious adverse event; SF-12: Short Form 12-item health survey; Pre-S1: pre-Season 1; Pre-S2: pre-Season 2; V: Visit 
● 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. 
1. Study visits should preferably be done on site or in the LTCF. If deemed necessary, study visits can be done at home. For the study contacts, multiple formats can be proposed by 
the study site. These contacts may be done via e-mail, text message, fax or phone call for example, or via a visit for LTCF participants. The most appropriate format should be 
agreed between site staff and the study participant. Text messages, e-mail 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). Receipt of the message must be confirmed by the participant or 
caregiver, as applicable. 
2. Visit 2b in SH (Pre-Season 1 visit) should be performed at the earliest 3 months before the start of Season 1 in SH. This Visit 2b should not be performed for participants that have 
their Visit 2 planned within 3 months before the start of Season 1. For all participants in SH that have their Visit 2 more than 3 months before the start of Season 1, Visit 2b should 
be planned as a stand-alone visit. Refer to Table 6 for details of the interval allowed for study visits. 

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3. Contacts 1 and 3 must not be performed before the 6-month post-vaccination time point to allow collection of safety data up to at least 6 months after each vaccination for each 
participant. These contacts can be combined with another contact or visit. 
4. Freely given and written informed consent must be obtained from each study participant prior to participation in the study. The participant’s informed consent may be obtained prior 
to Visit 1. 
5. In case the participant does not agree to continue the study for the annual revaccination, the study conclusion page of the eCRF should be completed. 
6. Any vaccination administered up to 1 year before administration of the first study vaccine dose should be recorded in the eCRF. Administration of Shingrix at any timepoint (even if 
longer than 1 year before the first study vaccination) should be recorded in the eCRF. 
7. If deemed necessary by the investigator. 
8. The blood samples at Visits 1 and 3 should be taken prior to vaccine administration. 
9. These blood samples should only be taken from participants in the reactogenicity and immunogenicity subset. 
10. A paper diary will be distributed to all study participants on each vaccination day (at Visits 1 and 3). All participants will record unsolicited AEs and concomitant 
medications/products on the day of each vaccination and for 29 subsequent days (Days 1-30). In addition, participants in the reactogenicity subset will be asked to record solicited 
events on the day of each vaccination and for 3 subsequent days (Days 1-4). 
11. SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to administration of the first study 
vaccine dose) up to study end. 
12. AF will be considered as adverse events of special interest (AESI) in this study and will be additionally reported in the AF follow-up questionnaire (electronic) in eCRF. The 
collection of AF will be performed following the AE/SAE reporting periods. For AF that were reported before the implementation of the Protocol Amendment 4, additional available 
information should be encoded in the specific AF follow-up questionnaire retrospectively. 

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Table 4 
Schedule of activities for ARI surveillance (Amended, 12 July 2023) 
Type of contact 
Bi-weekly 
and monthly 
contact1 
Participant 
call 
ARI visit2 
ARI FU 
contact3 
ARI closure 
contact3 
Addit. FU 
contact4 
Notes for more information and details 
ARI surveillance 
Instruct/remind participants of ARI surveillance 
procedures 
○ 
 
 
 
 
 
See Section 8.1.1.4 
Record contact dates 
● 
● 
 
 
 
 
See Section 8.1.1 
Schedule the ARI visit 
○5 
○ 
 
 
 
 
See Section 8.1.1.6.1  
Distribution of new material for nasal self-swab 
collection (including instructions)6 
 
 
○ 
 
 
 
See Section 8.1.1.6 
Record date of nasal self-swab collection6 
 
 
● 
 
 
 
See Section 8.1.1.6 
Nasal and throat swab sampling by the site staff 
 
 
● 
 
 
 
See Section 8.1.1.1.1  
Record ARI information 
●5 
● 
● 
● 
● 
● 
See Section 8.1.1.6 
HR-QoL questionnaires 
Completion of EQ-5D and SF-12 questionnaires by 
the participant 
 
 
● 
 
 
 
See Section 8.10.1  
Distribution of daily health questionnaires (to be 
completed in case of another ARI)6 
 
 
○ 
 
 
 
See Section 8.10.1  
Completion of daily health questionnaires by the 
participant6,7 
○5 
○ 
○ 
○ 
 
 
See Section 8.10.1  
Remind participant to complete the daily health 
questionnaires6 
○5 
○ 
○ 
○ 
 
 
See Section 8.10.1  
Check completion of the daily health questionnaires6 
 
 
○ 
○ 
 
 
See Section 8.1.1.6.1  
Remind participant to return the daily health 
questionnaires6 
 
 
 
○ 
 
 
See Section 8.10.1  
Enter daily health questionnaires data in eCRF6 
 
 
 
 
● 
 
See Section 8.10.1  
HCRU 
Record HCRU 
 
 
● 
● 
● 
● 
See Section 8.10.2  
Safety assessments 
Physical examination/Vital signs 
 
 
● 
 
 
 
See Section 8.2.2  
Lung auscultation 
 
 
● 
 
 
 
See Section 8.2.2.3 
Record oxygen saturation 
 
 
● 
 
 
 
See Section 8.2.2.4 
Record medications taken to treat ARI 
(prescribed/self-treatment) or an ARI-related 
complication 
 
 
● 
● 
● 
● 
See Table 15 for specific collection period 
and Section 6.5  

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Type of contact 
Bi-weekly 
and monthly 
contact1 
Participant 
call 
ARI visit2 
ARI FU 
contact3 
ARI closure 
contact3 
Addit. FU 
contact4 
Notes for more information and details 
Record intercurrent medical conditions 
● 
 
● 
● 
● 
● 
See Section 9.3.1.1  
Recording of all SAEs and pIMDs up to 6 months 
post-vaccination9 
● 
 
● 
● 
● 
● 
See Section 10.3.8  
Recording of fatal SAEs, SAEs related to study 
vaccination, COVID-19 cases and pIMDs related to 
study vaccination9 
● 
 
● 
● 
● 
● 
See Section 10.3.8  
Recording of AEs/SAEs leading to withdrawal from 
the study 
● 
 
● 
● 
● 
● 
See Section 10.3.8  
Recording of SAEs related to study participation, or 
to a concurrent GSK medication/vaccine8 
● 
 
● 
● 
● 
● 
See Section 10.3.8  
ARI: acute respiratory illness; EQ-5D; EuroQol 5-dimension health questionnaire; HCRU: healthcare resource utilization; HR-QoL: health-related quality of life; 
pIMDs: potential immune-mediated diseases; SAE: serious adverse event; SF-12: Short Form 12-item health survey; FU: follow-up 
● 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. 
1. These surveillance contacts will be performed every 2 weeks during the RSV seasons and every month during the inter-season periods. Multiple formats can be proposed by the 
study site to organize the scheduled contacts. This may be done via e-mail, text message, fax or phone call for example, or via a visit for LTCF participants. The most appropriate 
format should be agreed between site staff and the study participant. Text messages, e-mail 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). Receipt of the message must be confirmed by the 
participant or caregiver, as applicable. 
2. The ARI visit should preferably be done on site or in the LTCF. If deemed necessary, the visit can be done at home. 
3. Each ARI episode will be followed up through an ARI follow-up contact approximately 14 days after ARI onset and an ARI closure contact approximately 28 days after ARI onset, in 
case the ARI event was still ongoing at the first ARI follow-up contact. These contacts can be done via phone calls or visit to the LTCF. 
4. For participants with ARI/complications(s) lasting beyond the ARI closure contact, additional follow-up contacts will be done approximately every 2 weeks (post ARI closure contact) 
until the resolution of the ARI/complication(s) or study end. These additional follow-up contacts can be done via phone calls or visit to the LTCF. 
5. If an ARI is reported during a scheduled surveillance contact, then all the procedures expected at the “participant call” should be performed. 
6. Not applicable for ARI reported before Visit 2 (Day 31). 
7. The daily health questionnaires should be completed from the participant’s call (Day 2) until the end of the ARI episode or for maximum 14 consecutive days (i.e., from Day 2 until 
Day 15 at the latest). 
8. SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to administration of the first study 
vaccine dose) up to study end. 
9. AF will be considered as adverse events of special interest (AESI) in this study and will be additionally reported in the AF follow-up questionnaire (electronic) in eCRF. The 
collection of AF will be performed following the AE/SAE reporting periods. For AF that were reported before the implementation of the Protocol Amendment 4, additional available 
information should be encoded in the specific AF follow-up questionnaire retrospectively.  
 

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Table 5 
Intervals between study visits/contacts for all participants in 
Northern hemisphere (Amended, 12 July 2023) 
Interval3 
Length of interval  
Allowed interval 
Visit 1 → Visit 2  
30 days  
28-42 days1 
Visit 1 → Contact 1 
180 days  
180-210 days2 
Contact 2 (End of Season 1) 
Between 1 and 31 May Study Year 2 
Visit 3 (Pre-Season 2/Dose 2) 
Between 1 August and 30 September Study Year 24 
Visit 3 → Visit 4  
30 days  
28-42 days1 
Visit 3 → Contact 3 
180 days  
180-210 days2 
Contact 4 (End of Season 2) 
Between 1 and 31 May Study Year 3 
Visit 5NH (Pre-Season 3) 
Between 1 August and 30 September Study Year 34,5 
Visit 5NH → Visit 6NH6 
30 days  
28-42 days1 
Visit 5NH → Contact 56 
180 days  
180-210 days2 
Visit 7NH (End of Season 3) 
Between 1 and 31 May Study Year 4 
1. If Visits 2, 4 or 6NH occur within 28 or 29 days after the vaccination visit, the site staff should ensure that 
unsolicited AEs are reported up to 30 days post-vaccination. 
2. Contacts 1, 3 and 5 must not be performed before the 6-month post-vaccination time point to allow collection of 
safety data up to at least 6 months after each vaccination for each participant. These contacts can be combined 
with another contact or visit. 
3. If following the sample size re-assessment an additional cohort needs to be enrolled before the next season in NH 
(see Section 9.2.3), similar intervals will apply up to the end of the third season for those participants. Study Year 1 
corresponds to the year in which the enrollment started for the cohort. 
4. In exceptional cases, the revaccination dose can be given before 30 October. 
5. For participants in the NH who will have their Visit 5NH after the approval of the current Protocol 
Amendment 5, in exceptional cases Visit 5NH can be organized before 30 October. 
6. Visit 6NH and Contact 5 are not applicable for participants who will have their Visit 5NH after the approval 
of the current Protocol Amendment 5 and did not receive study intervention (Dose 3) at pre-Season 3 visit 
(Visit 5NH). 
Table 6 
Intervals between study visits/contacts for all participants in 
Southern hemisphere 
Interval 
Length of interval  
Allowed interval 
Visit 1 → Visit 2 
30 days 
28-42 days1 
Visit 2b (Pre-Season 1)2 
Between 1 December Study Year 1 and 28 February Study Year 2 
Visit 1 → Contact 1 
180 days  
180-210 days3 
Contact 2 (End of Season 1) 
Between 1 and 31 October Study Year 2 
Visit 3 (Pre-Season 2/Dose 2) 
Between 1 January and 28 February Study Year 34 
Visit 3 → Visit 4 
30 days 
28-42 days1 
Visit 3 → Contact 3 
180 days  
180-210 days3 
Contact 4 (End of Season 2) 
Between 1 and 31 October Study Year 3 
Visit 5SH 
Between 1 and 31 May Study Year 4 
1. If Visits 2 or 4 occur within 28 or 29 days after the vaccination visit, the site staff should ensure that unsolicited AEs 
are reported up to 30 days post-vaccination. 
2. Visit 2b in SH (Pre-Season 1 visit) should be performed at the earliest 3 months before the start of Season 1 in SH. 
This Visit 2b should not be performed for participants that have their Visit 2 planned within 3 months before the 
start of Season 1. For all participants in SH that have their Visit 2 more than 3 months before the start of Season 1, 
Visit 2b should be planned as a stand-alone visit. 
3. Contacts 1 and 3 must not be performed before the 6-month post-vaccination time point to allow collection of safety 
data up to at least 6 months after each vaccination for each participant. These contacts can be combined with 
another contact or visit. 
4. In exceptional cases, the revaccination dose can be given before 31 March. 

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Table 7 
Intervals between study visits/contacts for ARI surveillance 
Interval 
Length of interval 
Allowed interval 
Between each surveillance contact (planned or 
spontaneous report) during the RSV seasons1 
14 days2 
±3 days3 
Between each surveillance contact (planned or 
spontaneous report) during the inter-season 
periods1 
30 days2 
±5 days3 
ARI visit 
At 2 days from ARI onset4 
2-6 days from ARI onset4, 5 
ARI follow-up contact 
At 14 days from ARI onset4 
14-18 days from ARI onset4 
ARI closure contact 
At 28 days from ARI onset4 
28-35 days from ARI onset4, 6 
Between each additional follow-up contact7 
At 14 days from last FU contact 
±3 days 
1. Refer to Section 8.1.1.1 for details on the surveillance period and methods. 
2. Once an ARI event has ended, the scheduled surveillance contacts should resume for that participant. The first 
surveillance contact should be planned within maximum 14 days after the last ARI follow-up contact during the 
RSV seasons and within maximum 30 days after the last ARI follow-up contact during the inter-season periods. 
3. For logistical reasons, sites may pre-define the schedule for performing surveillance contacts. In case the site staff 
reaches the participant outside the schedule, the site may resume to the pre-defined schedule for the next contact. 
4. ARI onset (Day 1) is defined as the first day when the study participant presents at least 2 concomitant ARI 
symptoms/signs meeting the ARI case definition (see Table 10 in Section 4.2.1). 
5. In special circumstances (for example in case of suspected COVID-19 infection and pending COVID-19 test result, 
or self-quarantine) and if it is not possible to perform the ARI visit within 6 days after ARI onset (i.e., within Day 3 to 
Day 7), then the interval for this visit may be extended up to maximum 14 days after ARI onset (i.e., until Day 15). 
6. If the ARI event was still ongoing at the first ARI follow-up contact (Day 15), an ARI closure contact should be done 
approximately 28 days after ARI onset. These contacts can be done via phone calls or visit to the LTCF. 
7. Only applicable for participants with ARI/complications(s) lasting beyond the ARI closure contact. 
2. 
INTRODUCTION 
2.1. 
Study rationale (Amended, 12 July 2023) 
GSK has developed a new RSVPreF3 OA vaccine against RSV-associated (subtypes A 
and B) disease in adults ≥ 60 YOA. 
The purpose of the current study is to demonstrate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RT-PCR-confirmed LRTD caused by RSV A 
and/or B in adults ≥ 60 YOA, following a single dose of the RSVPreF3 OA vaccine and 
following annual revaccination. The vaccine cross-protection against RT-PCR-confirmed 
LRTD caused by human metapneumovirus (hMPV) will also be evaluated. In addition, 
the safety and immunogenicity of the vaccine will be assessed after each dose. 
The rationale for the study design is presented in Section 4.2. 
2.2. 
Background (Amended, 12 July 2023) 
RSV is a ribonucleic acid (RNA) virus of which 2 antigenically distinct subtypes exist, 
referred to as RSV A and RSV B [Borchers, 2013]. RSV is a highly contagious human 
pathogen that causes respiratory tract infections in people of all ages. In temperate 
climates throughout the world, RSV predictably causes fall-winter epidemics. In (sub) 
tropical regions, viral activity is more endemic, and outbreaks are less temporally 
focused. 

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As the global population ages, the morbidity and mortality of respiratory infections 
appear to be steadily increasing in the older adult population [Lee, 2013; Binder, 2017]. 
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 older adults (≥ 65 years) 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 older 
adults in industrialized countries; approximately 14.5% of these episodes involved a 
hospital admission [Nam, 2019]. Further information on RSV incidence and disease 
burden can be found in the Investigator’s Brochure (IB). 
Previous infection with RSV does not prevent subsequent infections. Therefore, re-
infection with RSV occurs throughout an individual’s lifetime and is common in all age 
groups [Simoes, 1999; Krilov, 2011]. Generally, these re-infections go undiagnosed 
because they usually manifest as common acute upper respiratory tract infections. 
However, in more vulnerable individuals (e.g., immunocompromised persons or older 
adults), re-infections can also lead to severe disease [Graham, 2011]. 
hMPV is an RNA pneumovirus related to RSV, sharing similar genomic/structural 
organizations and associated clinical manifestations [ICTV, 2019]. Similar to RSV, 
hMPV is a highly contagious human pathogen causing upper and lower respiratory tract 
infections in people of all ages. In older adults, clinical manifestations can be 
asymptomatic or ranging from mild upper respiratory tract infections to severe 
pneumonia [Walsh, 2008]. Older adults aged 65 years or above are at increased risk of 
severe hMPV disease and hospitalization [Falsey, 2003; Walsh, 2008; Widmer, 2012]. 
Rates of intensive care unit admissions, mechanical ventilation, length of hospital or 
intensive care unit stay were similar for hMPV, RSV and influenza infected adults [Haas, 
2013; Walsh, 2008; Widmer, 2012]. 
At the time of initiation of this study, no vaccine nor other prophylactic treatment was 
available against RSV or hMPV in older adults. Since then, GSK’s RSVPreF3 OA 
investigational vaccine was first approved for use in an adults ≥ 60 YOA in the US on 3 
May 2023, followed by the European Union on 6 June 2023. 
The RSVPreF3 OA investigational vaccine was administered for the first time to adults 
60–80 YOA according to a 0, 2-month intramuscular vaccination schedule in another 
clinical study (RSV OA=ADJ-002). The vaccine formulation and schedule used in the 
present study, i.e., RSVPreF3 recombinant antigen, 120 µg adjuvanted with AS01E as a 
single dose, was selected based on safety and immunogenicity data from the 
RSV OA=ADJ-002 study. In addition, the Phase 1 study RSV OA=ADJ-003 has been 
conducted in Japan to evaluate the safety, reactogenicity and immunogenicity of the 
RSVPreF3 OA investigational vaccine (RSVPreF3 recombinant antigen, 120 µg 
adjuvanted with AS01B) in 40 healthy ethnic Japanese adults 60-80 YOA. No safety 
concerns were identified so far. 
Please refer to the current IB for information regarding pre-clinical and clinical studies of 
the RSVPreF3 OA investigational vaccine. 

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2.3. 
Benefit/Risk assessment 
In this study, up to 12 500 participants will be exposed to at least one dose of the 
RSVPreF3 OA investigational vaccine, whereas up to 12 500 participants will receive a 
placebo (refer to Section 9.2 for more details on the number of participants to be 
enrolled). 
2.3.1. 
Risk assessment 
Information about the reasonably expected adverse events (AEs) and the known and 
expected benefits and potential risks (potential syncope, hypersensitivity) of the 
RSVPreF3 OA investigational vaccine or the adjuvant system (potential immune-
mediated diseases [pIMDs]) can be found in the IB and the Development Safety Update 
Report (DSUR). 
Intramuscular vaccination commonly precipitates a transient and self-limiting local 
inflammatory reaction. This may typically include pain at injection site, erythema and 
swelling. 
In addition to potential risks related to the vaccine, there may be risks related to the blood 
sampling planned in the study: 
• 
Pain and bruising may occur at the site where blood is drawn; as a mitigation 
strategy, a topical analgesic may be applied to the site where blood will be taken. 
• 
Syncope (fainting) can occur following or even before any blood draw as a 
psychogenic response to the needle insertion. 
For details of study procedures, dose and study design justification, refer to Sections 1.3 
and 4, respectively. 
2.3.2. 
Benefit assessment (Amended, 12 July 2023) 
At the start of this study, the efficacy of the RSVPreF3 OA investigational vaccine was 
not demonstrated yet. Hence it was unknown if the participants receiving the RSVPreF3 
OA investigational vaccine would benefit from this vaccination. Since then, the efficacy 
of RSVPreF3 OA investigational vaccine was demonstrated and the study primary 
confirmatory objective was met. One dose of RSVPreF3 OA investigational vaccine has 
shown a favorable benefit/risk profile. The vaccine was approved for use in an adults 
≥ 60 YOA in the US on 3 May 2023, followed by the European Union on 6 June 2023.  
The VE Analysis 3 data showed that revaccination administered approximately 12 
months after Dose 1 did not confer additional benefit in prevention of RSV-confirmed 
LRTD for the overall population of adults ≥ 60 YOA, while the second dose of vaccine 
has a clinically acceptable safety profile. The clinical development program will 
continue to evaluate longer term follow-up and the optimal timing for potential 
revaccination. 

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Another benefit for all study participants may include gaining of information about their 
general health status through the medical evaluations/assessments associated with this 
study (i.e., physical examination). 
2.3.3. 
Overall Benefit/Risk conclusion 
The RSVPreF3 OA investigational vaccine is in clinical development. Considering the 
measures taken to minimize the risk to participants in this study, the potential risks are 
justified by the potential benefits linked to the development of this vaccine. 
3. 
OBJECTIVES AND ENDPOINTS 
Table 8 
Study objectives and endpoints (Amended, 12 July 2023) 
Objectives 
Endpoints 
Primary 
To demonstrate the efficacy of a single dose of the 
RSVPreF3 OA investigational vaccine in the prevention of 
RSV-confirmed LRTD during the first season in adults 
≥ 60 YOA. 
Criterion: The lower limit (LL) of the 2-sided confidence 
interval (CI) for vaccine efficacy (VE) is above 20%. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*. 
Secondary 
Secondary – Efficacy 
Secondary confirmatory 
To demonstrate the efficacy of a single dose of the 
RSVPreF3 OA investigational vaccine in the prevention of 
RSV-confirmed LRTD in adults ≥ 60 YOA over several 
seasons. 
Criterion: The lower limit (LL) of the 2-sided confidence 
interval (CI) for vaccine efficacy (VE) is above 20%. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*. 
To demonstrate the efficacy of a single dose of the 
RSVPreF3 OA investigational vaccine followed by 
1 annual revaccination before Season 2 in the prevention 
of RSV-confirmed LRTD in adults ≥ 60 YOA over several 
seasons. 
Criterion: The LL of the 2-sided CI for VE is above 20%. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*. 
To demonstrate the efficacy of a single dose and 1 annual 
revaccination before Season 2 of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD for each RSV subtype (A and B) separately in 
adults ≥ 60 YOA over 3 seasons. 
Criterion: The LL of the 2-sided CI for VE is above 0%. 
First occurrence of RT-PCR-confirmed RSV-associated 
LRTD, according to the case definition*, for RSV subtype 
A and RSV subtype B separately. 
Other secondary descriptive 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD for each RSV subtype (A and B) separately in 
adults ≥ 60 YOA, following a single dose of the RSVPreF3 
OA investigational vaccine and following annual 
revaccination. 
First occurrence of RT-PCR-confirmed RSV-associated 
LRTD, according to the case definition*, for RSV subtype 
A and RSV subtype B separately. 

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Objectives 
Endpoints 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of hMPV-
confirmed LRTD in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine up to 
the end of Season 1. 
First occurrence of RT-PCR-confirmed hMPV-associated 
LRTD, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by age category, following a single dose of the 
RSVPreF3 OA investigational vaccine and following 
annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, in the 
following age categories: ≥ 65 YOA, ≥ 70 YOA and ≥ 80 
YOA. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by season in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, by 
season. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by year in adults ≥ 60 YOA, following a single dose 
of the RSVPreF3 OA investigational vaccine and following 
annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, by 
year. 
To evaluate the evolution of efficacy of a single dose of 
the RSVPreF3 OA investigational vaccine in the 
prevention of RSV-confirmed LRTD in adults ≥ 60 YOA 
over time. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD in adults ≥ 60 YOA by baseline comorbidities, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or 
B-associated LRTD according to the case definitions*, by 
baseline comorbidities. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by baseline frailty status in adults ≥ 60 YOA, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, by 
baseline frailty status. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of severe RSV-
confirmed LRTD in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated severe LRTD, according to the case 
definitions*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI in adults ≥ 60 YOA, following a single dose of the 
RSVPreF3 OA investigational vaccine and following 
annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated ARI, according to the case definition*. 

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Objectives 
Endpoints 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of any ARI and 
any LRTD in adults ≥ 60 YOA, following a single dose of 
the RSVPreF3 OA investigational vaccine and following 
annual revaccination. 
First occurrence of ARI or LRTD, according to the case 
definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of hospitalization 
due to respiratory diseases in adults ≥ 60 YOA, following 
a single dose of the RSVPreF3 OA investigational vaccine 
and following annual revaccination. 
• 
Occurrence of hospitalization due to respiratory 
diseases or due to a complication related to 
respiratory diseases during the RSV seasons† and 
during the entire follow-up.  
• 
Occurrence of hospitalization due to RSV-confirmed 
respiratory diseases or due to a complication related 
to RSV-confirmed respiratory diseases during the 
RSV seasons† and during the entire follow-up. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of complications 
related to RSV-confirmed ARI and any ARI in adults ≥ 60 
YOA, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
Occurrence of complication related to RSV-confirmed ARI 
or related to any ARI during the RSV seasons†, according 
to the case definition* and during the entire follow-up. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on lower respiratory tract 
symptoms in participants with RSV-confirmed ARI in the 
RSVPreF3 groups compared to the placebo group, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
Maximum FLU-PRO Chest score during the first 7 days 
from the onset of ARI symptoms for participants with RT-
PCR-confirmed RSV A and/or B-associated ARI. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on ARI total symptoms in 
participants with RSV-confirmed ARI in the RSVPreF3 
groups compared to the placebo group, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination. 
Estimated Least Squares mean FLU-PRO total score 
during the first 7 days from the onset of ARI symptoms for 
participants with RT-PCR-confirmed RSV A and/or B-
associated ARI. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on health utility score in 
participants with RSV-confirmed ARI in the RSVPreF3 
groups compared to the placebo group, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination. 
Estimated Least Squares mean EQ-5D utility score at the 
ARI visit for participants with RT-PCR-confirmed RSV A 
and/or B-associated ARI. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on physical functioning in 
participants with RSV-confirmed ARI in the RSVPreF3 
groups compared to the placebo group, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination. 
Estimated Least Squares mean SF-12 Physical 
Functioning score at the ARI visit for participants with RT-
PCR-confirmed RSV A and/or B-associated ARI. 
To describe RSV-confirmed ARI cases and RSV-
confirmed LRTD cases in the RSVPreF3 and Placebo 
groups. 
Descriptors of RT-PCR-confirmed RSV A and/or B ARI 
and LRTD cases, including duration of episodes, reported 
symptoms/signs and respiratory tract infection severity. 
Secondary – Immunogenicity 
To evaluate the humoral immune response to the 
RSVPreF3 OA investigational vaccine. 
In a subset of participants, at pre-Dose 1 (Day 1), 30 days 
post-Dose 1 (Day 31), pre-Dose 2 (pre-Season 2) and 
pre-Season 3: 
• 
RSVPreF3 IgG-binding antibody concentrations. 

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Objectives 
Endpoints 
• 
Neutralizing titers against RSV A. 
• 
Neutralizing titers against RSV B. 
Secondary – Safety 
To evaluate the reactogenicity of the RSVPreF3 OA 
investigational vaccine. 
In a subset of participants, occurrence, intensity and 
duration of solicited administration site and systemic 
events with an onset during the 4-day follow-up period 
after each vaccination (i.e., the day of vaccination and 
3 subsequent days). 
To evaluate the safety of the RSVPreF3 OA 
investigational vaccine. 
In all participants: 
• 
Occurrence of unsolicited AEs with an onset during 
the 30-day follow-up period after each vaccination 
(i.e., the day of vaccination and 29 subsequent 
days). 
• 
Occurrence of all serious adverse events (SAEs) 
from the day of vaccination up to 6 months after 
each vaccination. 
• 
Occurrence of all pIMDs from the day of vaccination 
up to 6 months after each vaccination. 
• 
Occurrence of SAEs related to study vaccination 
from Day 1 up to study end. 
• 
Occurrence of pIMDs related to study vaccination 
from Day 1 up to study end. 
• 
Occurrence of any fatal SAEs from Day 1 up to 
study end. 
Tertiary 
Tertiary – Efficacy 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV and/or 
hMPV-confirmed LRTD in adults ≥ 60 YOA, following a 
single dose of the RSVPreF3 OA investigational vaccine 
and following annual revaccination. 
First occurrence of RT-PCR-confirmed RSV and/or hMPV-
associated LRTD, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of hMPV-
confirmed LRTD in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination up to the end of Season 2 
and Season 3. 
First occurrence of RT-PCR-confirmed hMPV-associated 
LRTD, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of severe hMPV-
confirmed LRTD in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination. 
First occurrence of RT-PCR-confirmed hMPV-associated 
severe LRTD, according to the case definitions*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI for each RSV subtype (A and B) separately in adults 
≥ 60 YOA, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
First occurrence of RT-PCR-confirmed RSV-associated 
ARI, according to the case definition*, for RSV subtype A 
and RSV subtype B separately. 

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Objectives 
Endpoints 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI by age category, following a single dose of the 
RSVPreF3 OA investigational vaccine and following 
annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated ARI, according to the case definition*, in the 
following age categories: ≥ 65 YOA, ≥ 70 YOA and ≥ 80 
YOA. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI by season, following a single dose of the RSVPreF3 
OA investigational vaccine and following annual 
revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated ARI, according to the case definition*, by 
season. 
To evaluate the evolution of efficacy of a single dose of 
the RSVPreF3 OA investigational vaccine in the 
prevention of RSV-confirmed ARI over time. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated ARI, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI in adults ≥ 60 YOA by baseline comorbidities, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
First occurrence of RT-PCR-confirmed RSV A and/or 
B-associated ARI, according to the case definitions*, by 
baseline comorbidities. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of all-cause 
mortality during the RSV seasons† in adults ≥ 60 YOA, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
Occurrence of any death during the RSV seasons†. 
To estimate the proportion of participants with > 1 case of 
ARI or LRTD by season and participants reporting 
respiratory diseases in consecutive seasons, following a 
single dose of the RSVPreF3 OA investigational vaccine 
and following annual revaccination. 
Number of participants with > 1 case of ARI, LRTD, 
RT-PCR-confirmed RSV A and/or B-associated ARI and 
RT-PCR-confirmed RSV A and/or B-associated LRTD, 
according to the case definitions* by season and in 
consecutive seasons. 
To estimate the proportion of co-infections with other viral 
pathogens for RSV-confirmed or hMPV-confirmed ARI 
cases, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
Number of participants with other viral pathogens 
(detected by RT-PCR) co-existing with RSV or hMPV 
among RT-PCR-confirmed RSV or RT-PCR-confirmed 
hMPV ARI episodes.  
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on upper respiratory tract 
symptoms in participants with RSV-confirmed ARI in the 
RSVPreF3 groups compared to the Placebo group, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
Maximum FLU-PRO upper respiratory symptom score 
during the first 7 days from the onset of ARI symptoms for 
participants with RT-PCR-confirmed RSV A and/or B-
associated ARI. 
To assess the impact of the RSVPreF3 OA investigational 
vaccine on healthcare resource utilization (HCRU) for 
participants with RSV-confirmed ARI and any ARI, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
• 
Hospitalization rate during the ARI episode for 
participants with RT-PCR-confirmed RSV A and/or 
B-associated ARI and any ARI, according to the 
case definitions*. 
• 
Antibiotic use during the ARI episode for participants 
with RT-PCR-confirmed RSV A and/or B-associated 
ARI and any ARI, according to the case definitions*. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on patient-reported severity of 
respiratory symptoms in participants with RSV-confirmed 
LRTD in the RSVPreF3 groups compared to the Placebo 
Maximum patient global impression of severity (PGI-S) 
score during the first 7 days from the onset of ARI 
symptoms for participants with RT-PCR-confirmed RSV A 
and/or B-associated LRTD. 

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Objectives 
Endpoints 
group, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination. 
Tertiary - Immunogenicity and Safety 
To assess the correlation of the humoral immune 
response to the RSVPreF3 OA investigational vaccine at 
30 days post-Dose 1 with protection against RSV disease. 
RSVPreF3 IgG-binding antibody concentrations at 
pre-Dose 1 (Day 1), 30 days post-Dose 1 (Day 31) and 
pre-Season 3** in all participants with RSV disease 
compared to a subset of controls.‡ 
To evaluate the humoral immune response to the 
RSVPreF3 OA investigational vaccine by baseline frailty 
status. 
In a subset of participants, at pre-Dose 1 (Day 1), 30 days 
post-Dose 1 (Day 31), pre-Dose 2 (pre-Season 2) and 
pre-Season 3: 
• 
RSVPreF3 IgG-binding antibody concentrations 
classified by baseline frailty score. 
• 
Neutralizing titers against RSV A classified by 
baseline frailty score. 
• 
Neutralizing titers against RSV B classified by 
baseline frailty score. 
To further characterize immune responses to the 
RSVPreF3 OA investigational vaccine and/or the 
pathogens under study. 
Any further exploratory immunology to investigate RSV 
and/or hMPV-related immune responses. 
To evaluate the reactogenicity of the RSVPreF3 OA 
investigational vaccine by baseline frailty status. 
In a subset of participants, occurrence, intensity and 
duration of solicited administration site and systemic 
events with an onset during the 4-day follow-up period 
after the first vaccination (i.e., the day of vaccination and 
3 subsequent days) classified by baseline frailty score. 
* Case definitions are described in Section 4.2.1. 
† The RSV seasons defined for this study are from 1 October to 30 April in NH and from 1 March to 30 September in 
SH. 
‡ Additional testing such as but not limited to neutralization assay(s) and systems serology testing might be performed 
on the same subset of participants to investigate a correlate of protection. 
** Blood sample at pre-Season 3 is applicable for all participants in the NH who have their Visit 5NH after the 
approval of the current Protocol Amendment 5. 

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4. 
STUDY DESIGN  
4.1. 
Overall design (Amended, 12 July 2023) 
Figure 1 
Study design overview for (Amended, 12 July 2023) 
 
Note: For simplicity, the randomization in this figure is presented as 1:1 between the RSVPreF3 OA vaccine and the 
placebo group. Participants will be randomized with a ratio of 1:1:1:3 to 1 of 4 study groups (RSVPreF3 Lot 1/2/3 
versus Placebo) for Part 1 of the study and a ratio of 1:1 to 1 of 2 study groups (RSVPreF3 Lot 4 versus Placebo) for 
Part 2 before Season 1 (refer to the experimental design below and Section 6.3.2 for details).  
Note: If following the sample size re-assessment an additional cohort needs to be enrolled before the next season in 
NH (see Section 9.2.3), the participants enrolled in this cohort will follow the same study design as indicated in this 
figure. 

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RSV_annual: RSVPreF3 OA annual revaccinations group 
RSV_1dose: RSVPreF3 OA single vaccination group 
AE: adverse event; ARI: acute respiratory illness; NH: Northern hemisphere; SH: Southern hemisphere; 
pIMD: potential immune-mediated disease; RSV: respiratory syncytial virus; SAE: serious adverse event 
* Dose 3 only applies to participants in NH. 
† Depending on the time of enrollment, Visit 1 and Visit 2 in NH can take place during Season 1. 
** Contacts 1 and 3 must not be performed before the 6-month post-vaccination time point to allow collection of safety 
data up to at least 6 months after each vaccination for each participant. These contacts can be combined with another 
contact or visit. 
§ Visit 2b in SH (Pre-Season 1 visit) should be performed at the earliest 3 months before the start of Season 1 in SH. 
This Visit 2b should not be performed for participants that have their Visit 2 planned within 3 months before the start of 
Season 1. For all participants in SH that have their Visit 2 more than 3 months before the start of Season 1, Visit 2b 
should be planned as a stand-alone visit. 
*** Blood samples should only be taken from participants in the reactogenicity and immunogenicity subset in Part 1.‡ 
All SAEs related to study participation, or a GSK concomitant medication/vaccine are to be recorded from the time the 
participant consents to participate in the study. All other SAEs are to be reported after the first study vaccine 
administration. 
†† Some participants in the NH may have Visit 5NH before the approval of the current Protocol Amendment 5. 
These participants should receive Dose 3 pre-Season 3 and all subsequent study procedures should be 
performed as planned in Protocol Amendment 4. Please refer to the Table 1 for the details of the procedures to 
be performed in participants that have their Visit 5NH before the approval of this amendment.  
**** For participants in the NH who have their Visit 5NH before the approval of the current Protocol 
Amendment 5, a blood sample should be taken only if the participant is in the reactogenicity and 
immunogenicity subset. Please refer to the Table 1 for the details of the procedures to be performed in 
participants that have their Visit 5NH before the approval of this amendment. 
• 
Type of study: self-contained. 
• 
Experimental design: Phase 3, randomized, observer-blind, placebo-controlled 
multi-country study with 2 parts (see Figure 1): 
− 
Part 1 with 4 parallel groups randomized with a ratio of 1:1:1:3 (RSVPreF3 Lot 
1/2/3 versus Placebo) before Season 1. 
− 
Part 2 with 2 parallel groups randomized with a ratio of 1:1 (RSVPreF3 Lot 4 
versus Placebo) before Season 1, which will be initiated when the vaccine lots 
for Part 1 are no longer available at the study sites. 
Each of the 4 RSVPreF3 groups in both parts will be randomized before Season 2 
into 2 sub-groups (RSV_annual group and RSV_1dose group) with a 1:1 ratio. The 
RSV_annual group will receive an additional dose of RSVPreF3 OA vaccine before 
each subsequent season while the RSV_1dose group will receive 1 dose of placebo at 
the same timepoints. To maintain the study blind, participants who were initially 
randomized to the Placebo group will also receive additional doses of placebo at the 
same timepoints. 
At the time of pre-Season 3 (Visit 5NH), participants in the NH who will have their 
Visit 5NH before approval of the current Protocol Amendment 5, will receive the 
study intervention as planned according to their group allocation. Participants 
having their Visit 5NH after approval of the current Protocol Amendment 5 will 
not receive any study intervention at pre-Season 3 visit (Visit 5NH). 
• 
Randomization for the additional cohort enrolled in NH after sample size 
re-assessment: If following sample size re-assessment an additional cohort needs to 
be enrolled before the next season in NH (see Section 9.2.3), the participants in this 
additional cohort will be enrolled in 3 study groups (RSV_annual group, RSV_1dose 

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group and Placebo group) according to a 1:1:2 randomization ratio and will follow 
the same study design as indicated in Figure 1. They will have a blood sampling at 
Visit 1 and Visit 2 as for all study participants. There will be no subset for 
immunogenicity and reactogenicity for this cohort. 
Note: Blood sample at Visit 5NH is not applicable for this cohort because it was 
never enrolled. 
• 
Duration of the study: 
− 
Approximately 3 years per participant in NH (up to 3 consecutive RSV seasons). 
− 
Approximately 2.5 to 3 years per participant in SH (up to at least 2 consecutive 
RSV seasons). 
• 
Primary completion date: Case-driven: Last contact point at which a data for 
primary VE Analysis 1 will be collected. 
• 
Control: placebo saline solution. 
• 
Blinding: observer-blind. Refer to Section 6.3.5 for details. 
• 
Data collection: standardized electronic Case Report Form (eCRF). Solicited events 
and unsolicited AEs will be collected using a paper diary. 
• 
Study groups: Refer to Figure 1 and Table 9 for an overview of the study groups. 
 

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Table 9 
Study groups, intervention and blinding foreseen in the study (Amended, 12 July 2023) 
Study groups 
Number of participants* 
Age 
Intervention 
Blinding 
NH 
SH 
Total 
Visit 1 → Visit 3 
(Observer-blind) 
Visit 3 → 
Visit 7NH/Visit 5SH 
(Observer-blind) 
For Dose 1 
RSVPreF3_L1 
Up to 11 500** 
750-1 000** 
Up to 12 500** 
≥ 60 years 
RSVPreF3 OA investigational vaccine L1 
X 
 
RSVPreF3_L2 
RSVPreF3 OA investigational vaccine L2 
X 
 
RSVPreF3_L3 
RSVPreF3 OA investigational vaccine L3 
X 
 
RSVPreF3_L4 
RSVPreF3 OA investigational vaccine L4*** 
X 
 
Placebo 
Up to 11 500 
750-1 000 
Up to 12 500 
≥ 60 years 
Placebo 
X 
 
For annual revaccination 
RSV_L1_annual 
Up to 5 750 
375-500 
Up to 6 250 
≥ 60 years 
RSVPreF3 OA investigational vaccine 
 
X 
RSV_L2_annual 
 
X 
RSV_L3_annual 
 
X 
RSV_L4_annual 
 
X 
RSV_L1_1dose 
Up to 5 750 
375-500 
Up to 6 250 
≥ 60 years 
Placebo 
 
X 
RSV_L2_1dose 
 
X 
RSV_L3_1dose 
 
X 
RSV_L4_1dose 
 
X 
Placebo 
Up to 11 500 
750-1 000 
Up to 12 500 
≥ 60 years 
Placebo 
 
X 
Total 
Up to 23 000 
1 500-2 000 
Up to 25 000 
 
 
 
 
NH: Northern hemisphere; SH: Southern hemisphere; L1: Lot 1; L2: Lot 2; L3: Lot 3; L4: Lot 4 
* Numbers are approximate (see Section 9.2.1 for details on the sample size calculation). 
** Participants enrolled in the RSVPreF3 groups will receive vaccine Lots 1, 2 or 3. When these lots are no longer available at the site, the site will switch to Lot 4. This is applicable in 
both SH and NH. 
*** Re-supply lot for Part 2. 
 

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• 
Vaccination schedule: First dose of study vaccine (RSVPreF3 OA investigational 
vaccine or placebo) on Day 1 followed by annual revaccination of study vaccine 
(RSVPreF3 OA investigational vaccine or placebo) as follows: 
− 
Participants from the NH who will have their Visit 5NH before the approval of 
the current Protocol Amendment 5, will receive 2 additional doses, 1 before 
Season 2 and 1 before Season 3. 
− 
Participants from the NH who will have their Visit 5NH after the approval of 
the current Protocol Amendment 5, will not receive any study intervention at 
pre-Season 3 visit (Visit 5NH). These participants had received 1 additional 
dose before Season 2.  
− 
Participants from the SH will receive 1 additional dose before Season 2. 
• 
Safety monitoring: An IDMC, in addition to the existing GSK’s Safety Review 
Team (SRT), will oversee the safety of the study participants and study conduct 
(refer to Section 8.2.3). 
• 
ARI surveillance: Surveillance for ARI detection will be carried out during the 
entire study, via spontaneous reporting by the study participant (starting on the first 
vaccination day* [Visit 1]) and via scheduled site staff contacts (starting from Visit 2 
onwards) with different frequencies of contact during the RSV seasons and the inter-
season periods (refer to Section 8.1.1). Swab samples will be taken in all participants 
meeting pre-specified criteria for ARI case definition (refer to Section 4.2.1). 
Diagnosis and treatment of each ARI should be performed according to the local 
standard of care. 
* For detailed information on activities involved in ARI surveillance, refer to Table 
4. 
4.1.1. 
Overview of the recruitment plan 
The aim is to enroll between at least 16 000 and up to 23 000 participants in the NH and 
between 1 500 to 2 000 participants in the SH with a randomization ratio of 1:1:1:3 for 
Part 1 of the study (RSVPreF3 Lot 1/2/3 versus Placebo) and a randomization ratio of 1:1 
for Part 2 (RSVPreF3 Lot 4 versus Placebo) before Season 1. Refer to Section 9.2.1 for 
details on the sample size calculation. 
The recruitment plan may be adapted based on the actual number of participants enrolled 
in each hemisphere or within each sex. In case a hemisphere or country would fall behind 
in participant recruitment (in a specific age group or overall), a redistribution of the 
enrollment target per hemisphere/country may be made to allow the other participating 
country(ies) to enroll additional participants in an effort to ensure full and timely 
enrollment of the overall targeted number of participants specified in this protocol. 
The procedures for participants identification/recruitment have to be approved by the 
Independent Ethics Committee (IEC)/Institutional Review Board (IRB) together with the 
material intended for participants identification/recruitment and participants use. Refer to 
the Study Procedures Manual (SPM) for additional details. 

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4.1.2. 
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 40% of participants 60-69 YOA, approximately 30% of participants 
70-79 YOA and approximately 10% of participants ≥ 80 YOA. The remaining 20% 
can be distributed freely across the 3 age categories. 
• 
Approximately 40% of participants from each sex; the remaining 20% can be 
distributed freely between the 2 sexes. 
Participants from both community dwelling (CD) and long-term care facilities (LTCFs) 
may be enrolled. 
Allocation of participants to the reactogenicity and immunogenicity subset: 
Participants contributing to the reactogenicity and immunogenicity subset will be 
recruited from a selected number of countries and selected number of sites in Part 1. In 
the selected sites, the investigator will allocate the first participants in each age category 
to the reactogenicity and immunogenicity subset until the allocated target is reached. 
4.2. 
Scientific rationale for study design (Amended, 12 July 
2023) 
The study is designed as a Phase 3, observer-blind, placebo-controlled study enrolling 
adults ≥ 60 YOA, who will be followed up for 3 consecutive RSV seasons in the NH and 
at least 2 consecutive RSV seasons in the SH. The study population will be representative 
of the global population beyond 60 YOA. Older adults living in the community (CD 
participants) and LTCFs residents (LTCF participants) with medically stable conditions 
may be enrolled. Please refer to Section 10.5.2 (Glossary of terms) for the definition of 
CD participants and LTCF. 
There is uncertainty about the persistence of the immune response to the RSVPreF3 OA 
investigational vaccine administered as a single dose and the level of immune response 
that may be required for protection. In addition, older adults may require repeated dosing 
to maintain protection against the RSV disease over several seasons. This study has been 
designed to consider the possibility of a decline in the immune response and level of 
protection through the assessment of annual revaccination doses administered before the 
start of each season. 
For that reason, the study will not only evaluate the efficacy, immunogenicity, safety and 
reactogenicity profile following a single dose vaccination regimen of the RSVPreF3 OA 
investigational vaccine in adults ≥60 YOA, but will also evaluate the efficacy, safety and 
reactogenicity of additional vaccine doses through annual revaccination. The RSV_1dose 
group will allow the evaluation of multi-year protection of a single dose of the RSVPreF3 
OA vaccine and the RSV_annual group will allow the evaluation of VE of annual 
revaccination doses of the RSVPreF3 OA vaccine. 

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The results of VE Analysis 3 evaluating the efficacy and safety up to the end of 
Season 2 in the NH, showed that 1 dose of the RSVPreF3 OA vaccine is efficacious 
against RSV-LRTD and severe LRTD at least over 2 RSV seasons, and that a second 
dose of the study vaccine administered before Season 2 did not confer additional 
benefit in prevention of RSV-confirmed LRTD. Safety and reactogenicity data post-
Dose 2 were consistent with previous results from the Phase 3 program. 
Based on this observation, the study design was modified to remove the next annual 
revaccination dose of study vaccine (Dose 3 pre-Season 3) in the NH. The clinical 
development program will continue to evaluate long term follow-up and the optimal 
timing for revaccination. 
4.2.1. 
Case definitions for evaluation of vaccine efficacy 
All participants reporting at least 2 ARI symptoms/signs meeting the ARI case definition 
(see Table 10) will be followed up for ARI assessment. Diagnosis and treatment of each 
ARI should be performed according to the local standard of care. RT-PCR testing for 
RSV/hMPV will be performed at GSK clinical laboratory or designated laboratory. 
Therefore, all participants with ARI will be requested to follow all study procedures and 
study contacts defined for the ARI surveillance (i.e., reporting of ARI symptoms/signs, 
ARI visit and follow-up contacts, completion of QoL questionnaires, etc.). 
Table 10 
Case definitions for evaluation of vaccine efficacy 
Endpoint 
Case definition 
ARI  
(Trigger for swabbing) 
Presence of: 
• at least 2 respiratory symptoms/signs for at least 24 hours 
OR 
• at least 1 respiratory symptom/sign + 1 systemic symptom/sign for at least 24 hours 
Respiratory symptoms and signs 
- Nasal congestion/rhinorrhea 
- Sore throat 
- New or increased sputum 
- New or increased cough 
- New or increased dyspnea (shortness of 
breath) 
- New or increased wheezing3 
- New or increased crackles/ronchi4 based on 
chest auscultation 
- Respiratory rate ≥ 20 respirations/min4 
- Low or decreased oxygen saturation 
(= O2 saturation <95% or ≤90 % if pre-season 
baseline is <95%)4 
- Need for oxygen supplementation4 
Systemic symptoms and signs 
- Fever1/feverishness2 
- Fatigue 
- Body aches 
- Headache 
- Decreased appetite 
RT-PCR-confirmed RSV-
ARI or hMPV-ARI5 
An event meeting the case definition of ARI with at least one RSV-positive swab or at 
least one hMPV-positive swab detected by RT-PCR.6 

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Endpoint 
Case definition 
LRTD 
Presence of: 
• at least 2 lower respiratory symptoms/signs for at least 24 hours including at least 
1 lower respiratory SIGN 
OR 
• at least 3 lower respiratory symptoms for at least 24 hours 
Lower respiratory symptoms 
- New or increased sputum 
- New or increased cough 
- New or increased dyspnea 
(shortness of breath) 
Lower respiratory signs 
- New or increased wheezing3 
- New or increased crackles/ronchi4 based on chest 
auscultation 
- Respiratory rate ≥ 20 respirations/min4 
- Low or decreased oxygen saturation (= O2 saturation 
<95% or ≤90 % if pre-season baseline is <95%)4 
- Need for oxygen supplementation4 
RT-PCR-confirmed RSV-
LRTD or hMPV-LRTD5 
An event meeting the case definition of LRTD with at least one RSV-positive swab or at 
least one hMPV-positive swab detected by RT-PCR.6 
RT-PCR-confirmed 
severe RSV LRTD or 
severe hMPV LRTD – 
Definition 1 “Clinical 
symptomology” 5 
Presence of a LRTD with at least one of the following criteria: 
• 
at least 2 lower respiratory SIGNS 
• 
an LRTD episode assessed as ‘severe’ by the investigator7 
AND 
• with at least one RSV-positive or hMPV-positive swab detected by RT-PCR 
Lower respiratory signs 
- New or increased wheezing3 
- New or increased crackles/ronchi4 based on chest auscultation 
- Respiratory rate ≥ 20 respirations/min4 
- Low or decreased oxygen saturation (= O2 saturation <95% or ≤90 % if pre-season 
baseline is <95%)4 
- Need for oxygen supplementation4 
RT-PCR-confirmed 
severe RSV LRTD or 
severe hMPV LRTD – 
Definition 2 “Supportive 
therapy” 5 
Presence of a LRTD with at least one of the following criteria8: 
• 
Need for oxygen supplementation4 
• 
Need for positive airway pressure therapy (e.g., CPAP) 
• 
Need for other types of mechanical ventilation 
AND 
• 
with at least one RSV-positive or hMPV-positive swab detected by RT-PCR 
ARI: acute respiratory illness; LRTD: lower respiratory tract disease; RSV: respiratory syncytial virus 
hMPV: human metapneumovirus; RT-PCR: reverse transcription polymerase chain reaction 
1. Fever is defined as a temperature ≥ 38.0°C/100.4°F by any route. 
2. Feverishness is defined as the feeling of having fever without objective measurement. 
3. Reported by study participant or investigator. 
4. Reported by investigator. 
5. Throat and/or nasal swab samples collected at ARI visits for RT-PCR testing will be collected within 6 days after 
ARI onset (i.e., up to Day 7). In special circumstances (for example, in case of suspected COVID-19 infection and 
pending COVID-19 test result, or self-quarantine) and if it is not possible to perform the ARI visit within 6 days after 
ARI onset (i.e., within Day 3 to Day 7), then the interval for this visit and the site swab collection may be extended 
up to maximum 14 days after ARI onset (i.e., until Day 15). 
6. Refer to Section 9.4.1.2 for details on the counting of cases that are positive for both RSV and hMPV. 
7. The investigator will grade each ARI as mild, moderate or severe based on the grading scale presented in Table 
16. 
8. In case the participant was already receiving any of these for treating/controlling any pre-existing condition, any 
significant change or adaptation in the used therapy should be taken into account. 

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4.2.2. 
Rationale for the use of placebo (Amended, 12 July 2023) 
As there was no licensed RSV vaccine available at the time of initiation of this study, a 
placebo group (receiving saline solution) is used as control for the efficacy, 
safety/reactogenicity and immunogenicity assessments. 
4.2.3. 
Rationale for study blinding 
Given the difference in reconstitution and visual appearance of the RSVPreF3 OA 
investigational vaccine and the saline solution used as placebo, double blinding is not 
possible, and the study will be conducted in an observer-blind manner. Please refer to 
Section 10.5.2 (Glossary of Terms) for the definition of observer-blind. 
Further information on blinding and unblinding is provided in Section 6.3.5. 
4.3. 
Justification for dose  
Based on the results up to 1-month post-Dose 2 from study RSV OA=ADJ-002, a single 
dose regimen (0.5 mL) and the 120 µg RSVPreF3/AS01E formulation were selected for 
further evaluation in the Phase 3 clinical program. The RSV OA=ADJ-002 study was 
designed to assess the immunogenicity of a 2-dose AS01-adjuvanted or unadjuvanted 
vaccine administered according to a 0-, 2-month schedule with the aim to maximize the 
immune response against RSV and vaccine efficacy over several seasons. Based on the 
data from clinical development programs for AS01-adjuvanted protein antigen vaccines 
in OA, such as Shingrix and the chronic obstructive pulmonary disease (COPD) 
investigational vaccine, it was expected that immunological responses would reach 
higher levels 1-month post-Dose 2 as compared with 1-month post-Dose 1. However, the 
RSV OA=ADJ-002 results demonstrated that the second dose given 2 months after the 
first dose had no added value in terms of humoral and/or cellular immune responses. The 
humoral response, both in terms of RSV A neutralizing geometric mean titers (GMTs) 
and RSVPreF3-binding IgG geometric mean concentrations (GMCs), peaked 1 month 
after the first dose, and the second dose did not increase the level observed after first 
dose. For the rationale of the annual revaccinations, please refer to Section 4.2. 
The results from study RSV OA=ADJ-002 demonstrated statistically significant 
superiority of the 120 µg formulations in terms of RSV A neutralizing titers over at least 
one of the 30 µg and 60 µg formulations with the same adjuvant content or unadjuvanted. 
An increase in the RSVPreF3-binding IgG GMCs and fold increase over baseline was 
also observed with increase in antigen dose from 30 µg to 120 µg. The data demonstrated 
an immunologic benefit of any AS01E or AS01B formulations over unadjuvanted 
formulations in terms of frequency of RSVPreF3-specific CD4+ T cells expressing at 
least 2 markers. Importantly, despite lower baseline observed in OA, the AS01-
containing formulations induced CD4+ T cells frequencies at a close or similar level as in 
Young Adults, that is not observed with the unadjuvanted formulations. 
There was no safety concern detected in unadjuvanted groups to be linked to the 
RSVPreF3 antigen assessed for the first time in OA. The acceptable safety/reactogenicity 
profile in all 120 µg groups, together with the immunological benefit demonstrated for 
the 120 µg antigen dose, supports the selection of a 120 µg based formulation. The 

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results also showed that all the AS01-adjuvanted formulations evaluated are considered 
to have a clinically acceptable safety profile. The AS01-adjuvanted formulation with the 
lowest reactogenicity profile, i.e., the AS01E-based formulation, was selected. The 
immunological response observed after 1 vaccine dose of the AS01E-based formulation is 
considered adequate for a RSVPreF3 OA candidate vaccine. 
4.4. 
End of Study definition 
A participant is considered to have completed the study if he/she returns for the last visit 
or is available for the last scheduled procedure/contact as described in the protocol. 
End of Study (EoS): Release of the last testing results of samples collected at the last ARI 
visit. In these cases, EoS must be achieved no later than 8 months after Last Participant 
Last Visit (Visit 7NH/Visit 5SH). 
5. 
STUDY POPULATION 
5.1. 
Inclusion criteria for enrollment 
Adherence to these criteria as specified in the protocol is essential. Inclusion criteria 
deviations are not allowed because they can jeopardize the scientific integrity or 
regulatory acceptability of the study or participant safety. 
All participants must satisfy ALL of the following criteria at study entry: 
• 
Male or female participants ≥ 60 YOA at the time of first vaccination, who live in 
the community (CD participants) or in a LTCF (LTCF participants). 
Please refer to Section 10.5.2 (Glossary of Terms) for the definition of CD 
participants and LTCF. 
• 
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 and questionnaires, 
attend regular phone calls/study site visits, perform self-swabbing, ability to access 
and utilize a phone or other electronic communications). 
Note: In case of physical incapacity that would preclude the self-completion of the 
diary cards and/or questionnaires, 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 or in the LTCF). 
However, at no time, the site staff or caregiver will evaluate the participant’s health 
status while answering diaries and/or questionnaires or make decisions on behalf of 
the participant. Refer to Section 10.5.2 for the definition of caregiver. 
• 
Written or witnessed informed consent obtained from the participant prior to 
performance of any study specific procedure. 
• 
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 
specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to 
participate in this study if considered by the investigator as medically stable. 

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5.2. 
Exclusion criteria for enrollment 
Adherence to criteria specified in the protocol is essential. Exclusion criteria deviations 
are not allowed because they can potentially jeopardize the scientific integrity or 
regulatory acceptability of the study or safety of the participant. 
The following criteria should be checked at the time of study entry. The potential 
participant MUST NOT be included in the study if ANY exclusion criterion applies: 
5.2.1. 
Medical conditions 
• 
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). 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccine. 
• 
Hypersensitivity to latex. 
• 
Serious or unstable chronic illness. 
• 
Any history of dementia or any medical condition that moderately or severely 
impairs cognition. 
Note: If deemed necessary for clinical evaluation, the investigator can use tools such 
as Mini-Mental State Exam (MMSE), Mini-Cog or Montreal Cognitive Assessment 
(MoCA) to determine cognition levels of the participant. 
• 
Recurrent or un-controlled neurological disorders or seizures. Participants with 
medically-controlled active or chronic neurological diseases can be enrolled in the 
study as per investigator assessment, provided that their condition will allow them to 
comply with the requirements of the protocol (e.g., completion of the diary cards and 
questionnaires, attend regular phone calls/study site visits, perform self-swabbing). 
• 
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 to less than 3 years). 
• 
Any medical condition that in the judgment of the investigator would make 
intramuscular injection unsafe. 
5.2.2. 
Prior/Concomitant therapy 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study vaccine during the period beginning 30 days before the 
first study vaccine administration, or planned use during the study period. 
• 
Planned or actual administration of a vaccine not foreseen by the study protocol in 
the period starting 30 days before each dose and ending 30 days after each dose of 

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study vaccine administration, with the exception of inactivated and subunit influenza 
vaccines which can be administered up to 14 days before or from 14 days after each 
study vaccination. 
Note: In case an emergency mass vaccination for an unforeseen public health threat 
(e.g.: a pandemic) is recommended and/or organized by the public health 
authorities, outside the routine immunization program, the time period described 
above can be reduced if necessary for that vaccine provided it is used according to 
the local governmental recommendations and that the Sponsor is notified 
accordingly. 
• 
Previous vaccination with an RSV vaccine. 
• 
Administration of long-acting immune-modifying drugs or planned administration at 
any time during the study period (e.g., infliximab). 
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 90 days before the first study vaccine administration or 
planned administration during the study period. 
• 
Chronic administration (defined as more than 14 consecutive days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 
90 days prior to the first study vaccine administration or planned administration 
during the study period. For corticosteroids, this will mean prednisone ≥ 20 mg/day, 
or equivalent. Inhaled and topical steroids are allowed. 
5.2.3. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or invasive medical device). Refer to 
Section 10.5.2 for the definition of invasive medical device. 
5.2.4. 
Other exclusions 
• 
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. 
• 
Bedridden participants. 
• 
Planned move during the study period that will prohibit participating in the study 
until study end. This includes: 
− 
Planned move during the study period to another LTCF that will prohibit 
participation in the study until study end. 
− 
Planned move from the community to a LTCF that will prohibit participation in 
the study until study end. 
• 
Participation of any study personnel or their immediate dependants, family, or 
household members. 

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• 
Planned leave or holiday of 4 consecutive weeks or more during the RSV seasons* 
covered by the study, that would prohibit the reporting of ARI cases and attendance 
to ARI visit. 
*RSV seasons are from 1 October to 30 April in NH and from 1 March to 
30 September in SH. 
5.3. 
Caregiver support 
Study participants may decide to assign a caregiver to help them fulfilling the study 
procedures. Please refer to Section 10.5.2 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’s necessary. Each caregiver should receive the caregiver information 
letter before providing support to the study participant. 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 (for 
example in LTCF setting). 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 study staff, planning study visits, 
transcribing responses to questionnaires and diaries, performing the nasal swab, 
transportation to and from the study site, etc. However, at no time, the caregiver should 
evaluate the participant’s health status while answering diaries and/or questionnaires or 
make decisions on behalf of the participant. At the time of recruitment, the study staff 
should inform the participant of the possibility to appoint a caregiver. Then, at each study 
visit with the exception of the end of study visits (Visit 7NH/Visit 5SH), the site staff 
should check with the participant if he/she wishes to appoint a caregiver or if there were 
or will be changes in caregiver. 
Please refer to the SPM for additional information on the appointment of a caregiver. 
5.4. 
Screen failures 
Not applicable. 
6. 
STUDY INTERVENTION 
A ‘study intervention’ is defined as a set of investigational or marketed product(s) or 
placebo intended to be administered to a participant during the study. 
Refer to the SPM for additional details. 

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6.1. 
Study interventions administered (Amended, 12 July 2023) 
After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine will be prepared and administered as shown in Table 11 for Dose 1 and Table 12 
for the annual revaccination. Refer to Section 4.1 for the schedule of vaccine 
administration. 
Note that the RSVPreF3 OA investigational vaccine must be reconstituted before 
administration. Refer to the SPM for instructions on study vaccine reconstitution. 
The participants must be observed closely for at least 30 minutes after the administration 
of the vaccine. Appropriate medical treatment must be readily available during the 
observation period in case of anaphylaxis and/or syncope. 
For Dose 1: 
The RSVPreF3 study groups will receive adjuvanted vaccine consisting of unique 
combinations of RSVPreF3 antigen lots, i.e., Lot 1, Lot 2, Lot 3 or Lot 4, and 
extemporaneously reconstituted with AS01E adjuvant lots, i.e., Lot A, Lot B, Lot C and 
Lot D. It will result in 4 unique combinations. Before Season 1 in Part 1, the first 
3 unique combinations (Lot 1/Lot A, Lot 2/Lot B, Lot 3/Lot C) will be assigned 
randomly to the participants in the first 3 RSVPreF3 OA investigational vaccine lot 
groups. Before Season 1 in Part 2, the RSVPreF3 group will receive the 4th unique 
combination (Lot 4/Lot D). Refer to Section 4.1 for details on the study design and 
Section 6.3.2 for details on the randomization. 
For the annual revaccination: 
The RSV_annual group will receive an additional dose of RSVPreF3 OA vaccine before 
each subsequent RSV season while the RSV_1dose and Placebo groups will receive 1 
dose of placebo at the same timepoints*. Refer to Section 4.1 for details on the study 
design. 
* Participants in the NH who will have their Visit 5NH after the approval of the 
current Protocol Amendment 5 will not receive any study intervention at pre-Season 3 
visit (Visit 5NH). 

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Table 11 
Study interventions administered for Dose 1 
Study intervention 
name 
RSVPreF3 OA interventional 
vaccine Lot 1 
RSVPreF3 OA interventional 
vaccine Lot 2 
RSVPreF3 OA interventional 
vaccine Lot 3 
RSVPreF3 OA interventional 
vaccine Lot 4† 
Placebo 
Formulation 
RSVPreF3 (120 µg) Lot 1 
RSVPreF3 (120 µg) Lot 2 
RSVPreF3 (120 µg) Lot 3 
RSVPreF3 (120 µg) Lot 4 
NaCl 
AS01E Lot A: 
QS-21* (25 µg), MPL 
(25 µg), liposomes; Water for 
injections q.s. 0.5 mL 
AS01E Lot B: 
QS-21* (25 µg), MPL 
(25 µg), liposomes; Water for 
injections q.s. 0.5 mL 
AS01E Lot C: 
QS-21* (25 µg), MPL 
(25 µg), liposomes; Water for 
injections q.s. 0.5 mL 
AS01E Lot D: 
QS-21* (25 µg), MPL 
(25 µg), liposomes; Water for 
injections q.s. 0.5 mL 
Presentation 
RSVPreF3: Vial; Powder for 
suspension for injection 
RSVPreF3: Vial; Powder for 
suspension for injection 
RSVPreF3: Vial; Powder for 
suspension for injection 
RSVPreF3: Vial; Powder for 
suspension for injection 
Syringe 
AS01E: Vial; Suspension for 
injection 
AS01E: Vial; Suspension for 
injection 
AS01E: Vial; Suspension for 
injection 
AS01E: Vial; Suspension for 
injection 
Route of administration 
IM 
IM 
IM 
IM 
IM 
Administration site 
Location 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Laterality** 
Non-dominant 
Non-dominant 
Non-dominant 
Non-dominant 
Non-dominant 
Number of doses to be 
administered for Dose 1 
1 
1 
1 
1 
1 
Volume to be 
administered*** 
0.5 mL 
0.5 mL 
0.5 mL 
0.5 mL 
0.7 mL**** 
Packaging, labeling and 
TM 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for more details 
Refer to SPM for 
more details 
Manufacturer 
GSK 
GSK 
GSK 
GSK 
GSK 
IM: Intramuscular; SPM: Study Procedures Manual 
† Part 2 with the RSVPreF3 OA interventional vaccine Lot 4 will be initiated when the vaccine Lots 1/2/3 for Part 1 are no longer available at the study sites. 
*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 vaccine in the non-dominant arm, an injection in the dominant arm may be 
performed. 
*** Refer to the SPM for reconstitution guidance. 
**** The volume of the saline pre-filled syringe may be between 0.6 mL and 0.8 mL. The full volume is to be injected. 
 

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Table 12 
Study interventions administered for annual revaccination 
(Amended, 12 July 2023) 
Study intervention name 
RSVPreF3 OA interventional 
vaccine revaccination lot 
Placebo 
Formulation 
RSVPreF3 (120 µg) revaccination lot 
NaCl 
AS01E revaccination lot: 
QS-21* (25 µg), MPL (25 µg), 
liposomes; Water for injections q.s. 
0.5 mL 
Presentation 
RSVPreF3: Vial; Powder for 
suspension for injection 
Syringe 
AS01E: Vial; Suspension for injection 
Route of administration 
IM 
IM 
Location 
Deltoid 
Deltoid 
Laterality** 
Non-dominant 
Non-dominant 
Number of doses to be 
administered for annual 
revaccination  
RSV_annual group: 
2 doses in NH† 
1 dose in SH 
RSV_1dose and Placebo groups: 
2 doses in NH† 
1 dose in SH 
Volume to be administered*** 
0.5 mL 
0.7 mL**** 
Packaging, labeling and TM 
Refer to SPM for more details 
Refer to SPM for more details 
Manufacturer 
GSK 
GSK 
IM: Intramuscular; SPM: Study Procedures Manual 
*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 vaccine in the 
non-dominant arm, an injection in the dominant arm may be performed. 
*** Refer to the SPM for reconstitution guidance. 
**** The volume of the saline pre-filled syringe may be between 0.6 mL and 0.8 mL. The full volume is to be injected. 
† Participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 5, 
will not receive any study intervention at pre-Season 3 visit (Visit 5NH). 
6.2. 
Preparation/Handling/Storage/Accountability 
The study vaccine must be stored in a safe, locked place at the temperature specified on 
the vaccine label. The storage temperature should be continuously monitored with 
calibrated (if not validated) temperature monitoring device(s) and recorded. Only 
authorized study personnel should be allowed access to the study vaccine. Storage 
conditions will be assessed by a sponsor study contact during pre-study activities. Refer 
to the section on Study Supplies in the SPM for more details on storage and handling of 
the study vaccine. 
6.3. 
Measures to minimize bias: randomization and blinding 
6.3.1. 
Participant identification 
Participant identification numbers will be assigned to the participants who have 
consented to participate in the study, according to the range of participant identification 
numbers allocated to each study center. 

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6.3.2. 
Randomization to study intervention (Amended, 12 July 2023) 
For Dose 1, the randomization will be stratified by part: 
• 
In Part 1, the study participants will be randomly assigned in a 1:1:1:3 ratio to 1 of 
the 4 study groups at Visit 1 (Day 1). 
• 
In Part 2, the study participants will be randomly assigned in a 1:1 ratio to 1 of the 
2 study groups at Visit 1 (Day 1). Part 2 will be initiated when the vaccine lots for 
Part 1 are no longer available at the study sites. 
To allow GSK to take advantage of greater rates of recruitment in this multi-center study 
and to thus reduce the overall study recruitment period, an over-randomization of 
supplies will be prepared. 
At Visit 3 (pre-Season 2), all participants who received 1 of the RSVPreF3 vaccine lots 
will be re-randomized in a 1:1 ratio into 2 sub-groups (RSV_annual group and 
RSV_1dose group) to receive annual revaccination (Dose 2 and Dose 3* in NH and Dose 
2 in SH). 
* Participants in the NH who will have their Visit 5NH after the approval of the 
current Protocol Amendment 5 will not receive any study intervention at pre-Season 3 
visit (Visit 5NH). 
The randomization of supplies within blocks will be performed at GSK, using MATerial 
EXcellence (MAtEx), a program developed for use in Statistical Analysis System (SAS) 
(Cary, NC, United States [US]) by GSK. Entire blocks will be shipped to the study 
centers/warehouse(s). 
6.3.3. 
Intervention allocation to the participant 
An automated internet-based system (Source data Base for Internet Randomization 
[SBIR]) will be used for randomization and for identification of intervention material. 
For Dose 1 in Part 1, the system’s randomization algorithm will use a stratification by 
subset (participants included in reactogenicity/immunogenicity subset or not) and a 
minimization procedure accounting for center, age and region within each subset. For 
Dose 1 in Part 2, the system’s randomization algorithm will use a minimization procedure 
accounting for center, age and region. Minimization factors will have equal weight in the 
minimization algorithm. 
The intervention numbers will be allocated by component. 
Upon providing the participant identification number and the participant’s category for 
all minimization factors, the randomization system will determine the study group and 
will provide the intervention number to be used for the vaccination. 

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When all participants will be randomized for their Dose 1 in the SBIR system, a re-
randomization will be run as follows: 
• 
The randomization file related to Dose 1 will be extracted from SBIR. 
• 
A re-randomization of the participants included in the RSVPreF3 groups will be 
prepared to identify which of those participants will be allocated to the RSV_annual 
groups or to the RSV_1dose groups in a 1:1 ratio. 
This re-randomization will be accounting for:  
− 
The different stratification and minimization factors used for the initial 
randomization: part (Part 1 or Part 2), subset (participants included in 
reactogenicity/immunogenicity subset or not), center, age and region; 
− 
The RSVPreF3 OA investigational vaccine lot allocated for Dose 1 (Lot 1, 2, 3 
or 4). 
• 
The updated randomization file including the allocation of participants to one of the 
2 groups for each lot (RSV_annual group or RSV_1dose group) will be uploaded in 
SBIR. 
The re-randomization file will be prepared by an unblinded independent statistician. It 
will not be accounting for any data collected in the eCRF, but only for data collected in 
SBIR for the allocation to the initial study group. 
Upon providing the participant identification number, the randomization system will 
provide the intervention number to be used for the re-vaccination doses. 
When SBIR is not available, please refer to the SBIR user guide or SPM for specific 
instructions. 
Refer to the SPM for additional information relative to the intervention number 
allocation. 
6.3.4. 
Allocation of participants to assay subsets 
Evaluation of solicited events and the humoral immune response will be performed in a 
subset of participants, referred to as reactogenicity and immunogenicity subset. This 
subset will include approximately 1800 participants (corresponding to ~7% of the total 
study population) from the 3 RSVPreF3 OA investigational vaccine lot groups and 
placebo group (1:1:1:3 ratio) in Part 1, including participants from NH and SH, as 
indicated in Table 13. 

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Table 13 
Number of participants in reactogenicity and immunogenicity subset 
(Amended, 12 July 2023) 
For Dose 1 
 
RSVPreF3_L1 
RSVPreF3_L2 
RSVPreF3_L3 
Placebo 
Total 
NH 
~270 
~270 
~270 
~810 
~1620 
SH 
~30 
~30 
~30 
~90 
~180 
For Dose 2 
 
RSV_annual group 
RSV_1dose group 
Placebo 
Total 
NH 
~405 
~405 
~810 
~1620 
SH 
~45 
~45 
~90 
~180 
For immunogenicity pre-Season 3 
 
RSV_annual group 
RSV_1dose group 
Placebo 
Total 
NH 
~405 
~405 
~810 
~1620 
NH: Northern hemisphere; SH: Southern hemisphere. 
Participants contributing to the reactogenicity and immunogenicity subset will be 
recruited from a selected number of countries and selected number of sites. In the 
selected sites, the investigator will allocate the first participants in each age category to 
the reactogenicity and immunogenicity subset until the allocated target is reached. 
At time of randomization for Dose 1, the subset will be entered in SBIR as stratification 
factor. A randomization blocking scheme (1:1:1:3 ratio) will be used to ensure that 
balance between interventions is maintained. The randomization algorithm will use a 
minimization procedure accounting for center, age and region within the subset. All 
minimization factors will have equal weight in the minimization algorithm. 
6.3.5. 
Blinding and unblinding  
Data will be collected in an observer-blind manner. To do so, vaccine will be prepared 
and administered by qualified study personnel (unblinded) who will not participate in 
data collection, evaluation or review of any study endpoint (i.e., reactogenicity, safety, 
efficacy). 
The unblinded study personnel are allowed to transcribe source data into the eCRF 
without interpretation or generation of data. 
The laboratory in charge of the sample testing will be blinded to the intervention 
assignment. Codes will be used to link the participant and study (without any link to the 
intervention attributed to the participant) to each sample. 
At different analyses, there will be a risk of individual unblinding. Given that summary 
safety results may unblind some specific participants (e.g., an AE occurring only in a 
single group), anyone having access to these analyses could become unblinded regarding 
that specific case. In order to maintain the whole team (Central, Local, Investigators) and 
participants blinded at the individual participant level, a firewall team will be set up. This 
firewall team will allow all analyses until the implementation of Protocol Amendment 4 
to be performed and results reported to the relevant authorities while the study blind is 
maintained. In case no participant is reported in 1 group (e.g., a certain event being only 
reported in participants in the other study group), the blinding of results is managed by an 

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Independent External Statistician (IES). In this situation, exact results per group are not 
provided to the blinded team members and the investigators. The firewall team will 
review the results before they are distributed to the study team, to prevent these data 
potentially leading to unblinding at participant level of the study team. Further details of 
this approach can be found in the firewall charter. 
For analyses planned as of the implementation of Protocol Amendment 4, GSK RSV OA 
team members will be unblinded at the individual participant level in order to support the 
regulatory activities and study results interpretation, with the exception of GSK RSV OA 
team members involved in clinical evaluation (i.e., personnel involved in data review and 
validation, ARI/LRTD case adjudication, laboratory testing), study participants, 
investigators and site personnel involved in the clinical evaluation of the participants, 
who will remain blinded at the individual participant level up to end of study. In case no 
participant is reported in 1 group (e.g., a certain event being only reported in participants 
in the other study group), exact results per group will not be provided to blinded team 
members and the investigators. The firewall team will no longer be active. 
A participant may continue in the study if that participant’s intervention assignment is 
unblinded (see Sections 6.3.5.1 and 6.3.5.2). 
6.3.5.1. 
Emergency unblinding  
Unblinding a participant’s individual intervention number should occur ONLY in case of 
a medical emergency when knowledge of the intervention is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention via SBIR. 
As back-up process, the investigator has the option of contacting a GSK Helpdesk (refer 
to the Table 14) if he/she needs help performing the unblinding (i.e., he/she cannot access 
SBIR). 
A non-investigator physician (e.g., physician from emergency room) or 
participant/caregiver member may also request emergency unblinding either via the 
investigator (preferred option) or via the GSK Helpdesk (back-up process). The 
patient/participant card lists contact information for both the investigator and GSK 
Helpdesk. 
GSK’s Global Safety staff may unblind the intervention assignment for any participant 
with an SAE. If the SAE requires that an expedited regulatory report be sent to one or 
more regulatory agencies, a copy of the report, identifying the participant’s intervention 
assignment, may be sent to investigators in accordance with local regulations and/or GSK 
policy. 

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Table 14 
Contact information for emergency unblinding  
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and e-mail 
Toll-free number: 
Australia: 
 
Belgium: 
 
Canada: 
 
Estonia: 
 
Finland: 
 
Germany: 
 
Italy: 
 
Japan: 
 
Mexico: 
 
Russia: 
 
South Africa: 
 
South Korea: 
 
Spain: 
 
United Kingdom:
 
United States: 
 
Phone (for all countries where the toll-free number is not available): 
 
Fax: 
 
E-mail: 
 
6.3.5.2. 
Emergency unblinding prior to regulatory reporting of SAEs 
GSK policy (which incorporates ICH E2A guidance, the EU Clinical Trial Directive and 
US Federal Regulations) is to unblind the report of any unexpected SAE and which is 
attributable/suspected to be attributable to the study vaccine, prior to regulatory reporting. 
Vaccines Clinical Safety and Pharmacovigilance (VCSP) is responsible for unblinding 
the intervention assignment in accordance with the specified timeframes for expedited 
reporting of SAEs (refer to the Section 10.3.10.1). 
In addition, GSK VCSP staff may unblind the intervention assignment for any participant 
with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or a Serious Adverse 
Event that is fatal or life-threatening. If the SAE requires an expedited regulatory report 
be sent to 1 or more regulatory agencies, a copy of the report, identifying the participant’s 
intervention assignment, may be sent to investigators in accordance with local regulations 
and/or GSK policy. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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6.4. 
Study intervention compliance 
As this is an observer-blind study, vaccine preparation and administration will be done by 
authorized medical personnel who will not participate in any of the study clinical 
evaluation assays. Vaccination will be performed under medical supervision. The date of 
each dose administration will be recorded in the source documents and in the eCRF. 
6.5. 
Concomitant therapy (Amended, 12 July 2023) 
At each study visit/contact, the investigator or delegate should question the participant 
about any medications/products taken and vaccinations received by the participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medication, except vitamins and dietary supplements, administered 
during the 30-day period following each dose of study vaccine (Day 1 to Day 30 
after each dose). 
• 
All concomitant vaccination during the entire study period. 
• 
All concomitant medication including vaccines/products which may explain/cause/be 
used to treat an SAE/pIMD as defined in Sections 8.3.1 and 10.3.8. These must also 
be recorded on 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 each 
study vaccination day (Day 1, pre-Season 2 and pre-Season 3*) in the absence of 
ANY symptom and in anticipation of a reaction to the vaccination. 
* Not applicable for participants in the NH who will have their Visit 5NH after the 
approval of the current Protocol Amendment 5 and will not receive any study 
intervention at pre-Season 3 visit (Visit 5NH).  
• 
All concomitant medications taken for the treatment of an ARI (including prescribed 
drugs [e.g. antibiotics] and self-treatment) or for an ARI-related complication. 
• 
All concomitant medications including vaccines/products leading to discontinuation 
of the study intervention or an elimination from the analysis (refer to Section 5.2.2 
for details). 
Refer to Table 15 for an overview of the timing for recording of concomitant medication 
during the study. 
The Local Medical Lead (LML) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
 

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Table 15 
Timing of collection of concomitant medication to be recorded (Amended, 12 July 2023) 
 
Dose 1 
 
 
Dose 2 
 
 
Dose 3* 
 
 
Study 
Conclusion 
 
Day 1 
post-D1 
Day 30 
post-D1 
 
Day 1 
post-D2 
Day 30 
post-D2 
 
Day 1 
post-D3 
Day 30 
post-D3 
 
All concomitant medication, except vitamins and dietary supplements 
 
 
 
 
 
 
*** 
*** 
 
 
All concomitant vaccination 
 
 
 
 
 
 
 
 
 
 
All concomitant medication including vaccines/products which may 
explain/cause/be used to treat an SAE/pIMD/AF** 
 
 
 
 
 
 
 
 
 
 
Any prophylactic medication 
 
 
 
 
 
 
*** 
 
 
 
All concomitant medications taken for the treatment of an ARI or for 
an ARI-related complication 
 
 
 
 
 
 
 
 
 
 
Any investigational or non-registered product 
 
 
 
 
 
 
 
 
 
 
Chronic administration (defined as more than 14 consecutive days in 
total) of immunosuppressants or other immune-modifying drugs 
 
 
 
 
 
 
 
 
 
 
Administration of immunoglobulins and/or any blood products 
 
 
 
 
 
 
 
 
 
 
Administration of long-acting immune-modifying drugs 
 
 
 
 
 
 
 
 
 
 
AF: Atrial Fibrillation; D: Dose; ARI: acute respiratory illness; SAE: serious adverse event; pIMD: potential immune-mediated disease;  
Note: The collection period for the concomitant medications to be recorded in eCRF is indicated in grey. 
* Only applicable for participants in Northern hemisphere. 
** 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. 
*** Not applicable for participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 5 and will not receive any study 
intervention at pre-Season 3 visit (Visit 5NH). 

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6.6. 
Dose modification 
Not applicable. 
6.7. 
Intervention after the end of the study 
During the study conclusion visit, the investigator will ask each participant if they are 
interested in participating in a booster /long-term study. If a participant is not interested, 
the reason for refusal will be documented, when available, in the participant’s eCRF. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention (Amended, 12 July 
2023) 
‘Discontinuation’ of study intervention means any participant who has not received all 
planned doses of vaccine. A participant who discontinued study intervention may, if 
deemed appropriate by the investigator, continue other study procedures (e.g., subsequent 
dose, efficacy, safety or immunogenicity) if planned in the study protocol. 
The primary reason for premature discontinuation of the study intervention will be 
documented in the eCRF based on the following: 
• 
Adverse event requiring expedited reporting to GSK 
• 
Unsolicited non-serious AE 
• 
Solicited event 
• 
Not willing to be vaccinated 
• 
Other (specify). 
Refer to Section 7.1.2 for contraindications to subsequent vaccination. Refer to Section 
10.5.2 (glossary of terms) for the definition of intervention. 
Participants who do not consent for the annual revaccination will be considered 
withdrawals from the study. 
7.1.1. 
Criteria for temporary delay for enrollment and/or vaccination 
Study vaccine administration may be postponed within the permitted timeframe for each 
study vaccination within each country until transient circumstances cited below are 
resolved: 
• 
Acute disease and/or fever at the time of vaccination. Fever is defined as a 
temperature ≥ 38.0°C/100.4°F by any route. The route for measuring temperature 
can be oral, axillary or tympanic. 

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• 
Participants with symptoms suggestive of active Coronavirus Disease 2019 (COVID-
19) infection (e.g. fever, cough, etc.). The return to the site of the participant will 
follow the specific guidance from local public health and other competent authorities 
(e.g., free of symptoms, COVID-19 negative testing, etc.). 
• 
Participants with known COVID-19 positive contacts within the past 14 days may be 
vaccinated at the discretion of the investigator at least 14 days after the exposure if 
the participant remains symptom free. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be vaccinated at the discretion of the investigator. 
• 
In case of administration of inactivated and subunit influenza vaccines: 
Postponement of study vaccine administration within given protocol timelines to 
allow respect of the 14 day-interval between flu vaccination and study vaccine 
administration. 
Refer to Table 5 and Table 6 in Section 1.3 for the allowed time intervals in Northern and 
Southern hemispheres, respectively. 
7.1.2. 
Contraindications to subsequent vaccine administration 
(Amended, 12 July 2023) 
Participants must be evaluated to confirm that there are no contraindications for 
subsequent vaccination before administering each additional study vaccine dose. 
Participants who meet any of the criteria listed below or criteria listed in Sections 5.2.1, 
5.2.2 and 5.2.3 should not receive additional vaccinations. However, these participants 
should be encouraged to continue other study procedures at the discretion of the 
investigator (Section 10.3.8.2). The relevant criteria for discontinuing vaccination must 
be recorded in the eCRF. 
• 
Participants who experience any SAE judged to be possibly or probably related to 
the study vaccine or non-study concomitant vaccines, including hypersensitivity 
reactions. 
• 
Participants who develop any new condition which, in the opinion of the 
investigator, may pose additional risk to the participant if he/she continues to 
participate in the study. 
• 
Occurrence of a new pIMD or the exacerbation of an existing pIMD that, in the 
opinion of the investigator, exposes the participant to unacceptable risk from 
subsequent vaccination. In such cases, the investigator should use his/her clinical 
judgment prior to administering the next dose of the vaccine. Refer to Section 
10.3.5.1 for the definition of pIMDs. 
Note: This section is not applicable at pre-Season 3 visit for participants in the NH who 
will have their Visit 5NH after the approval of the current Protocol Amendment 5 and 
will not receive any study intervention at pre-Season 3 visit (Visit 5NH). 

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7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this participant from the date of withdrawal/last contact. 
From an analysis perspective, a ‘withdrawal’ from the study refers to any participant who 
did not return for the concluding visit foreseen in the protocol. Investigators will attempt 
to contact those participants who do not return for scheduled visits or follow-up. All data 
and samples collected until the date of withdrawal/last contact of the participant will be 
used for the analysis. 
The primary reason for study withdrawal will be documented in the eCRF based on the 
list below: 
• 
AEs requiring expedited reporting to GSK (refer to Section 10.3.10.1 for details) 
• 
Unsolicited non-serious AE 
• 
Solicited event 
• 
Withdrawal by participant, not due to an AE* 
• 
Migrated/moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify). 
* If a participant is withdrawn from the study because he/she has withdrawn consent and 
provided the reason for its withdrawal, the investigator must document this reason in the 
eCRF. 
Participants who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigators will 
follow participants who are withdrawn from the study as result of an SAE/AE until the 
event is resolved (see Section 10.3.8.2). 
7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if he or she fails to return for 
scheduled visits and is unable to be contacted by the study site. 
Please refer to the SPM for a description of the actions to be taken before considering the 
participant as lost to follow-up. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
(AMENDED, 12 JULY 2023) 
Study procedures and their timings are summarized in Table 1 and Table 2 for 
participants in NH, Table 3 for participants in SH and Table 4 for ARI surveillance 
(Section 1.3). The intervals between study visits are provided in Table 5, Table 6 and 
Table 7, respectively. Study visits should preferably be done on site or in the LTCF. If 
deemed necessary and not possible for study participant to come to site, study visits can 
be done at home. 
Adherence to the protocol is required for study conduct. 
Protocol waivers or exemptions are not allowed unless necessary for the management of 
an immediate safety concern. 
Immediate safety concerns should be discussed with the sponsor as soon as they occur or 
when the study team is aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
The SPM provides the investigator and site personnel with administrative and detailed 
technical information that does not impact participant safety. 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, the 
following measures may be implemented for enrolled participants: 
• 
Safety follow-up may be made by a telephone call, other means of virtual contact or 
home visit (from the site staff or from home care service system), if appropriate. 
• 
Diary cards may be transmitted from and to the site by electronic or conventional 
mail or collected at the participant’s residence. 
• 
Visits for suspected ARI may take place in a different location* other than the study 
site or at participant’s home. If this is not feasible, then the medical evaluation of 
ARI may take place virtually with documentation of ARI symptoms and other 
relevant ARI information by phone or other means of virtual live contact. 
• 
Biological samples may be collected at a different location* other than the study site 
or at participant’s home. Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use. 
• 
Throat and/or nasal swab samples collected at ARI visits may be taken by someone 
else than the site staff (for example, a swab sample may be taken by the participant 
or caregiver) with site staff supervision and guidance, if required by local 
regulations. 

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• 
If despite best efforts it is not possible to perform the ARI visit within the interval 
pre-defined in the protocol (see Table 7) (for example in case of suspected COVID-
19 infection and pending COVID-19 test result, or self-quarantine), then the interval 
for this visit may be extended up to maximum 14 days after ARI onset (i.e., until 
Day 15, refer to Figure 3 for ARI flow). In any case, the participant should be 
encouraged to take the self-swab as per protocol (i.e., preferably within 48 hours 
after ARI onset but not later than 5 days after ARI onset) to maximize the chance to 
detect the virus. 
* It is the investigator’s responsibility to identify an alternate location. The investigator 
should ensure that this alternate location meets ICH GCP requirements, such as 
adequate facilities to perform study procedures, appropriate training of the staff and 
documented delegation of responsibilities in this location. This alternate location should 
be covered by proper insurance for the conduct of study on participants by investigator 
and staff at a site other than the designated study site. Refer to EMA Guidance on the 
Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic (version 
2, 27 March, 2020) for more details. 
Refer to the SPM for further details on decentralized clinical trial solutions. 
Impact on the per protocol sets for efficacy and immunogenicity will be determined on a 
case by case basis. 
8.1. 
Efficacy and immunogenicity assessments 
8.1.1. 
Efficacy assessments 
8.1.1.1. 
ARI surveillance period and methods 
Surveillance for detection of ARI episodes will be carried out during the entire study, via 
spontaneous reporting by the study participant (starting on the day of first vaccination* 
[Visit 1]) and by scheduled site staff contacts (starting from Visit 2 onwards) with 
different frequencies of contact during the RSV seasons and the inter-season periods. 
Based on the observed RSV circulation during the season, the ARI surveillance and/or 
the DLP for analyses could be adapted for the ongoing and/or subsequent seasons. Refer 
to Figure 2 for details on ARI surveillance. ARI episodes will be captured via 2 
complementary methods: 1) spontaneous reporting by the participant (see Section 
8.1.1.4) scheduled site staff contacts (see Section 8.1.1.4). 
* For detailed information on activities involved in ARI surveillance, refer to Table 4. 
Swab samples will be taken in all participants meeting pre-specified criteria for ARI case 
definition (see Table 10 in Section 4.2.1). Diagnosis and treatment of each ARI should be 
performed according to the local standard of care. 

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8.1.1.1.1. Nasal self-swab training with the study participant 
At Visit 2, the study participants may be invited to practice a nasal self-swab in the 
presence of site staff to guide them through the instructions and the procedure. The nasal 
self-swab training can be repeated at any subsequent visit if the participant raises the need 
for a new training. This swab should be discarded after the training, it should not be sent 
to the central laboratory. 
ARI surveillance starts as of Visit 1, however no nasal self-swab will be requested from 
the participant for ARI episodes occurring before Visit 2. 
8.1.1.2. 
Definitions for ARI surveillance 
• 
ARI onset (Day 1): will be defined as the first day when the study participant 
presents at least 2 concomitant ARI symptoms/signs meeting the ARI case definition 
(see Table 10 in Section 4.2.1). The ARI case must be confirmed by the 
investigator/site staff or delegate during the ARI visit. 
Note: The start and end date of each individual symptom and the presence/absence of 
each sign will be recorded in the eCRF. It may happen that the start date of an 
individual symptom/sign is before the ARI onset date, if the first symptom/sign 
started before the second symptom/sign needed to reach the ARI case definition. 
• 
ARI end: will be defined as the first day when all ARI symptoms/signs of the 
participant have returned to baseline or when they diminished significantly as judged 
by the investigator. 
• 
New ARI episode: An ARI episode will be considered as a new episode only after 
the resolution of the previous one. Between 2 ARI episodes, there must be at least 
7 days free of symptoms/signs (or at baseline level) or at least 7 days with 
significantly diminished symptoms/signs as judged by the investigator. 
• 
Complications: The following complications of interest will be collected through 
the entire study, starting on the first vaccination day (Visit 1). The relationship of 
these complications to an ARI episode will be assessed by the investigator. 
− 
Respiratory complications: 
• 
Pneumonia: A clinical diagnosis of pneumonia based on signs and 
symptoms, with or without chest radiograph that demonstrates a new or 
progressive infiltrate. 
• 
New diagnosis of COPD or exacerbation of COPD: A new diagnosis of 
COPD or, in a participant with previously diagnosed COPD, a worsening of 
COPD necessitating to increase the dosage or modify the treatment 
administered. 
• 
New diagnosis of asthma or exacerbation of asthma: A new diagnosis of 
asthma or, in a participant with previously diagnosed asthma, a worsening 
of asthma necessitating to increase the dosage or modify the treatment 
administered. 

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• 
Other respiratory complications: Other diagnosis of respiratory illness, 
including new diagnosis or exacerbation of a pre-existing respiratory 
disease (e.g., emphysema, chronic bronchitis). 
− 
Non-respiratory complications: 
• 
New onset or worsening congestive heart failure (CHF), 
• 
Myocardial infarction (MI), 
• 
Stroke, 
• 
Diabetes, 
• 
Other non-respiratory complications judged related to an ARI episode by 
the Investigator. 
8.1.1.3. 
ARI capture and follow-up 
ARI episodes will be captured via 2 complementary methods: 1) spontaneous reporting 
by the participant and 2) scheduled site staff contacts. 
Each ARI episode (including if several episodes occur in the same participant) will be 
assigned a sequential case number. All relevant ARI information will be reported in a 
specific ARI eCRF screen. 
8.1.1.4. 
Spontaneous reporting by the participant 
Participants will be instructed to contact spontaneously the investigator/site staff 
promptly if they experience at least 2 ARI symptoms/signs (see Table 10 in Section 
4.2.1). The surveillance for ARI will start on the first vaccination day (Visit 1). At Visit 
1, participants will be provided with instruction material to guide them in the detection of 
ARI symptoms/signs. At Visit 2, participants will be invited to practice nasal self-swab 
collection (refer to Section 8.1.1.1.1). Note that no nasal self-swab will be requested from 
the participant for ARI episodes occurring before Visit 2. 
At each study visit/contact, participants should be reminded to contact the 
investigator/site staff if they experience respiratory symptoms meeting the ARI case 
definition. 
8.1.1.5. 
Scheduled site staff contacts (Amended, 12 July 2023) 
As of Visit 2 onwards, the site staff will contact the participants regularly during the 
entire study to check if they have experienced any respiratory symptoms meeting the ARI 
case definition (see Table 10 in Section 4.2.1). These contacts will be performed: 
• 
every 2 weeks during the RSV seasons, 
• 
every month during the inter-season periods. 
The RSV seasons defined for this study are from 1 October to 30 April in NH and from 
1 March to 30 September in SH. 

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Figure 2 
ARI surveillance in Northern and Southern hemispheres (Amended, 
12 July 2023) 
 
NH: Northern hemisphere; SH: Southern hemisphere. 
In some SH countries, recruitment might start during an RSV Season (Season 0). 
Surveillance for ARI will be carried out during the entire study, via spontaneous reporting by the study participant 
(starting on the day of first vaccination [Visit 1]) and by scheduled site staff contacts (starting from Visit 2 onwards) with 
different frequencies of contact during the RSV seasons and the inter-season periods. 
The site staff surveillance contacts will be performed: every 2 weeks during the RSV seasons (Solid blue) and every 
month during the inter-season periods (Shaded blue). The RSV seasons defined for this study are: from 1 October to 
30 April in NH and from 1 March to 30 September in SH. Based on the observed RSV circulation during the season, 
the ARI surveillance and/or the DLP for analyses could be adapted for the ongoing and/or subsequent seasons. 
Note: If following the sample size re-assessment an additional cohort needs to be enrolled before the next season in 
NH (see Section 9.2.3), similar ARI surveillance will apply up to the end of the third season for those participants. 
Study Year 1 corresponds to the year in which the enrollment started for the cohort. 
* The last study visit in SH (Visit 5 SH) will occur approximately 2 months after the start of Season 3 in SH; yet the site 
staff surveillance contacts will be performed monthly during these last months (i.e., continuation of the inter-season 
frequency of contacts). 
Multiple formats can be proposed by the site staff to organize these surveillance contacts. 
This may be done via e-mail, text message, fax or phone call for example, or via a visit 
for LTCF participants. The most appropriate format should be agreed between site staff 
and the study participant. Text messages, e-mail 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). 
Receipt of the message must be confirmed by the participant or caregiver, as applicable. 
At each scheduled contact, participants will be asked if they have experienced: 
• 
Any symptoms/signs meeting the ARI case definition (see Table 10 in Section 4.2.1). 
• 
Any of the following respiratory complications: 
− 
Pneumonia 
− 
New diagnosis of COPD or exacerbation of COPD 
− 
New diagnosis of asthma or exacerbation of asthma 
− 
Other respiratory complications 
Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec
Northern hemisphere
Inter-season
Season 1 NH
Inter-season
Season 2 NH
Southern hemisphere
Season 0 SH
Inter-season
Season 1 SH
Inter-season
Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec
Northern hemisphere
Season 2 NH (continues) 
Inter-season
Season 3 NH
 Last study visit (Visit 7  NH)
Southern hemisphere
Season 2 SH
Inter-season
S3 SH*
 Last study visit (Visit 5 SH)
Study Year 1
Study Year 2
Study Year 3
Study Year 4

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• 
Any of the following non-respiratory complications: 
− 
New onset or worsening congestive heart failure (CHF), 
− 
Myocardial infarction (MI), 
− 
Stroke, 
− 
Diabetes, 
− 
Other non-respiratory complications judged related to an ARI episode by the 
investigator, 
• 
Any hospitalization or visit to a healthcare practitioner for a respiratory disease. 
• 
AEs, SAEs, AESIs (including pIMDs and AF)*. 
Note: AEs, SAEs, and AESIs (including pIMDs and AF) should be reported to GSK 
during specified follow-up periods as described in Section 10.3.8. 
• 
Any COVID-19 infection (suspected, probable or confirmed). 
• 
Participants will be reminded to contact the site staff in case they experience any 
ARI symptoms/signs. 
If no ARI symptoms/signs are reported during the contact, the investigator/site staff 
should record date of contact and absence of ARI symptoms/signs in the eCRF. If ARI 
symptoms/signs are reported, please refer to Section 8.1.1.6.2. 
*Note: In this study AF will be collected as AESIs. See definition of AESI in Section 
10.3.5. 
8.1.1.6. 
ARI procedures 
8.1.1.6.1. Primary route to capture ARI episodes 
Spontaneous reporting by the participant should be the main route to capture ARI 
episodes and the related procedures are described in Figure 3 and the sections below. 
Note that if an ARI event meets the definition of AE or SAE it should also be reported as 
AE/SAE according to the specified follow-up periods described in Section 10.3.8. If an 
ARI is a suspected, probable or confirmed COVID-19 case as per World Health 
Organization (WHO) case definitions, the COVID-19 specific eCRF page should be 
completed. Testing for detection of SARS-CoV-2 infections should be done according to 
local requirements and via local testing facilities. 

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Figure 3 
ARI capture and follow-up 
 
The ARI visit should preferably be done on site or in the LTCF. If deemed necessary, the ARI visit can be done at 
home. ARI follow-up contacts on Day 15, Day 29 and the additional follow-up contact can be done via phone calls or 
visit to the LTCF. 
Nasal self-swab collection and completion of daily health questionnaires are not applicable for ARI episodes reported 
before Visit 2. 
* In special circumstances (for example in case of suspected COVID-19 infection and pending COVID-19 test result, or 
self-quarantine) and if it is not possible to perform the ARI visit within 6 days after ARI onset (i.e., within Day 3 to Day 
7), then the interval for this visit may be extended up to maximum 14 days after ARI onset (i.e., until Day 15). If the ARI 
visit takes place between Day 10 and Day 15, then the first follow-up contact may be skipped. 
In case of at least 2 concomitant ARI symptoms/signs identified by the participant, the 
following visits and contacts will take place (refer to Table 7 for the intervals allowed for 
each contact): 
• 
Participant’s call (Day 2): Within 24 hours of the appearance of at least 
2 concomitant ARI symptoms/signs, the participant should call the site staff. During 
the phone call: 
− 
Record ARI symptoms/signs: The site staff will record the ARI 
symptoms/signs reported by the participant in the eCRF and record the onset 
date of each symptom mentioned during the call. 
− 
Schedule ARI visit: The site staff will organize an ARI visit within the per 
protocol window. (Refer to the note for special circumstances in the ARI visit 
detailed below). 
− 
Reminders for participant procedures: The participant should be reminded by 
site staff to take a nasal self-swab (Note: this is not applicable for ARI episodes 
reported before Visit 2). The self-collected swab should be done preferably 
within 48 hours of ARI onset but not later than 5 days after ARI onset. The 
Complete daily health questionnaires from Day 2 until max 
Day 15
Take nasal 
self-swab
Call the site
2 symptoms 
detected by 
the study 
participant
Complete EQ-5D and 
SF-12 during visit
Activities performed by 
the study participant
Confirm if the case meets 
the ARI case definition:
1) If ARI is not confirmed: 
provide alternative 
diagnosis and stop other 
ARI-related procedures
2) If ARI is confirmed:
- Take nasal/throat swab
- Follow the other study 
procedures for ARI visit
Record ARI 
info 
Record ARI 
follow-up info
Record ARI follow-up info
Timepoints
DAY 1 
ARI onset
DAY 2
Participant’s 
call
DAY 3-7*
ARI visit
DAY  15 
ARI follow-up 
contact
DAY 29 
ARI closure 
contact
Every 2 weeks
Additional follow-up contact 
(if needed)
Interval 
allowed
Day 1 + 24h
Day 1 + 48h to 6 days
Day 1 +
14 to 18 days
Day 1 +
28 to 35 days
14 to 18 days since last call
Activities performed by 
the PI or designate
Share ARI 
follow-up
Share ARI 
follow-up
Share ARI follow-up
Remind 
participant to 
take the self-
swab and to 
complete the 
daily health 
questionnaires 
Remind participant to call if 
the event gets worse
Remind 
participant 
when to stop 
daily health 
questionnaires 
and give 
instructions to 
return these 
Close the ARI 
if it has ended
Close the ARI if it has ended
Record ARI 
follow-up 
info
Close the 
ARI if it has 
ended
Schedule an 
ARI visit
Explain how to 
return the swab

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participant will be reminded on the storage conditions and return instructions of 
the swab sample. The self-swab should be returned to the study site within 
2 days after collection or, if not feasible within 2 days, the swab should be 
returned to site as soon as possible. 
− 
Reminder to start completing the daily health questionnaires: The 
questionnaires should be completed from the participant’s call (Day 2) until the 
end of the ARI episode or for maximum 14 consecutive days (i.e., from Day 2 
until Day 15 at the latest) (Note: this is not applicable for ARI episodes reported 
before Visit 2). Each study site should define upfront the most appropriate 
method(s) for collection of questionnaires completed by the participant (via 
mail, service courier, or other). 
• 
ARI visit (Days 3-7)*: The ARI visit should take place soon after ARI onset, ideally 
48 hours after ARI onset, but no later than 6 days after ARI onset. Ideally, and in 
most cases, the ARI visit should be scheduled at least 1 day after the participant’s 
self-swab** (i.e., the nasal self-swab taken by the participant and the nasal and throat 
swab samples taken by the qualified site staff should not be done on the same day). If 
for logistical or medical reasons the ARI visit must be scheduled on the same day 
than the participant call, it is recommended to take the nasal and throat swab during 
the visit and to omit the self-swab** taken by the participant, but this should remain 
exceptional. 
* Note: In special circumstances, (for example in case of suspected COVID-19 
infection and pending COVID-19 test result, or self-quarantine) and if it is not 
possible to perform the ARI visit within 6 days after ARI onset (i.e., within Day 3 to 
Day 7), then the interval for ARI visit may be extended up to maximum 14 days after 
ARI onset (i.e., until Day 15). If the ARI visit occurs within 7 to 9 days after ARI 
onset (i.e., within Day 8 to Day 10), then the remaining follow-up contacts (i.e., Day 
15 and Day 29) should be performed as described below. If the ARI visit occurs 
between 10 to 14 days after ARI onset (i.e., within Day 11 to Day 15), then the first 
follow-up contact (i.e., Day 15 contact) can be skipped; the next contact will be the 
Day 29 contact. In any case, the participant should be encouraged to take the self-
swab as per protocol (i.e., preferably within 48 hours after ARI onset but not later 
than 5 days after ARI onset) to maximize the chance to detect the virus. 
** Note: the nasal self-swab collection is not applicable for ARI episodes reported 
before Visit 2. 
During the ARI visit the following procedure should be performed (refer also to 
Table 4 in Section 1.3): 
− 
Physical examination, body temperature and vital signs: refer to Section 
8.2.2. 
− 
Pulse oximetry: refer to Section 8.2.2.4. 
− 
Confirmation of ARI: The investigator or designee will confirm if the event 
meets the ARI case definition (see Table 10 in Section 4.2.1). 
If the ARI is NOT confirmed, the investigator or designee will record the 
alternative diagnosis in the eCRF. No other swab sample should be taken and 
other ARI-related procedures should not be performed. The participant should 

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be instructed to stop completing the daily health questionnaires. Refer to the 
SPM for details on the handling of self-swab samples and the daily health 
questionnaires in case ARI is not confirmed. The management of the participant 
illness should follow local standard of care. 
If the ARI is confirmed (i.e., the event met the ARI case definition), the 
investigator or designee will record the ARI information in the eCRF and follow 
all ARI-related procedures (see Table 4 in Section 1.3). The ARI episode should 
be treated accordingly to local standard of care. 
− 
Record ARI information: The investigator or designee will assess clinical 
signs and/or symptoms of ARI, record the onset date of each symptom 
diagnosed/mentioned during the visit and record the presence/absence of each 
sign detected based on auscultation. The investigator should provide a clinical 
diagnosis and assess the intensity of the ARI according to the intensity grading 
provided in Table 16 . 
If any laboratory testing is performed locally for the identification of respiratory 
pathogens for the ARI, the date of the testing, method of test, specimen material 
type, the results and the references of commercial PCR diagnostic kit (if 
applicable) should be recorded in the eCRF. 
Table 16 
Intensity grading for ARI/LRTD episode 
Mild 
= 
An ARI/LRTD episode which is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
Moderate 
= 
An ARI/LRTD episode which is sufficiently discomforting to interfere with normal everyday 
activities. 
Severe 
= 
An ARI/LRTD episode which prevents normal, everyday activities. Such an event would, 
for example, prevent attendance at work and would necessitate the administration of 
corrective therapy. 
− 
Record date of self-swab: The site staff will record in the eCRF the date when 
the self-swab was taken by the participant (Note: this is not applicable for ARI 
episodes reported before Visit 2). 
− 
Nasal and throat swab sampling: For each ARI reported after the first 
vaccination visit (Visit 1), qualified staff from the study team will collect one 
swab of cells and secretions from each nostril and one swab from throat. After 
collection, both swabs will be placed in the same tube. Full details for obtaining 
nasal and throat sample are provided in the SPM. 
The swab samples will allow to assess the potential RSV and hMPV infections 
by RT-PCR at a sponsor or sponsor-designated laboratory. 
− 
Record treatment prescribed/self-treatment: Any medication taken for ARI 
(including self-medication) since ARI onset until resolution of the episode will 
be recorded in the eCRF with medical indication and start/end dates of the 
treatment. The same will be applicable to medication(s) prescribed to treat any 
ARI-related complications. 

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− 
Collection of HCRU: Each participant will be asked to answer questions on 
healthcare utilization since ARI onset until resolution of the episode. Refer to 
Section 8.10.2 for an overview of HCRU data to be recorded in the participant’s 
eCRF. 
− 
HR-QoL questionnaires: Participants will be asked to complete HR-QoL 
questionnaires (EQ-5D and SF-12) during the ARI visit. All HR-QoL 
questionnaires will be completed by the participant (or with the assistance of 
their caregiver in case of physical incapacity) in the presence of site staff. 
− 
Reminders: The participants should be reminded to contact the site staff if the 
ARI worsens. The need for additional visits or contacts for the medical 
management of the ARI should be assessed by the investigator and follow the 
local standard of care. 
The participant will also be reminded to complete the daily health questionnaires 
until the end of the ARI or for maximum 14 days (Note: this is not applicable for 
ARI episodes reported before Visit 2). 
− 
Recording of AEs, SAEs and other events of interest: refer to Section 8.3. 
− 
Distribution of new material: At each ARI visit (regardless, if the ARI is 
confirmed or not), the site staff should distribute new self-swabbing material and 
new daily health questionnaires to the study participant for the next ARI episode 
(Note: this is not applicable for ARI episodes reported before Visit 2). 
• 
ARI follow-up contact (Day 15): Each ARI episode will be followed up by the 
investigator/site staff through an ARI follow-up contact (phone call or visit to the 
LTCF) approximately 14 days after ARI onset. If due to special circumstances (for 
example a suspected COVID-19 infection or pending COVID-19 test result, or self-
quarantine), the ARI visit occurs between 10 to 14 days after ARI onset (i.e., within 
Day 11 to Day 15), then the first follow-up contact (i.e., Day 15 contact) can be 
skipped; the next contact will be the Day 29 contact. 
− 
ARI follow-up information will be recorded in the eCRF: onset and end date of 
each symptom (including new symptoms) should be captured. Any update on 
the diagnosis, the medication taken to treat the ARI and ARI intensity will be 
recorded. For each ARI the maximum intensity should be recorded. 
If any laboratory testing is performed locally for the identification of respiratory 
pathogens for the ARI, the date of the testing, method of test, specimen material 
type, the results and the references of commercial PCR diagnostic kit (if 
applicable) should be recorded in the eCRF. 
− 
Daily health questionnaires: The participant will be reminded to complete the 
daily health questionnaires until Day 15 at the latest in case the ARI is still 
ongoing. The participant should also be reminded when to stop completing the 
questionnaires and how the completed questionnaires should be returned to the 
site (Note: this is not applicable for ARI episodes reported before Visit 2). 
− 
HCRU should also be recorded. 
− 
Recording of AEs, SAEs and other events of interest: refer to Section 8.3. 

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• 
If the ARI ended before the follow-up call, the ARI outcome should be recorded and 
the scheduled surveillance contacts should resume for that participant. 
• 
ARI closure contact (Day 29): If the ARI event was still ongoing at the first ARI 
follow-up contact, the investigator/site staff will contact again the participant 
approximately 28 days after ARI onset to check on the resolution of the ARI episode. 
ARI follow-up information and ARI closure will be recorded and the scheduled 
surveillance contacts should resume for that participant. 
• 
Additional follow-up contact: For participants with complication(s) lasting beyond 
the ARI closure contact, additional follow-up contacts will be done approximately 
every 2 weeks post ARI closure contact until the resolution of the 
ARI/complication(s) or until study end. 
• 
If between the different ARI visit/contacts, the participant was seen by another 
healthcare provider (HCP) for the ARI, the investigator/site staff should attempt to 
get maximum information on the ARI episode, diagnosis and results of any 
laboratory test done for identification of respiratory pathogens. 
• 
Re-starting scheduled surveillance contacts after ARI end: Once an ARI event 
has ended, the surveillance contacts should resume for that participant. The first 
surveillance contact should be planned: 
− 
within maximum 14 days after the last ARI follow-up contact if the last FU 
contact was done during the RSV seasons, or 
− 
within a maximum of 30 days if it’s during the inter-season period. 
8.1.1.6.2. Other routes to capture ARI episodes 
In some situations, the site staff might be informed of an ARI that was not immediately 
reported by the participant. The site staff could become aware of these ARI during a 
surveillance contact, via the participant’s call (later than 24 hours after ARI onset), via 
the participant’s caregiver or via the LTCF staff or hospital staff, for example. 
If the participant was seen by another healthcare provider (HCP) for the ARI, the 
investigator/site staff should attempt to get maximum information on the ARI episode, 
diagnosis and results of any laboratory test done for identification of respiratory 
pathogens. 
Note that if an ARI event meets the definition of AE or SAE it should also be reported as 
AE/SAE according to the specified follow-up periods described in Section 10.3.8. If an 
ARI is a suspected, probable or confirmed COVID-19 case as per WHO case definitions 
[WHO, 2020], the COVID-19 specific eCRF page should be completed. 
a. If, at the time of notification, the ARI is still ongoing and is reported within the 
interval allowed for ARI visit: 
− 
The site staff should encourage the participant to take a nasal self-swab* and to 
complete the daily health questionnaires***. The site staff will organize an ARI 
visit within the per protocol window**. Refer to Section 8.1.1.6.3 for guidance 
in case of hospitalization during an ARI episode. 

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*Note: The self-swab should not be done if the ARI visit is planned on the same 
day. The nasal and throat swab will be taken during the ARI visit. 
** Note: In special circumstances (for example in case of suspected COVID-19 
infection and pending COVID-19 test result, or self-quarantine) and if it is not 
possible to perform the ARI visit within 6 days after ARI onset, then the interval 
for this visit may be extended up to maximum 14 days after ARI onset (i.e., until 
Day 15). 
*** Note: If the ARI is reported more than 7 days after the ARI onset (i.e., on 
Day 8 or later), then the daily health questionnaires should not be completed for 
that ARI. 
− 
The procedures for the ARI visit and the nasal and throat swab samples as well 
as the subsequent follow-up contacts should be performed as described in Figure 
3 and Section 8.1.1.6.1. 
b. If, at the time of notification, the ARI is still ongoing but is reported outside of 
interval allowed for ARI visit: 
− 
The site staff should document the available ARI information, signs and 
symptoms in the eCRF but no swab samples should be taken, the daily health 
questionnaires should not be completed and no ARI visit should be organized. 
The need for additional visits or contacts for the medical management of the 
ARI should be assessed by the investigator and follow the local standard of care. 
− 
The procedures for the subsequent follow-up contacts (Day 15 and/or Day 29 
and/or additional follow-up calls) should be performed as described in Figure 3 
and Section 8.1.1.6.1. 
c. 
If the ARI symptoms/signs are gone at the time of notification: 
− 
The site staff should document the available ARI information, signs and 
symptoms in the eCRF and close the ARI. No swab samples should be taken. 
The daily health questionnaires should not be completed, and no ARI visit 
should be organized. 
8.1.1.6.3. Hospitalization during an ARI episode 
If a study participant is hospitalized during an ARI episode, the site staff should make 
best efforts to collect the relevant information and swab samples for efficacy assessment. 
Note that if the event also qualifies as an SAE, it should be reported to GSK during 
specified follow-up periods as described in Section 10.3.8. If an ARI is a suspected, 
probable or confirmed COVID-19 case as per WHO case definitions [WHO, 2020], the 
COVID-19 specific eCRF page should be completed. 
a. If the participant is hospitalized before the ARI visit: 
− 
The site staff should try to collect a swab sample (either at hospital or at the 
participant’s residence) within 6 days after ARI onset. The swab sample can be 
either self-collected by the participant (nasal self-swab) or by the site staff (nasal 
and throat swab). 

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− 
Whenever feasible, the other procedures for the ARI visit should be performed 
within 6 days after ARI onset* (see Table 4) and the daily health questionnaires 
should be completed. 
* Note: In special circumstances (for example in case of suspected COVID-19 
infection and pending COVID-19 test result, or self-quarantine) and if it is not 
possible to perform the ARI visit procedures within 6 days after ARI onset, then 
the interval for this visit may be extended up to maximum 14 days after ARI 
onset (i.e., until Day 15). 
− 
The investigator or designee should collect relevant information on the 
hospitalization and ARI episode including diagnosis, ARI signs and symptoms, 
results of any laboratory test done for identification of respiratory pathogens 
during the hospitalization and outcome of the hospitalization. 
− 
The subsequent ARI follow-up contacts should be performed as described in 
Figure 3 and Section 8.1.1.6.1. 
b. If the participant is hospitalized after the ARI visit: 
− 
The investigator or designee should collect relevant information on the 
hospitalization and ARI episode including diagnosis, ARI signs and symptoms, 
results of any laboratory test done for identification of respiratory pathogens 
during the hospitalization and outcome of the hospitalization. 
− 
The subsequent ARI follow-up contacts should be performed as described in 
Figure 3 and Section 8.1.1.6.1. 
8.1.2. 
Immunogenicity assessments  
The immunogenicity of the vaccine will be evaluated by assessing the humoral immune 
response at different timepoints. 
Serological assays for the characterization of the humoral immune response include 
ELISA for measurement of IgG antibodies binding to the RSVPreF3 protein and 
neutralization assay for determination of functional antibodies against RSV A and 
RSV B. RSVPreF3 IgG-binding ELISA and neutralization testing for RSV A and RSV B 
will be performed for participants included in the reactogenicity and immunogenicity 
subset. To evaluate the correlation between humoral immune response and protection, 
RSVPreF3 IgG-binding ELISA will also be tested on participants with RSV-confirmed 
disease and in a subset of control participants. A correlate of protection might also be 
investigated by testing the same subset by other relevant assays such as neutralization 
assay(s) and systems serology. 
Additional assessments, including but not limited to ELISA or other relevant assays for 
hMPV serological testing, may be conducted. 

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8.1.3. 
Biological samples 
Collected biological samples will be used for protocol-mandated research and purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. 
Future findings may make it desirable to use the samples acquired in this study for future 
research not described in this protocol. Therefore, all participants in countries where this 
is allowed will be asked to give a specific consent to allow GSK or a contracted partner 
to use the samples for future research. Future research will be subject to prior IEC/IRB 
approval if required per local legislation. 
Information on further investigations and their rationale can be obtained from GSK. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant. 
Collected samples will be stored for a maximum of 20 years. This storage period begins 
when the last participant performed the last study visit, unless local rules, regulations or 
guidelines require different timeframes or procedures, which would then be in line with 
participant consent. These extra requirements need to be communicated formally to, and 
discussed and agreed with GSK. 
8.1.3.1. 
Biological samples for efficacy assessment 
Swab samples will be taken in all participants meeting pre-specified criteria for case 
definition and evaluation of VE, according to the timing detailed in Section 8.1.1.6 (refer 
to Section 4.2.1) (see Table 17). 
Table 17 
Biological samples for efficacy assessment 
Sample type 
Timepoint 
Subset name 
Nasal self-swab specimen 
Case-driven 
All participants reporting at least 2 ARI symptoms/signs 
meeting the ARI case definition (see Table 10 in Section 
4.2.1) 
Nasal/throat swab specimen 
collected by qualified site staff 
Case-driven  
(ARI visit) 
All participants reporting at least 2 ARI symptoms/signs 
meeting the ARI case definition (see Table 10 in Section 
4.2.1) 
8.1.3.2. 
Biological samples for immunogenicity assessment (Amended, 12 July 
2023) 
A blood sample will be taken from all participants in both hemispheres at pre-Dose 1 
(Day 1), 1-month post-Dose 1 (Day 31) and from all participants at Visit 5NH* to allow 
the evaluation of a potential correlate of protection. In addition, the immune response to 
the RSVPreF3 OA investigational vaccine will be further evaluated at other timepoints in 
a subset of participants (see Table 18). 

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The overall volume of blood that will be collected during the entire study period is as 
follows: 
• 
~60 mL (3 x 20 mL) for participants in the reactogenicity and immunogenicity 
subset from SH, 
• 
~80 mL (4 x 20 mL) for participants in the reactogenicity and immunogenicity 
subset from NH, 
• 
~40 mL (2 x 20 mL) for all other participants in SH. 
• 
~60 mL (3 x 20 mL) for all other participants in NH* 
* Applicable after the approval of the current Protocol Amendment 5. 
Table 18 
Biological samples for immunogenicity assessment (Amended, 
12 July 2023) 
Sample type 
Quantity 
Unit 
Timepoint 
Subset name* 
Blood for correlate of 
protection 
20 
mL 
Visit 1 (Day 1, pre-Dose 1) 
Visit 2 (Day 31, post-Dose 1) 
All participants 
20 
mL 
Visit 5NH (Pre Season 3) 
All participants*** 
Blood for antibody 
measurement 
20 
mL 
Visit 3 (Pre Season 2, pre-Dose 2) 
Visit 5NH (Pre Season 3) 
Immunogenicity subset** 
* Refer to Section 6.3.4 for subset description. 
** Reactogenicity and immunogenicity subset (see Section 6.3.4). 
***All participants in the NH who will have their Visit 5NH after the approval of the current Protocol 
Amendment 5 including participants in the immunogenicity subset. 
Note: After the approval of the current Protocol Amendment 5, participants from the 
immunogenicity subset will still provide only 1 blood sample at Visit 5NH. This sample 
will be used for both the assessment of humoral immune response and evaluation of 
correlate of protection.  
8.1.4. 
Laboratory assays 
Please refer to the Section 10.2 for a brief description of the assays performed in the 
study. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 
GSK clinical laboratories have established a Quality System supported by procedures. 
The activities of GSK clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. 
8.1.4.1. 
Laboratory assays for efficacy assessment 
For ARI cases identified during the efficacy surveillance, the potential RSV infections 
will be assessed by RT-PCR testing of swab samples (see Table 19). The multiplex PCR 
assay that will be used to assess the potential hMPV infections will also detect by default 
the potential infection to Adenovirus, Enterovirus and Parainfluenza viruses. Swab 

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samples that are positive for RSV and/or hMPV by RT-PCR will be further tested for 
additional respiratory viruses such as Influenza, Bocavirus, Coronavirus and Rhinovirus 
for detection of potential viral co-infections. 
Further assessment of samples negative for RSV and negative for hMPV by RT-PCR 
may be performed with multiplex PCR if deemed necessary. 
Additional viral/bacterial diagnosis or characterization testing on the swab samples may 
be done, if deemed necessary for accurate interpretation of the data and/or should such 
assays become available at the GSK laboratory or a laboratory designated by GSK. 
Table 19 
Laboratory assays for molecular biology (PCR tests) 
System 
Component 
Method 
Laboratory* 
All nasal self-swab 
collected by the 
participant and 
nasal/throat swab 
specimen taken at ARI 
visit 
Respiratory Syncytial Virus A RNA 
Respiratory Syncytial Virus B RNA 
Quantitative RT-PCR 
GSK**  
All nasal self-swab 
collected by the 
participant and 
nasal/throat swab 
specimen taken at ARI 
visit 
Human adenovirus (AdV) 
Human metapneumovirus (hMPV) 
Human enterovirus (HEV) 
Human parainfluenza virus including at least 
types 1, 2, 3 and 4 (PIV1, PIV2, PIV3 and PIV4) 
Multiplex RT-PCR  
GSK** 
All nasal self-swab 
collected by the 
participant and 
nasal/throat swab 
specimen taken at ARI 
visit that are RSV A/B 
and/or hMPV positive by 
RT-PCR 
Influenza A virus (Flu A) 
Influenza B virus (Flu B) 
Human respiratory syncytial virus A (RSV A) 
Human respiratory syncytial virus B (RSV B) 
Human Influenza A virus subtype H1 (Flu A-H1) 
Human Influenza A virus subtype H3 (Flu A-H3) 
Human Influenza A virus subtype H1pdm09  
(Flu A-H1pdm09) 
Human bocavirus 1/2/3/4 (HBoV) 
Human rhinovirus A/B/C (HRV) 
Human coronavirus including at least 229E, 
NL63, OC43 and SARS-COV-2 species 
Multiplex RT-PCR 
GSK** 
RT-PCR: reverse transcription polymerase chain reaction 
* Refer to the list of clinical laboratories for details. 
** GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium. CLS may 
delegate testing to GSK Research laboratories in Rixensart, Belgium; Rockville, USA; Sienna, Italy or to a contracted 
CRO. 
8.1.4.2. 
Laboratory assays for immunogenicity assessment  
Serological assays for the characterization of the humoral immune response include 
ELISA for measurement of IgG antibodies binding to the RSVPreF3 protein and 
neutralization assay for determination of functional capacity of serum to protect cells 
against RSV A and RSV B (see Table 20). 

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Table 20 
Laboratory assays for humoral immune response (antibody 
determination)  
System 
Component 
Method 
Laboratory* 
Serum 
RSVPreF3-binding IgG antibody 
ELISA 
GSK** 
Serum 
Respiratory Syncytial Virus A antibody 
Neutralization 
GSK** 
Serum 
Respiratory Syncytial Virus B antibody 
Neutralization 
GSK** 
ELISA: enzyme-linked immunosorbent assay; IgG: immunoglobulin G 
* Refer to the list of clinical laboratories for details. 
** GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium. CLS may 
delegate testing to GSK Research laboratories in Rixensart, Belgium; Rockville, USA; Sienna, Italy or to a contracted 
CRO. 
8.1.5. 
Immunological read-outs (Amended, 12 July 2023) 
Table 21 
Immunological read-outs (Amended, 12 July 2023) 
Blood sampling 
time point 
Subset tested 
No. 
samples 
tested 
Component 
Components 
priority rank 
Type of 
contact 
and time 
point 
Sampling 
time 
point 
Visit 1 
(Day 1) 
Pre-Dose 
1 
Immunogenicity subset* 
~1800 
RSV A neutralizing antibody 
1 
RSV B neutralizing antibody 
2 
RSVPreF3-binding IgG 
antibody 
3 
All participants with RSV disease + 
Subset of controls** 
Case-
driven** 
RSVPreF3-binding IgG 
antibody 
- 
Visit 2 
(Day 31) 
30 days 
post-
Dose 1 
Immunogenicity subset* 
~1800 
RSV A neutralizing antibody 
1 
RSV B neutralizing antibody 
2 
RSVPreF3-binding IgG 
antibody 
3 
All participants with RSV disease + 
Subset of controls** 
Case-
driven** 
RSVPreF3-binding IgG 
antibody 
- 
Visit 3 
(Pre S2) 
Pre-Dose 
2 
Immunogenicity subset* 
~1800 
RSV A neutralizing antibody 
1 
RSV B neutralizing antibody 
2 
RSVPreF3-binding IgG 
antibody 
3 
Visit 5NH 
(Pre S3) 
Pre-
Season 3 
Immunogenicity subset* 
~1620 
RSV A neutralizing antibody 
1 
RSV B neutralizing antibody 
2 
RSVPreF3-binding IgG 
antibody 
3 
All participants with RSV disease 
+ Subset of controls** 
Case-
driven** 
RSVPreF3-binding IgG 
antibody 
- 
RSV = respiratory syncytial virus; IgG = immunoglobulin G 
* Reactogenicity and immunogenicity subset (see Section 6.3.4). 
** A blood sample will be taken in all participants at Visit 1 and Visit 2 to allow the evaluation of a potential correlate of 
protection. RSVPreF3 ELISA will be tested on all participants with RSV-confirmed disease and in a subset of control 
participants. Additional testing such as but not limited to neutralization assay(s) and systems serology testing might be 
performed on the same subset of participants to investigate a correlate of protection. After approval of this Protocol 
Amendment 5, a blood sample will also be taken at Visit 5NH. 
In case of insufficient blood sample volume to perform assays for all antibodies, the 
samples will be analyzed according to priority ranking provided in Table 21. 

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8.1.6. 
Molecular biology read-outs  
Table 22 
Molecular biology tests on swab samples 
Sampling time point 
Subset tested 
No. samples 
tested 
Component 
Components 
priority rank 
Type of contact 
and time point 
Sampling 
time point 
Sampling of 
nasal self-swab Unscheduled 
All participants with at 
least 2 ARI 
symptoms/signs* 
Case-driven 
RSV A/B RNA 
1 
Human adenovirus (AdV) 
Human metapneumovirus 
(hMPV) 
Human enterovirus (HEV) 
Human parainfluenza virus 
including at least types 1, 
2, 3 and 4 (PIV1, PIV2, 
PIV3 and PIV4) 
2 
All RSV A/B or hMPV 
positive swab samples** Case-driven 
Respiratory virus panel 
- 
ARI visit (nasal 
and throat 
swabs) 
Unscheduled 
All participants with at 
least 2 ARI 
symptoms/signs* 
Case-driven 
RSV A/B RNA 
1 
Human adenovirus (AdV) 
Human metapneumovirus 
(hMPV) 
Human enterovirus (HEV) 
Human parainfluenza virus 
including at least types 1, 
2, 3 and 4 (PIV1, PIV2, 
PIV3 and PIV4) 
2 
All RSV A/B or hMPV 
positive swab samples** Case-driven 
Respiratory virus panel 
- 
ARI: acute respiratory illness ; hMPV: human metapneumovirus; RSV: respiratory syncytial virus 
* RSV A/B and hMPV RT-PCR will be performed on all specimen from participants with at least 2 ARI symptoms/signs 
meeting the ARI case definition as per Table 10 in Section 4.2.1. 
** Respiratory virus panel (multiplex PCR) will be performed on all swabs RSV-A/B and/or hMPV positive by RT-PCR. 
Further assessment of RSV A/B and hMPV negative samples may be performed with multiplex PCR if deemed 
necessary. 
8.1.7. 
Immunological correlates of protection (Amended, 12 July 2023) 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen used in the RSVPreF3 OA investigational vaccine. 
This study will attempt to correlate humoral immune responses at Day 31 post-Dose 1 
and at pre-Season 3 (Visit 5NH) with protection against RSV-confirmed disease (see 
Section 9.4.5.4.1). Additional testing such as but not limited to neutralization assay(s) 
and systems serology testing might be performed on a subset of participants with 
RSV-confirmed disease and in a subset of control participants. 

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8.2. 
Safety assessments 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and any 
designees remain responsible for following up AEs that are serious, considered related to 
the study intervention or the study, or that caused the participant to discontinue the study. 
8.2.1. 
Pre-vaccination procedures 
8.2.1.1. 
Collection of demographic data 
Prior to the first study vaccination at Visit 1, record demographic data such as year of 
birth, sex, race*, ethnicity*, geographical hemisphere location (Northern/Southern 
hemisphere) and type of residence (CD/LTCF) in the participant’s eCRF. 
*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. 
8.2.1.2. 
Measure/record height and weight 
Prior to the first study vaccination at Visit 1, measure the participant’s height and weight 
and record the values in the eCRF. 
8.2.1.3. 
Medical history 
Prior to the first study vaccination at Visit 1, obtain the participant’s medical history by 
interviewing the participant and/or review of the participant’s medical records. Record 
any relevant pre-existing conditions, signs and/or symptoms present prior to the first 
study vaccination in the eCRF. 
A pre-defined list of comorbidities to be recorded will be available in the eCRF. 
8.2.1.4. 
Vaccination history 
Prior to the first study vaccination at Visit 1, obtain the participant’s vaccination history 
by interviewing the participant and/or review of the participant’s vaccination records. 
Any vaccine administered up to 1 year before the first study vaccine administration 
should be recorded in the eCRF with date of vaccination. For history of influenza 
vaccination, information about the vaccine formulation (e.g., adjuvanted or non-
adjuvanted or high-dose) should be recorded. 

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Administration of Shingrix at any timepoint (even if longer than 1 year before the first 
study vaccine administration) should be recorded in the eCRF. The date of vaccinations 
should be collected and recorded in the eCRF. 
8.2.1.5. 
Smoking status and smoking exposure history 
Prior to the first study vaccination at Visit 1, the smoking status will be collected in the 
eCRF, differentiating tobacco use (cigarettes, cigars, cigarillos, pipes …) and use of 
electronic smoking devices (e-cigarettes). Refer to Section 10.5.2 for the definitions of 
current and former smoker. 
Smoking exposure history should be recorded as number of years for both current and 
former smokers. When applicable, the number of years of exposure should be collected 
separately for tobacco and electronic smoking devices. 
All data will be recorded in the participant’s eCRF. 
8.2.1.6. 
Pre-vaccination body temperature 
The body temperature of each participant needs to be measured prior to any study vaccine 
administration and recorded in the eCRF. The route for measuring temperature can be 
oral, axillary or tympanic. If the participant has fever (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. 
8.2.1.7. 
Distribution of paper diary cards (Amended, 12 July 2023) 
A paper diary card will be distributed as follows: 
• 
To all participants at Visit 1 (Day 1), Visit 3 (pre-Season 2) and Visit 5NH (pre-
Season 3)* to note down any unsolicited AE as well as any medication and 
vaccination taken in the 30-day period following vaccination. 
• 
To participants in the reactogenicity and immunogenicity subset at Visit 1 (Day 
1),Visit 3 (pre-Season 2) and Visit 5NH (pre-Season 3)* to note down any solicited 
event, any unsolicited AE as well as any medication and vaccination taken in the 30-
day period following vaccination. 
*Not applicable for participants in the NH who will have their Visit 5NH after the 
approval of the current Protocol Amendment 5. Refer to Table 2 for details. 
Refer to Section 10.3.8 for guidelines. 
8.2.2. 
Procedures carried out at vaccination and non-vaccination visits 
8.2.2.1. 
Physical examination 
A physical examination should be performed at Visit 1 (Day 1 pre-Dose 1), Visit 2b 
(pre-Season 1 in SH), Visit 3 (pre-Season 2) and Visit 5NH (pre-Season 3) and at each 

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ARI visit. Collected information needs to be recorded in the eCRF. If the investigator 
determines that the participant’s health on the day of vaccination temporarily precludes 
vaccination, the visit will be rescheduled. 
Physical examination at other study visits 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. 
Treatment of any abnormality observed during physical examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. 
8.2.2.2. 
Body temperature during ARI episode 
The body temperature of the participant should be measured at the ARI visit(s) and 
recorded in the eCRF. The route for measuring temperature can be oral, axillary or 
tympanic. 
8.2.2.3. 
Lung auscultation (Amended, 12 July 2023) 
Lung auscultation should be performed at Visit 1 (Day 1 pre-Dose 1), Visit 2b 
(pre-Season 1 in SH), Visit 3 (pre-Season 2), Visit 5NH (pre-Season 3) and at each ARI 
visit. Collected information needs to be recorded in the study participant’s medical 
records. 
Lung auscultation at Visit 2 (Day 31 post-Dose 1/pre-Season 1), Visit 4 (Day 31 post-
Dose 2), Visit 6NH (Day 31 post-Dose 3)*, Visit 5SH (end of study) and Visit 7NH (end 
Season 3) 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. 
* Visit 6NH is not applicable for participants in the NH who will have their Visit 5NH 
after the approval of the current Protocol Amendment 5. Refer to Table 2 for details. 
8.2.2.4. 
Pulse oximetry 
Peripheral arterial oxygen saturation (SpO2%) will be assessed using pulse oximetry at 
Visit 1 (Day 1 pre-Dose 1), Visit 2b (pre-Season 1 in SH), Visit 3 (pre-Season 2), 
Visit 5NH (pre-Season 3) and at each ARI visit. Collected information needs to be 
recorded in the eCRF. 
For the purpose of the study, the same validated oxygen saturation device will be 
provided to each study site. 
8.2.2.5. 
Vital signs 
Resting vital signs should be checked at Visit 1 (Day 1 pre-Dose 1), Visit 2b (pre-Season 
1 in SH), Visit 3 (pre-Season 2) and Visit 5NH (pre-Season 3) and at each ARI visit. 

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Vital signs are to be taken before blood collection for laboratory tests and will consist of 
systolic/diastolic blood pressure, heart rate and respiratory rate after at least 10 minutes of 
rest by counting the number of breaths for 1 minute. Collected information needs to be 
recorded in the eCRF. 
8.2.3. 
Safety monitoring  
An IDMC will be appointed and operating under a charter to oversee the safety of 
participants and study conduct. 
An IDMC is an independent group of experts established by GSK that advises GSK. The 
primary responsibilities of the IDMC are to (1) periodically review and evaluate the 
accumulated unblinded data with the RSVPreF3 OA investigational vaccine and (2) make 
recommendations to the sponsor (see also Section 9.6). 
The IDMC includes experts in the field of geriatric medicine, internal medicine, 
epidemiology and biostatistics. 
In addition to the IDMC, the existing project’s SRT will review safety data on a regular 
basis as well. As of the implementation of Protocol Amendment 4, SRT will review 
unblinded safety data. 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
other events of interest 
8.3.1. 
Time period and frequency for collecting AE, SAE and other 
safety information (Amended, 12 July 2023) 
An overview of the protocol-required reporting periods for AEs, SAEs, and AESIs 
(including pIMDs and AF) is given in Table 23. 

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Table 23 
Timeframes for collecting and reporting of safety information (Amended, 12 July 2023) 
 
Pre- 
Vacc* 
 
Dose 
1 
 
 
 
 
 
Dose 
2 
 
 
 
 
 
Dose 
3#  
 
 
 
 
 
 
 
 
Day 
1 
post-
Dose 
1 
Day 
4 
post-
Dose 
1 
Day 
30 
post-
Dose 
1 
 
6 
months 
post- 
Dose 
1*** 
 
Day 
1 
post-
Dose 
2 
Day 
4 
post-
Dose 
2 
Day 
30 
post-
Dose 
2 
 
6 
months 
post- 
Dose 
2*** 
 
Day 
1 
post- 
Dose 
3# 
Day 
4 
post-
Dose 
3# 
Day 
30 
post-
Dose 
3# 
 
6 
months 
post- 
Dose 
3***, # 
 
Study 
conclusion 
Solicited administration 
site and systemic 
events** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs†  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SAEs†  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
‡ 
 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All pIMDs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
‡ 
 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study  
vaccination†  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
pIMDs related to study 
vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Pre- 
Vacc* 
 
Dose 
1 
 
 
 
 
 
Dose 
2 
 
 
 
 
 
Dose 
3#  
 
 
 
 
 
 
 
 
Day 
1 
post-
Dose 
1 
Day 
4 
post-
Dose 
1 
Day 
30 
post-
Dose 
1 
 
6 
months 
post- 
Dose 
1*** 
 
Day 
1 
post-
Dose 
2 
Day 
4 
post-
Dose 
2 
Day 
30 
post-
Dose 
2 
 
6 
months 
post- 
Dose 
2*** 
 
Day 
1 
post- 
Dose 
3# 
Day 
4 
post-
Dose 
3# 
Day 
30 
post-
Dose 
3# 
 
6 
months 
post- 
Dose 
3***, # 
 
Study 
conclusion 
SAEs related to study 
participation or 
concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatal SAEs†  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the 
study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Covid-19 cases 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intercurrent medical 
conditions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vacc: vaccination; AE: adverse event; SAE: serious adverse event; pIMD: potential immune mediated disease 
* Corresponds to day when informed consent is obtained (Day 1, prior to Dose 1). 
** Only for participants in the reactogenicity and immunogenicity subset. 
*** 6 months post-vaccination for each participant. 
# Dose 3 is only applicable for participants in the NH who will have their Visit 5NH before the approval of the current Protocol Amendment 5. 
‡For participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 5, solicited, unsolicited AEs and all SAEs and pIMDs 
occurring after Visit 5NH will not be collected. 
† Atrial fibrillation (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 will be performed according to the SAE reporting period. Fatal AF and 

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Serious AF judged as related to study vaccination will be performed according to the fatal SAE and related SAE reporting period, respectively. For AF that were reported before the 
implementation of the Protocol Amendment 4, additional available information should be encoded in the specific AF follow-up questionnaire retrospectively. 

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The investigator or designee will record and immediately report all SAEs to the sponsor 
or designee via the Expedited AE Reporting Form. This reporting should, under no 
circumstances, occur later than 24 hours after the investigator becomes aware of an SAE, 
as indicated in Section 10.3.10. The investigator will submit any updated SAE data to the 
sponsor 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 periods defined in Table 23 . Investigators are not obligated to actively seek 
AEs or SAEs in former study participants. However, if the investigator learns of any 
SAE, including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study vaccine, the 
investigator will promptly notify the Study Contact for Reporting SAEs mentioned in 
Table 25. 
8.3.2. 
Method of detecting AEs and SAEs and other events 
Methods of detecting and recording AE/SAE/AESI (including pIMDs and AF) are 
detailed in Section 10.3.8. The assessment of AE/SAE intensity, causality and outcome 
are provided in the Section 10.3.9. 
Open-ended and non-leading verbal questioning of the participants is the preferred 
method of acquiring information related to an AE/SAE/AESI (including pIMDs and AF). 
8.3.3. 
Regulatory reporting requirements for SAEs and other events  
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/AESI (including pIMDs and AF), he/she must report it to GSK 
using the required documentation, and within the timeframes, mentioned in Table 24. 
This is essential for meeting legal obligations and ethical responsibilities for participant 
safety and the safety of a study intervention under clinical investigation. 
For SAEs/AESIs (including pIMDs and AF), the investigator will always provide an 
assessment of causality at the time of the initial report, as defined in Section 10.3.9.2. 
Local regulatory requirements and sponsor policy for the preparation of an investigator 
safety report for Suspected Unexpected Serious Adverse Reactions (SUSAR) must be 
followed. These reports will be forwarded to investigators as necessary. 
The sponsor has a legal responsibility to notify local authorities and other regulatory 
agencies about the safety of a study intervention under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements related to safety reporting to 
the regulatory authority, IRB/IEC, and investigators. 
Please refer to Section 10.3.10 for further details regarding the reporting of SAEs/AESIs 
(including pIMDs and AF). 

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Table 24 
Timeframes for submitting serious adverse event and other events 
reports to GSK  
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
electronic Expedited Adverse 
Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
Serious AF†  
24 hours* ‡ 
electronic Expedited Adverse 
Events Report + AF follow-up 
questionnaire 
24 hours* 
electronic Expedited Adverse 
Events Report + AF follow-up 
questionnaire 
pIMDs 
24 hours** ‡  
electronic Expedited Adverse 
Events Report 
24 hours* 
electronic Expedited Adverse 
Events 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 a pIMD. 
‡ The investigator will be required to confirm review of the SAE/pIMD causality by ticking the ‘reviewed’ box in the 
electronic Expedited Adverse Events Report within 72 hours of submission of the SAE/pIMD. 
†Only AF meeting SAE definition will be reported in electronic Expedited AE 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. 
8.3.4. 
Contact information for reporting of SAEs, AESIs (including 
pIMDs and AF)  
Table 25 
Contact information for reporting of SAEs, AESIs (including pIMDs 
and AF)  
Study contact for questions regarding SAEs/AESIs (including pIMDs and AF) 
Refer to the local study contact information document 
Back-up study contact for reporting SAEs/AESIs (including pIMDs and AF) 
Available 24/24 hours and 7/7 days: 
 
GSK Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: 
 or 
 
E-mail address: 
 
US sites only: 
Fax:
 
Canadian sites only: 
Fax: 
 
8.3.5. 
Treatment of adverse events  
Any medication which may explain/cause/be used to treat an SAE/pIMD should be 
recorded in the Expedited Adverse Event Report of the participant’s eCRF screen (refer 
to Section 10.3.10.1). For the AF, this information will be captured in the Expedited 
Adverse Events Report and in the AF follow-up questionnaire in eCRF. 
PPD
PPD
PPD
PPD
PPD

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8.3.6. 
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 
keep the participant card in his/her possession at all times throughout the study. In an 
emergency, this card serves to inform the responsible attending physician/caregiver that 
the participant is in a clinical study and that relevant information may be obtained by 
contacting the investigator. 
8.4. 
Frailty status assessment 
To characterize the study population and determine if frailty may influence the safety, 
efficacy or immune response following administration of the study vaccine, the 
participants’ frailty status will be assessed at study entry (refer to Section 10.5.2 for the 
definition of frailty). Data should be recorded in the eCRF. 
The frailty status will be determined using the Gait speed test (refer to the SPM for 
details). 
8.5. 
Treatment of overdose 
Not applicable. 
8.6. 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.7. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.8. 
Genetics 
Genetics are not evaluated in this study. 
8.9. 
Biomarkers 
Biomarkers for pharmacogenetics are not evaluated in this study. 
8.10. 
Health outcomes 
Economic outcome measures such as HCRU data associated with healthcare encounters, 
will be collected in the eCRF or another data collection method (participant 
questionnaires, etc.) by the investigator and study site personnel for participants reporting 
ARI cases. The statistical analyses must be adjusted for protocol-mandated procedures, 
tests, and encounters. 

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8.10.1. 
Completion of HR-QoL questionnaires 
The EQ-5D and SF-12 questionnaires will be distributed and explained by the 
investigator or site staff and will be completed by all participants in the presence of site 
staff at Visit 1 (Day 1), Visit 3 (pre-Season 2) and Visit 5NH (pre-Season 3) and at the 
ARI visit for participants with ARI. Completeness of these questionnaires will be 
checked by the site staff in presence of the participant. 
In addition, the daily paper health questionnaires will be distributed to all participants at 
Visit 2 (Day 31 post-Dose 1), Visit 3 (pre-Season 2) and Visit 5NH (pre-Season 3). 
The daily health questionnaires include: 
• 
The Influenza patient-reported outcome (FLU-PRO) questionnaire, 
• 
The Patient Global Impression of Severity (PGI-S), 
• 
The Patient Global Impression of Change (PGI-C). 
The 3 questionnaires will be explained by the investigator or site staff and a first copy 
will be completed by all participants in the presence of site staff at Visit 2 as a baseline 
measurement. For each ARI episode, participants will be required to complete a copy of 
the health questionnaires at home daily starting from the day after the ARI onset until 
resolution of the episode or for a maximum of 14 days. (Note: completion of the daily 
health questionnaires is not applicable for ARI episodes reported before Visit 2). 
Note: 
• 
In case of physical incapacity that would preclude the self-completion of the 
questionnaires, either site staff can assist the participant (for questionnaires 
completed during site visits) or the participant may designate a caregiver for 
transcribing responses to the questionnaire. However, at no time, the caregiver/site 
staff will evaluate the participant’s health status, answer questionnaires or make 
decisions on behalf of the participant. Refer to Section 10.5.2 for definition of 
caregiver. 
• 
In case the questionnaire was completed with the assistance of a caregiver/site staff, 
this should be recorded on the questionnaire. 
Please refer to the SPM for more information on the questionnaires, including data 
collection. 
8.10.2. 
HCRU 
For all participants reporting an ARI episode, scheduled and unscheduled healthcare use 
linked to the ARI will be recorded in the eCRF. This will include: 
• 
Number of physician visits (General practitioner or specialist), 
• 
Emergency department visits, 
• 
Intensive care unit admissions, 

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• 
Hospitalizations, 
• 
Treatment (including oxygen therapy, use of mechanical ventilation, medication 
[e.g., antibiotics]). 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
9.1.1. 
Primary objective 
The primary objective of VE of a single dose of the RSVPreF3 OA investigational 
vaccine in the prevention of RSV-confirmed LRTD during the first season in adults ≥ 60 
years will be evaluated using a 1-sided test at alpha=2.5% level: 
• 
Criterion: VE will be demonstrated if the LL of the 2-sided 95% CIs is above 20%. 
VE Analysis 1: 
The final analysis of the primary objective will be case-driven. It will be performed when 
at least 56 cases of RSV-confirmed LRTDs have been accrued in the primary cohort for 
efficacy. 
This analysis will also include data from participants enrolled in SH available at that 
time. 
If the number of cases triggering VE Analysis 1 (at least 56 cases) is not achieved at the 
end of Season 1 in NH, an optional interim analysis might be performed when at least 
35 cases have been accrued (at the end of Season 1 in NH or later). In that case, an 
adjustment of the Type I error will be done in order to maintain the overall significance 
level at 2.5%. The Wang-Tsiatis approach which is an alpha spending method giving 
boundaries between O’Brien-Fleming and Pocock boundaries will be used [Wang, 1987] 
to determine the adjusted alpha levels for the interim (α1) and the final (α2) analyses. If 
the interim analysis is performed, then the final analysis will be performed when at least 
60 cases are accrued in the primary cohort for efficacy or when all data associated to the 
primary objective are available. 
Table 26 provides the 1-sided adjusted alpha levels obtained using the Wang-Tsiatis 
method with Δ = 0.3, depending on the quantity of information accumulated at the time 
of interim analysis (using gsDesign package in R). 

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Table 26 
One-sided alpha levels for interim and final analyses using Wang-
Tsiatis method, according to information accumulated at interim 
analysis 
 
Interim 
Final 
Information 
α1 
n1 
Power 
α2 
n2 
0.59 
0.0108 
35 
54% 
0.0193 
59 
0.65 
0.0120 
38 
59% 
0.0191 
59 
0.7 
0.0130 
41 
66% 
0.0191 
59 
0.75 
0.0141 
44 
69% 
0.0191 
59 
0.80 
0.0153 
47 
77% 
0.0193 
58 
Information=proportion of number of cases at interim analysis over those at final analysis 
n1=number of cases at interim; n2=number of cases at final analysis 
α1=1-sided alpha used for interim analysis; α2=1-sided alpha used for final analysis  
Power calculated assuming a vaccine efficacy of 70% 
9.1.2. 
Secondary objectives (Amended, 12 July 2023) 
The confirmatory secondary objectives are the following: 
• 
To demonstrate the efficacy of a single dose of the RSVPreF3 OA investigational 
vaccine in the prevention of RSV-confirmed LRTD in adults ≥ 60 YOA over several 
seasons. 
Criterion: The LL of the 2-sided CI for VE is above 20%. 
• 
To demonstrate the efficacy of a single dose of RSVPreF3 OA investigational 
vaccine followed by 1 annual revaccination before Season 2 in the prevention of 
RSV-confirmed LRTD in adults ≥ 60 YOA over several seasons. 
Criterion: The LL of the 2-sided CI for VE is above 20%. 
• 
To demonstrate the efficacy of a single dose and 1 annual revaccination before 
Season 2 of RSVPreF3 OA investigational vaccine in the prevention of RSV-
confirmed LRTD for each RSV subtype (A and B) separately in adults ≥ 60 YOA 
over 3 seasons. 
Criterion: The LL of the 2-sided CI for VE is above 0%. 
VE Analysis 2 after Season 1 in NH: 
The confirmatory secondary objective assessing VE of a single dose of the RSVPreF3 
OA vaccine in the prevention of RSV-confirmed LRTD in adults ≥ 60 years after 
Season 1 in NH will be evaluated conditionally to the success of the primary objective 
(success indicated by the black arrows in Figure 4) using a 1-sided test at alpha=2.5% 
level. 
VE Analysis 2 will be performed when participants in NH have been followed until the 
end of the first season in NH (30 April), i.e., when all ARI with onset visit and swabs 
collected until the end of the season (30 April) are adjudicated and RSV qRT-PCR results 
are available. 

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VE Analysis 2 will be performed if at least 1 additional RSV-confirmed ARI has been 
reported since VE Analysis 1 and if there are at least 2-3 weeks between the data lock 
point dates of the 2 analyses. 
VE of a single dose over 2 and 3 seasons: 
• 
The confirmatory secondary objective assessing VE of a single dose with RSVPreF3 
OA vaccine in the prevention of RSV-confirmed LRTD in adults ≥ 60 years after 
Season 2 in NH (S1+S2NH) will be evaluated conditionally to the success of the 
previous objective evaluating VE after Season 1 in NH (see Figure 4). A Bonferroni 
adjustment of alpha for multiplicity will be applied. Therefore, this analysis will be 
done using a 1-sided test at alpha=1.25% level. 
• 
The confirmatory secondary objective assessing VE of a single dose with RSVPreF3 
OA vaccine in the prevention of RSV-confirmed LRTD in adults ≥ 60 years after 
Season 3 in NH (S1+S2+S3NH) will be evaluated conditionally to the success of the 
single dose objective after Season 2 (see Figure 4). This analysis will be done using a 
1-sided test at alpha=1.25% level. 
• 
The confirmatory secondary objective assessing VE of a single dose with RSVPreF3 
OA vaccine in the prevention of RSV-confirmed LRTD for each RSV subtype (A 
and B) separately in adults ≥ 60 years after Season 3 in NH (S1+S2+S3NH) will be 
evaluated conditionally to the success of the RSV objective of single dose after 
Season 3. This analysis will be done using a 1-sided test at alpha=1.25% level. 
Analysis will be case-driven and will be performed if at least 61 cases are accrued 
for each subtype (RSV A and RSV B). The RSV A objective will be tested first, and 
if demonstrated, the RSV B objective will also be tested (see Figure 4). 
VE of the 1 annual revaccination given before Season 2 over 2 and 3 seasons: 
• 
The confirmatory secondary objective assessing VE of the annual revaccination 
given before Season 2 with RSVPreF3 OA vaccine in the prevention of RSV-
confirmed LRTD in adults ≥ 60 years after Season 2 in NH (S1+A2NH) will be 
evaluated conditionally to the success of the previous objective evaluating VE after 
Season 1 in NH (see Figure 4). A Bonferroni adjustment of alpha for multiplicity 
will be applied. Therefore, this analysis will be done using a 1-sided test at 
alpha=1.25% level. 
• 
The confirmatory secondary objective assessing VE of the annual revaccination 
given before Season 2 with RSVPreF3 OA vaccine in the prevention of RSV-
confirmed LRTD in adults ≥ 60 years after Season 3 in NH (S1+A2+A3NH) will be 
evaluated conditionally to the success of the annual revaccination objective after 
Season 2 (see Figure 4). This analysis will be done using a 1-sided test at 
alpha=1.25% level. 
• 
The confirmatory secondary objective assessing VE of the annual revaccination 
given before Season 2 with RSVPreF3 OA vaccine in the prevention of RSV-
confirmed LRTD for each RSV subtype (A and B) separately in adults ≥ 60 years 
after Season 3 in NH (S1+A2+A3NH) will be evaluated conditionally to the success 
of the RSV objective of annual revaccination after Season 3 (see Figure 4). 

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Analysis will be case-driven and will be performed if at least 49 cases are accrued 
for each subtype (RSV A and RSV B). The RSV A objective will be tested first, and 
if demonstrated, the RSV B objective will also be tested (see Figure 4). 
Note that participants who received a third dose of RSVPreF3 OA investigational 
vaccine will not be included in the evaluation of annual revaccination over 3 seasons. 
Figure 4 presents the sequence of analysis if at least 56 cases have been accrued before 
the end of Season 1 in NH. 
Figure 4 
Sequential evaluation of primary and confirmatory secondary 
objectives (Amended, 12 July 2023) 
 
 
S1/S2/S3=Season 1/2/3 after a single dose 
A2/A3 = Annual evaluation during Season 2/3 (after 1 revaccination given before Season 2) 
VE against RSV LRTDs α=2.5%
After at least 56 cases
VE on S1
Primary objective - Case-driven
Analysis after S2NH
VE against RSV LRTDs α=2.5%
At end of season 1 in NH*
VE on S1
Analysis after S2NH
VE against RSV LRTDs
Annual vaccination α=1.25%
VE on S1+A2NH
Analysis after S3NH
VE on S1+A2+A3NH
VE against RSV LRTDs
Annual vaccination α=1.25%
VE against RSV LRTDs over 3 
seasons α=1.25%
VE against RSV LRTDs over 
2 seasons α=1.25%
VE on S1+S2NH
Analysis after S3NH         
VE on S1+S2+S3NH
Analysis after S1NH
VE against RSV A LRTDs
Annual vaccination α=1.25%
Case driven: at least 49 cases
VE against RSV B LRTDs
Annual vaccination α=1.25%
Case driven: at least 49 cases
VE against RSV A LRTDs
over 3 seasons α=1.25%
Case driven: at least 61 cases
VE against RSV B LRTDs
over 3 seasons α=1.25%
Case driven: at least 61 cases
Confirmatory secondary objectives over several seasons

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NH = Northern Hemisphere; Season 3 is only applicable in the NH 
VE=Vaccine efficacy 
* The end of S1NH analysis will be performed if at least 1 additional RSV-confirmed ARI has been reported since the 
analysis of the primary objective and if there are at least 2-3 weeks between the database cut-off dates of the 2 
analyses. 
Note: VE analysis by subtype will be case-driven and will be performed if at least 49/61 cases are accrued for each 
subtype, i.e., RSV A and RSV B. 
All the objectives will be evaluated, but if one of them fails to be demonstrated, the 
remaining subsequent analysis will be performed as descriptive, and the Type I error may 
not be fully controlled. 
If the 56 cases are not accrued before the end of the Season 1 in NH, an optional interim 
analysis might be performed when at least 35 cases are accrued (at the end of Season 1 in 
NH or later). In that case, the interim analysis will be tested using a 1-sided test at 
adjusted alpha level α1 and the final analysis will be performed when at least 60 cases are 
accrued (or when all data associated to the primary objective are available) using a 1-
sided test at adjusted alpha level α2 (see Table 26). 
If an interim analysis is performed, the adjusted alpha levels used for testing of the 
secondary confirmatory objectives will be evaluated by simulations and will be further 
described in the Statistical Analysis Plan (SAP). 
9.2. 
Sample size determination 
The study will enroll up to 25 000 participants, distributed as follows: 
• 
Between at least 16 000 and up to 23 000 participants in the NH, and 
• 
Between 1 500 and 2 000 participants in the SH. 
Approximately 1 800 participants will be included in the reactogenicity and 
immunogenicity subset with 1 620 participants in NH and 180 participants in SH. 
The sections below describe the assumptions and methodology used for the sample size 
calculation. 
Withdrawals will not be replaced. 
9.2.1. 
Primary objective: Vaccine efficacy 
The overall Type I error is equal to 2.5% (1-sided alpha=0.025). The sample size has 
been calculated based on the number of cases needed to demonstrate a VE against 
RSV confirmed LRTD during the first season in NH, with the criterion of a LL of the 
95% CIs >20%. 
Hypothesis to show VE can be written as follows: 
H0: VE  20% versus Ha: VE >20% 

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And can also be translated using proportions: 
H0 : p ≥ p0 = 0.4444 versus Ha : p < p0 
Using a 1-sided exact binomial test (Pass 2019, Exact test for one proportion, 1-sided 
alpha=0.025), at least 56 cases of RSV-confirmed LRTDs are needed in the primary 
cohort for efficacy to have at least 90% power to demonstrate a significant VE (LL of 
95% CI > 20%), assuming a true VE of 70% (p=0.2308). 
Therefore, assuming an attack rate of RSV-confirmed LRTD around 0.6% during the first 
season, and that approximately 10% of the vaccinated participants will be non-evaluable 
for the primary analysis of efficacy, a minimum of 16 000 participants has to be enrolled 
to reach the expected number of cases in NH. 
However, due to the potential impact of COVID-19 pandemic measures on the RSV 
circulation and the difficulty to estimate the attack rate for the first season of the study, 
the sample size could be increased up to 23 000 participants in NH to mitigate the risk of 
a lower attack rate, as shown in Table 27. 
Table 27 
Total sample size to be enrolled in the NH to ensure at least 90% 
power to demonstrate the primary objective depending on attack 
rate, assuming a non-evaluable rate of 10% 
Number of cases needed for Primary objective 
Attack rate 
Sample size 
56 RSV-confirmed LRTD 
0.6% 
16 000 
 
0.55% 
17 500 
 
0.5% 
19 200 
 
0.45% 
21 500 
 
0.42% 
23 000 
 
0.4% 
24 000 
If an interim analysis is performed, the power to demonstrate the primary objective with 
at least 35 cases at interim is at least 54% (see Table 26). For the final analysis, at least 
60 cases will be needed (at adjusted alpha level= α2, see Table 26), to have at least 90% 
power to demonstrate the primary objective. 
9.2.2. 
Secondary objectives (Amended, 12 July 2023) 
Table 28 provides the expected total number of RSV LRTD cases and the power for each 
analysis assuming: 
• 
a minimum sample size of 16 000 participants in NH and of 1500 participants in SH, 
• 
a maximum sample size of 23 000 participants in NH and of 2000 participants in SH, 
• 
a non-evaluable rate of 10% for the efficacy analysis, 
• 
a dropout rate of 20% between each season, 
• 
an attack rate of 0.6% at each season for RSV-confirmed LRTDs, 
• 
a VE against RSV-confirmed LRTDs of 70% over 1 season after Dose 1 (Season 1) 
and after 1 revaccination dose (Season 2), VE of 65% at Season 3. 

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• 
a VE against RSV-confirmed LRTDs of 70/65/60% at Season 1/2/3 after a single 
dose, respectively. 
Table 28 
Power to demonstrate secondary confirmatory objectives 
(Amended, 12 July 2023) 
Endpoint 
(success criterion) 
Sample size 
AR 
Analysis 
Expected number 
of cases 
Power (1-sided 
alpha=1.25%) 
RSV-confirmed 
LRTDs (LL>20%) 
16000+1500 
0.6% 
S1+A2NH 
101 
97.7% 
 
 
S1+A2+A3NH 
137  
99.1% 
 
 
 
S1+S2NH 
102 
95.8% 
 
 
 
S1+S2+S3NH 
139 
98.2% 
 
23000+2000 
0.6% 
S1+A2NH 
144 
99.8% 
 
 
 
S1+A2+A3NH 
196  
≥99.9% 
 
 
 
S1+S2NH 
146 
99.5% 
 
 
 
S1+S2+S3NH 
198 
99.8% 
S1/S2/S3 = Seasons 1/2/3; A2/A3=Annual evaluation during Season 2/3 (after 1 revaccination given before Season 
2); LL = lower limit 
NH=North Hemisphere; AR=Attack rate; VE=vaccine efficacy 
Power computed using Pass 2019, Exact test for one proportion, 1-sided alpha=0.0125 
For the confirmatory secondary objective of VE against RSV-confirmed LRTD for each 
RSV subtype (A and B) separately after 3 seasons in NH, the analysis will be case-driven 
and will be performed if the trigger is reached for both RSV A and RSV B separately. 
The trigger has been computed to have 90% power to demonstrate each objective 
sequentially: 
• 
For VE of a single dose: at least 61 cases are needed to have at least 90% power to 
demonstrate a significant VE (LL of 97.5% CI >0%); 
• 
For VE of annual revaccination: at least 49 cases are needed to have at least 90% 
power to demonstrate a significant VE (LL of 97.5% CI >0%). 
9.2.2.1. 
Expected number of RSV-confirmed LRTD cases (Amended, 12 July 
2023) 
As examples, Table 29 and Table 30 summarize the number of participants and number 
of RSV-confirmed LRTD cases expected after each season in each hemisphere for each 
schedule based on the assumptions used to compute the minimum sample size of 16 000 
participants in the NH and 1500 participants in the SH. 
Table 29 
Expected number of RSV-confirmed LRTD cases for the evaluation 
of VE of the single dose 
 
N at start of season 
Expected 
Attack rate 
Expected 
Season 
RSVPreF3 
group 
RSV_1dose 
group 
Placebo 
group 
vaccine 
efficacy 
Placebo 
group 
Vaccine 
group 
number 
of cases* 
S1NH 
8000 
- 
8000 
70% 
0.60% 
0.18% 
56 
S1SH 
750 
- 
750 
70% 
0.60% 
0.18% 
5 
S2NH 
- 
3200 
6400 
65% 
0.60% 
0.21% 
40 
S2SH 
- 
300 
600 
65% 
0.60% 
0.21% 
3 
S3NH 
- 
2560 
5120 
60% 
0.60% 
0.24% 
33 
VE: Vaccine Efficacy 
S1NH= End of Season 1 in Northern Hemisphere 

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S2NH= End of Season 2 in Northern Hemisphere for participants receiving a single dose 
S3NH= End of Season 3 in Northern Hemisphere for participants receiving a single dose 
S1SH= End of Season 1 in Southern Hemisphere 
S2SH= End of Season 2 in Southern Hemisphere for participants receiving a single dose 
* Considering a dropout rate between 2 seasons=20% and a non-evaluable rate=10% 
Table 30 
Expected number of RSV-confirmed LRTD cases for the evaluation 
of VE of the annual revaccination (Amended, 12 July 2023) 
 
N at start of season 
Expected 
Attack rate 
Expected 
Season 
RSVPreF3 
group 
RSV_annual 
group 
Placebo 
group 
vaccine 
efficacy 
Placebo 
group 
Vaccine 
group 
number 
of cases* 
S1NH 
8000 
- 
8000 
70% 
0.60% 
0.18% 
56 
S1SH 
750 
- 
750 
70% 
0.60% 
0.18% 
5 
A2NH 
- 
3200 
6400 
70% 
0.60% 
0.18% 
39 
A2SH 
- 
300 
600 
70% 
0.60% 
0.18% 
3 
A3NH 
- 
2560 
5120 
65% 
0.60% 
0.18% 
32 
VE: vaccine efficacy 
S1NH= End of Season 1 in the Northern Hemisphere 
A2NH= End of Season 2 in the Northern Hemisphere for participants receiving a revaccination dose 
A3NH= End of Season 3 in the Northern Hemisphere for participants receiving 1 revaccination dose before Season 2. 
S1SH= End of Season 1 in the Southern Hemisphere 
A2SH= End of Season 2 in the Southern Hemisphere for participants receiving a revaccination dose 
* Considering a dropout rate between 2 seasons=20% and a non-evaluable rate=10% 
9.2.3. 
Sample size re-assessment 
The number of RSV-confirmed LRTD cases for the primary objective will be monitored 
on an ongoing basis during Season 1. This will be performed in a blinded way by 
counting the total number of cases reported overall in the pooled RSV and Placebo 
groups. 
If the total number of cases reported up to early April is low compared to the trigger for 
analysis (at least 56 cases), a second cohort (new participants) might be enrolled before 
the next season in NH, in order to continue the accrual of the cases at the next season 
(Season 1 of second cohort) and to increase the number of cases needed to demonstrate 
the primary objective. 
At the time of evaluation, the following rule will be applied for the enrollment of the 
second cohort: 
• 
If the total number of cases is greater than 50 cases or lower than 12 cases: No 
enrollment of second cohort. The monitoring will continue and VE Analysis 1 will 
be performed as described in Section 9.1.1. 
• 
If the total number of cases is included in [12, 50 cases]: Enrollment of a second 
cohort. In that case, new participants in NH will be enrolled and vaccinated before 
the next season in NH. The monitoring will continue and VE Analysis 1 will be 
performed as described in Section 9.1.1. 
The study will be extended and will end when participants of the second cohort have 
been followed up to 3 consecutive RSV seasons. 

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According to feasibility of enrollment of this second cohort before the next season, it is 
estimated that a maximum number of 10 000 participants might be enrolled in the second 
cohort. 
GSK can decide to cancel this re-enrollment if the final analysis (at least 56 cases) is 
performed at the end of Season 1 in NH or if the interim analysis is successful. 
The participants in this second cohort will be randomized in 3 study groups: RSV_annual 
group, RSV_1dose group and Placebo group, according to a 1:1:2 randomization ratio, 
and they will follow the same study procedures as participants of the first cohort. 
The system’s randomization algorithm will use a minimization procedure accounting for 
center, age and region. Minimization factors will have equal weight in the minimization 
algorithm. 
9.2.4. 
Reactogenicity subset 
Solicited events information will be collected for a subset of participants using paper 
diaries. Approximately 1800 participants will be included in the reactogenicity subset 
from both NH and SH (see Table 13). 
Table 31 presents the probability to observe at least one event, depending on the true AE 
rate, for 900 participants per group as well as for smaller subsets, as reactogenicity 
analysis might be done on several subgroups (e.g., by age category, region). A subset of 
900 participants per group would provide a probability of 98.9% to observe at least one 
event with a true incidence rate of 0.5%. 
Table 31 
Probability (%) to observe at least one event depending on AE 
incidence 
N in subset 
Probability (%) to observe at least 1 event 
depending on AE incidence 
0.1% 
0.5% 
1% 
2% 
3% 
50 
4.88 
22.17 
39.50 
63.58 
78.19 
100 
9.52 
39.42 
63.40 
86.74 
95.24 
200 
18.14 
63.30 
86.60 
98.24 
99.77 
300 
25.93 
77.77 
95.10 
99.77 
>99.9 
400 
32.98 
86.53 
98.20 
>99.9 
>99.9 
500 
39.36 
91.84 
>99% 
>99.9 
>99.9 
700 
50.36 
97.01 
>99% 
>99.9 
>99.9 
900 
59.36 
98.90 
>99% 
>99.9 
>99.9 

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9.3. 
Populations for analyses (Amended, 12 July 2023) 
Table 32 
Populations for analyses 
Analysis set 
Description 
Enrolled set 
Participants who agreed to participate in a clinical study after completion of the 
informed consent process*. 
Exposed Set (ES) 
All participants who received at least the first dose of the study intervention. The 
allocation in a group is done in function of the administered intervention. 
Per Protocol Set for 
immunogenicity (PPSi) 
All participants who received at least the first dose of the study intervention to which 
they were randomized, have post-vaccination immunogenicity data available, and did 
not meet protocol deviations that lead to exclusion. 
Solicited Safety Set 
All participants who received at least the first dose of the study intervention (Exposed 
Set) and have solicited safety data. 
*All participants enrolled and included in the database will be part of the enrolled set. 
Exposed Set Dose 2 and Exposed Set Dose 3 including all participants who received 
the 2nd and the 3rd dose, respectively, will also be used to report analysis on post-Dose 
2/3 data. 
In addition, the following populations will be defined for efficacy analyses (refer to 
Section 9.4.3 for detailed information on the analysis set): 
• 
Modified Exposed Set (mES): the mES will be the primary population for efficacy 
analysis on RSV-confirmed cases. It will include all participants who received at 
least the first dose of the study intervention (ES) and who did not report an RSV-
confirmed ARI prior to Day 15 after each vaccination. The allocation in a group is 
done in function of the administered intervention. 
mES will be defined by dose as follows: 
• 
mES: participants who received Dose 1 and who did not report RSV ARI within 
15 days post-Dose 1, 
• 
mES Dose 2: participants who received Dose 2 and who did not report RSV ARI 
within 15 days post-Dose 2, 
• 
mES Dose 3: participants who received Dose 3 and who did not report RSV ARI 
within 15 days post-Dose 3. 
Note that participants who received a third dose of RSVPreF3 OA investigational 
vaccine will not be included in the primary evaluation of annual revaccination 
over 3 seasons. Details will be provided in the SAP. 
• 
Per Protocol set for efficacy (PPSe): the PPSe will include all participants included 
in the mES who: 
− 
received at least the first dose of the study vaccine to which they were 
randomized, 
− 
did not have protocol deviations leading to exclusion. 
The list of protocol deviations leading to exclusion from PPS will be defined in the SAP 
prior to study start. 

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In addition, the following populations will be defined for analyses of patient-reported 
outcomes (i.e., EQ-5D, SF-12 and daily health questionnaires): 
• 
mES RSV-confirmed ARI cases: All participants in the mES-RSV who have an 
RT-PCR-confirmed RSV case. 
• 
mES RSV-confirmed LRTD cases: All participants in the mES-RSV who have an 
RT-PCR-confirmed RSV-LRTD case. 
9.3.1. 
Criteria for elimination from analysis 
9.3.1.1. 
Intercurrent medical conditions and concomitant 
medications/products/vaccines that may lead to elimination of a 
participant from per protocol analyses 
If the participant meets one of the criteria mentioned in Section 5.2.1 (medical 
conditions) or Section 5.2.2 (concomitant therapy), he/she may be eliminated from the 
PPSe and PPSi. 
In addition, participants may be eliminated from the PPSi 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. 
9.4. 
Statistical analyses 
The SAP will be finalized prior to First Participant First Visit and will include a more 
technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses of the most important endpoints 
including primary and key secondary endpoints. 
For all statistical analyses described in this section, the 4 RSVPreF3 vaccine lots will be 
pooled and results will be presented for RSVPreF3 group, RSV_annual group or 
RSV_1dose group versus Placebo group. 
9.4.1. 
General considerations 
9.4.1.1. 
Demography 
For a given participant and a given demographic variable, missing measurements will not 
be replaced. 
9.4.1.2. 
Efficacy 
All reported ARI cases will be reviewed by blinded, qualified GSK staff members to 
determine whether certain investigator-reported events meet the definition of efficacy 
endpoints (LRTD and severe LRTD), using pre-defined endpoint criteria. This review 
will be made on clinical criteria (signs/symptoms) and independently of the results of the 
RSV RT-PCR. 

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Detailed information on this adjudication process, including for data obtained by 
methodologies which are not protocol-specified or for missing data, will be described in 
the adjudication charter. 
For a given participant and a given efficacy measurement, missing or non-evaluable 
measurements will not be imputed for the primary analysis. The missing endpoint and 
censoring are supposed to occur independently, and the pattern of the missingness being 
either Completely At Random (MCAR) or Missing At Random (MAR) only. 
The potential RSV or hMPV infections, including the potential infection to Adenovirus, 
Enterovirus and Parainfluenza viruses, will be assessed by RT-PCR testing of swab 
samples (see Table 19). Swab samples that are positive for RSV and/or hMPV by RT-
PCR will be tested by a multiplex PCR (panel of viruses) for detection of potential viral 
co-infection. 
A case that is positive by the quantitative RT-PCR for RSV A and/or RSV B will be 
counted as an RSV-confirmed case, whatever the result for RSVA/B tested by multiplex 
RT-PCR, for hMPV or other respiratory virus tested by multiplex RT-PCR (co-infection). 
A case that is positive by multiplex RT-PCR for hMPV will be counted as a hMPV-
confirmed case, whatever the result for RSV A/B or other respiratory virus (co-infection). 
The events linked to primary and secondary efficacy outcomes will be identified and in 
case multiple events are observed for the same participant, only the first event will be 
considered for the primary analysis of all primary/secondary endpoints. 
Therefore, for the primary analysis of the primary objective, the number of RSV-
confirmed LRTD will be computed on the first occurrence of qRT-PCR-confirmed RSV 
A and/or RSV B associated LRTD, starting on Day 15 after the first vaccination for 
analysis on the mES-RSV and the PPSe. 
For analysis on the ES, the analysis will include the first occurrence of the RSV-
confirmed LRTD case reported after the first vaccination (starting from Visit 1). 
9.4.1.3. 
Immunogenicity 
• 
Any missing or non-evaluable immunogenicity measurement will not be replaced. 
The descriptive analysis performed for each assay at each time point will exclude 
participants with a missing or non-evaluable measurement. 
• 
The geometric mean titers/concentrations (GMTs/GMCs) will be computed by 
taking the anti-logarithm of the arithmetic mean of the log10 transformed 
titers/concentrations. 
• 
A seronegative participant will be defined as a participant whose antibody 
titer/concentration is below the cut-off value of the assay. A seropositive participant 
is a participant whose antibody titer/concentration is greater than or equal to the cut-
off value of the assay. 

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• 
Antibody titers/concentrations below the assay cut-off will be given an arbitrary 
value of half the assay cut-off for the purpose of GMT/GMC calculation. Antibody 
titers/concentrations above the upper limit of quantification (ULOQ) of the assay 
will be given an arbitrary value of the ULOQ for the purpose of GMT/GMC 
calculation. 
• 
The mean geometric increase (MGI) is defined as the geometric mean of the within 
participant ratios of the post-vaccination titer/concentration over the pre-vaccination 
titer/concentration. 
9.4.1.4. 
Reactogenicity/Safety  
• 
For a given participant and the analysis of solicited events within 4 days post-
vaccination, missing or non-evaluable measurements will not be replaced. Therefore, 
the analysis of solicited events will include only vaccinated participants with 
documented solicited safety data (i.e., paper diary completed). 
• 
For analysis of unsolicited AEs, SAEs, AESIs (including pIMDs and AF) and 
concomitant medications, all vaccinated participants will be considered. Participants 
who did not report an event or concomitant medication will be considered as 
participants without the event or the concomitant medication respectively. 
9.4.1.5. 
Quality of life 
• 
The FLU-PRO version 2.0 is a 32-item daily diary assessing influenza signs and 
symptoms across 6 body systems: Nose (4 items), Throat (3 items), Eyes (3 items), 
Chest/Respiratory (7 items, i.e., LRTI), Gastrointestinal (4 items), and 
Body/Systemic (11 items). Respondents are asked to rate each sign or symptom on a 
5-point ordinal scale, with higher scores indicating a more frequent sign or symptom. 
For 27 of the items, the scale is as follows: 0 (“Not at all”), 1 (“A little bit”), 
2 (“Somewhat”), 3 (“Quite a bit”), and 4 (“Very much”). For 2 items, severity is 
assessed in terms of numerical frequency, i.e., vomiting or diarrhea (0 times, 1 time, 
2 times, 3 times, or 4 or more times); with the final 3 items; frequency of sneezing, 
coughing, and coughed up mucus or phlegm evaluated on a scale from 0 (“Never”) 
to 4 (“Always”). The FLU-PRO total score is computed as the mean score across all 
32 items comprising the instrument. Total scores can range from 0 (symptom free) to 
4 (very severe symptoms). 
In addition, a score assessing the symptoms associated with upper respiratory 
systems will be computed as the mean score across the 10 items that make up the 
Nose, Throat and Eyes domains. 
Six individual domain scores will also be computed, representing symptom severity 
in each of the assessed body areas: Nose, Throat, Eyes, Chest/Respiratory (i.e., 
LRTD), Gastrointestinal and Body/Systemic. Each domain score is calculated as the 
mean of all items comprising that domain, with scores ranging from 0 to 4. 
• 
The PGI-S and the PGI-C are 2 patient-reported questions on the severity of 
symptoms and the change in symptoms, respectively. The PGI-S classifies the 
severity of symptoms into 5 categories (No symptoms, Mild, Moderate, Severe, 

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Very severe). The PGI-C classifies the change in symptoms from the previous day 
into 7 categories (Much better, Somewhat better, A little better, About the same, 
A little worse, Somewhat worse and Much worse). 
• 
The EQ-5D health utility questionnaire, described through 5 dimensions scores (i.e., 
mobility, self-care, usual activities, pain/discomfort and anxiety/depression) will be 
converted into generate health profiles, i.e., a respondent who responds 1 (no 
problem/no symptom) to all 5 items has a profile “11111” and similarly a participant 
who responds with the highest level of difficulty or symptom to all items has a 
profile “33333”. These profiles are subsequently converted to a continuous single 
index utility score using a 1 to 1 matching. 
• 
The SF-12 questionnaire is a multi-purpose health survey with 12 questions. The SF-
12 covers 8 HR-QoL domains (physical functioning, role physical, bodily pain, 
general health, vitality, social functioning, role emotional and mental health). From 
these domains, summary scores for the physical component and mental component 
are computed. Scale scores will be constructed following the summated ratings and 
standardized SF-12 scoring algorithms. 
9.4.2. 
Demographics and participants disposition 
Demographic characteristics (age at first vaccination in years, BMI, sex, race, ethnicity, 
geographical hemisphere location (Northern/Southern), type of residence (CD/LTCF), 
vital signs, comorbidities, frailty status and smoking status) will be summarized by group 
using descriptive statistics: 
• 
Frequency tables will be generated for categorical variables such as race; 
• 
Mean, median, standard deviation and range will be provided for continuous data as 
age. 
The number of doses of the study vaccine administered will be tabulated by group. 
The distribution of participants will be tabulated as a whole and per group, for each age 
category, for each country and for each subset. 
The following age categories will be considered in the analysis: ≥65 years, ≥70 years, 
≥80 years, 60-69 years, 70-79 years. 
Withdrawal status will be summarized by group using descriptive statistics: 
• 
The number of participants enrolled into the study as well as the number of 
participants excluded from PP analyses will be tabulated. 
• 
The numbers of withdrawn participants will be tabulated according to the reason for 
withdrawal. 
Participant disposition in the ES, mES and PPS (PPSi and PPSe) will be reported as a 
whole and per group, and for each age category. 

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9.4.3. 
Primary endpoint 
The primary efficacy analysis will be performed on the mES-RSV. In addition, a second 
analysis will be performed on the PPSe and on the ES to complement the primary 
analysis. 
The primary analysis of VE in terms of occurrence of RSV-confirmed LRTD will be 
evaluated using the conditional exact binomial method based on the Poisson model 
[Chan, 1998]. This method computes an exact CI around the rate ratio (ratio of the event 
rates in the vaccine versus control groups). The analysis will consider the exact inference 
on the relative risk, adjusted by age categories and regions, conditionally to the total 
number of cases observed and time at risk. VE is defined as 1 minus the relative risk. 
For the primary analysis on the mES-RSV and the analysis on the PPSe, the time at risk 
will correspond to the period starting on Day 15 after the first vaccination up to the first 
occurrence of event or up to censoring. 
For the analysis on the ES, the full period after the first vaccination up to the first 
occurrence of event or censoring will be considered for the time at risk. 
During the surveillance period, all events related to the efficacy endpoints will be 
collected (see Section 8.1.1), but only the first event of RSV-confirmed LRTD will be 
considered for the primary analysis of efficacy endpoints. 
For a given participant, the first occurrence of LRTD will be considered as a confirmed 
RSV positive case for primary efficacy analysis if: 
• 
At least 1 sample is tested positive for RSV A and/or RSV B by GSK qRT-PCR, or 
• 
At least 1 sample is tested positive for RSV A and/or B by an external PCR test 
(non-GSK), if a GSK qRT-PCR result is not available. 
A sensitivity analysis of the primary efficacy endpoint will be performed considering the 
RSV cases confirmed by the GSK qRT-PCR only, i.e., excluding the ones identified by 
an external laboratory. 
A second sensitivity analysis of the primary efficacy endpoint will be performed 
excluding RSV cases with respiratory co-infections (e.g., hMPV, SARS-CoV-2, FLU, 
etc.). 
The methodology will be detailed in the SAP. 
9.4.4. 
Secondary endpoints 
9.4.4.1. 
Efficacy (Amended, 12 July 2023) 
The primary analysis of secondary efficacy endpoints will be performed on the mES (see 
details in Section 9.3). In addition, for secondary confirmatory objectives, a second 
analysis will be performed on the PPSe and on the ES to complement the primary 
analysis. 

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The ES will be the primary population for secondary efficacy endpoints not related to 
RSV. 
The same methodology as described for the primary endpoint (see Section 9.4.3) will be 
used to analyze the secondary efficacy endpoints described below. For the analysis over 
2 or 3 seasons, the model will include season as covariate, in addition to age category and 
region. The first occurrence of the event meeting the case definition according to the 
endpoint will be considered for the primary analysis of those secondary efficacy 
endpoints. 
Analysis of secondary efficacy endpoints will be performed at each VE analysis when 
applicable (see Section 9.5.1). 
The following endpoints will be evaluated following a single dose of the RSVPreF3 OA 
investigational vaccine and following 1 annual revaccination dose given before Season 2. 
Note that participants who received a third dose of RSVPreF3 OA investigational 
vaccine will not be included in the primary evaluation of annual revaccination over 3 
seasons. Secondary analysis of the annual revaccination on participants who received 
3 doses of RSVPreF3 OA investigational vaccine might be performed depending on the 
number of participants who will receive the Dose 3. Details will be provided in the SAP. 
Confirmatory objectives 
• 
VE against RSV-confirmed LRTD over 3 seasons: VE will be evaluated at the end of 
Season 1 in NH, over 2 seasons at the end of Season 2 in NH and over 3 seasons at 
the end of Season 3 in NH. 
• 
VE against RSV-confirmed LRTD by RSV subtype over 3 seasons: on RSV A and 
RSV B qRT-PCR-confirmed cases separately. This will be evaluated after the end of 
Season 3 in NH. 
Other secondary objectives 
• 
VE against RSV-confirmed LRTD by RSV subtype: on RSV-A and RSV-B qRT-
PCR-confirmed cases separately. 
• 
VE against hMPV-confirmed LRTD, up to the end of Season 1. 
• 
VE against RSV-confirmed LRTD by age category: on participants ≥65 YOA, 
≥70 YOA and ≥80 YOA at the time of first vaccination. 
VE will also be computed for participants in 60-69 YOA and 70-79 YOA. 
• 
VE against RSV-confirmed LRTD by season: 
− 
VE during Season 1 in NH and SH, including first occurrence of cases reported 
during Season 1 from Day 15 after the first vaccination; 
− 
VE during Season 2 in NH and SH, including first occurrence of cases reported 
during Season 2 and excluding from the analysis participants who already 
reported an RSV-confirmed LRTD before the start of Season 2; 

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− 
VE during Season 3 in NH and SH (partial Season 3 in SH), including first 
occurrence of cases reported during Season 3 and excluding from the analysis 
participants who already reported an RSV-confirmed LRTD before the start of 
Season 3. 
The time at risk for the analysis by season will be the period from the start of the 
corresponding season until the event, until the end of the season or until the last 
contact date for drop-out participants. 
• 
VE against RSV-confirmed LRTD by year: 
− 
VE during the first year post-vaccination (Year 1) in NH and SH, including first 
occurrence of cases reported from Day 15 post-Dose 1 up to Dose 2 
administration; 
− 
VE during the second year post-vaccination (Year 2) in NH and SH, including 
first occurrence of cases reported from Day 15 post-Dose 2 up to 12 months 
post-Dose 2 in NH and SH, or up to Dose 3 administration in NH; 
− 
VE during the third year post-vaccination (Year 3) in NH and SH, including first 
occurrence of cases reported from 12 months post-Dose 2 in NH up to study 
end. 
• 
VE against RSV-confirmed LRTD by baseline comorbidities: using the Charlson 
Comorbidity Index and according to comorbidities of interest: 
− 
COPD, 
− 
Asthma, 
− 
Any chronic respiratory/pulmonary disease, 
− 
Diabetes mellitus Type 1 or Type 2, 
− 
Chronic heart failure, 
− 
Advanced liver or renal disease. 
• 
VE against RSV-confirmed LRTD by baseline frailty status. 
• 
VE against severe RSV-confirmed LRTD according to the case definition 1 and case 
definition 2; 
• 
VE against RSV-confirmed ARI. 
• 
VE against any ARI and any LRTD. 
• 
Hospitalizations and complications: 
VE in the prevention of hospitalization and complications during RSV seasons and 
during the entire follow-up will be evaluated for: 
− 
Hospitalization due to respiratory diseases and due to complication related to 
respiratory diseases, 
− 
Hospitalization due to RSV-confirmed respiratory diseases and due to 
complication related to RSV-confirmed respiratory diseases, 

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− 
Complications related to RSV-confirmed ARI, 
− 
Complications related to any ARI. 
• 
VE over time: The evolution of VE of a single dose of the RSVPreF3 OA vaccine 
against RSV-confirmed LRTDs over time will be explored using the Cox 
proportional hazard regression model. The model assumes that the ratio between 2 
hazards (vaccine versus placebo) does not depend on time. This assumption will be 
checked by a test based on the Schoenfeld residuals. In addition, the VE analysis will 
be performed by splitting participants in 2 groups according to the time of 
vaccination. 
For all RSV-confirmed ARI and LRTD cases, descriptive statistics will also be computed 
to summarize the number of episodes reported, the duration of the RSV episodes, the 
occurrence of each reported symptoms and signs, including the need for oxygen 
supplementation, and the occurrence of cases according to severity (see Section 8.1.1.6.1 
for severity assessment). 
9.4.4.2. 
Immunogenicity 
The primary analysis of immunogenicity will be performed on the PPSi for participants 
included in the immunogenicity and reactogenicity subset. 
If in any study group the percentage of vaccinated participants with serological results 
excluded from the PPSi is more than 5%, a second analysis based on the ES for 
participants in the reactogenicity and immunogenicity subset will be performed to 
complement the PPSi analysis. 
An immunogenicity analysis based on ES will include all vaccinated participants 
included in the reactogenicity and immunogenicity subset for whom immunogenicity data 
are available. 
For each group, each immunological assay and at each time point that blood samples are 
collected, the following analysis will be tabulated: 
• 
Percentage of participants with antibody titers/concentrations above pre-defined 
assay cut-offs and their 95% CIs; 
• 
GMT/GMCs and their 95% CIs; 
• 
Distribution of antibody titers/concentrations using reverse cumulative curves; 
• 
MGI with 95% CI. 
9.4.4.3. 
Safety  
Reactogenicity analysis will be performed on the Solicited Safety set, for participants 
included in the immunogenicity and reactogenicity subset. 
All other safety analyses will be performed on all participants included in the ES. 

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Reactogenicity analyses will include the following summaries by group: 
• 
The number and percentage of participants with at least one administration site event 
(solicited and unsolicited), with at least one systemic event (solicited and 
unsolicited) and with any AE (solicited and unsolicited) with an onset during the 4 
day or 30-day follow-up period after vaccination will be tabulated with exact 95% CI 
after each dose. The same computations will be done for Grade 3 AEs, for Grade 3 
non-serious AEs and for AEs resulting in a medically attended visit. 
Those analyses will present all solicited and unsolicited AEs, including SAEs (unless 
otherwise specified) and will be performed on the ES. 
• 
The number and percentage of participants reporting each individual solicited 
administration site or systemic event (any grade, Grade 3 and resulting in medically 
attended visit) with an onset during the 4-day follow-up period after vaccination will 
be tabulated with exact 95% CI after each dose. 
• 
For fever, the number and percentage of participants reporting fever by half degree 
(°C) cumulative increments and fever resulting in medically attended visit with an 
onset during the 4-day follow-up period after vaccination will be tabulated after each 
dose. In addition, the prevalence of any and Grade 3 fever will be presented 
graphically over time after each dose. 
• 
The number of days with solicited events reported with an onset during the 4-day 
follow-up period will be tabulated after each dose for each individual solicited event 
using descriptive statistics (mean, min, Q1, median, Q3, maximum). 
Safety analyses will include the following summaries by group on the ES: 
• 
The number and percentage of participants with any unsolicited AEs with an onset 
during the 30-day follow-up period with its exact 95% CI will be tabulated after each 
dose by group and by MedDRA Primary System Organ Class (SOC), High Level 
Term (HLT) and Preferred Term (PT). Similar tabulation will be done for Grade 3 
unsolicited AEs, for any causally related unsolicited AEs, for Grade 3 causally 
related unsolicited AEs and for unsolicited AEs resulting in a medically attended 
visit. 
The analyses of unsolicited AEs will include SAEs (unless otherwise specified). 
• 
The verbatim reports of unsolicited AEs, including SAE, will be reviewed by a 
qualified person and the signs and symptoms will be coded according to the 
MedDRA Dictionary for Adverse Reaction Terminology. Every verbatim term will 
be matched with the appropriate Preferred Term. 
• 
The number and percentage of participants with at least one report of SAE classified 
by MedDRA Primary SOC, HLT and PT and reported from vaccination up to 
6 months after vaccination will be tabulated after each dose with exact 95% CI. The 
same tabulation will be presented for pIMDs, fatal SAEs, causally related SAEs and 
causally related pIMDs. 
• 
The number and percentage of participants with at least one report of causally related 
SAE classified by MedDRA Primary SOC, HLT and PT and reported during the 
entire study period will be tabulated after each dose from Day 1 up to study end with 

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exact 95% CI. The same tabulation will be presented for fatal SAEs and causally 
related pIMDs. 
• 
SAEs/pIMDs will also be described in detail in a tabular listing. 
• 
The number and percentage of participants starting a concomitant medication (any 
medication and any antipyretic) during the 4-day and the 30-day follow-up period 
after each dose will be tabulated with exact 95% CI. 
• 
AEs/SAEs leading to study/intervention discontinuation from first vaccination up to 
study end will be tabulated. 

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9.4.4.4. 
Quality of life 
All analysis of patient-reported outcomes (i.e., EQ-5D, SF-12 and the daily health 
questionnaires) for RSV-confirmed cases will be carried out on the mES RSV-confirmed 
ARI cohort or mES RSV-confirmed LRTD cohort, as appropriate. Data will be analyzed 
using descriptive statistics for the multi-item SF-12, EQ-5D and FLU-PRO scales for 
each study group at each time point. 
Descriptive statistics of the EQ-5D, SF-12 and FLU-PRO scales completed pre-Seasons 1 
and 2 will be presented for the mES. 
For each confirmed case of RSV, the maximum score for FLU-PRO scale scores (e.g., 
Chest and upper respiratory) during the first RT-PCR-confirmed RSV episode during the 
first 7 days from the onset of ARI symptoms will be calculated. The maximum FLU-PRO 
scores (e.g., Chest and upper respiratory) during the first 7 days from the onset of ARI 
symptoms will be compared between study groups using a Wilcoxon non-parametric test. 
Estimated Least Squares mean FLU-PRO total score during the first 7 days from the 
onset of RSV-ARI episode for participants with RT-PCR-confirmed RSV, will be 
analyzed using a repeated measures analysis of variance (ANOVA) model. The model 
will be fitted including terms for age category, region and study group by time 
interaction. The least squares mean (LSMEANS) estimates for time by study group and 
the difference in least squares means and associated P-values will be obtained from the 
ANOVA model. The PROC MIXED procedure in SAS will be used to carry out the 
ANOVA, with all terms fitted as fixed effects. 
The study group difference in LSMEANS of the SF-12 physical functioning scores and 
EQ-5D utility score at the initial ARI visit will be estimated using repeated measures 
mixed effects model including the timepoints: pre-season, initial ARI visit, and pre-next-
season visit. The model will include age categories and region as fixed effects. 
The endpoints will be evaluated following a single dose of the RSVPreF3 OA 
investigational vaccine and following the annual revaccination dose. 
9.4.5. 
Tertiary/exploratory endpoints 
9.4.5.1. 
Efficacy (Amended, 12 July 2023) 
The same methodology as described for the primary and secondary endpoints (see 
Sections 9.4.3 and 9.4.4.1, respectively) will be used to analyze the tertiary endpoints. 
The following endpoints will be evaluated following a single dose of the RSVPreF3 OA 
investigational vaccine and following the annual revaccination given before Season 2 : 
• 
VE against RSV and/or hMPV-confirmed LRTDs, 
• 
VE against hMPV-confirmed LRTDs up to the end of Season 2 and Season 3, 
• 
VE against severe hMPV-confirmed LRTDs according to the case definition 1 and 
case definition 2, 

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• 
VE against hMPV-confirmed ARI, 
• 
VE against RSV-confirmed ARI by subtype, by age category and by season, 
• 
VE against RSV-confirmed ARIs by baseline comorbidities: using the Charlson 
index and according to comorbidities of interest (as listed in Section 9.4.4.1), 
• 
VE in the prevention of any death (all-cause mortality) during the RSV seasons. 
The evolution of VE of a single dose of RSVPreF3 OA vaccine against RSV-confirmed 
ARI over time will be explored using the Cox proportional hazard regression model. The 
model assumes that the ratio between 2 hazards (vaccine versus placebo) does not depend 
on time. This assumption will be checked by a test based on the Schoenfeld residuals. In 
addition, the VE analysis will be performed by splitting participants in 2 groups 
according to the time of vaccination. 
The number and percentage of participants who reported more than 1 case of the 
following event will be tabulated by group, by season and also in consecutive seasons: 
any ARI, any LRTD, RSV-confirmed ARI, RSV-confirmed LRTD (according to the case 
definitions). 
The number and percentage of participants with other viral pathogens (detected by 
multiplex RT-PCR) co-existing with RSV or hMPV among RT-PCR-confirmed RSV or 
hMPV ARI episodes will be tabulated by group. 
9.4.5.2. 
Analysis of HCRU 
Descriptive analysis of HCRU will be performed for participants with RSV-confirmed 
ARI or with any ARI and will be reported by group: 
• 
The number/percentage of participants who were hospitalized during the ARI 
episode or complication related to ARI, 
• 
The number/percentage of participants who received antibiotics for the treatment of 
ARI or complication related to ARI. 
For any other count variables that will be reported (e.g., any medication or any medical 
visit), the number and percentage of events/participants will be presented by group. 
9.4.5.3. 
Quality of life 
The maximum PGI-S score during the first 7 days from the onset of ARI symptoms for 
the first RT-PCR-confirmed RSV LRTD episode will be calculated. The maximum PGI-
S score during the first 7 days from the onset of ARI symptoms will be compared 
between study groups using a Wilcoxon non-parametric test. 

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9.4.5.4. 
Immunogenicity 
9.4.5.4.1. Correlate of protection (Amended, 12 July 2023) 
An exploratory analysis will be implemented in attempt to correlate the humoral immune 
response to the RSVPreF3 OA investigational vaccine with protection against RSV-
confirmed disease. 
For that purpose, blood samples for humoral immune response will be collected from all 
participants at pre-Dose 1 (Day 1), 1-month post-Dose 1 (Day 31) and at Visit 5NH* and 
may be tested for correlate of protection analysis in all participants with RSV-confirmed 
disease and in a subset of control participants. 
There are 2 main strategies to define a subset of control: case-cohort and nested case 
control. For the same number of participants, both methods provide similar results. 
However, the case-cohort strategy has the advantage to be more flexible in terms of data 
exploration and modelling [Borgan, 2000]. 
Statistical analysis will be done in several steps: 
1. Identification of Correlate of Risk: identify immunological response that correlates 
with the endpoint used to measure VE. 
2. Validation of Correlate of Protection, which is a correlate of risk that is validated to 
predict a certain level of protection from the targeted endpoint. 
3. Evaluation of a cut-off for protection: identify a “protective threshold” or humoral 
immune response level that distinguishes protected and unprotected individuals. 
Further details on the methodology to assess the correlate of protection will be given in a 
separate SAP. 
* The blood sample at Visit 5NH is applicable after approval of the current Protocol 
Amendment 5. 
9.4.5.4.2. Within groups analysis 
The immunogenicity analysis will also be performed by age category (≥ 65 YOA, 
≥ 70 YOA, ≥ 80 YOA, 60-69 YOA, 70-79 YOA), by hemisphere (NH and SH), by 
region and by baseline frailty status. 
9.4.5.5. 
Safety 
The reactogenicity and safety analysis will also be performed by age category ≥ 65 YOA, 
≥ 70 YOA, ≥ 80 YOA, 60-69 YOA, 70-79 YOA), by hemisphere (NH and SH) and by 
region. 
The analysis of reactogenicity (solicited administration site and systemic events) will also 
be performed by baseline frailty status. 

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9.5. 
Interim analyses 
The optional interim analysis is described in the below sequence of analyses. 
9.5.1. 
Sequence of analyses (Amended, 12 July 2023) 
This section is presenting the timing for each analysis. More information on the statistical 
link between the confirmatory objectives can be found in Section 9.1 (Figure 4). 
Analyses to evaluate objectives and endpoints will be performed in several steps: 
1. VE Analysis 1 – Season 1 (Primary Objective): 
The final analysis of the primary objective will be case-driven. It will be performed when 
at least 56 cases of RSV-confirmed LRTDs have been accrued in the primary cohort for 
efficacy. 
An optional interim analysis might be performed if the number of cases triggering VE 
Analysis 1 (at least 56 cases) is not achieved at the end of Season 1 in NH. This interim 
analysis will be performed if at least 35 cases have been accrued (at the end of Season 1 
in NH or later). In that case, an adjustment of the Type I error will be done in order to 
maintain the overall significance level at 2.5%. The Wang-Tsiatis approach which is an 
alpha spending method giving boundaries between O’Brien-Fleming and Pocock 
boundaries will be used [Wang, 1987] to determine the adjusted alpha levels for the 
interim (α1) and the final (α2) analyses. The final analysis will be performed when at 
least 60 cases are accrued or when all data associated to the primary objective are 
available. 
All data related to efficacy, safety and immunogenicity objectives available at that time 
will also be analyzed. 
2. VE Analysis 2 – End of Season 1 in NH: 
A second VE analysis will be performed when participants in NH have been followed 
until the end of the first season in NH (30 April). 
All analysis generated at VE Analysis 1 will be performed at VE Analysis 2 in order to 
have an end of Season 1 analysis, if at least 1 additional RSV-confirmed ARI has been 
reported since VE Analysis 1 and if there are at least 2-3 weeks between the database cut-
off dates of the 2 analyses. 
If data related to endpoints not available at VE Analysis 1 become available at end of 
Season 1, the analysis might be performed at VE Analysis 2. 
All data related to efficacy and immunogenicity objectives available at that time will also 
be analyzed. 
3. Safety analysis: 
An analysis of safety will be performed when all safety data up to 6 months post-Dose 1 
will be available for all participants in NH and SH. 

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4. VE Analysis 3: end of Season 2 in NH  
A fourth analysis will be performed to evaluate the efficacy, safety and immunogenicity 
objectives over 2 seasons, when all participants in NH have been followed until the end 
of second season (S2) in NH. 
All the analyses described above will be performed on data as complete and as clean as 
possible, by an unblinded IES. The unblinded analyses will be shared with an unblinded 
committee independent from the project (firewall). Access to individual intervention 
codes and laboratory data will be restricted to the IES in charge of the analyses. 
The firewall will review the unblinded summaries to prevent the potential risk of 
unblinding at participant level. If the summary results may lead to the unblinding of some 
specific participants (e.g., in case an event occurred only in 1 group), the blinding of 
results will be managed by the IES. In this situation, exact results per group will not be 
provided to the study team. Only blinded data will be released to the blinded study team 
members and investigators. Further details of this approach can be found in the firewall 
charter. The firewall team will no longer be active as of the implementation of Protocol 
Amendment 4 as of which point study statisticians will perform the analyses and manage 
the blinding of results for blinded study team members and investigators. 
No individual data listings with the participant numbers information will be disseminated 
to the investigators at this point of time. 
5. VE Analysis 4: end of Season 2 in NH and SH 
An analysis will be performed to evaluate the efficacy, safety and immunogenicity 
objectives over 2 seasons, when all participants in NH and SH have been followed until 
the end of second season (S2) in SH. 
6. VE Analysis 5: end of Season 3 in NH 
An analysis will be performed to evaluate the efficacy, safety and immunogenicity 
objectives over 3 seasons, when all participants in NH have been followed until the end 
of third season (S3) in NH. 
7. VE Analysis 6: End of Study analysis 
This analysis will be performed at the end of the study, i.e., when all participants (except 
drop-outs) will have completed the last study visit: end of Season 3 (S3) in NH (Visit 
7NH) and end of study in SH (Visit 5SH). 
Individual data listings will only be generated at this stage. 
9.6. 
Independent Data Monitoring Committee (IDMC) (Amended) 
Unblinded evaluation of safety data will be performed by an IDMC on a regular basis. In 
preparation of the IDMC meetings, unblinded analyses will be performed by an IES to 
maintain the study blind. Only the outcomes and recommendations of the IDMC will be 
communicated to the study team. Operational details will be provided in the IDMC 
Charter. 

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A firewall team will be set up in order to allow the planned analyses to be performed and 
results shared with the IDMC, while the study blind is maintained to the whole team and 
participants. All details of this approach can be found in the firewall charter. As of 
implementation of the Protocol Amendment 4, the firewall team will no longer be active. 
Refer to Section 6.3.5 for further details. 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable ICH Good Clinical Practice (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 for review and 
approval. These documents will be signed and dated by the investigator before the 
study is initiated. 
• 
Any protocol amendments will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
GSK will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 

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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 financial interest information prior initiation 
of the center and at the end of the study. Investigators are responsible for providing a 
Financial Disclosure update if their financial interests change at any point during their 
participation in a study and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. 
Freely given and written/witnessed informed consent must be obtained from each 
participant and/or each participant’s witness, prior to participation in the study. The 
participant’s informed consent may be obtained prior to Visit 1. In addition, in case a 
caregiver is assigned by the participant to help with the study procedures, the caregiver 
must receive an information letter prior to supporting study participant, that describes the 
role and data that will be collected from the caregiver. 
The content of informed consent form must meet the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written or witnessed informed consent 
was obtained before the participant was enrolled in the study and the date the consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
Participants must be re-consented to the most current version of the ICF(s) or an ICF 
addendum during their participation in the study. 
A copy of the ICF(s) must be provided to the participants. 

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10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the sponsor. 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. 
The participants must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. 
The participants must be informed of their rights regarding the use of their personal data 
in accordance with the data privacy Section of the ICF. 
The participants must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
GSK will also ensure protection of the personal data of the investigator and site staff 
which will be collected within the framework and for the purpose of the study in 
accordance with the Data Privacy Notice that will be sent to the site staff. 
10.1.5. 
Committees structure 
GSK will obtain favorable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country. This includes IRBs/IECs for review and approval of 
the protocol and subsequent amendments, ICF and any other documentation. 
10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study register in compliance with the 
applicable regulations/GSK policy. GSK will aim to register protocols summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines. 
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical trial registers. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the investigator 
with the full summary of the study results. The investigator is encouraged to share the 
summary results with the study participants, as appropriate. 
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis (end of study analysis). 

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GSK intends to make anonymized patient-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by trial 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents including source documents. The storage system used during the trial and for 
archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval. 
Essential trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g., source documents, CRF), the copy should fulfill the 
requirements for certified copies. 
All participant data relating to the study will be recorded in the eCRF 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 electronically 
signing the eCRF. 
The investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial participants (Section 
10.5.2 for the exact definition of source documents) that supports information entered in 
the eCRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies. 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data. 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data should be traceable, should not 
obscure the original entry, and should be explained if necessary (e.g., via an audit trail). 
The safety and rights of participants must be protected, and study be conducted in 
accordance with the currently approved protocol and any other study agreements, ICH 
GCP, and all applicable regulatory requirements. 
Trial records and source documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report /equivalent summary unless local regulations or institutional 
policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 

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10.1.8. 
Source documents 
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Investigator should maintain a record of the location(s) 
of their source documents. 
Data 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 needs 
to ensure that relevant source documents are available on site. The investigator may need 
to request previous medical records, current medical records or transfer records, 
depending on the study. 
Definition of what constitutes source data and source documents can be found in Section 
10.5.2. 
10.1.9. 
Study and site closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure will 
occur upon study completion. A study site is considered closed when all required 
data/documents and study supplies have been collected and a study site closure visit has 
been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development. 
The investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the Study Conclusion screen in the eCRF. 
10.1.10. 
Publication policy 
GSK aims to submit for publication the results of the study in searchable, peer reviewed 
scientific literature within 18 months from Last Participant Last Visit (LPLV) for 
interventional studies and follows the guidance from the International Committee of 
Medical Journal Editors. 

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10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
Laboratory assays for immune response 
RSV A/B neutralization assay 
The serum neutralization assay is a functional assay that measures the ability of serum 
antibodies to neutralize RSV entry and replication in a host cell line. 
Virus neutralization is performed by incubating a fixed amount of RSV A strain (Long, 
ATCC No. VR-26) or RSV-B strain (18537, ATCC No. VR-1580) with serial dilutions of 
the test serum. The serum-virus mixture is then transferred onto a layer of Vero cells 
(African Green Monkey, kidney, Cercopitheus aethiops, ATCC CCL 81) and incubated 
for 2 days to allow infection of the Vero cells by non-neutralized virus and the formation 
of plaques in the cell layer. Following a fixation step, RSV-infected cells are detected 
using a primary antibody directed against RSV (Polyclonal anti-RSV A/B IgG) and a 
secondary antibody conjugated to 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 neutralizing 
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]. 
The ED60 neutralizing titers will also be converted in concentration in International Units 
per milliliter (IU/mL). Secondary standard calibrated against the international reference 
(NIBSC 16/284) will be included in the runs. 
RSVPreF3 protein IgG ELISA 
Responses to the RSVPreF3 antigen will be evaluated by an indirect ELISA allowing the 
detection and the quantification of RSVPreF3 IgG binding antibodies in human serum 
samples. 
The principle of these assays is as follows: RSVPreF3 protein antigen will be adsorbed 
onto a 96-well polystyrene microplate. After washing and blocking steps, dilutions of 
serum samples, controls and standards will be added to the coated microplate. A 
reference standard curve will be prepared using a pool of commercial human serum 
containing anti-RSV antibodies. After incubation, the microplate will be washed to 
remove unbound primary antibodies. Bound IgG will be detected by the addition of a 
secondary anti-human antibody (total IgG-specific), conjugated to HRP. Bound 
antibodies are quantified by the addition of the HRP substrate, tetramethylbenzidine 
(TMB) and hydrogen peroxide, whereby a colored product develops proportionally to the 
amount of anti-RSVPreF3 protein total IgG antibodies present in the serum sample. The 
optical density of each sample dilution is then interpolated on the reference standard. The 
corresponding antibody concentration, corrected for the dilution factor, is expressed in 
arbitrary ELISA Laboratory Units per milliliter (ELU/mL). 

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Any further exploratory immunology testing might be performed to investigate RSV 
and/or hMPV-related immune responses. 
10.2.2. 
Laboratory assays for molecular biology 
Quantitative RT-PCR able to discriminate RSV A and RSV B subtypes 
Briefly, RSV A and RSV B RNAs extracted from the nasal/throat swabs are detected in a 
duplex RT-PCR format using specific amplification primers and fluorescent probes 
designed in the RSV N gene, encoding the RSV nucleocapsid protein. The process 
involves nucleic acids extraction, conversion of RNA to complementary 
deoxyribonucleic acid by reverse transcription and detection by real-time PCR reaction 
using a calibration curve (absolute quantitation). The RSV viral load is reported as copies 
of RSV RNA per mL of sample. 
Qualitative multiplex RT-PCR for detection of a panel of viruses including hMPV 
A qualitative multiplex RT-PCR assay is used for the detection and identification of 
multiple respiratory virus nucleic acids in the nasal/throat swabs. The following virus 
types and subtypes can be identified in the assay: 
• 
Human adenovirus (AdV) 
• 
Human metapneumovirus (hMPV) 
• 
Human enterovirus (HEV) 
• 
Human parainfluenza virus including at least types 1, 2, 3 and 4 (PIV1, PIV2, PIV3 
and PIV4). 
Qualitative multiplex RT-PCR for detection of additional respiratory viruses 
A qualitative multiplex RT-PCR assay is used for the detection and identification of 
multiple respiratory virus nucleic acids in the nasal/throat swabs. The following virus 
types and subtypes can be identified in the assay: 
• 
Influenza A virus (Flu A) 
• 
Influenza B virus (Flu B) 
• 
Human respiratory syncytial virus A (RSV A) 
• 
Human respiratory syncytial virus B (RSV B) 
• 
Human Influenza A virus subtype H1 (Flu A-H1) 
• 
Human Influenza A virus subtype H3 (Flu A-H3) 
• 
Human Influenza A virus subtype H1pdm09 (Flu A-H1pdm09) 
• 
Human bocavirus ½/3/4 (HBoV) 
• 
Human rhinovirus A/B/C 
• 
Human coronavirus including at least 229E, NL63, OC43 and SARS-CoV-2 species 

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Following total nucleic acids extraction, viruses are detected by multiplex real-time RT-
PCR assays targeting the above-mentioned viruses. A comparative analysis of the 
fluorescence intensities of each target is performed to detect the viruses present in the 
sample. 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting 
10.3.1. 
Definition of an Adverse Event (AE) 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of 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 study intervention. 
10.3.1.1. 
Events meeting the AE definition 
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study vaccine administration even 
though they may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
vaccine or a concurrent medication (overdose per se should not be reported as an 
AE/SAE). 
• 
Signs or symptoms temporally associated with study vaccine administration. 
• 
Signs, symptoms that require medical attention (e.g., hospital stays, physician 
visits and emergency room visits). 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated 
procedures (i.e., invasive procedures, modification of participant’s previous 
therapeutic regimen). 
• 
Clinically significant abnormal laboratory findings or other abnormal assessments 
that are present at baseline and significantly worsen following the start of the study 
will also be reported as AEs or SAEs. 
• 
AEs to be recorded as solicited events are described in the Section 10.3.3. All 
other AEs will be recorded as UNSOLICITED AEs. 

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10.3.1.2. 
Events NOT meeting the AE definition 
• 
Situations where an untoward medical occurrence did not occur (e.g., social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
• 
Pre-existing conditions or signs and/or symptoms present in a participant prior to 
the first study vaccination. These events will be recorded in the medical history 
Section of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline. 
• 
Clinically significant abnormal laboratory findings or other abnormal assessments 
that are associated with the disease being studied, unless judged by the investigator 
as more severe than expected for the participant’s condition, or that are present or 
detected at the start of the study and do not worsen. 
10.3.2. 
Definition of a Serious Adverse Event (SAE) 
An SAE is any untoward medical occurrence that: 
a. 
Results in death. 
b. Is life-threatening 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the participant was at risk of death at the time of the event. It does not refer 
to an event, which hypothetically might have caused death, had it been more 
severe. 
c. 
Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the participant has been admitted at 
the hospital or emergency ward for observation and/or treatment that would not 
have been appropriate in the physician’s office or in an out-patient setting. 
Complications that occur during hospitalization are also considered as AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the 
event will also be considered serious. When in doubt as to whether 
‘hospitalization’ occurred, or was necessary, the AE should be considered serious. 
d. Results in disability/incapacity 
Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza-like illness, and accidental trauma 
(e.g., sprained ankle) which may interfere or prevent everyday life functions but 
do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant. 

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f. 
Other situations 
Medical or scientific judgment should be exercised in deciding whether reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These should also 
be considered serious. Examples of such events are invasive or malignant cancers, 
intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization. 
10.3.3. 
Solicited events 
a. Solicited administration site events 
The following administration site events will be solicited from participants in the 
reactogenicity and immunogenicity subset: 
Table 33 
Solicited administration site events 
Pain  
Erythema 
Swelling  
b. Solicited systemic events 
The following systemic events will be solicited from participants in the reactogenicity 
and immunogenicity subset: 
Table 34 
Solicited systemic events 
Fever 
Headache 
Fatigue 
Myalgia 
Arthralgia 
Note: Participants will be instructed to measure and record the oral, axillary or tympanic 
body temperature in the evening. Should additional temperature measurements be 
performed at other times of day, participants will be instructed to record the highest 
temperature in the paper diary card. 
10.3.4. 
Unsolicited adverse events 
An unsolicited AE is an adverse event that was not solicited and that was spontaneously 
communicated by a participant who has signed the informed consent. Unsolicited AEs 
include serious and non-serious AEs. 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or emergency room visit, or visit to/by a health care provider). 
The participants will be instructed to contact the site as soon as possible to report 

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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 participant 
will be collected during interview with the participants and by review of available 
medical records at the next visit. 
10.3.5. 
Adverse events of special interest (AESIs)  
Adverse events of special interest (AESIs) collected during this study include potential 
immune-mediated diseases (pIMDs) and AF. 
10.3.5.1. 
Potential immune-mediated diseases  
pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory 
and/or neurologic disorders of interest which may or may not have an autoimmune 
etiology. AEs that need to be recorded and reported as pIMDs include those listed in 
Table 35 (refer to Section 10.3.8.1 for reporting details). 
However, the investigator will exercise his/her medical and scientific judgment to 
determine whether other diseases have an autoimmune origin (i.e., pathophysiology 
involving systemic or organ-specific pathogenic autoantibodies) and should also be 
recorded as a pIMD. 
Table 35 
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 

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Medical Concept 
Additional Notes 
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) 
• 
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 
 
Grave's 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 (Reiter's Syndrome) 
• 
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 Reynolds syndrome (RS), 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) 
• 
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) 

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Medical Concept 
Additional Notes 
• 
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 
• 
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 
 

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Medical Concept 
Additional Notes 
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) 
• 
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) 
• 
Wegener's granulomatosis 
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 
 
10.3.5.2. 
Atrial fibrillation 
AEs of AF are considered as AESI in this study. 
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 the AF, 
should be recorded and reported as AEs but not as AESI until the final or definitive 

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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. 
10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs 
In the absence of a diagnosis, abnormal laboratory findings (e.g., clinical chemistry, 
hematology, urinalysis) or other abnormal assessments the investigator considers 
clinically significant will be recorded as an AE or SAE if they meet the definition of an 
AE or SAE (refer to the Sections 10.3 and 10.3.2). 
The investigator will exercise his or her medical and scientific judgment in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant. 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs 
10.3.7.1. 
Pregnancy 
Not applicable for the study population. 
10.3.8. 
Recording and follow-up of AEs, SAEs, AESIs (including pIMDs 
and AF) (Amended, 12 July 2023) 
The participants will be instructed to contact the investigator immediately should the 
participants manifest any signs or symptoms they perceive as serious. 
When an AE/SAE/AESI (including pIMDs and AF) occurs, it is the responsibility of the 
investigator to review all documentation (e.g., hospital progress notes, laboratory and 
diagnostics reports) relative to the event. The investigator will then record all relevant 
information regarding an AE/SAE/AESI (including pIMDs and AF) in the eCRF. The 
investigator is not allowed to send photocopies of the participant’s medical records to 
GSK instead of appropriately completing the eCRF. However, there may be instances 
when copies of medical records for certain cases are requested by GSK. In this instance, 
all participant identifiers will be blinded on the copies of the medical records prior to 
submission to GSK. 
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE/AESI (including pIMDs and AF) and not the individual 
signs/symptoms. 
A paper diary will be used in this study to capture solicited administration site or 
systemic events in participants in the reactogenicity and immunogenicity subset and 
unsolicited AEs in all participants. The participant should be trained on how and when to 

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complete each field of the paper diary. If a participant is unable or not willing to 
complete the paper diary him/herself, he/she may be helped by a caregiver (refer to 
Section 10.5.2 for the definition of caregiver). 
Any individual(s) who performs the measurements of administration site or systemic 
events and who will enter the information into the paper diary, e.g. the study caregiver, 
should have received a caregiver information letter explaining the role of the caregiver 
prior to completing the diary card. If any other individual than the participant is making 
entries in the paper diary, their identity should be documented in the participant’s source 
record. 
• 
Collect and verify completed diary cards during discussion with the participant on 
Visit 2 (Day 31 post-Dose 1), Visit 4 (Day 31 post-Dose 2) and Visit 6NH (Day 31 
post-Dose3)*. 
• 
Any unreturned diary cards 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. 
* Not applicable for participants in the NH who will have their Visit 5NH after the 
approval of the current Protocol Amendment 5 and will not receive any study 
intervention at pre-Season 3 visit (Visit 5NH). 
Refer to the SPM for more information regarding the use of the paper diary. 
10.3.8.1. 
Time period for collecting and recording AEs, SAEs, AESIs (including 
pIMDs and AF)  
Refer to Table 23 in Section 8.3.1 for an overview of the protocol-required reporting 
periods for AEs, SAEs and pIMDs. AF reporting will follow the same reporting periods 
as for AEs and SAEs. 
All solicited events with an onset during the 4-day period following each study vaccine 
administration in participants enrolled in the reactogenicity and immunogenicity subset 
must be recorded into the paper diary, irrespective of intensity. 
All unsolicited AEs with an onset during the 30-day period following each study vaccine 
administration in all participants must be recorded into the paper diary, irrespective of 
intensity or whether or not they are considered vaccination-related. All other AEs 
occurring within this time frame should be recorded into the appropriate section of the 
eCRF, irrespective of intensity or whether or not they are considered vaccination-related. 
Non-serious AF with an onset during the 30-day period following each study vaccine 
administration will be collected. 
SAEs, serious AF and pIMDs will be collected and recorded from the day of vaccination 
up to 6 months post-vaccination for each dose. 

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All SAEs and pIMDs considered vaccination-related, any fatal SAEs and AEs/SAEs 
leading to withdrawal from the study will be collected and recorded from the time of 
receipt of first study vaccine until the participant is discharged from the study. In 
addition, SAEs related to study participation or to a concurrent GSK medication/vaccine 
will be collected from the time of consent obtained until the participant is discharged 
from the study. 
10.3.8.2. 
Follow-up of AEs, SAEs, AESIs (including pIMDs and AF)  
After the initial report of an AE/SAE/pIMD or any other event of interest for the study, 
the investigator is required to proactively follow each participant at subsequent 
visits/contacts. All SAEs, AESIs (including pIMDs and AF) (as defined in Section 
10.3.5), will be followed until the event is resolved, stabilized, otherwise explained, or 
the participant is lost to follow-up. 
Refer to Section 10.3.10 for timeframes and further information on how to report SAEs, 
pIMDs and other events. 
10.3.8.2.1. Follow-up during the study  
AEs (serious or non-serious), AESIs (including pIMDs and AF) documented at a 
previous visit/contact and defined as not recovered/not resolved or recovering/resolving 
will be reviewed at subsequent visits/contacts until the end of the study or the participant 
is lost to follow-up. 
If participant dies during participation in the study or during a recognized follow-up 
period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.8.2.2. Follow-up after the participant is discharged from the study  
The investigator will provide any new or updated relevant information on previously 
reported SAE/pIMD to GSK using a paper/electronic Expedited Adverse Events Report, 
as applicable. For AF cases, the investigator will provide any new or updated relevant 
information on previously reported AF to GSK using a paper/electronic Expedited 
Adverse Events Report and the AF follow-up questionnaire as applicable. 
The investigator is obliged to perform or arrange for the conduct of supplemental clinical 
examinations/tests and/or evaluations to elucidate the nature and/or causality of the AE or 
SAE as fully as possible. 
10.3.8.3. 
Updating of SAE, AESI (including pIMD and AF) information after 
removal of write access to the participant’s eCRF  
When additional SAE, AESI (including pIMD and AF) information is received after 
removal of write access to the participant’s eCRF, new or updated information should be 
recorded on the appropriate paper report, with all changes signed and dated by the 
investigator. The updated report should be faxed to the Study Contact for Reporting 
SAEs (refer to the Section 8.3.4 or to GSK Clinical Safety and Pharmacovigilance 
department within the defined reporting time frames specified in the Table 24. 

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10.3.9. 
Assessment of intensity and toxicity 
10.3.9.1. 
Assessment of intensity 
The intensity of the following solicited events will be assessed as described: 
Table 36 
Intensity scales for solicited events in adults 
Event 
Intensity grade 
Parameter 
Pain at the injection site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal every day activities 
 
2 
Moderate: Painful when limb is moved and interferes with 
every day activities 
 
3 
Severe: Significant pain at rest. Prevents normal every 
day activities 
Erythema at the injection site 
Record greatest surface diameter in mm 
Swelling at the injection site 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C/°F 
Headache 
0 
Normal 
 
1 
Mild: Headache that is easily tolerated 
 
2 
Moderate: Headache that interferes with normal activity 
 
3 
Severe: Headache that prevents normal activity 
Fatigue 
0 
Normal 
 
1 
Mild: Fatigue that is easily tolerated 
 
2 
Moderate: Fatigue that interferes with normal activity 
 
3 
Severe: Fatigue that prevents normal activity 
Myalgia 
0 
Normal 
 
1 
Mild: Myalgia that is easily tolerated 
 
2 
Moderate: Myalgia that interferes with normal activity 
 
3 
Severe: Myalgia that prevents normal activity 
Arthralgia 
0 
Normal 
 
1 
Mild: Arthralgia that is easily tolerated 
 
2 
Moderate: Arthralgia that interferes with normal activity 
 
3 
Severe: Arthralgia that prevents normal activity 
* Fever is defined as a temperature ≥ 38.0°C/100.4°F by any route. The route for measuring temperature can be oral, 
axillary or tympanic. 
The maximum intensity of local injection site erythema/swelling and fever will be scored 
at GSK as follows: 
Intensity grade 
Erythema/Swelling 
Fever 
0 
 20 mm 
< 38.0°C (100.4°F) 
1 
> 20 -  50 mm 
≥ 38.0°C (100.4°F) -  38.5°C (101.3°F) 
2 
> 50 -  100 mm 
> 38.5°C (101.3°F) -  39.0°C (102.2°F) 
3 
> 100 mm 
> 39.0°C (102.2°F) 
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgment. 

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The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the participant, causing 
minimal discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities 
(In adults, such an AE would, for example, prevent attendance at 
work and would necessitate the administration of corrective 
therapy.) 
An AE that is assessed as Grade 3 (severe) should not be confused with 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. 
10.3.9.2. 
Assessment of causality 
The investigator must assess the relationship between the study vaccine and the 
occurrence of each unsolicited AE/SAE using clinical judgment. Where several different 
vaccines/products were administered, the investigator should specify, when possible, if 
the unsolicited AE/SAE could be causally related to a specific vaccine/product (i.e., 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine/product cannot be determined, the investigator should indicate the 
unsolicited AE/SAE to be related to all products. 
Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study vaccine will be considered and investigated. The investigator will also consult the 
IB to determine his/her assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study vaccine? 
YES 
: 
There is a reasonable possibility that the study vaccine contributed to 
the AE. 
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study vaccine. There are other, more likely causes, 
and administration of the study vaccine is not suspected to have 
contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible 
contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 

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• 
Other medication. 
• 
Protocol-required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the vaccine, if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify). 
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Expedited 
Adverse Events Report to GSK. 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. The investigator may change his/her opinion of causality after 
receiving additional information and update the SAE information accordingly. 
10.3.9.3. 
Medically attended visits 
For each solicited event and unsolicited AE the participant experiences, the participant 
will be asked if he/she received medical attention defined as hospitalization, or an 
otherwise unscheduled visit to or from medical personnel for any reason, including 
emergency room visits. This information will be recorded in the eCRF. 
10.3.9.4. 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
10.3.10. 
Reporting of SAEs, AESIs (including pIMDs and AF)  
10.3.10.1. Events requiring expedited reporting to GSK 
Once an investigator becomes aware that an SAE has occurred in a study participant, the 
investigator (or designee) must complete information in the electronic Expedited Adverse 
Events Report WITHIN 24 HOURS. The report will always be completed as thoroughly 
as possible with all available details of the event. 

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Even if the investigator does not have all information regarding an SAE, the report 
should still be completed within 24 hours. Once additional relevant information is 
received, the report should be updated WITHIN 24 HOURS. The investigator will always 
provide an assessment of causality at the time of the initial report. 
Refer to the Table 24 for the details on timeframes for reporting of SAEs/AESIs 
(including pIMDs and AF). 
The investigator will be required to confirm the review of the SAE causality by ticking 
the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 hours of 
submission of the SAE. 
Refer to the Section 10.3.10.2 for the back-up system in case the electronic reporting 
system does not work. 
10.3.10.2. Back-up system in case facsimile or electronic reporting system does 
not work 
In rare circumstances if the electronic reporting system does not work, the investigator 
(or designee) must fax completed, dated and signed paper Expedited Adverse Events 
Report to the Study Contact for Reporting SAEs (refer to the Sponsor Information) or to 
GSK Clinical Safety and Pharmacovigilance department within 24 hours. 
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
within 24 hours upon electronic reporting system is resumed. The information reported 
through the electronic SAE reporting system will be considered valid for regulatory 
reporting purposes. 
10.4. 
Appendix 4: Country-specific requirements 
10.4.1. 
Japan 
10.4.1.1. 
Regulatory and ethical considerations 
The study will be conducted in accordance with “the Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (MHW Notification 
No.28 dated 27 March 1997)” and Law for Ensuring the Quality, Efficacy, and Safety of 
Drugs and Medical Devices. 
The statement “I agree to assume responsibility for the proper conduct of the study at this 
site.” On the Investigator Protocol Agreement Page means the investigator’s 
responsibility as defined by Japanese GCP. 
GSK Japan will submit the CTN to the regulatory authorities in accordance with Law for 
Ensuring the Quality, Efficacy, and Safety of Drugs and Medical Device before 
conclusion of any contract for the conduct of the study with study sites. 

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10.4.1.2. 
Informed consent 
Prior to participation in the study, the investigator (or sub-investigator) should fully 
inform the potential participant including the written approval given by the IRB. The 
investigator (or sub-investigator) should provide the participant ample time and 
opportunity to inquire about details of the study. The participant should sign and 
personally date the consent form. If the participant wishes to consider the content of the 
written information at home, he/she may sign the consent form at home. The person who 
conducted the informed consent discussion and the study collaborator giving 
supplementary explanation, where applicable, should sign and personally date the consent 
form. The investigator (or designee) should retain this signed and dated form (and other 
written information) together with the source medical records, such as clinical charts (in 
accordance with the rules for records retention, if any, at each medical institution) and 
give a copy to the participant. 
10.4.1.3. 
Study administrative structure 
Sponsor Information and List of Medical Institutions and Investigators are included in 
Exhibit 1 and Exhibit 2, respectively. 
10.4.1.4. 
Unapproved medical device 
If unapproved medical devices are used in the study, further details will be added in 
Exhibit 3. In case no unapproved medical devices are used, Exhibit 3 will not be attached. 
10.4.2. 
Germany 
10.4.2.1. 
Explanatory statement concerning gender distribution (Article 7, 
Paragraph 2 (12) of the German GCP order) 
Recruitment will include both males and females with a balance between both gender. It 
is intended to enroll at least 40% of participants from each gender; the remaining 20% 
can be distributed freely between the 2 gender. 
There is no intention to conduct specific analyses investigating the relationship between 
the gender of the participants and the efficacy, immunogenicity or safety of GSK’s 
RSVPreF3 OA investigational vaccine. 
10.4.2.2. 
Remote Monitoring and Source Data Verification 
When onsite monitoring is not permissible due to site/local restrictions (e.g., in case of an 
epidemic and/or pandemic), remote monitoring may be employed that ensures all of the 
following requirements are met: 
• 
Monitoring plan and execution details [remote source data verification (rSDV) 
method and scope of activities] are outlined in the Study Remote Monitoring Plan 
and Study Specific Risk Register. 

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• 
Remote monitoring method to be employed is permitted by local regulations, agreed 
upon by study site and approved by IRB/EC. 
• 
Appropriate security systems/provisions are in place to ensure protection of patient 
data and shared information. 
• 
Participants sign ICF including disclosure of remote monitoring for 
(redacted/anonymized) patient data with security provisions in place. 
Prior to any rSDV activity, a written agreement by the Investigator will be obtained. The 
agreement includes the extent and the method of rSDV activities. 
The Monitoring Plan and Study Specific Risk Register will be updated to include rSDV 
activities. Clinical Research Associates will be guided for the conduct of rSDV. 
10.4.3. 
Republic of Korea 
10.4.3.1. 
Study participants exclusion criteria for enrollment  
Per local Regulation on Approval for Enforcement Regulation on the Safety of 
Pharmaceuticals, etc., Article 24 paragraph 2, a study participant cannot be enrolled in a 
trial if he or she has “participated as a subject in a clinical trial targeting healthy people 
within the last 6 months.” 
Therefore, in order to comply with this local requirement, investigators from Republic of 
Korea should carefully check, before enrolling each participant in the study, that they 
have not participated in any other clinical study targeting healthy people within the last 
6 months prior to enrollment/first study vaccination. 
10.4.3.2. 
Safety monitoring  
In addition, the following points should be noted concerning safety monitoring: 
• 
No safety “holding rules” or criteria for pausing or early termination have been 
defined for this study. 
• 
An Independent Data Monitoring Committee (IDMC) has been put in place and will 
be in charge of reviewing unblinded safety data on an agreed schedule. 
• 
It will be at the IDMC discretion to recommend, if deemed necessary, that the study 
recruitment is paused or terminated based on their unblinded data reviews. 
• 
In addition to the IDMC reviews, GSK’s SRT will perform regular reviews of 
blinded data and may request the IDMC to perform ad-hoc unblinded reviews if any 
potential safety concern is suspected based on blinded data. As of the 
implementation of Protocol Amendment 4, SRT will review unblinded safety data. 

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10.5. 
Appendix 5: Abbreviations and glossary of terms 
10.5.1. 
List of abbreviations (Amended, 12 July 2023) 
AE: 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AF 
Atrial Fibrillation 
ANOVA: 
Analysis of Variance 
ARI: 
Acute Respiratory Illness 
AS01B: 
Adjuvant System containing MPL, QS-21 and liposome (50 μg 
MPL and 50 μg QS-21) 
AS01E: 
Adjuvant System containing MPL, QS-21 and liposome (25 μg 
MPL and 25 μg QS-21) 
BMI: 
Body Mass Index 
CD: 
Community Dwelling 
CHF: 
Congestive Heart Failure 
CI: 
Confidence Interval 
CLS: 
Clinical Laboratory Sciences 
COPD: 
Chronic Obstructive Pulmonary Disease 
COVID-19: 
Coronavirus Disease 2019 
DLP 
Data Lock Point 
eCRF: 
electronic Case Report Form 
ELISA: 
Enzyme-Linked Immunosorbent Assay 
EQ-5D: 
EuroQol 5 dimension health questionnaire 
ES : 
Exposed Set 
FLU-PRO : 
InFLUenza Patient-Reported Outcome 
GMC: 
Geometric Mean Concentration 
GMT: 
Geometric Mean Titer 

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GSK: 
GlaxoSmithKline Biologicals SA 
HCP: 
Healthcare Provider 
HCRU: 
Healthcare Resource Utilization 
HLT: 
High Level Term 
hMPV: 
Human Metapneumovirus 
HRP: 
Horseradish Peroxidase 
HR-QoL: 
Health-Related Quality of Life 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
IDMC: 
Independent Data Monitoring Committee 
IEC: 
Independent Ethics Committee 
IES: 
Independent External Statistician 
IgG: 
Immunoglobulin G 
IRB: 
Institutional Review Board 
LL: 
Lower Limit 
LML: 
Local Medical lead 
LRTD: 
Lower Respiratory Tract Disease 
LSMEANS: 
Least Squares Mean 
LTCF: 
Long-Term Care Facility 
MedDRA: 
Medical Dictionary for Regulatory Activities 
mES: 
modified Exposed Set 
MGI: 
Mean Geometric Increase 
MI: 
Myocardial Infarction 
MPL: 
3-O-desacyl-4’- monophosphoryl lipid A (produced by GSK) 
NH: 
Northern Hemisphere 

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PCR: 
Polymerase Chain Reaction 
PGI-C: 
Patient Global Impression of Change 
PGI-S: 
Patient Global Impression of Severity 
pIMD: 
Potential Immune-Mediated Disease 
PPSe: 
Per Protocol Set for efficacy 
PPSi: 
Per Protocol Set for immunogenicity 
PT: 
Preferred Term 
QS-21: 
Quillaja saponaria Molina, fraction 21 (Licensed by GSK from 
Antigenics LLC, a wholly owned subsidiary of Agenus Inc., a 
Delaware, USA corporation) 
RNA: 
Ribonucleic Acid 
rSDV: 
remote Source Data Verification 
RSV: 
Respiratory Syncytial Virus 
RSVPreF3 OA: RSV PreFusion protein 3 Older Adult 
RT-PCR: 
Reverse Transcription Polymerase Chain Reaction 
S1/S2/S3: 
Season ½/3 
SAE: 
Serious Adverse Event 
SAP: 
Statistical Analysis Plan 
SBIR: 
Source data Base for Internet Randomization 
SF-12: 
A Short Form 12-item health survey 
SH: 
Southern Hemisphere 
SOC: 
System Organ Class 
SPM: 
Study Procedures Manual 
SRT: 
Safety Review Team 
ULOQ: 
Upper Limit Of Quantification 
US: 
United States 

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VE: 
Vaccine Efficacy 
WHO: 
World Health Organization 
YOA: 
Years Of Age 
10.5.2. 
Glossary of terms  
 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the use 
of a medicinal product, whether or not considered related to 
the medicinal product. 
An adverse event (AE) can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product. For marketed 
medicinal products, this also includes failure to produce 
expected benefits (i.e., lack of efficacy), abuse or misuse. 
Adverse event of 
special interest: 
An adverse event of special interest (serious or non-serious) 
is one of scientific and medical concern specific to the 
sponsor’s product or program, for which ongoing monitoring 
and rapid communication by the investigator to the sponsor 
can be appropriate. Such an event might warrant further 
investigation in order to characterize and understand it. 
Depending on the nature of the event, rapid communication 
by the trial sponsor to other parties (e.g., regulators) might 
also be warranted. 
Blinding: 
A procedure in which one or more parties to the trial are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the trial, 
and only when the data are cleaned to an acceptable level of 
quality will appropriate personnel be unblinded or when 
required in case of a serious adverse event. 
In an observer-blind study, the participant, the site and 
sponsor personnel involved in the clinical evaluation of the 
participants are blinded while other study personnel may be 
aware of the intervention assignment. 
Caregiver: 
A ‘caregiver’ is a person who has a continuous caring role 
for a participant or may be a person having substantial 
periods of contact with a participant and/or is engaged in 
his/her daily health care (e.g., a relative of the participant 
including family members or friends, a nurse or LTCF staff 

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who helps with daily activities in case of residence in a 
LTCF). 
In the context of this study, a caregiver can be appointed by 
the participant to oversee and support the participant’s 
compliance with protocol-specific procedures (such as 
transcribing responses to questionnaires and diaries, 
receiving phone calls, planning study visits, performing the 
nasal self-swab, etc.). However, at no time, the caregiver 
should evaluate the participant’s health status while 
answering diaries and/or questionnaires or make decisions 
on behalf of the participant. 
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. 
Community Dwelling 
participants: 
Participants who live in the community, either independently 
or with relatives, without the availability of permanent (24 
hours a day, 7 days a week) professional on-site assistance 
with activities of daily living, nursing or medical care. 
Current smoker: 
A person who is currently smoking or who has stopped 
smoking within 6 months before study start.  
Designee: 
A qualified person appointed by the investigator or sponsor 
to take over a specific part of their trial-related duties or 
responsibilities. 
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolled participant: 
‘Enrolled’ means a participant’s/LAR’s agreement to 
participate in a clinical study following completion of the 
informed consent process. Potential participants who are 
screened for the purpose of 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 9.3 for the definition of ‘enrolled’ 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. 
eTrack: 
GSK’s tracking tool for clinical trials. 

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Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, included 
in the per protocol analysis (see Section 9.3 for details on 
criteria for evaluability). 
Former smoker: 
A person who stopped smoking for at least 6 months at the 
time of study start. 
Frailty: 
Frailty is a term used in geriatric medicine to identify older 
adults who are at increased risk of poor clinical outcomes, 
such as incident disability, cognitive decline, falls, 
hospitalization, institutionalization, or increased mortality. 
Frailty represents a reduction in resistance to stressors 
leading to increased clinical vulnerability and adverse health 
outcomes. 
Immunological 
correlate of 
protection: 
A correlate of risk that has been validated to predict a certain 
level of protection from the targeted endpoint. 
Intervention: 
Term used throughout the clinical study to denote a set of 
investigational product(s) or marketed product(s) or placebo 
intended to be administered to a participant. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Invasive medical 
device: 
A device which, in whole or in part, penetrates inside the 
body, either through a body orifice or through the surface of 
the body. 
Investigational 
vaccine: 
A pharmaceutical form of an active ingredient being tested 
in a clinical trial, including a product with a marketing 
authorization when used in a way different from the 
approved form, or when used for an unapproved indication, 
or when used to gain further information about an approved 
use. 
Synonym: Investigational Medicinal Product. 

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Investigator: 
A person responsible for the conduct of the clinical trial at a 
trial site. If a trial is conducted by a team of individuals at a 
trial site, the investigator is the responsible leader of the 
team and may be called the principal investigator. 
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified individual or 
party to perform those trial-related duties and functions. 
Long-term care 
facility: 
A collective institutional setting (i.e., where some aspects of 
daily life, such as having meals, are shared) where care is 
provided for older people who reside in the facility 24 hours 
a day, 7 days a week, for an indefinite period of time. 
On-site personal assistance with activities of daily living is 
provided, while nursing and medical care may be provided 
on-site or by nursing and medical professionals from an 
organization external to the setting. 
The term long-term care facility may include nursing homes, 
care homes, elderly care centers, assisted living facilities 
and/or others. 
Participant: 
Term used throughout the protocol to denote an individual 
who has been contacted to participate or participates in the 
clinical study, either as a recipient of the vaccine or as a 
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 that the final participant was examined or received 
an intervention for the purpose of final collection of data for 
all primary outcomes, whether the clinical trial was 
concluded according to the pre-specified protocol or was 
terminated. 
Protocol 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 
Biologicals 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. 

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Randomization: 
Process of random attribution of intervention to participants 
to reduce selection bias. 
Self-contained study: 
Study with objectives not linked to the data of another study. 
Site Monitor: 
An individual assigned by the sponsor and responsible for 
assuring proper conduct of clinical studies at one or more 
investigational sites. 
Solicited event: 
Events to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively 
solicited from the participant or an observer during a 
specified post-vaccination follow-up period. 
Source data: 
All information in original records and certified copies of 
original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction 
and evaluation of the trial. Source data are contained in 
source documents (original records or certified copies). 
Source documents: 
Original legible documents, data, and records (e.g., hospital 
records, clinical and office charts, laboratory notes, 
memoranda, participants’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after 
verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-
rays, participant files, and records kept at the pharmacy, at 
the laboratories and at medico-technical departments 
involved in the clinical trial). 
Study 
vaccine/product: 
Any investigational vaccine/product being tested and/or any 
authorized use of a vaccine/product/placebo as a reference or 
administered concomitantly, in a clinical trial that evaluates 
the use of an investigational vaccine/product. 
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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10.5.3. 
List of trademarks  
Trademarks of the GSK group of companies 
 
Generic description 
Shingrix 
 
Herpes zoster vaccine (recombinant, adjuvanted) 
 
Trademarks not owned by the GlaxoSmithKline 
group of companies 
 
Generic description 
TrueBlue Peroxidase Substrate (Seracare Life 
Sciences Inc.) 
 
A highly sensitive chromagenic substrate for 
visualization of horseradish peroxidase-labeled 
reporter reagents 
10.6. 
Appendix 6: Protocol Amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment 
is located directly before the Table of Contents (TOC). 
DOCUMENT HISTORY 
Document 
Date of Issue 
Original Protocol 
16 October 2020 
Amendment 1 
25 February 2021 
Amendment 2 
6 October 2021 
Amendment 3 
24 January 2022 
Amendment 4 
23 March 2023 
Amendment 5 
12 July 2023 
 

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Amendments summary of changes table: 
Document 
Date of issue 
Section # and title 
Description of change 
Brief rationale 
Amendment 1 
25 February 2021 
1.1. (Synopsis), 2.1. (Study rationale), 
3. (Objectives and endpoints), 4.1. (Overall 
design), 6.1. (Study interventions 
administered), 9. (Statistical considerations), 
10.5.1. (List of abbreviations) 
The lot-to-lot consistency evaluation has been 
removed. 
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 1 
25 February 2021 
2.3. (Benefit/Risk assessment), 4.1. (Overall 
design), 4.1.1. (Overview of the recruitment 
plan), 6.1. (Study interventions administered), 
6.3.2. (Randomization to study intervention), 
6.3.3. (Intervention allocation to the 
participant), 9.2. (Sample size determination) 
A second part with a 4th RSVPreF3 group (Lot 4) 
and additional placebo recipients has been added 
for a total sample size up to 23 000 (randomization 
ratio 1:1) in NH. The target sample size in SH 
remains unchanged. The study design, study 
intervention and sample size have been adapted 
accordingly. 
To increase the sample size to 
mitigate a potential lower attack 
rate of circulating respiratory 
viruses observed during the 
COVID-19 pandemic. 
Amendment 1 
25 February 2021 
1.1. (Synopsis), 1.3. (Schedule of activities), 
4.1. ( Overall design), 8.1.1. (Efficacy 
assessments) 
ARI surveillance period will start on the day of 
vaccination (Visit 1) instead of 1 month post-
vaccination (Visit 2). 
To collect data for all ARI cases 
starting from the day of 
vaccination. 
Amendment 1 
25 February 2021 
3. (Objectives and endpoints), 8.1.2. 
(Immunogenicity assessments), 8.1.5. 
(Immunological read-outs), 8.1.7. 
(Immunological correlates of protection) 
Neutralization assay was added as test which may 
be performed to investigate a correlate of 
protection. 
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 1 
25 February 2021 
4.2.1. (Case definitions for evaluation of 
vaccine efficacy) 
A second case definition for severe LRTD was 
added. 
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 1 
25 February 2021 
6.1. (Study interventions administered) 
The antigen dose was removed from the 
presentation of the RSVPreF3 OA investigational 
vaccine lots. 
The antigen dose is not required 
for the presentation, which should 
only reflect the formulation dose 
form and formulation unit of 
presentation. 
Amendment 1 
25 February 2021 
6.3.3. (Intervention allocation to the 
participant) 
Minimization factors were updated to exclude sex 
and setting and subset as stratification factor was 
added. 
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 1 
25 February 2021 
8. (Study assessments and procedures) 
An additional measure was added to allow 
collection of swab samples by another person than 
the site staff, in case this is required to comply with 
To allow study conduct in line 
with guidance from local public 
health or other competent 

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local guidelines (e.g., during the COVID-19 
pandemic). 
authorities during special 
circumstances such as the 
COVID-19 pandemic. 
Amendment 1 
25 February 2021 
9.4.3. (Primary endpoint)  
Wording for sensitivity analysis of the primary 
efficacy endpoint for RSV cases confirmed by the 
GSK qRT-PCR was added.  
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 1 
25 February 2021 
1.3. (Schedule of activities), 9.5.1. (Sequence 
of analyses) 
Order of the analyses has changed. A first 
analysis of the safety and immunogenicity 
objectives will be performed when all safety data 
up to 6 months post-vaccination will be available 
for all participants in NH. 
To evaluate safety data as soon 
as possible to build knowledge for 
the benefit/risk profile 
assessment. 
Amendment 1 
25 February 2021 
10.4. (Appendix 4: Country-specific 
requirements) 
Country-specific guidance for the Republic of 
Korea was included. 
To comply with legislation from 
the Republic of Korea. 
Amendment 2 
6 October 2021 
3. (Objectives and endpoints) 
The primary objective wording was updated to 
allow the assessment of the primary vaccine 
efficacy (VE) after having accrued at least 56 
cases (case-driven only), which could happen 
before reaching the end of Season 1. The 
evaluation of VE at the end of Season 1 will be 
done as part of the secondary confirmatory 
objective evaluating VE over several seasons. In 
addition, the tertiary descriptive objective 
evaluating VE against any ARI and any LRTD has 
been moved to a secondary descriptive objective. 
To allow assessment of the 
primary objective once the 
required number of cases have 
been accumulated. 
Amendment 2 
6 October 2021 
3. (Objectives and endpoints), 9.1.2. 
(Secondary objectives) 
Table structure updated to identify the subcategory 
for secondary confirmatory objectives and 
endpoints. 
The figure on sequential evaluation of primary and 
confirmatory secondary objectives was updated 
accordingly to indicate the confirmatory objectives 
to be analyzed. 
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 2 
6 October 2021 
3. (Objectives and endpoints), 8.1.2. 
(Immunogenicity assessments), 8.1.4.2. 
The evaluation of neutralizing antibody titers 
against RSV B was added to the secondary and 
tertiary immunogenicity endpoints for the pre-
To implement the outcome of 
consultations with regulatory 
authorities. 

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Brief rationale 
(Laboratory assays for immunogenicity 
assessment), 
8.1.5. (Immunological read-outs) 
vaccination (Day 1), 30 days post-vaccination (Day 
31), pre-Season 2 and pre-Season 3 time points. 
Amendment 2 
6 October 2021 
9. (Statistical consideration) 
The sequence of analyses and power for analyses 
were updated based on the trigger for analysis of 
the primary objective (case-driven only) and to 
include an optional interim analysis in case the 
number of cases triggering the final analysis of the 
primary objective is not achieved at the end of 
Season 1 in NH. 
The methodology for sample size re-assessment 
for enrollment of a second cohort before Season 2 
in NH was also updated. 
To allow assessment of the 
primary objective once the 
required number of cases have 
been accumulated. 
To allow an interim assessment 
of the primary objective at the 
end of Season 1 in NH or later if 
the trigger for the final primary 
analysis is not reached at the end 
of Season 1 in NH. 
Amendment 2 
6 October 2021 
9.3. (Populations for analyses) 
The case counting for the analysis on the modified 
Exposed Set was updated to start on Day 15 after 
vaccination. 
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 2 
6 October 2021 
10.4. (Appendix 4: Country-specific 
requirements) 
Guidance on remote monitoring and source data 
verification was added. 
To comply with local regulations 
in Germany. 
Amendment 3 
24 January 2022 
1.3. (Schedule of activities), 8.3.1. (Time 
period and frequency for collecting AE, SAE 
and other safety information) 
Study visits/contacts and time points were added 
for all participants at 1 and 6 months post each 
annual revaccination dose. 
To collect solicited adverse 
events during the 4-day follow-up 
period after each dose in the 
reactogenicity and 
immunogenicity subset, 
unsolicited adverse events during 
the 30-day follow-up period after 
each dose and SAEs/pIMDs 
during the 6-month follow-up 
period after each dose. 
Amendment 3 
24 January 2022 
2.1. (Study rationale), 3. (Objectives and 
endpoints) 
The confirmatory assessment of VE of annual 
revaccination doses and the descriptive evaluation 
of year-by-year VE for the annual revaccination 
doses were added. In addition, the safety and 
reactogenicity objectives were updated to include 
the additional assessment timepoints. 
To allow assessment of the 
vaccine efficacy and safety 
following annual revaccinations 
with the RSVPreF3 OA vaccine. 

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Amendment 3 
24 January 2022 
3. (Objectives and endpoints) 
A confirmatory secondary efficacy objective was 
added to assess VE against RSV subtypes A and 
B separately over 3 seasons, conditionally to the 
number of cases accrued for both types. 
To allow the confirmatory 
demonstration of VE by RSV 
subtype at the end of Season 3. 
Amendment 3 
24 January 2022 
3. (Objectives and endpoints) 
The assessment of VE against hMPV was 
upgraded from secondary descriptive to secondary 
confirmatory objective. 
To implement the outcome of 
consultations with regulatory 
authorities. 
Amendment 3 
24 January 2022 
4. (Study design), 
8.1.5. (Immunological read-outs), 8.2. (Safety 
assessments) 
The following items were added: 
• 
Re-randomization of the RSVPreF3 group 
prior to Season 2 into 2 sub-groups 
(RSV_annual group receiving annual 
revaccinations and RSV_1dose group 
receiving single dose vaccination followed 
by placebo) in a (1:1) ratio. 
• 
Annual revaccination with placebo for 
participants in the Placebo group. 
• 
Addition of study visits/contacts for all 
participants at 1 and 6 months post each 
annual revaccination dose. 
Addition of safety (for all participants) and 
reactogenicity (for participants in the reactogenicity 
and immunogenicity subset) follow-up after each 
annual revaccination dose. 
To allow assessment of the 
efficacy and safety following 
annual revaccinations with the 
RSVPreF3 OA vaccine. 
Amendment 3 
24 January 2022 
5. (Study population) 7.1. (Discontinuation of 
study intervention), 7.1.2. (Contraindications 
to subsequent vaccine administration) 
The sections were adapted following the inclusion 
of annual revaccination doses. 
To comply with implementation of 
annual revaccination doses 
throughout the protocol. 
Amendment 3 
24 January 2022 
6. (Study intervention) 
The numbers of doses to be administered per 
group and intervention allocation (randomization) 
was updated to include annual revaccination 
doses. 
To allow assessment of the 
efficacy and safety following 
annual revaccinations with the 
RSVPreF3 OA vaccine. 
Amendment 3 
24 January 2022 
9. (Statistical consideration) 
The sequence of analyses and power for analyses 
were updated based on the inclusion of 
confirmatory assessment of VE of annual 
revaccination doses, and the confirmatory 
assessment of VE against hMPV. 
To implement the outcome of 
consultations with regulatory 
authorities and allow assessment 
of the efficacy and safety 
following annual revaccinations 
with the RSVPreF3 OA vaccine. 

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Brief rationale 
Amendment 3 
24 January 2022 
10.3.5 (Potential immune-mediated diseases) 
The table with list of pIMDs has been updated. 
To include emerging possible 
immune-mediated events of 
interest in the context of 
COVID-19 vaccine safety 
monitoring. 
Amendment 4 
23 March 2023 
1.1 Synopsis; 
1.3 Schedule of activities; 
4.1 Overall design; 
4.2.1 Case definitions for evaluation of 
vaccine efficacy; 
6.5 Concomitant therapy; 
8.1.6. Molecular biology read-outs; 
10.5.1. List of abbreviations 
ARI is defined as acute respiratory illness instead 
of acute respiratory infection.  
The case definition for ARI 
includes the clinical 
manifestations of symptoms/signs 
in addition to positive reverse 
transcription polymerase chain 
reaction (RT-PCR) test results. 
Amendment 4 
23 March 2023 
1.3 Schedule of activities; 
6.5 Concomitant therapy; 
8.1.1.5. Scheduled site staff contacts; 
8.3.1. Time period and frequency for 
collecting AE, SAE and other safety 
information; 
8.3.2 Method of detecting AEs and SAEs and 
other events; 
8.3.3. Regulatory reporting requirements for 
SAEs and other events; 
8.3.4. Contact information for reporting SAEs, 
AESIs (including potential immune-mediated 
diseases [pIMDs] and AF); 
8.3.5. Treatment of adverse events; 
9.4.1.4. Reactogenicity/Safety; 
10.3.5. Adverse events of special interest; 
10.3.5.2. Atrial fibrillation; 
10.3.8. Recording and follow-up of AEs, 
SAEs, AESIs (including pIMDs and AF); 
10.3.8.1. Time period for collecting and 
recording AEs, SAEs, AESIs (including pIMDs 
and AF); 
AF adverse events meeting the AEs or serious 
adverse events (SAEs) definitions will be 
considered as AESI in this study and additional 
information on these events is to be reported in the 
AF follow-up questionnaire in electronic case 
report form (eCRF). 
An imbalance in cases of AFs in 
the 30-days post Dose 1 was 
observed. These safety data 
were reviewed by the SRT and 
the IDMC, and no safety signals 
were identified. However, GSK is 
of the opinion that a detailed 
assessment of all AF cases is 
required. 

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10.3.8.2. Follow-up of AEs, SAEs, AESIs 
(including pIMDs and AF); 
10.3.8.2.1. Follow-up during the study; 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study; 
10.3.8.3. Updating of SAE, AESI (including 
pIMD and AF) information after removal of 
write access to the participant’s eCRF; 
10.3.10. Reporting of SAEs, AESIs (including 
pIMD and AF); 
10.5.1. List of abbreviations; 
10.5.2. Glossary of terms 
Amendment 4 
23 March 2023 
10.3.5.1. pIMDs 
The list of pIMDs has been updated. 
The list has been updated 
following a regular safety review 
and in line with Medical 
Dictionary for Regulatory 
Activities (MedDRA) updates 
Amendment 4 
23 March 2023 
3 Objectives and endpoints; 
9.1.2. Secondary objectives; 
9.2.2. Secondary objectives; 
9.2.2.1 Expected number of RSV-confirmed 
LRTD cases; 
9.3 Population for analyses; 
9.4.4.1. Efficacy; 
9.4.5.1 Efficacy; 
The secondary confirmatory objective of vaccine 
efficacy (VE) against human metapneumovirus 
(hMPV) over 3 seasons has been removed and 
the secondary descriptive objective evaluating VE 
against hMPV after Season 2 and Season 3 has 
been downgraded to tertiary objective. 
As no VE against hMPV was 
observed at VE Analysis 1. 
Amendment 4 
23 March 2023 
3 Objectives and endpoints; 
4.3 Justification for dose; 
8.1.2. Immunogenicity assessments; 
8.1.4.2. Laboratory assays for 
immunogenicity assessment; 
8.1.5. Immunological read-outs; 
10.2.1 Laboratory assays for immune 
response; 
The terminology for respiratory syncytial virus 
(RSV) A/RSV B neutralizing titers and RSVPreF3-
binding IgG has been clarified. 
This nomenclature more precisely 
reflects what is indeed measured 
by the neutralization assay and 
the enzyme-linked 
immunosorbent assay (ELISA) 
respectively. 
Amendment 4 
23 March 2023 
6.3.5 Blinding and unblinding; 
6.3.5.1 Emergency blinding; 
8.2.3. Safety monitoring; 
As of the implementation of Protocol Amendment 
4, GSK RSV OA team members will be unblinded 
at the individual participant level with the exception 
To simplify the blinding 
procedures at the sponsor level 

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9.5.1. Sequence of analyses 
9.6 Independent Data Monitoring Committee 
10.4.3.2 Safety monitoring 
of GSK RSV OA team members involved in clinical 
evaluation (i.e., data review and validation, 
ARI/LRTD case review and adjudication, and 
laboratory testing) as well as investigators and 
study participants who will remain blinded until the 
end of study. 
The firewall team will no longer be active as of the 
implementation of Protocol Amendment 4 as of 
which point study statisticians will perform the 
analyses and manage the blinding of results for 
blinded study team members and investigators. 
As of the implementation of Protocol Amendment 
4, SRT can review unblinded data.  
to reduce complexity in sharing 
study-related information. 
Amendment 4 
23 March 2023 
9.5.1. Sequence of analyses 
The following analyses have been added: 
• 
VE Analysis 4: end of season 2 in Northern 
hemisphere (NH) and Southern hemisphere 
(SH): 
An analysis will be performed to evaluate the 
efficacy, safety and immunogenicity 
objectives over 2 seasons, when all 
participants in NH and SH have been 
followed until the end of second season (S2) 
in SH. 
• 
VE Analysis 5: end of season 3 in NH: 
An analysis will be performed to evaluate the 
efficacy, safety and immunogenicity 
objectives over 3 seasons, when all 
participants in NH have been followed until 
the end of third season (S3) in NH. 
VE Analysis 4 End of Study Analysis becomes VE 
Analysis 6. 
To evaluate persistence of VE 
more regularly and to support 
discussions with recommending 
bodies. 
Amendment 4 
23 March 2023 
10.4 Country-specific requirements 
Country specific requirements for Brazil and 
France have been removed. 
These countries that were initially 
planned, finally did not participate 
in this study. 
Amendment 4 
23 March 2023 
6.3.5.1. Emergency unblinding; 
The section has been updated to reflect that 
GSK’s Global Safety staff may unblind the 
For alignment with current 
protocol template. 

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intervention assignment for any participant with an 
SAE. If the SAE requires that an expedited 
regulatory report be sent to one or more regulatory 
agencies, a copy of the report, identifying the 
participant’s intervention assignment, may be sent 
to investigators in accordance with local 
regulations and/or GSK policy. 
Amendment 4 
23 March 2023 
9.3 Population for analyses 
Modified exposed set (mES) specific definition for 
hMPV was removed and mES definition after each 
dose was clarified. 
As no VE against hMPV was 
observed at VE Analysis 1, the 
confirmatory objective was 
removed and no specific mES for 
hMPV will be used for analysis. 
Clarification of mES by dose for 
RSV endpoints was added to be 
aligned with the statistical 
analysis plan (SAP). 
Amendment 4 
23 March 2023 
9.4.4.1 Efficacy 
The reporting periods for RSV-confirmed LRTD 
cases for the VE analysis by year have been 
clarified.  
For alignment with the SAP, and 
to take into account the 
revaccination. 
Amendment 4 
23 March 2023 
3 Objectives and endpoints 
9.4.4.1 Efficacy 
It has been clarified that VE in the prevention of 
hospitalization and complications will be evaluated 
during RSV seasons and during the entire follow-
up. 
To cover the entire period post-
vaccination as for the other 
endpoints. 
Amendment 4 
23 March 2023 
9.4.4.3 Safety 
The section has been updated to clarify that SAEs, 
pIMDs, fatal SAEs, causally related SAEs and 
causally related pIMDs occurring within 6 months 
post-vaccination will be tabulated after each dose, 
and that causally related SAEs, fatal SAEs and 
causally related pIMDs will be tabulated after each 
dose from Day 1 up to study end.  
For alignment with the SAP, and 
to take into account the 
revaccination. 
Amendment 4 
23 March 2023 
8.1.1.1 ARI surveillance period and methods 
Addition of flexibility in defining the data lock point 
(DLP) for the upcoming analyses for the ongoing 
and/or subsequent seasons.  
To take into consideration the 
RSV circulation. 
 

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Detailed description of the current Protocol Amendment: 
Title 
A Phase 3, randomized, placebo-controlled, observer 
blind, multi-country study to demonstrate the efficacy of 
a single dose and annual revaccination doses of GSK’s 
RSVPreF3 OA investigational vaccine in adults aged 60 
years and above. 
Sponsor signatory 
 
Marie Van Der Wielen, MD 
Clinical Project Lead, MD 
RSV Older Adults 
Section 1. 
PROTOCOL SUMMARY 
Section 1.1. 
Synopsis 
GlaxoSmithKline Biologicals SA (GSK) is developing an investigational vaccine, has 
developed a new RSV PreFusion protein F3 Older Adult (RSVPreF3 OA) vaccine 
against respiratory syncytial virus (RSV)-associated (subtypes A and B) disease in adults 
≥ 60 years of age (YOA). 
Section 1.3. 
Schedule of activities 
For participants who will have the Visit 5NH (pre-Season 3 visit) taking place 
BEFORE the approval of this Protocol Amendment 5, the study procedures should be 
performed according to the previously approved protocol amendment version. Refer to 
Table 1 for details.  
For participants who will have the Visit 5NH (pre-Season 3 visit) taking place AFTER 
the approval of this Protocol Amendment 5, the study procedures should be performed 
according to the current Protocol Amendment 5: Dose 3 administration should be 
cancelled as well as other procedures related to Dose 3 administration. Visit 6NH and 
Contact 5 should be cancelled for these participants. Blood sample should be collected 
for all participants at Visit 5NH. Refer to Table 2 for details.  
Timeframe for Visit 5NH are defined in Table 5. 
 

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Table 1 
Schedule of activities for all participants in Northern hemisphere that have their Visit 5NH BEFORE approval of this 
Protocol Amendment 5 
Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH 
V6NH 
C52 
V7NH Notes for more information 
and details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 End S1 Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 Pre S3 
Dose 3 
Day 31 
Post-D3 
Month 6 
Post-D3 End S3 
Study group and intervention 
number allocation 
○ 
 
 
 
○ 
 
 
 
○ 
 
 
 
See Sections 6.3.2 and 
6.3.3 
Note: The double-line borders indicate the analyses, which will be performed on data that are as clean as possible: VE Analysis 2 at the end of Season 1 in NH, Safety analysis when 
all safety data up to 6 months post-Dose 1 will be available for all participants in NH and SH, VE Analysis 3 after at least 2 seasons in NH and 1 season in SH, and VE Analysis 4 6 
after 3 seasons in NH and 2 seasons in SH (end of study). VE Analysis 1 will be case-driven. Additional analyses, not indicated in this table, will be performed as detailed in refer 
to Section 9.5.1 for details. 
3 Freely given and written informed consent must be obtained from each study participant prior to participation in the study. The participant’s informed consent may be obtained prior to 
Visit 1 and Visit 3. In addition, participants should sign the ICF addendum for revaccination (Protocol Amendment 3) at Visit 3.  
4 In case the participant does not agree to continue the study for the annual revaccinations, the study conclusion page of the eCRF should be completed. 
11 Atrial fibrillation (AF) will be considered as adverse events of special interest (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. For AF that were reported before the implementation of the this Protocol Amendment 4, 
additional available information should be encoded in the specific AF follow-up questionnaire retrospectively. 

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Table 2 
Schedule of activities for participants in Northern hemisphere that have their Visit 5NH AFTER the approval of this 
Protocol Amendment 5 
Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH V6NH11 
C511 
V7NH Notes for more 
information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 
End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
Pre S3 
Dose 3 
 
Day 31 
Post-
D3 
Month 6  
Post-D3 End S3 
Study participant informed 
consent 
●3 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.1.3 
Study participant informed 
consent for annual 
revaccination 
 
 
 
 
● 
 
 
 
 
 
 
 
 
Study participant informed 
consent addendum for 
Protocol Amendment 5 
 
 
 
 
 
 
 
 
● 
 
 
 
 
Distribution of participant 
card 
○ 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.3.6 
Check inclusion/exclusion 
criteria 
● 
 
 
 
 
 
 
 
 
 
 
 
See Sections 5.1 
and 5.2 
Check with participant if 
he/she will appoint a 
caregiver and distribute 
information letter(s) to 
caregiver, when applicable 
○ 
○ 
 
 
○ 
○ 
 
 
○ 
 
 
 
See Sections 5.3 
and 10.1.3 
Baseline and demography 
assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 
Measure/record height and 
weight 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 
Record medical history 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.3 
Record history of vaccine 
administration4 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.4 
Physical examination/Vital 
signs 
● 
○5 
 
 
● 
○5 
 
 
● 
 
 
○5 
See Section 8.2.2 
Lung auscultation 
○ 
○5 
 
 
○ 
○5 
 
 
○ 
 
 
○5 
See Section 8.2.2.3 
Record oxygen saturation 
● 
 
 
 
● 
 
 
 
● 
 
 
 
See Section 8.2.2.4 

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Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH V6NH11 
C511 
V7NH Notes for more 
information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 
End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
Pre S3 
Dose 3 
 
Day 31 
Post-
D3 
Month 6  
Post-D3 End S3 
Record smoking status and 
smoking exposure history 
(including electronic smoking 
devices) 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.5. 
Refer to Section 
10.5.2 for 
definitions of 
current and former 
smoker. 
Clinical specimens for 
laboratory assays 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling in all 
participants (~20 mL) 
●6 
● 
 
 
 
 
 
 
●12 
 
 
 
See Section 8.1.3.2 
Blood sampling in subset 
(~20 mL)7  
 
 
 
 
●6 
 
 
 
● 
 
 
 
See Section 8.1.3.2 
Vaccine(s) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check criteria for temporary 
delay for enrollment and/or 
vaccination 
○ 
 
 
 
○ 
 
 
 
 
 
 
 
See Section 7.1.1 
Check contraindications to 
vaccination 
 
 
 
 
○ 
 
 
 
 
 
 
 
See Section 7.1.2 
Study group and intervention 
number allocation 
○ 
 
 
 
○ 
 
 
 
 
 
 
 
See Sections 6.3.2 
and 6.3.3 
Record pre-vaccination body 
temperature 
● 
 
 
 
● 
 
 
 
 
 
 
 
The route for 
measuring 
temperature can be 
oral, axillary or 
tympanic (see 
Section 8.2.1.6). 
Vaccine administration 
(including 30-minute post-
vaccination observation) 
● 
 
 
 
● 
 
 
 
 
 
 
 
See Section 6.1 
Safety assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Distribute paper diary cards8 
○ 
 
 
 
○ 
 
 
 
 
 
 
 
See Section 8.2.1.7 
Return of paper diary cards 
 
○ 
 
 
 
○ 
 
 
 
 
 
 
See Section 10.3.8 

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Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH V6NH11 
C511 
V7NH Notes for more 
information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 
End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
Pre S3 
Dose 3 
 
Day 31 
Post-
D3 
Month 6  
Post-D3 End S3 
Record solicited 
administration site and 
systemic events (Days 1-4) in 
the reactogenicity subset 
● 
● 
 
 
● 
● 
 
 
 
 
 
 
See Section 10.3.8 
Record unsolicited AEs (Days 
1-30) in all participants10 
● 
● 
 
 
● 
● 
 
 
 
 
 
 
See Section 10.3.8 
Record concomitant 
medications/vaccinations 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Table 15 for 
specific collection 
period and Section 
6.5 
Record intercurrent medical 
conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 9.3.1.1 
Record all SAEs and pIMDs10 
● 
● 
● 
 
● 
● 
● 
 
● 
 
 
 
See Section 10.3.8 
Record fatal SAEs, SAEs 
related to study vaccination, 
COVID-19 cases and pIMDs 
related to study vaccination10 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 10.3.8 
Record AEs/SAEs leading to 
withdrawal from the study 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 10.3.8 
Record SAEs related to study 
participation, or to a 
concurrent GSK 
medication/vaccine9 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
 
● 
See Section 10.3.8 
ARI surveillance 
 
 
 
 
 
 
 
 
 
 
 
 
 
Instruct/remind participants of 
ARI surveillance 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
○ 
 
 
 
See Section 8.1.1 
Nasal self-swab training with 
the study participant 
 
○ 
 
 
 
 
 
 
 
 
 
 
See Section 
8.1.1.1.1 
Distribute material for nasal 
self-swab collection 
(including instructions) 
 
○ 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 8.1.1 

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Type of contact for NH1 
V1 
V2 
C12 
C2 
V3 
V4 
C32 
C4 
V5NH V6NH11 
C511 
V7NH Notes for more 
information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 
Month 6 
Post-D1 
End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
Pre S3 
Dose 3 
 
Day 31 
Post-
D3 
Month 6  
Post-D3 End S3 
Frailty status 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess frailty status with Gait 
Speed test 
● 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.4 
HR-QoL questionnaires 
 
 
 
 
 
 
 
 
 
 
 
 
 
Distribute the daily health 
questionnaires for 
participants to complete at 
home in case of ARI 
 
○ 
 
 
○ 
 
 
 
○ 
 
 
 
See Section 8.10.1 
Completion of daily health 
questionnaires by the 
participant 
 
● 
 
 
 
 
 
 
 
 
 
 
See Section 8.10.1 
Completion of EQ-5D and 
SF-12 questionnaires by the 
participant 
● 
 
 
 
● 
 
 
 
● 
 
 
 
See Section 8.10.1 
Study conclusion for NH 
 
 
 
 
 
 
 
 
 
 
 
● 
See Section 4.4 
Note: The double-line borders indicate the analyses, which will be performed on data that are as clean as possible: VE Analysis 2 at the end of Season 1 in NH, Safety 
analysis when all safety data up to 6 months post-Dose 1 will be available for all participants in NH and SH, VE Analysis 3 after at least 2 seasons in NH and 1 season in 
SH, and VE Analysis 6 after 3 seasons in NH and 2 seasons in SH (end of study). VE Analysis 1 will be case-driven. Additional analyses, not indicated in this table, will be 
performed as detailed in Section 9.5.1. 
Note: If following the sample size re-assessment an additional cohort needs to be enrolled before the next season in NH (see Section 9.2.3), the participants enrolled in 
this cohort will follow the same schedule of activities as indicated in this table. 
ARI: acute respiratory illness; C: Contact; D: Dose; EQ-5D: EuroQol 5-dimension health questionnaire; HR-QoL: health-related quality of life; pIMDs: potential immune-
mediated diseases; S: Season; SAE: serious adverse event; SF-12: Short Form 12-item health survey; Pre-S1: pre-Season 1; Pre-S2: pre-Season 2; Pre-S3: pre-Season 3; 
V: Visit. 
● 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. 
1. 
Study visits should preferably be done on site or in the LTCF. If deemed necessary, study visits can be done at home. For the study contacts, multiple formats can be 
proposed by the study site. These contacts may be done via e-mail, text message, fax or phone call for example, or via a visit for LTCF participants. The most 
appropriate format should be agreed between site staff and the study participant. Text messages, e-mail 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). 
Receipt of the message must be confirmed by the participant or caregiver, as applicable. 
2. 
Contacts 1 and 3 must not be performed before the 6-month post-vaccination time point to allow collection of safety data up to at least 6 months after each 
vaccination for each participant. These contacts can be combined with another contact or visit. 

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3. 
Freely given and written informed consent must be obtained from each study participant prior to participation in the study. The participant’s informed consent may be 
obtained prior to Visit 1. In addition, participants should sign the ICF addendum for revaccination (Protocol Amendment 3) at Visit 3 and ICF addendum for Protocol 
Amendment 5 at Visit 5NH. 
4. 
Any vaccination administered up to 1 year before administration of the first study vaccine dose should be recorded in the eCRF. Administration of Shingrix at any 
timepoint (even if longer than 1 year before the first study vaccination) should be recorded in the eCRF. 
5. 
If deemed necessary by the investigator. 
6. 
The blood samples at Visits 1 and 3 should be taken prior to vaccine administration. 
7. 
The blood samples at Visit 3 should only be taken from participants in the reactogenicity and immunogenicity subset. 
8. 
A paper diary will be distributed to all study participants on each vaccination day (at Visits 1 and 3). All participants will record unsolicited AEs and concomitant 
medications/products on the day of each vaccination and for 29 subsequent days (Days 1-30). In addition, participants in the reactogenicity subset will be asked to record 
solicited events on the day of each vaccination and for 3 subsequent days (Days 1-4). 
9. 
SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to administration of the 
first study vaccine dose) up to study end. 
10. 
Atrial fibrillation (AF) will be considered as adverse events of special interest (AESI) in this study and will be additionally reported in the AF follow-up questionnaire 
(electronic) in eCRF. The collection of AF will be performed following the AE/SAE reporting periods. For AF that were reported before the implementation of the Protocol 
Amendment 4, additional available information should be encoded in the specific AF follow-up questionnaire retrospectively. 
11. 
Visit 6NH and Contact 5 are not applicable for participants that did not receive the Dose 3 but are not removed from the schedule of activities table as these 
timepoints still appear in the eCRFs. 
12. At Visit 5NH, a blood sample of 20 mL should be taken from all participants including the participants of the immunogenicity and reactogenicity subset. 
Table 3 
Schedule of activities for all participants in Southern hemisphere  
Type of contact for SH1 
V1 
V2 
V2b2 
C13 
C2 
V3 
V4 
C33 
C4 
V5SH Notes for more information and 
details 
Timepoint 
Day 1 
Dose 1 
Day 31 
Post-D1 Pre S1 Month 6 
Post-D1 End S1 
Pre S2 
Dose 2 
Day 31 
Post-D2 
Month 6 
Post-D2 End S2 
End of 
study 
Study participant informed consent for 
annual revaccinations5 
 
 
 
 
 
● 
 
 
 
 
 
5 In case the participant does not agree to continue the study for the annual revaccinations, the study conclusion page of the eCRF should be completed. 
12Atrial fibrillation (AF) will be considered as adverse events of special interest (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. For AF that were reported before the implementation of this the Protocol 
Amendment 4, additional available information should be encoded in the specific AF follow-up questionnaire retrospectively. 
Table 4 
Schedule of activities for ARI surveillance 
10. 
AF will be considered as adverse events of special interest (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. For AF that were reported before the implementation of the this Protocol Amendment 4, additional 
available information should be encoded in the specific AF follow-up questionnaire retrospectively.  

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Table 5 
Intervals between study visits/contacts for all participants in Northern hemisphere 
Interval3 
Length of interval  
Allowed interval 
Visit 5NH (Pre-Season 3/Dose 3) 
Between 1 August and 30 September Study Year 34,5 
Visit 5NH → Visit 6NH6 
30 days  
28-42 days1 
Visit 5NH → Contact 56 
180 days  
180-210 days2 
5. For participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 5, in exceptional cases, Visit 5NH can be organized before 
30 October. 
6. Visit 6NH and Contact 5 are not applicable for participants who will have their Visit 5NH after the approval of the current Protocol Amendment 5 and did not receive any 
study intervention (Dose 3) at pre-Season 3 visit (Visit 5NH). 
 

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Section 2.1. 
Study rationale 
GSK is developing an investigational vaccine has developed a new RSVPreF3 OA 
vaccine against RSV-associated (subtypes A and B) disease in adults ≥ 60 YOA.  
The purpose of the current study is to demonstrate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RT-PCR-confirmed LRTD caused by RSV A 
and/or B in adults ≥ 60 YOA, following a single dose of the RSVPreF3 OA vaccine and 
following annual revaccination doses. The vaccine cross-protection against RT-PCR-
confirmed LRTD caused by human metapneumovirus (hMPV) will also be evaluated. In 
addition, the safety and immunogenicity of the vaccine will be assessed after each dose. 
Section 2.2. 
Background 
At the time of initiation of this study, There is currently no vaccine or nor other 
prophylactic treatment was available against RSV or hMPV in older adults. Since then, 
GSK’s RSVPreF3 OA investigational vaccine was first approved for use in an adults ≥ 
60 YOA in the US on 3 May 2023, followed by the European Union on 6 June 2023 
Currently available treatment for RSV and hMPV infections in this age group is generally 
supportive in nature. 
Section 2.3.2. Benefit assessment 
At the start of this study, the efficacy of the RSVPreF3 OA investigational vaccine was 
not demonstrated yet. Hence it was unknown if tThe participants receiving the 
RSVPreF3 OA investigational vaccine may not directly would benefit from this 
vaccination because the vaccine efficacy (VE) has not been assessed yet. Since then, the 
efficacy of RSVPreF3 OA investigational vaccine was demonstrated and the study 
primary confirmatory objective was met. One dose of RSVPreF3 OA vaccine has 
shown a favorable benefit/risk profile. The vaccine was approved for use in an adults 
≥ 60 YOA in the US on 3 May 2023, followed by the European Union on 6 June 2023. 
The VE Analysis 3 data showed that revaccination administered approximately 12 
months after Dose 1 did not confer additional benefit in prevention of RSV-confirmed 
LRTD for the overall population of adults ≥ 60 YOA, while the second dose of vaccine 
has a clinically acceptable safety profile. The clinical development program will 
continue to evaluate longer term follow-up and the optimal timing for potential 
revaccination. Hence, it is not known whether the RSVPreF3 OA investigational vaccine 
is effective in protecting against RSV disease. 
An indirect benefit is that the information obtained in this study will aid the development 
of an RSV vaccine, which is intended to prevent disease associated with RSV infection in 
older adults. 

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Section 3. 
OBJECTIVES AND ENDPOINTS 
Table 8 
Study objectives and endpoints 
Objectives 
Endpoints 
Secondary 
Secondary – Efficacy 
Secondary confirmatory 
To demonstrate the efficacy of a single dose of the 
RSVPreF3 OA investigational vaccine followed by 1 
annual revaccination before Season 2doses in the 
prevention of RSV-confirmed LRTD in adults ≥ 60 YOA 
over several seasons. 
Criterion: The LL of the 2-sided CI for VE is above 20%. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*. 
To demonstrate the efficacy of a single dose and 1 annual 
revaccination before Season 2 doses of the RSVPreF3 
OA investigational vaccine in the prevention of RSV-
confirmed LRTD for each RSV subtype (A and B) 
separately in adults ≥ 60 YOA over 3 seasons. 
Criterion: The LL of the 2-sided CI for VE is above 0%. 
First occurrence of RT-PCR-confirmed RSV-associated 
LRTD, according to the case definition*, for RSV subtype 
A and RSV subtype B separately. 
Other secondary descriptive 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD for each RSV subtype (A and B) separately in 
adults ≥ 60 YOA, following a single dose of the RSVPreF3 
OA investigational vaccine and following annual 
revaccination doses. 
First occurrence of RT-PCR-confirmed RSV-associated 
LRTD, according to the case definition*, for RSV subtype 
A and RSV subtype B separately. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by age category, following a single dose of the 
RSVPreF3 OA investigational vaccine and following 
annual revaccination doses. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, in the 
following age categories: ≥ 65 YOA, ≥ 70 YOA and ≥ 80 
YOA. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by season in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination doses. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, by 
season. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by year in adults ≥ 60 YOA, following a single dose 
of the RSVPreF3 OA investigational vaccine and following 
annual revaccination doses. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, by 
year. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD in adults ≥ 60 YOA by baseline comorbidities, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
First occurrence of RT-PCR-confirmed RSV A and/or 
B-associated LRTD according to the case definitions*, by 
baseline comorbidities. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
LRTD by baseline frailty status in adults ≥ 60 YOA, 
following a single dose of the RSVPreF3 OA 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated LRTD, according to the case definition*, by 
baseline frailty status. 

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Objectives 
Endpoints 
investigational vaccine and following annual revaccination 
doses. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of severe RSV-
confirmed LRTD in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination doses. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated severe LRTD, according to the case 
definitions*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI in adults ≥ 60 YOA, following a single dose of the 
RSVPreF3 OA investigational vaccine and following 
annual revaccination doses. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated ARI, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of any ARI and 
any LRTD in adults ≥ 60 YOA, following a single dose of 
the RSVPreF3 OA investigational vaccine and following 
annual revaccination doses. 
First occurrence of ARI or LRTD, according to the case 
definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of hospitalization 
due to respiratory diseases in adults ≥ 60 YOA, following 
a single dose of the RSVPreF3 OA investigational vaccine 
and following annual revaccination doses. 
• 
Occurrence of hospitalization due to respiratory 
diseases or due to a complication related to 
respiratory diseases during the RSV seasons† and 
during the entire follow-up.  
• 
Occurrence of hospitalization due to RSV-confirmed 
respiratory diseases or due to a complication related 
to RSV-confirmed respiratory diseases during the 
RSV seasons† and during the entire follow-up. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of complications 
related to RSV-confirmed ARI and any ARI in adults ≥ 60 
YOA, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
Occurrence of complication related to RSV-confirmed ARI 
or related to any ARI during the RSV seasons†, according 
to the case definition* and during the entire follow-up. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on lower respiratory tract 
symptoms in participants with RSV-confirmed ARI in the 
RSVPreF3 groups compared to the placebo group, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
Maximum FLU-PRO Chest score during the first 7 days 
from the onset of ARI symptoms for participants with RT-
PCR-confirmed RSV A and/or B-associated ARI. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on ARI total symptoms in 
participants with RSV-confirmed ARI in the RSVPreF3 
groups compared to the placebo group, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination doses. 
Estimated Least Squares mean FLU-PRO total score 
during the first 7 days from the onset of ARI symptoms for 
participants with RT-PCR-confirmed RSV A and/or B-
associated ARI. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on health utility score in 
participants with RSV-confirmed ARI in the RSVPreF3 
groups compared to the placebo group, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination doses. 
Estimated Least Squares mean EQ-5D utility score at the 
ARI visit for participants with RT-PCR-confirmed RSV A 
and/or B-associated ARI. 

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Objectives 
Endpoints 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on physical functioning in 
participants with RSV-confirmed ARI in the RSVPreF3 
groups compared to the placebo group, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination doses. 
Estimated Least Squares mean SF-12 Physical 
Functioning score at the ARI visit for participants with RT-
PCR-confirmed RSV A and/or B-associated ARI. 
Secondary – Immunogenicity 
To evaluate the humoral immune response to the 
RSVPreF3 OA investigational vaccine. 
In a subset of participants, at pre-Dose 1 (Day 1), 30 days 
post-Dose 1 (Day 31), pre-Dose 2 (pre-Season 2) and 
pre-Dose 3 (pre-Season 3): 
• 
RSVPreF3 IgG-binding antibody concentrations. 
• 
Neutralizing titers against RSV A. 
• 
Neutralizing titers against RSV B. 
Tertiary 
Tertiary – Efficacy 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV and/or 
hMPV-confirmed LRTD in adults ≥ 60 YOA, following a 
single dose of the RSVPreF3 OA investigational vaccine 
and following annual revaccination doses. 
First occurrence of RT-PCR-confirmed RSV and/or hMPV-
associated LRTD, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of hMPV-
confirmed LRTD in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination doses up to the end of 
Season 2 and Season 3. 
First occurrence of RT-PCR-confirmed hMPV-associated 
LRTD, according to the case definition*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of severe hMPV-
confirmed LRTD in adults ≥ 60 YOA, following a single 
dose of the RSVPreF3 OA investigational vaccine and 
following annual revaccination doses. 
First occurrence of RT-PCR-confirmed hMPV-associated 
severe LRTD, according to the case definitions*. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI for each RSV subtype (A and B) separately in adults 
≥ 60 YOA, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
First occurrence of RT-PCR-confirmed RSV-associated 
ARI, according to the case definition*, for RSV subtype A 
and RSV subtype B separately. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI by age category, following a single dose of the 
RSVPreF3 OA investigational vaccine and following 
annual revaccination doses. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated ARI, according to the case definition*, in the 
following age categories: ≥ 65 YOA, ≥ 70 YOA and ≥ 80 
YOA. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI by season, following a single dose of the RSVPreF3 
OA investigational vaccine and following annual 
revaccination doses. 
First occurrence of RT-PCR-confirmed RSV A and/or B-
associated ARI, according to the case definition*, by 
season. 

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Objectives 
Endpoints 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of RSV-confirmed 
ARI in adults ≥ 60 YOA by baseline comorbidities, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
First occurrence of RT-PCR-confirmed RSV A and/or 
B-associated ARI, according to the case definitions*, by 
baseline comorbidities. 
To evaluate the efficacy of the RSVPreF3 OA 
investigational vaccine in the prevention of all-cause 
mortality during the RSV seasons† in adults ≥ 60 YOA, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
Occurrence of any death during the RSV seasons†. 
To estimate the proportion of participants with > 1 case of 
ARI or LRTD by season and participants reporting 
respiratory diseases in consecutive seasons, following a 
single dose of the RSVPreF3 OA investigational vaccine 
and following annual revaccination doses. 
Number of participants with > 1 case of ARI, LRTD, 
RT-PCR-confirmed RSV A and/or B-associated ARI and 
RT-PCR-confirmed RSV A and/or B-associated LRTD, 
according to the case definitions* by season and in 
consecutive seasons. 
To estimate the proportion of co-infections with other viral 
pathogens for RSV-confirmed or hMPV-confirmed ARI 
cases, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
Number of participants with other viral pathogens 
(detected by RT-PCR) co-existing with RSV or hMPV 
among RT-PCR-confirmed RSV or RT-PCR-confirmed 
hMPV ARI episodes.  
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on upper respiratory tract 
symptoms in participants with RSV-confirmed ARI in the 
RSVPreF3 groups compared to the Placebo group, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
Maximum FLU-PRO upper respiratory symptom score 
during the first 7 days from the onset of ARI symptoms for 
participants with RT-PCR-confirmed RSV A and/or B-
associated ARI. 
To assess the impact of the RSVPreF3 OA investigational 
vaccine on healthcare resource utilization (HCRU) for 
participants with RSV-confirmed ARI and any ARI, 
following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
• 
Hospitalization rate during the ARI episode for 
participants with RT-PCR-confirmed RSV A and/or 
B-associated ARI and any ARI, according to the 
case definitions*. 
• 
Antibiotic use during the ARI episode for participants 
with RT-PCR-confirmed RSV A and/or B-associated 
ARI and any ARI, according to the case definitions*. 
To evaluate the impact of the RSVPreF3 OA 
investigational vaccine on patient-reported severity of 
respiratory symptoms in participants with RSV-confirmed 
LRTD in the RSVPreF3 groups compared to the Placebo 
group, following a single dose of the RSVPreF3 OA 
investigational vaccine and following annual revaccination 
doses. 
Maximum patient global impression of severity (PGI-S) 
score during the first 7 days from the onset of ARI 
symptoms for participants with RT-PCR-confirmed RSV A 
and/or B-associated LRTD. 
Tertiary - Immunogenicity and Safety 
To assess the correlation of the humoral immune 
response to the RSVPreF3 OA investigational vaccine at 
30 days post-Dose 1 with protection against RSV disease. 
RSVPreF3 IgG-binding antibody concentrations at 
pre-Dose 1 (Day 1), and 30 days post-Dose 1 (Day 31) 
and pre-Season 3** in all participants with RSV disease 
compared to a subset of controls.‡ 

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Objectives 
Endpoints 
To evaluate the humoral immune response to the 
RSVPreF3 OA investigational vaccine by baseline frailty 
status. 
In a subset of participants, at pre-Dose 1 (Day 1), 30 days 
post-Dose 1 (Day 31), pre-Dose 2 (pre-Season 2) and 
pre-Dose 3 (pre-Season 3): 
• 
RSVPreF3 IgG-binding antibody concentrations 
classified by baseline frailty score. 
• 
Neutralizing titers against RSV A classified by 
baseline frailty score. 
• 
Neutralizing titers against RSV B classified by 
baseline frailty score. 
** Blood sample at pre-Season 3 is applicable for all participants in the NH who have their Visit 5NH after the 
approval of the current Protocol Amendment 5. 

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Section 4.1. 
Overall design  
Figure 1 
Study design overview  
 
 
** Contacts 1 and 3 and 5 must not be performed before the 6-month post-vaccination time point to allow collection of 
safety data up to at least 6 months after each vaccination for each participant. These contacts can be combined with 
another contact or visit. 
††Some participants in the NH may have Visit 5NH before the approval of the current Protocol Amendment 5. 
These participants should receive Dose 3 pre-Season 3 and all subsequent study procedures should be 
performed as planned in Protocol Amendment 4. Please refer to the Table 1 for the details of the procedures to 
be performed in participants that have their Visit 5NH before the approval of this amendment. 
**** For participants in the NH who have their Visit 5NH before the approval of the current Protocol 
Amendment 5, a blood sample should be taken only if the participant is in the reactogenicity and 

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immunogenicity subset. Please refer to the Table 1 for the details of the procedures to be performed in 
participants that have their Visit 5NH before the approval of this amendment. 
Each of the 4 RSVPreF3 groups in both parts will be randomized before Season 2 
into 2 sub-groups (RSV_annual group and RSV_1dose group) with a 1:1 ratio. The 
RSV_annual group will receive an additional dose of RSVPreF3 OA vaccine before 
each subsequent season, while the RSV_1dose group will receive 1 dose of placebo 
at the same timepoints. To maintain the study blind, participants who were initially 
randomized to the Placebo group will also receive additional doses of placebo at the 
same timepoints. 
At the time of pre-Season 3 (Visit 5NH), participants in the NH who will have their 
Visit 5NH before approval of the current Protocol Amendment 5, will receive the 
study intervention as planned according to their group allocation. Participants 
having their Visit 5NH after approval of the current Protocol Amendment 5 will 
not receive any study intervention at pre-Season 3 visit (Visit 5NH). 
• 
Randomization for the additional cohort enrolled in NH after sample size re 
assessment: If following sample size re-assessment an additional cohort needs to be 
enrolled before the next season in NH (see Section 9.2.3), the participants in this 
additional cohort will be enrolled in 3 study groups (RSV_annual group, RSV_1dose 
group and Placebo group) according to a 1:1:2 randomization ratio and will follow 
the same study design as indicated in Figure 1. They will have a blood sampling at 
Visit 1 and Visit 2 as for all study participants. There will be no subset for 
immunogenicity and reactogenicity for this cohort. 
Note: Blood sample at Visit 5NH is not applicable for this cohort because it was 
never enrolled. 
Table 9 
Study groups, intervention and blinding foreseen in the study 
For annual revaccination doses 
RSV_L1_annual 
Up to 
5 750 
375-
500 
Up to 
6 250 
≥ 60 
years 
RSVPreF3 OA 
investigational vaccine 
 
X 
RSV_L2_annual 
 
X 
RSV_L3_annual 
 
X 
• 
Vaccination schedule: First dose of study vaccine (RSVPreF3 OA investigational 
vaccine or placebo) on Day 1 followed by annual revaccination doses of study 
vaccine (RSVPreF3 OA investigational vaccine or placebo) as follows:  
− 
Participants from the NH who will have their Visit 5NH before the approval of 
the current Protocol Amendment 5, will receive 2 additional doses, 1 before 
Season 2 and 1 before Season 3. 
− 
Participants from the NH who will have their Visit 5NH after the approval of 
the current Protocol Amendment 5, will not receive any study intervention at 
pre-Season 3 visit (Visit 5NH). These participants had received 1 additional 
dose before Season 2.  
− 
Participants from the SH will receive 1 additional dose before Season 2. 

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Section 4.2. 
Scientific rationale for study design 
The study is designed as a Phase 3, observer-blind, placebo-controlled study enrolling 
adults ≥ ³ 60 YOA, who will be followed up for 3 consecutive RSV seasons in the NH 
and at least 2 consecutive RSV seasons in the SH. 
The results of VE Analysis 3 evaluating the efficacy and safety up to the end of Season 
2 in the NH, showed that 1 dose of the RSVPreF3 OA vaccine is efficacious against 
RSV-LRTD and severe LRTD at least over 2 RSV seasons, and that a second dose of 
the study vaccine administered before Season 2 did not confer additional benefit in 
prevention of RSV-confirmed LRTD. Safety and reactogenicity data post-Dose 2 were 
consistent with previous results from the Phase 3 program. 
Based on this observation, the study design was modified to remove the next annual 
revaccination dose of study vaccine (Dose 3 pre-Season 3) in the NH. The clinical 
development program will continue to evaluate longer term follow-up and the optimal 
timing for revaccination. 
Section 4.2.2. Rationale for the use of placebo 
As there is was currently no licensed RSV vaccine available at the time of initiation of 
this study, a placebo group (receiving saline solution) is will be used as control for the 
efficacy, safety/reactogenicity and immunogenicity assessments. 
Section 6.1. 
Study interventions administered 
After completing all prerequisite procedures prior to vaccination, one dose of study 
vaccine will be prepared and administered as shown in Table 10 for Dose 1 and Table 11 
for the annual revaccination doses. Refer to Section 4.1 for the schedule of vaccine 
administration. 
For the annual revaccination doses: 
The RSV_annual group will receive an additional dose of RSVPreF3 OA vaccine before 
each subsequent RSV season while the RSV_1dose and Placebo groups will receive 1 
dose of placebo at the same timepoints*. Refer to Section 4.1 for details on the study 
design. 
* Participants in the NH who will have their Visit 5NH after the approval of the 
current Protocol Amendment 5, will not receive any study intervention at pre-Season 3 
visit (Visit 5NH). 
Table 12 
Study interventions administered for annual revaccination doses  
Number of doses to be 
administered for annual 
revaccinations  
RSV_annual group: 
2 doses in NH† 
1 dose in SH 
RSV_1dose and Placebo groups: 
2 doses in NH† 
1 dose in SH 
† Participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 5, 
will not receive any study intervention at pre-Season 3 visit (Visit 5NH). 

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Section 6.3.2. Randomization to study intervention 
At Visit 3 (pre-Season 2), all participants who received 1 of the RSVPreF3 vaccine lots 
will be re-randomized in a 1:1 ratio into 2 sub-groups (RSV_annual group and 
RSV_1dose group) to receive annual revaccination doses (Dose 2 and Dose 3* in NH and 
Dose 2 in SH). 
* Participants in the NH who will have their Visit 5NH after the approval of the 
current Protocol Amendment 5 will not receive any study intervention at pre-Season 3 
visit (Visit 5NH). 
Table 13 
Number of participants in reactogenicity and immunogenicity subset 
For immunogenicity pre-Season 3 For Dose 3 
 
RSV_annual group 
RSV_1dose group 
Placebo 
Total 
NH 
~405 
~405 
~810 
~1620 
Section 6.5. 
Concomitant therapy 
• 
Any prophylactic medication (e.g., analgesics, antipyretics) administered on each 
study vaccination day (Day 1, pre-Season 2 and pre-Season 3*) in the absence of 
ANY symptom and in anticipation of a reaction to the vaccination. 
* Not applicable for participants in the NH who will have their Visit 5NH after the 
approval of the current Protocol Amendment 5 and will not receive any study 
intervention at pre-Season 3 visit (Visit 5NH). 
 

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Table 15 
Timing of collection of concomitant medication to be recorded  
 
Dose 1 
 
 
Dose 2 
 
 
Dose 3* 
 
 
Study 
Conclusion 
 
Day 1 
post-D1 
Day 30 
post-D1 
 
Day 1 
post-D2 
Day 30 
post-D2 
 
Day 1 
post-D3 
Day 30 
post-D3 
 
All concomitant medication, except vitamins and dietary supplements 
 
 
 
 
 
 
*** 
*** 
 
 
Any prophylactic medication 
 
 
 
 
 
 
*** 
 
 
 
All concomitant medication including vaccines/products which may 
explain/cause/be used to treat an SAE/pIMD/AF** 
 
 
 
 
 
 
 
 
 
 
*** Not applicable for participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 5 and will not receive any study 
intervention at pre-Season 3 visit (Visit 5NH). 
 

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Section 7.1. 
Discontinuation of study intervention 
Participants who do not consent for the annual revaccinations will be considered 
withdrawals from the study. 
Section 7.1.2. Contraindications to subsequent vaccine administration 
Note: This section is not applicable at pre-Season 3 visit for participants in the NH who 
will have their Visit 5NH after the approval of the current Protocol Amendment 5 and 
will not receive any study intervention at pre-Season 3 visit (Visit 5NH). 
Section 8. 
STUDY ASSESSMENTS AND PROCEDURES  
Study procedures and their timings are summarized in Table 1 and Table 2 for 
participants in NH, Table 3 for participants in SH and Table 4 for ARI surveillance 
(Section 1.3). 
Figure 2 
ARI surveillance in Northern and Southern hemispheres 
 
* The last study visit in SH (Visit 54 SH) will occur approximately 2 months after the start of Season 3 in SH; yet the 
site staff surveillance contacts will be performed monthly during these last months (i.e., continuation of the inter-
season frequency of contacts). 
Section 8.1.3.2. 
Biological samples for immunogenicity assessment 
A blood sample will be taken from all participants in both hemispheres at pre-Dose 1 
(Day 1), and 1-month post-Dose 1 (Day 31) and from all participants at Visit 5NH* to 
allow the evaluation of a potential correlate of protection. In addition, the immune 
response to the RSVPreF3 OA investigational vaccine will be further evaluated at other 
timepoints in a subset of participants (see Table 18). 
The overall volume of blood that will be collected during the entire study period is as 
follows: 
• 
~60 mL (3 x 20 mL) for participants in the reactogenicity and immunogenicity 
subset from SH, 
• 
~80 mL (4 x 20 mL) for participants in the reactogenicity and immunogenicity 
subset from NH, 
Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec
Northern hemisphere
Inter-season
Season 1 NH
Inter-season
Season 2 NH
Southern hemisphere
Season 0 SH
Inter-season
Season 1 SH
Inter-season
Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun
Jul
Aug Sep Oct Nov Dec
Northern hemisphere
Season 2 NH (continues) 
Inter-season
Season 3 NH
 Last study visit (Visit 7 6 NH)
Southern hemisphere
Season 2 SH
Inter-season
S3 SH*
 Last study visit (Visit 5 4  SH)
Study Year 1
Study Year 2
Study Year 3
Study Year 4

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• 
~40 mL (2 x 20 mL) for all other participants in SH and NH. 
• 
~60 mL (3 x 20 mL) for all other participants in NH* 
* Applicable after the approval of the current Protocol Amendment 5.  
Table 18 
Biological samples for immunogenicity assessment 
Sample type 
Quantity 
Unit 
Timepoint 
Subset name* 
Blood for correlate of 
protection 
20 
mL 
Visit 1 (Day 1, pre-Dose 1) 
Visit 2 (Day 31, post-Dose 1) 
All participants 
 
20 
mL 
Visit 5NH (Pre Season 3) 
All participants*** 
Blood for antibody 
measurement 
20 
mL 
Visit 3 (Pre Season 2, pre-Dose 2) 
Visit 5NH (Pre Season 3, pre-Dose 3) 
Immunogenicity subset** 
***All participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 
5 including participants in the immunogenicity subset.  
Note: After the approval of the current Protocol Amendment 5, participants from the 
immunogenicity subset will still provide only 1 blood sample at Visit 5NH. This sample 
will be used for both the assessment of humoral immune response and evaluation of 
correlate of protection.  
Section 8.1.5. Immunological read-outs 
Table 21 
Immunological read-outs 
Blood sampling time point 
Subset tested 
No. 
samples 
tested 
Component 
Components 
priority rank 
Type of contact 
and time point 
Sampling 
time point 
Visit 5NH (Pre S3) Pre-Dose 3 
Season 3 
Immunogenicity 
subset* 
~1620 
RSV A neutralizing antibody 
1 
RSV B neutralizing antibody 
2 
RSVPreF3-binding IgG antibody 
3 
All participants 
with RSV disease 
+ Subset of 
controls** 
Case-
driven** 
RSVPreF3-binding IgG antibody 
- 
** A blood sample will be taken in all participants at Visit 1 and Visit 2 to allow the evaluation of a potential correlate of 
protection. RSVPreF3 ELISA will be tested on all participants with RSV-confirmed disease and in a subset of 
control participants. Additional testing such as but not limited to neutralization assay(s) and systems serology 
testing might be performed on the same subset of participants to investigate a correlate of protection. After 
approval of this Protocol Amendment 5, a blood sample will also be taken at Visit 5NH. 
8.1.7. Immunological correlates of protection  
This study will attempt to correlate humoral immune responses at Day 31 post-Dose 1 
and at pre-Season 3 (Visit 5NH) with protection against RSV-confirmed disease (see 
Section 9.4.5.4.1 ).  

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Section 8.2.1.7. 
Distribution of paper diary cards 
A paper diary card will be distributed as follows: 
• 
To all participants at Visit 1 (Day 1), Visit 3 (pre-Season 2) and Visit 5NH (pre-
Season 3)* to note down any unsolicited AE as well as any medication and 
vaccination taken in the 30-day period following vaccination. 
• 
To participants in the reactogenicity and immunogenicity subset at Visit 1 (Day 1), 
Visit 3 (pre-Season 2) and Visit 5NH (pre-Season 3)* to note down any solicited 
event, any unsolicited AE as well as any medication and vaccination taken in the 30-
day period following vaccination. 
*Not applicable for participants in the NH who will have their Visit 5NH after the 
approval of the current Protocol Amendment 5. Refer to Table 2 for details. 
Section 8.2.2.3. 
Lung auscultation 
Lung auscultation at Visit 2 (Day 31 post-Dose 1/pre-Season 1), Visit 4 (Day 31 post-
Dose 2), Visit 6NH (Day 31 post-Dose 3)*, Visit 5SH (end of study) and Visit 7NH (end 
Season 3) 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. 
* Visit 6NH is not applicable for participants in the NH who will have their Visit 5NH 
after the approval of the current Protocol Amendment 5. Refer to Table 2 for details. 
Section 8.3.1. Time period and frequency for collecting AE, SAE and other safety 
information 
 

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Table 23 
Timeframes for collecting and reporting of safety information 
 
Pre- 
Vacc
* 
 
Dos
e 1 
 
 
 
 
 
Dos
e 2 
 
 
 
 
 
Dos
e 3#  
 
 
 
 
 
 
 
Day 
1 
post
-
Dos
e 1 
Day 
4 
post
-
Dos
e 1 
Day 
30 
post
-
Dos
e 1 
 
6 
month
s post- 
Dose 
1*** 
 
Day 
1 
post
-
Dos
e 2 
Day 
4 
post
-
Dos
e 2 
Day 
30 
post
-
Dos
e 2 
 
6 
month
s post- 
Dose 
2*** 
 
Day 
1 
post
- 
Dos
e 3# 
Day 
4 
post
-
Dos
e 3# 
Day 
30 
post
-
Dos
e 3# 
 
6 
month
s post- 
Dose 
3***, # 
Study 
conclusio
n 
Solicited administration site 
and systemic events** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs†  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SAEs†  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
‡ 
 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All pIMDs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‡ 
‡ 
‡ 
 
‡ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
# Dose 3 is only applicable for participants in the NH who will have their Visit 5NH before the approval of the current Protocol Amendment 5. 
‡For participants in the NH who will have their Visit 5NH after the approval of the current Protocol Amendment 5, solicited and unsolicited AEs and all SAEs and pIMDs 
occurring after Visit 5NH will not be collected. 
† Atrial fibrillation (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 will be performed according to the SAE reporting period. Fatal AF and 
Serious AF judged as related to study vaccination will be performed according to the fatal SAE and related SAE reporting period, respectively. For AF that were reported before the 
implementation of the this Protocol Amendment 4, additional available information should be encoded in the specific AF follow-up questionnaire retrospectively. 

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Section 9. 
STATISTICAL CONSIDERATIONS 
9.1.2. Secondary objectives 
• 
To demonstrate the efficacy of a single dose of RSVPreF3 OA investigational 
vaccine followed by 1 annual revaccinations before Season 2 in the prevention of 
RSV-confirmed LRTD in adults ≥ 60 YOA over several seasons. 
Criterion: The LL of the 2-sided CI for VE is above 20%. 
• 
To demonstrate the efficacy of a single dose and 1 annual revaccination before 
Season 2 doses of RSVPreF3 OA investigational vaccine in the prevention of RSV-
confirmed LRTD for each RSV subtype (A and B) separately in adults ≥ 60 YOA 
over 3 seasons. 
Criterion: The LL of the 2-sided CI for VE is above 0%. 
VE of the 1 annual revaccination given before Season 2 over 2 and 3 seasons: 
• 
The confirmatory secondary objective assessing VE of the annual revaccination 
given before Season 2 with RSVPreF3 OA vaccine in the prevention of RSV-
confirmed LRTD in adults ≥ 60 years after Season 2 in NH (S1+A2NH) will be 
evaluated conditionally to the success of the previous objective evaluating VE after 
Season 1 in NH (see Figure 4). A Bonferroni adjustment of alpha for multiplicity 
will be applied. Therefore, this analysis will be done using a 1-sided test at 
alpha=1.25% level. 
• 
The confirmatory secondary objective assessing VE of an the annual revaccination 
given before Season 2 with RSVPreF3 OA vaccine in the prevention of RSV-
confirmed LRTD in adults ≥ 60 years after Season 3 in NH (S1+A2+A3NH) will be 
evaluated conditionally to the success of the annual revaccination objective after 
Season 2 (see Figure 4). This analysis will be done using a 1-sided test at 
alpha=1.25% level. 
• 
The confirmatory secondary objective assessing VE of an the annual revaccination 
given before Season 2 with RSVPreF3 OA vaccine in the prevention of RSV-
confirmed LRTD for each RSV subtype (A and B) separately in adults ≥ 60 years 
after Season 3 in NH (S1+A2+A3NH) will be evaluated conditionally to the success 
of the RSV objective of annual revaccination after Season 3 (see Figure 4). 
Analysis will be case-driven and will be performed if at least 49 cases are accrued 
for each subtype (RSV A and RSV B). The RSV A objective will be tested first, and 
if demonstrated, the RSV B objective will also be tested (see Figure 4). 
Note that participants who received a third dose of RSVPreF3 OA investigational 
vaccine will not be included in the evaluation of annual revaccination over 3 seasons. 
Figure 4 
Sequential evaluation of primary and confirmatory secondary 
objectives 
A2/A3 = Annual evaluation during Season 2/3 (after 1 revaccination given before Season 2) 

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Section 9.2.2. Secondary objectives 
• 
a VE against RSV-confirmed LRTDs of 70% over 1 season after Dose 1 (Season 1) 
and after 1 revaccination dose (Season 2) each dose, VE of 65% at Season 3. 
Table 28 
Power to demonstrate secondary confirmatory objectives 
Endpoint 
(success criterion) 
Sample size 
AR 
Analysis 
Expected number 
of cases 
Power (1-sided 
alpha=1.25%) 
RSV-confirmed 
LRTDs (LL>20%) 
16000+1500 
0.6% 
S1+A2NH 
101 
97.7% 
 
 
S1+A2+A3NH 
137 6 
99.16% 
 
 
 
S1+S2NH 
102 
95.8% 
 
 
 
S1+S2+S3NH 
139 
98.2% 
 
23000+2000 
0.6% 
S1+A2NH 
144 
99.8% 
 
 
 
S1+A2+A3NH 
196 5 
≥99.9% 
 
 
 
S1+S2NH 
146 
99.5% 
 
 
 
S1+S2+S3NH 
198 
99.8% 
S1/S2/S3 = Seasons 1/2/3; A2/A3=Annual evaluation during Season 2/3 (after 1 revaccination given before Season 
2); LL = lower limit 
Table 30 
Expected number of RSV-confirmed LRTD cases for the evaluation of 
VE of the annual revaccination 
 
N at start of season 
Expected 
Attack rate 
Expected 
Season 
RSVPreF3 
group 
RSV_annual 
group 
Placebo 
group 
vaccine 
efficacy 
Placebo 
group 
Vaccine 
group 
number 
of cases* 
A3NH 
- 
2560 
5120 
70 65% 
0.60% 
0.18% 
32 1 
A3NH= End of Season 3 in the Northern Hemisphere for participants receiving 21 revaccination doses before Season 
2. 
Section 9.3. 
Populations for analyses 
Exposed Set Dose 2 and Exposed Set Dose 3 including all participants who received 
the 2nd and the 3rd dose, respectively, will also be used to report analysis on post-Dose 
2/3 data. 
mES will be defined by dose as follows: 
• 
mES: participants who received Dose 1 and who did not report RSV ARI within 15 
days post-Dose 1, 
• 
mES Dose 2: participants who received Dose 2 and who did not report RSV ARI 
within 15 days post-Dose 2, 
• 
mES Dose 3: participants who received Dose 3 and who did not report RSV ARI 
within 15 days post-Dose 3. 
Note that participants who received a third dose of RSVPreF3 OA investigational 
vaccine will not be included in the primary evaluation of annual revaccination over 3 
seasons. Details will be provided in the SAP. 
• 
Per Protocol set for efficacy (PPSe): the PPSe will include all participants included 
in the mES who: 

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− 
received at least the first dose of the study vaccine to which they were 
randomized, 
− 
have data available for efficacy endpoint measures, 
− 
did not have protocol deviations leading to exclusion. 
Section 9.4.4.1. 
Efficacy 
The same methodology as described for the primary endpoint (see Section 9.4.3) will be 
used to analyze the secondary efficacy endpoints described below. For the analysis over 2 
or 3 seasons (VE Analysis 3 and 4), the model will include season as covariate, in 
addition to age category and region. The first occurrence of the event meeting the case 
definition according to the endpoint will be considered for the primary analysis of those 
secondary efficacy endpoints. 
The following endpoints will be evaluated following a single dose of the RSVPreF3 OA 
investigational vaccine and following 1 annual revaccination doses given before Season 
2. 
Note that participants who received a third dose of RSVPreF3 OA investigational 
vaccine will not be included in the primary evaluation of annual revaccination over 3 
seasons. Secondary analysis of the annual revaccination on participants who received 
3 doses of RSVPreF3 OA investigational vaccine might be performed depending on the 
number of participants who will receive the Dose 3. Details will be provided in the SAP. 
Other secondary objectives 
− 
VE during the second year post-vaccination (Year 2) in NH and SH, including 
first occurrence of cases reported from Day 15 post-Dose 2 up to Dose 3 
administration in NH, and up to 12 months post-Dose 2 in NH and SH, or up to 
Dose 3 administration in NH in SH; 
− 
VE during the third year post-vaccination (Year 3) in NH and SH, including first 
occurrence of cases reported from 12 months Day 15 post-Dose 23 in NH up to 
study end. 
Section 9.4.4.4. 
Quality of life 
The endpoints will be evaluated following a single dose of the RSVPreF3 OA 
investigational vaccine and following the annual revaccination doses. 
Section 9.4.5.1. 
Efficacy 
The same methodology as described for the primary and secondary endpoints (see 
Sections 9.4.3 and 9.4.4.1, respectively) will be used to analyze the tertiary endpoints. 
The following endpoints will be evaluated following a single dose of the RSVPreF3 OA 
investigational vaccine and following the annual revaccination given before Season 2 
doses: 

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Section 9.4.5.4.1. 
Correlate of protection 
For that purpose, blood samples for humoral immune response will be collected from all 
participants at pre-Dose 1 (Day 1) and, 1-month post-Dose 1 (Day 31) and at Visit 5NH* 
and may be tested for correlate of protection analysis in all participants with RSV-
confirmed disease and in a subset of control participants. 
* The blood sample at Visit 5NH is applicable after approval of the current Protocol 
Amendment 5. 
Section 9.5.1. Sequence of analyses 
5. VE Analysis 4: end of Season 2 in NH and SH 
6. An analysis will be performed to evaluate the efficacy, safety and immunogenicity 
objectives over 2 seasons, when all participants in NH and SH have been followed until 
the end of second season (S2) in SH. 
7 6. VE Analysis 5: end of Season 3 in NH 
An analysis will be performed to evaluate the efficacy, safety and immunogenicity 
objectives over 3 seasons, when all participants in NH have been followed until the end 
of third season (S3) in NH. 
7. VE Analysis 6: End of Study analysis 
Section 9.6. 
Independent Data Monitoring Committee (IDMC) 
A firewall team will be set up in order to allow the planned analyses to be performed and 
results shared with the IDMC, while the study blind is maintained to the whole team and 
participants. All details of this approach can be found in the firewall charter. As of 
implementation of theis Protocol Amendment 4, the firewall team will no longer be 
active. Refer to Section 6.3.5 for further details. 
Section 10.3.8. 
Recording and follow-up of AEs, SAEs, AESIs (including 
pIMDs and AF) 
• 
Collect and verify completed diary cards during discussion with the participant on 
Visit 2 (Day 31 post-Dose 1), Visit 4 (Day 31 post-Dose 2) and Visit 6NH (Day 31 
post-Dose 3)*. 
* Not applicable for participants in the NH who will have their Visit 5NH after the 
approval of the current Protocol Amendment 5 and will not receive any study 
intervention at pre-Season 3 visit (Visit 5NH). 
Section 10.5.1. 
List of abbreviations 
AS01B: 
Adjuvant System containing MPL, QS-21 and liposome (50 μg 
MPL and 50 μmg QS-21) 
AS01E: 
Adjuvant System containing MPL, QS-21 and liposome (25 μg 
MPL and 25 μmg QS-21) 
DLP 
Data Lock Point 

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11. 
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Signature Page for  212494 TMF-16228234 v2.0
Signature Page for TMF-16228234 v2.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 12-Jul-2023 09:49:46 GMT+0000
PPD