A Phase 3, Randomized, Open-label, Multi-country Study to Evaluate the Immunogenicity, Safety, Reactogenicity and Persistence of a Single Dose of the RSVPreF3 OA Investigational Vaccine and Different Revaccination Schedules in Adults Aged 60 Years and Above
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

Protocol Amendment 1
Study ID:  212496
Official Title of Study: A phase 3, randomized, open-label, multi-country study to 
evaluate the immunogenicity, safety, reactogenicity and persistence of a single dose 
of the RSVPreF3 OA investigational vaccine and different revaccination schedules in 
adults aged 60 years and above.
NCT number: NCT04732871
EudraCT number:  2019-004680-51
Date of Document: 01-APR-2022

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Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut, 89 
1330 Rixensart, Belgium 
Primary Study vaccine and 
number 
GlaxoSmithKline Biologicals SA (GSK)’s 
investigational respiratory syncytial virus (RSV) 
vaccine BIO RSV OA=ADJ (GSK3844766A) 
eTrack study number and 
abbreviated title 
212496 (RSV OA=ADJ-004) 
EudraCT number 
2019-004680-51 
Date of protocol 
Final: 20 October 2020 
Date of protocol amendment 
Amendment 1 Final: 01 April 2022 
Title 
A phase 3, randomized, open-label, multi-country 
study to evaluate the immunogenicity, safety, 
reactogenicity and persistence of a single dose of 
the RSVPreF3 OA investigational vaccine and 
different revaccination schedules in adults aged 
60 years and above. 
Short title 
Immunogenicity, safety, reactogenicity and 
persistence of an 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 1 Sponsor Signatory Approval 
eTrack study number and 
abbreviated title 
212496 (RSV OA=ADJ-004) 
EudraCT number 
2019-004680-51 
Date of protocol 
Final: 20 October 2020 
Date of protocol amendment 
Amendment 1 Final: 01 April 2022 
Title 
A phase 3, randomized, open-label, multi-country 
study to evaluate the immunogenicity, safety, 
reactogenicity and persistence of a single dose of 
the RSVPreF3 OA investigational vaccine and 
different revaccination schedules in adults aged 
60 years and above. 
Sponsor signatory 
Veronica Hulstrøm 
Clinical and Epidemiology R&D Project Lead 
RSV Older Adults 
 
 
Signature 
 
 
 
Date 
 
 
 
Note: Not applicable if an alternative signature process (e.g. electronic signature or 
email approval) is used to get the sponsor approval. 

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Protocol Amendment 1 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 Biologicals SA (GSK). 
• 
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 representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational 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 
212496 (RSV OA=ADJ-004) 
EudraCT number 
2019-004680-51 
Date of protocol 
Final: 20 October 2020 
Date of protocol amendment Amendment 1 Final: 01 April 2022 
Title 
A phase 3, randomized, open-label, multi-country study 
to evaluate the immunogenicity, safety, reactogenicity 
and persistence of a single dose of the RSVPreF3 OA 
investigational vaccine and different revaccination 
schedules 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

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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut, 89 
1330 Rixensart, Belgium 
2. Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
3. Sponsor Study Monitor 
Refer to 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 8.3.3.1. 
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
5. GSK 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 1 
01 April 2022 
Original Protocol 
28 October 2020 
Amendment 1: 01 April 2022 
Overall rationale for the Amendment: 
Immunogenicity data from other studies using the same study intervention showed that 
following a two-dose vaccination schedule (0-2-month schedule), the immune response 
gradually declines over time but remains above baseline value up to 18 months 
post-Dose 2 and that a re-vaccination at 18 months post-Dose 2 (i.e., 20 months 
post-Dose 1) induced humoral and cellular immune responses. 
Consequently, as there are unknowns about (1) the persistence of the immune response to 
the RSVPreF3 OA investigational vaccine administered as a single dose and (2) the level 
of immune response that may be required for protection, the RSV OA=ADJ-004 
(212496) Protocol has been amended to define the timing of the revaccination for 
participants in the RSV_flexible revaccination group. The revaccination will be 
administered in this group at Month 24 (i.e., approximately two years after the first dose). 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Section 1.3. Schedule of 
Activities 
Table 2 was updated with the addition 
of (1) a revaccination (and related study 
procedures) at Month 24 and (2) a new 
follow-up visit at Month 25. 
The timing of the revaccination with 
RSVPreF3 OA investigational vaccine for 
participants in the RSV_flexible 
revaccination group 2 years after the first 
one was implemented. 
Tables 1, 2 and 3 were updated to 
clarify that (1) on vaccination days, 
blood samples were to be taken before 
vaccination and (2) that the 6-month 
post-vaccination safety follow-up should 
be performed at least 6 months after 
each vaccination. 
Some study procedures were clarified. 
New interval (Month 24 → Month 25) 
for the RSV_flexible revaccination 
group was added in Table 5. 
A new follow-up visit after revaccination 
has been added for these participants. 

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Section # and title 
Description of change 
Brief rationale 
Section 4.1. Overall design 
Section 4.2 Scientific 
rationale for study design 
Section 6.1. Study 
interventions administered 
(Table 8) 
Section 6.5. Concomitant 
therapy 
Section 7.1.2. Contra-
indications to subsequent 
vaccine administration 
Section 8.1. Efficacy 
and/or immunogenicity 
assessments 
Section 10.3.8. Recording 
and follow-up of AEs, 
SAEs and pIMDs 
Where applicable, it was stated that 
participants from the RSV_flexible 
revaccination group will receive an 
additional dose of the RSVPreF3 OA 
investigational vaccine at Month 24 and 
that they will need to come to the study 
site for an additional follow-up visit one 
month later (Month 25). Consequently, 
some sections were adapted/aligned 
with the implementation of this 
revaccination timing. 
Results from previous studies using the 
same study intervention showed that 
participants from this group might benefit 
from an additional dose at that timepoint. 
Section 9.2. Sample size 
calculation 
Section 9.2.5. Evaluation 
of humoral immune 
response at Month 25 
(secondary objective) 
Section 9.2.6. Evaluation 
of cellular immune 
response at Month 25 
(secondary objective) 
Section 9.2.7. Evaluation 
of reactogenicity and 
safety profile following 
revaccination in the 
RSV_annual and 
RSV_flexible 
revaccination groups 
Section 9.4.1. General 
considerations 
Section 9.5.1.1. Analyses 
for objectives and 
endpoints 
These sections were updated where 
applicable following the implementation 
of a revaccination with an additional 
dose of the RSVPreF3 OA 
investigational vaccine at Month 24 for 
participants from the RSV_flexible 
revaccination group. 
Results from previous studies using the 
same study intervention showed that 
participants from this group might benefit 
from an additional dose at that timepoint. 

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Section # and title 
Description of change 
Brief rationale 
Section 9.3. Population 
for analyses 
Section 9.4.1.2. 
Immunogenicity 
Section 9.4.2. 
Demographics and 
participants’ disposition 
Section 9.4.3.1. Humoral 
immune response – up to 
Month 12 
Section 9.4.4.1. Humoral 
immune response 
Section 9.4.4.2. Cell-
mediated immune 
response 
Section 9.4.4.3. Safety 
analysis 
Analyses were updated. 
Following the addition of a revaccination at 
Month 24 for the RSV_flexible 
revaccination group, and to align with other 
Phase 3 RSV OA studies, some 
immunogenicity and safety analyses were 
updated/clarified. 
Section 10.3.5.1. Potential 
immune-mediated diseases The list of pIMDs has been revised. 
The list has been updated following a 
regular safety review and to include 
possible immune-mediated adverse events 
of special interest. 
Section 10.4.2. 
Requirements for 
Germany 
Remote Source Data Verification 
(rSDV) during exceptional situations in 
Germany was added. 
Instructions with regards to remote 
monitoring were added to allow this study 
procedure to be performed even in case of 
exceptional circumstances (e.g., in case of 
a lockdown). 
 

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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
Document history ..................................................................................................... 7 
List of main changes in the protocol and their rationale: ........................................... 7 
1. 
PROTOCOL SUMMARY ........................................................................................ 18 
1.1. 
Synopsis ..................................................................................................... 18 
1.2. 
Schema ...................................................................................................... 18 
1.3. 
Schedule of Activities (Amended: 01 April 2022) ......................................... 18 
2. 
INTRODUCTION .................................................................................................... 29 
2.1. 
Study Rationale .......................................................................................... 29 
2.2. 
Background ................................................................................................ 29 
2.3. 
Benefit/Risk Assessment ............................................................................ 30 
2.3.1. 
Risk Assessment ......................................................................... 30 
2.3.2. 
Benefit Assessment ..................................................................... 30 
2.3.3. 
Overall Benefit/Risk Conclusion ................................................... 30 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 31 
4. 
STUDY DESIGN .................................................................................................... 32 
4.1. 
Overall Design ............................................................................................ 32 
4.1.1. 
Overview of the recruitment plan ................................................. 34 
4.2. 
Scientific rationale for study design (Amended: 01 April 2022) .................... 35 
4.3. 
Justification for dose ................................................................................... 35 
4.4. 
End of Study definition ................................................................................ 36 
5. 
STUDY POPULATION ........................................................................................... 36 
5.1. 
Inclusion criteria for enrolment .................................................................... 36 
5.2. 
Exclusion criteria for enrolment ................................................................... 37 
5.2.1. 
Medical conditions ....................................................................... 37 
5.2.2. 
Prior/Concomitant therapy ........................................................... 37 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 38 
5.2.4. 
Other exclusions .......................................................................... 38 
5.2.5. 
Caregiver support ........................................................................ 39 
5.3. 
Lifestyle considerations ............................................................................... 39 
5.4. 
Screen failures ............................................................................................ 39 
6. 
STUDY INTERVENTION ........................................................................................ 39 
6.1. 
Study interventions administered ................................................................ 39 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 40 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 40 
6.3.1. 
Participant identification ............................................................... 40 
6.3.2. 
Randomization to study intervention ............................................ 40 
6.3.3. 
Intervention allocation to the participant ....................................... 41 
6.3.4. 
Allocation of participants to assay subsets ................................... 41 
6.3.5. 
Blinding and unblinding ................................................................ 42 
6.3.5.1. 
Emergency unblinding ................................................ 42 

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6.4. 
Study intervention compliance (Amended: 01 April 2022) ........................... 43 
6.5. 
Concomitant therapy (Amended: 01 April 2022).......................................... 43 
6.6. 
Dose modification ....................................................................................... 45 
6.7. 
Intervention after the end of the study ......................................................... 45 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 45 
7.1. 
Discontinuation of study intervention ........................................................... 45 
7.1.1. 
Criteria for temporary delay for enrolment and/or 
vaccination ................................................................................... 45 
7.1.2. 
Contraindications to subsequent vaccine administration 
(Amended: 01 April 2022) ............................................................ 46 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 46 
7.3. 
Lost to follow-up.......................................................................................... 47 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 48 
8.1. 
Efficacy and/or immunogenicity assessments ............................................. 49 
8.1.1. 
Biological samples (Amended: 01 April 2022) .............................. 49 
8.1.2. 
Laboratory assays ....................................................................... 50 
8.1.3. 
Immunological read-outs .............................................................. 51 
8.1.4. 
Immunological correlates of protection ......................................... 52 
8.2. 
Safety Assessments ................................................................................... 52 
8.2.1. 
Pre-vaccination procedures ......................................................... 52 
8.2.1.1. 
Collection of demographic data .................................. 52 
8.2.1.2. 
Medical history ........................................................... 52 
8.2.1.3. 
Vaccination history ..................................................... 53 
8.2.1.4. 
Smoking status and smoking exposure history ........... 53 
8.2.1.5. 
History-directed physical examination ........................ 53 
8.2.1.6. 
Pre-vaccination body temperature .............................. 53 
8.2.1.7. 
Distribution of paper diary cards ................................. 54 
8.2.2. 
Safety monitoring ......................................................................... 54 
8.3. 
AEs, SAEs and other events of interest ...................................................... 54 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information ............................................................... 54 
8.3.2. 
Method of detecting AEs, SAEs and other events ........................ 56 
8.3.3. 
Regulatory reporting requirements for SAEs and other 
events .......................................................................................... 56 
8.3.3.1. 
Contact information for reporting of SAEs and 
pIMDs ......................................................................... 57 
8.3.4. 
Treatment of adverse events ....................................................... 57 
8.3.5. 
Participant card ............................................................................ 57 
8.4. 
Treatment of overdose ................................................................................ 58 
8.5. 
Pharmacokinetics ....................................................................................... 58 
8.6. 
Pharmacodynamics .................................................................................... 58 
8.7. 
Genetics ..................................................................................................... 58 
8.8. 
Biomarkers ................................................................................................. 58 
8.9. 
Health outcomes ......................................................................................... 58 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 58 
9.1. 
Statistical hypotheses ................................................................................. 58 
9.2. 
Sample size determination (Amended: 01 April 2022)................................. 58 

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9.2.1. 
Evaluation of humoral immune response up to Month 12 
(primary objective and first secondary objective).......................... 59 
9.2.2. 
Evaluation of the cellular immune response up to Month 
12 (secondary objective) .............................................................. 60 
9.2.3. 
Evaluation of humoral and cellular immune response at 
Month 13 (secondary objective) ................................................... 60 
9.2.4. 
Evaluation of humoral and cellular immune response at 
Month 25 in the RSV_annual and RSV_flexible 
revaccination groups (secondary objective) (Amended: 01 
April 2022) ................................................................................... 61 
9.2.5. 
Evaluation of reactogenicity and safety profile following 
revaccination in the RSV_annual and RSV_flexible 
revaccination groups (Amended: 01 April 2022)........................... 63 
9.3. 
Populations for analyses (Amended: 01 April 2022) .................................... 63 
9.3.1. 
Criteria for elimination from analysis ............................................ 64 
9.3.1.1. 
Intercurrent medical conditions and 
concomitant medications/products/vaccines 
that may lead to elimination of a participant 
from per-protocol analyses ......................................... 64 
9.4. 
Statistical analyses ..................................................................................... 64 
9.4.1. 
General considerations (Amended: 01 April 2022) ....................... 64 
9.4.1.1. 
Demography ............................................................... 64 
9.4.1.2. 
Immunogenicity (Amended: 01 April 2022) ................. 64 
9.4.1.3. 
Reactogenicity/Safety ................................................. 65 
9.4.2. 
Demographics and participants’ disposition (Amended: 01 
April 2022) ................................................................................... 65 
9.4.3. 
Primary endpoints ........................................................................ 66 
9.4.3.1. 
Humoral immune response – up to Month 12 
(Amended: 01 April 2022) ........................................... 66 
9.4.4. 
Secondary endpoints ................................................................... 67 
9.4.4.1. 
Humoral immune response (Amended: 01 April 
2022) .......................................................................... 67 
9.4.4.2. 
Cell-mediated immune response (Amended: 01 
April 2022) .................................................................. 67 
9.4.4.3. 
Safety analysis (Amended: 01 April 2022) .................. 68 
9.4.5. 
Tertiary/exploratory endpoints (Amended: 01 April 2022) ............ 69 
9.5. 
Interim analyses .......................................................................................... 70 
9.5.1. 
Sequence of analyses.................................................................. 70 
9.5.1.1. 
Analyses for objectives and endpoints 
(Amended: 01 April 2022) ........................................... 70 
9.5.2. 
Statistical consideration for interim analysis ................................. 70 
9.6. 
Data Monitoring Committee (DMC) ............................................................. 70 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 71 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 71 
10.1.1. 
Regulatory and ethical considerations ......................................... 71 
10.1.2. 
Financial disclosure ..................................................................... 71 
10.1.3. 
Informed consent process ............................................................ 72 
10.1.4. 
Data protection ............................................................................ 72 
10.1.5. 
Committees structure ................................................................... 73 

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10.1.6. 
Dissemination of clinical study data ............................................. 73 
10.1.7. 
Data quality assurance ................................................................ 73 
10.1.8. 
Source documents ....................................................................... 74 
10.1.9. 
Study and site closure.................................................................. 75 
10.1.10. Publication policy ......................................................................... 75 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 75 
10.2.1. 
Laboratory assays (Amended: 01 April 2020) .............................. 75 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting AEs .................................... 77 
10.3.1. 
Definition of an AE ....................................................................... 77 
10.3.1.1. Events Meeting the AE Definition ............................... 77 
10.3.1.2. Events NOT Meeting the AE Definition ....................... 78 
10.3.2. 
Definition of an SAE ..................................................................... 78 
10.3.3. 
Solicited events............................................................................ 79 
10.3.4. 
Unsolicited AEs............................................................................ 80 
10.3.5. 
Adverse events of special interest................................................ 80 
10.3.5.1. Potential immune-mediated diseases ......................... 80 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 89 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs ..................... 89 
10.3.7.1. Pregnancy .................................................................. 89 
10.3.8. 
Recording and follow-up of AEs, SAEs and pIMDs 
(Amended: 01 April 2022) ............................................................ 89 
10.3.8.1. Time period for collecting and recording AEs, 
SAEs and pIMDs ........................................................ 90 
10.3.8.2. Follow-up of AEs, SAEs, pIMDs or any other 
events of interest ........................................................ 90 
10.3.8.2.1. Follow-up during the study ...................... 91 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study ...................... 91 
10.3.8.3. Updating of SAE and pIMD information after 
removal of write access to the participant’s 
eCRF .......................................................................... 91 
10.3.9. 
Assessment of intensity and toxicity ............................................. 92 
10.3.9.1. Assessment of intensity .............................................. 92 
10.3.9.2. Assessment of causality ............................................. 93 
10.3.9.3. Medically attended visits ............................................. 94 
10.3.9.4. Assessment of outcomes............................................ 94 
10.3.10. Reporting of SAEs, pIMDs ........................................................... 95 
10.3.10.1. Events requiring expedited reporting to GSK .............. 95 
10.3.10.2. Back-up system in case facsimile or electronic 
reporting system does not work .................................. 95 
10.4. 
Appendix 4: Country-specific requirements ................................................. 96 
10.4.1. 
Requirements for Japan ............................................................... 96 
10.4.1.1. Regulatory and ethical considerations ........................ 96 
10.4.1.2. Informed consent ........................................................ 96 
10.4.1.3. Study administrative structure .................................... 96 
10.4.1.4. Unapproved medical device ....................................... 96 
10.4.2. 
Requirements for Germany (Amended: 01 April 2022) ................. 97 
10.5. 
Appendix 5: Abbreviations and glossary of terms ...................................... 100 
10.5.1. 
List of abbreviations (Amended: 01 April 2022) .......................... 100 
10.5.2. 
Glossary of terms (Amended: 01 April 2022) ............................. 102 

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10.6. 
Appendix 8: Protocol Amendment History ................................................. 107 
11. REFERENCES ..................................................................................................... 136 
 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of activities: RSV_annual* (Amended: 01 April 2022) ............. 19 
Table 2 
Schedule of activities: RSV_flexible revaccination* (Amended: 01 
April 2022) .............................................................................................. 22 
Table 3 
Schedule of activities: RSV_1dose* (Amended: 01 April 2022) .............. 25 
Table 4 
Intervals between study visits for group RSV_annual ............................. 28 
Table 5 
Intervals between study visits for groups RSV_flexible 
revaccination and RSV_1dose (Amended: 01 April 2022) ...................... 28 
Table 6 
Study objectives and endpoints .............................................................. 31 
Table 7 
Study groups, intervention and blinding foreseen in the study 
(Amended: 01 April 2022) ...................................................................... 34 
Table 8 
Study intervention administered (Amended: 01 April 2022) .................... 40 
Table 9 
Contact information for emergency unblinding ....................................... 42 
Table 10 
Timing of collection of concomitant medication (Amended: 01 
April 2022) .............................................................................................. 44 
Table 11 
Biological samples (Amended: 01 April 2022) ........................................ 49 
Table 12 
Laboratory assays .................................................................................. 50 
Table 13 
Immunological read-outs (Amended: 01 April 2022) ............................... 51 
Table 14 
Timeframes for collecting and reporting of safety information ................. 55 
Table 15 
Timeframes for submitting serious adverse event and other 
events reports to GSK ............................................................................ 57 
Table 16 
Contact information for reporting of SAEs and pIMDs (Amended: 
01 April 2022) ......................................................................................... 57 
Table 17 
Precision and 95% confidence interval on the geometric mean 
antibody titers and concentrations at Month 12 based on different 
values of standard deviations for 804 evaluable participants in 
the (RSV_annual, RSV_flexible revaccination and RSV_1dose) 
pooled groups ........................................................................................ 59 
Table 18 
Precision and 95% confidence interval on the geometric mean of 
the frequency of RSVPreF3-Specific CD4+ T cells at Month 12 
based on different values of standard deviations for 460 
evaluable participants in the (RSV_annual, RSV_flexible 
revaccination and RSV_1dose) pooled groups ....................................... 60 

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Table 19 
Precision and 95% confidence interval on the geometric mean 
antibody titers/concentrations and of the frequency of 
RSVPreF3-Specific CD4+ T cells at Month 13 based on different 
values of standard deviations for 276 evaluable participants in 
the RSV_annual group ........................................................................... 61 
Table 20 
Precision and 95% confidence interval on the geometric mean 
antibody titers/concentrations and of the frequency of 
RSVPreF3-specific CD4+ T cells at Month 25 based on different 
values of standard deviations for 220 evaluable participants in 
the RSV_annual group ........................................................................... 62 
Table 21 
Precision and 95% confidence interval on the geometric mean 
antibody titers/concentrations at Month 25 based on different 
values of standard deviations for 211 evaluable participants in 
the RSV_flexible revaccination group ..................................................... 62 
Table 22 
Precision and 95% confidence interval of the frequency of 
RSVPreF3-specific CD4+ T cells at Month 25 based on different 
values of standard deviations for 74 evaluable participants in the 
RSV_flexible revaccination group ........................................................... 62 
Table 23 
Probability (%) to observe at least one AE depending on the AE 
true incidence rate with 990 and 330 participants in the 
RSV_annual and RSV_flexible revaccination groups, 
respectively ............................................................................................ 63 
Table 24 
Populations for analyses (Amended: 01 April 2022) ............................... 63 
Table 25 
Solicited administration site events......................................................... 79 
Table 26 
Solicited systemic events ....................................................................... 79 
Table 27 
List of potential immune-mediated diseases (pIMDs) (Amended: 
01 April 2022) ......................................................................................... 81 
Table 28 
Intensity scales for solicited events in adults .......................................... 92 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview (Amended: 01 April 2022) .................................. 32 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale: 
GlaxoSmithKline Biologicals SA (GSK) is developing a new RSV PreFusion protein 3 
Older Adult (RSVPreF3 OA) investigational vaccine against respiratory syncytial virus 
(RSV)-associated (subtypes A and B) disease in adults  60 years of age (YOA). 
The RSVPreF3 OA investigational vaccine was administered intramuscularly for the first 
time to adults 60-80 YOA according to a 0, 2-month vaccination schedule in another 
clinical study (RSV OA=ADJ-002). The vaccine formulation and schedule to be used in 
the present study was selected based on safety and immunogenicity data from the 
RSV OA=ADJ-002 study. 
The RSV OA=ADJ-004 is conducted to evaluate the safety, reactogenicity, 
immunogenicity profile and long-term persistence of the immune response up to 3 years 
following a single dose vaccination regimen of the RSVPreF3 OA investigational vaccine 
in adults ≥ 60 YOA. Considering the uncertainty on the persistence of the immune 
response, this study is also designed to evaluate the immunogenicity, safety and 
reactogenicity of additional vaccine doses according to different revaccination schedules 
(annual revaccination or revaccination at a later stage). The rationale for the study design 
is presented in Section 4.2. 
Objectives and Endpoints: Refer to Table 6. 
1.2. 
Schema 
Refer to Figure 1 for a schematic presentation of the study design. 
1.3. 
Schedule of Activities (Amended: 01 April 2022) 
Study visits should preferably be done on site. As of Protocol Amendment 1 
implementation, if deemed necessary, local regulations allow, and quality of study 
procedures is maintained, study visits during the follow-up phases can be done at home 
or at the long-term care facility (LTCF), as per local regulation. Home visits are not 
allowed for the cell-mediated immunity (CMI) subset (due to sensitivity of CMI 
samples), except in special circumstances and with the approval of the GSK Central study 
team. For participants without blood sample collections (i.e., for participants only being 
followed up for safety), contact should be attempted only if site visit is not possible at 
Months 6, 18, 30 and 36. For contacts, multiple formats can be proposed by the study 
site. These contacts may be done via email, text message, or phone call for example. The 
most appropriate format should be agreed between site staff and the study participant. 
Messaging services and email 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, then 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. 

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Table 1 
Schedule of activities: RSV_annual* (Amended: 01 April 2022) 
Type (V = visit, C = contact)** 
V 
V 
V/C 
V 
V 
V/C(7) 
V 
V 
V/C(7) 
V/C 
Notes 
Timepoint 
D1 
D31 
M6 
M12 
M13 
M18(7) 
M24 
M25 
M30(7) 
M36 
Study participant informed consent1 
● 
 
 
 
 
 
 
 
 
 
See Section 10.1.3 for details 
Check with participant if he/she will 
appoint a caregiver and distribute 
caregiver information letter, when 
applicable 
O 
O 
O 
O 
O 
O 
O 
O 
O 
O 
See Section 5.2.5 for details 
Distribution of participant card 
O 
 
 
 
 
 
 
 
 
 
See Section 8.3.5 for details 
Check inclusion/exclusion criteria  
● 
 
 
 
 
 
 
 
 
 
See Sections 5.1 and 5.2 for Inclusion and 
Exclusion criteria 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Recording smoking status and smoking 
exposure history, including electronic 
smoking devices 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.4 for more information. Refer 
to the Glossary of terms for definitions of current 
and former smoker 
Recording medical history 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
Recording history of any vaccine 
administration2 
● 
 
 
 
 
 
 
 
 
 
See Section 8.2.1.3 for more information 
Vaccine 
Randomization 
● 
 
 
 
 
 
 
 
 
 
See Section 6.3 for more information 
Check criteria for temporary delay for 
enrolment and vaccination 
O 
 
 
O 
 
 
O 
 
 
 
See Section 7.1.1 for more information 
Check contraindications to vaccination 
 
 
 
O 
 
 
O 
 
 
 
See Section 7.1.2 for more information 
Recording pre-vaccination body 
temperature 
● 
 
 
● 
 
 
● 
 
 
 
See Section 8.2.1.6 for more information. The 
route for measuring temperature can be oral, 
axillary or tympanic. Fever is defined as 
temperature 38.0°C/100.4°F regardless the 
location of measurement 
History-directed physical examination 
O 
 
 
O 
 
 
O 
 
 
 
See Section 8.2.1.5 for more information 
Study group and intervention number 
allocation 
O 
 
 
 
 
 
 
 
 
 
See Sections 6.3.2 and 6.3.3 for more 
information 
Intervention number allocation for 
subsequent doses 
 
 
 
O 
 
 
O 
 
 
 
See Section 6.3.3 for more information 
Recording of administered intervention 
number 
● 
 
 
● 
 
 
● 
 
 
 
The number of each administered study 
intervention must be recorded in the eCRF 

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Type (V = visit, C = contact)** 
V 
V 
V/C 
V 
V 
V/C(7) 
V 
V 
V/C(7) 
V/C 
Notes 
Timepoint 
D1 
D31 
M6 
M12 
M13 
M18(7) 
M24 
M25 
M30(7) 
M36 
Vaccine administration (including 
30-minute post-vaccination observation) 
● 
 
 
● 
 
 
● 
 
 
 
See Section 6.1 for more information 
Clinical specimens for laboratory assays 
Blood sampling for antibody 
determination, from HI subset3 (10 mL) 
● 
● 
● 
● 
● 
● 
●6 
● 
● 
● 
See Section 8.1.1 for more information 
Blood sampling for CMI, from CMI 
subset3 (25 mL) 
● 
● 
● 
● 
● 
● 
●6 
● 
● 
● 
See Section 8.1.1 for more information 
Safety assessments 
Recording any concomitant 
medication/vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 6.5 for more information 
Recording any intercurrent medical 
conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 9.3.1.1 for more information 
Distribution of paper diary cards for 
solicited events and unsolicited AEs 
O 
 
 
O 
 
 
O 
 
 
 
See Section 8.2.1.7 for more information 
Return of paper diary cards  
 
O 
 
 
O 
 
 
O 
 
 
Recording of solicited events (Days 1–4 
post-vaccination) 
● 
● 
 
● 
● 
 
● 
● 
 
 
See Section 10.3.8 for more information 
Recording of unsolicited AEs (Days 1–30 
post-vaccination)  
● 
● 
 
● 
● 
 
● 
● 
 
 
See Section 10.3.8 for more information 
Recording of pIMDs and SAEs4 
● 
● 
● 
● 
● 
● 
● 
● 
● 
 
See Section 10.3.8 for more information 
Recording of fatal SAEs, SAEs related to 
study vaccination and pIMDs related to 
study vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording AEs/SAEs leading to 
withdrawal from the study 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine5 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Study Conclusion 
 
 
 
 
 
 
 
 
 
● 
See Section 4.4 for more information 
Note: The double-line borders indicate analyses which will be performed on all data obtained up to these timepoints. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
V = visit, C = contact; D = day; M = month; AE = adverse event; CMI = cell-mediated immunity; pIMDs = potential immune-mediated diseases; SAE = serious adverse event; 
eCRF = electronic case report form. 

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*Refer to Table 7 for the description of study groups. 
**Study visits should preferably be done on site. As of Protocol Amendment 1 implementation, if deemed necessary, local regulations allow, and quality of study procedures is 
maintained, study visits during the follow-up phases can be done at home or at the LTCF, as per local regulation. Home visits are not allowed for the CMI subset (due to sensitivity 
of CMI samples), except in special circumstances and with the approval of the GSK Central study team. For participants without blood sample collections (i.e., for participants only 
being followed up for safety), contact should be attempted only if site visit is not possible at Months 6, 18, 30 and 36. For contacts, multiple formats can be proposed by the study site. 
These contacts may be done via email, text message, or phone call for example. The most appropriate format should be agreed between site staff and the study participant. Messaging 
services and email 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, then 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. 
1 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. 
2 Any vaccination administered up to 1 year before administration of the first dose of study vaccine should be recorded in the eCRF. Administration of Shingrix at any timepoint (even if 
longer than 1 year before the first study dose) should be recorded in the eCRF. 
3 Blood samples for humoral immunity (HI) and for CMI will be taken from the same ~345 participants. The remaining ~645 participants will have no blood draws. Refer to Section 6.3.4 
for details. 
4 Recording of any SAE or any pIMD should only be done in the 6-month post-vaccination period, i.e., from Day 1 to Month 6, from Month 12 to Month 18, and from Month 24 to 
Month 30. 
5 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 Dose 1) up to study 
end. 
6 Blood sampling should be performed prior to vaccination (this has been clarified for the vaccination visit occurring after implementation of Protocol Amendment 1). 
7 Visits/contacts at Month 18 and Month 30 must not be performed before the 6-month post-vaccination timepoint to allow collection of safety data up to at least 6 months 
after each vaccination for each participant (this has been clarified for the vaccination visit occurring after implementation of Protocol Amendment 1). 

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Table 2 
Schedule of activities: RSV_flexible revaccination* (Amended: 01 April 2022) 
Type (V = visit)** 
V 
V 
V 
V 
V 
V 
V 
V(8) 
V 
Notes 
Timepoint 
D1 
D31 
M6 
M12 
M18 
M24 
M25 
M30(8) 
M36 
Study participant informed consent1 
● 
 
 
 
 
 
 
 
 
See Section 10.1.3 for details 
Check with participant if he/she will appoint 
a caregiver and distribute caregiver 
information letter, when applicable 
O 
O 
O 
O 
O 
O 
O 
O 
O 
See Section 5.2.5 for details 
Distribution of participant card 
O 
 
 
 
 
 
 
 
 
See Section 8.3.5 for details 
Check inclusion/exclusion criteria 
● 
 
 
 
 
 
 
 
 
See Sections 5.1 and 5.2 for Inclusion and 
Exclusion criteria 
Collect demographic data 
● 
 
 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Recording smoking status and smoking 
exposure history, including electronic 
smoking devices 
● 
 
 
 
 
 
 
 
 
See Section 8.2.1.4 for more information. 
Refer to the Glossary of terms for definitions 
of current and former smoker 
Recording medical history 
● 
 
 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
Recording history of any vaccine 
administration 2 
● 
 
 
 
 
 
 
 
 
See Section 8.2.1.3 for more information 
Vaccine 
Randomization 
● 
 
 
 
 
 
 
 
 
See Section 6.3 for more information 
Check criteria for temporary delay for 
enrolment and vaccination 
O 
 
 
 
 
O 
 
 
 
See Section 7.1.1 for more information 
Check contraindications to vaccination 
 
 
 
 
 
O 
 
 
 
See Section 7.1.2 for more information 
Recording pre-vaccination body temperature 
● 
 
 
 
 
● 
 
 
 
See Section 8.2.1.6 for more information. The 
route for measuring temperature can be oral, 
axillary or tympanic. Fever is defined as 
temperature  38.0°C/100.4°F regardless the 
location of measurement 
History-directed physical examination 
O 
 
 
 
 
O 
 
 
 
See Section 8.2.1.5 for more information 
Study group and intervention number 
allocation 
O 
 
 
 
 
 
 
 
 
See Sections 6.3.2 and 6.3.3 for more 
information 
Intervention number allocation for 
subsequent dose 
 
 
 
 
 
O 
 
 
 
See Section 6.3.3 for more information 
Recording of administered intervention 
number 
● 
 
 
 
 
● 
 
 
 
The number of each administered study 
intervention must be recorded in the eCRF 

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Type (V = visit)** 
V 
V 
V 
V 
V 
V 
V 
V(8) 
V 
Notes 
Timepoint 
D1 
D31 
M6 
M12 
M18 
M24 
M25 
M30(8) 
M36 
Vaccine administration (including 30-minute 
post-vaccination observation) 
● 
 
 
 
 
● 
 
 
 
See Section 6.1 for more information 
Clinical specimens for laboratory assays 
Blood sampling for antibody determination, 
from all participants3 (10 mL) 
● 
● 
● 
● 
● 
●7 
● 
● 
● 
See Section 8.1.1 for more information 
Blood sampling for CMI, from CMI subset4 
(25 mL) 
● 
● 
● 
● 
● 
●7 
● 
● 
● 
See Section 8.1.1 for more information 
Safety assessments 
Recording any concomitant 
medication/vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 6.5 for more information 
Recording any intercurrent medical 
conditions 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 9.3.1.1 for more information 
Distribution of paper diary cards for solicited 
events and unsolicited AEs 
O 
 
 
 
 
O 
 
 
 
See Section 8.2.1.7 for more information 
Return of paper diary cards 
 
O 
 
 
 
 
O 
 
 
Recording of solicited events (Days 1–4 
post-vaccination) 
● 
● 
 
 
 
● 
● 
 
 
See Section 10.3.8 for more information 
Recording of unsolicited AEs (Days 1–30 
post-vaccination) 
● 
● 
 
 
 
● 
● 
 
 
See Section 10.3.8 for more information 
Recording of pIMDs and SAEs5 
● 
● 
● 
 
 
● 
● 
● 
 
See Section 10.3.8 for more information 
Recording of fatal SAEs, SAEs related to 
study vaccination and pIMDs related to 
study vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording AEs/SAEs leading to withdrawal 
from the study 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine6 
● 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Study Conclusion 
 
 
 
 
 
 
 
 
● 
See Section 4.4 for more information 
Note: The double-line borders indicate analyses which will be performed on all data obtained up to these timepoints. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
V = visit, D = day; M = month; AE = adverse event; CMI = cell-mediated immunity; pIMDs = potential immune-mediated diseases; SAE = serious adverse event; eCRF = electronic 
case report form. 

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*Refer to Table 7 for the description of study groups. 
**Study visits should preferably be done on site. As of Protocol Amendment 1 implementation, if deemed necessary, local regulations allow, and quality of study procedures is 
maintained, study visits during the follow-up phases for the humoral subset can be done at home or at the LTCF, as per local regulation. Home visits are not allowed for the CMI 
subset (due to sensitivity of CMI samples) except in special circumstances and with the approval of the GSK Central study team. 
1 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. 
2 Any vaccination administered up to 1 year before administration of the first dose of study vaccine should be recorded in the eCRF. Administration of Shingrix at any timepoint (even if 
longer than 1 year before the first study dose) should be recorded in the eCRF. 
3 Blood samples for humoral immunity will be taken from all participants. Refer to Section 6.3.4 for details. 
4 CMI blood samples should only be taken from ~115 participants. Refer to Section 6.3.4 for details. 
5 Recording of any SAE or any pIMD should only be done in the 6-month post-vaccination period, i.e., from Day 1 to Month 6 and from Month 24 to Month 30. 
6 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 Dose 1) up to study 
end. 
7 Blood sampling should be performed prior to vaccination (this has been clarified for the revaccination visit occurring after implementation of Protocol Amendment 1). 
8 Visits at Month 30 must not be performed before the 6-month post-vaccination timepoint to allow collection of safety data up to at least 6 months after each vaccination 
for each participant (this has been clarified for the revaccination visit occurring after implementation of Protocol Amendment 1). 

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Table 3 
Schedule of activities: RSV_1dose* (Amended: 01 April 2022) 
Type (V = visit)** 
V 
V 
V 
V 
V 
V 
V 
V 
Notes 
Timepoint 
D1 
D31 
M6 
M12 
M18 
M24 
M30 
M36 
Study participant informed consent1 
● 
 
 
 
 
 
 
 
See Section 10.1.3 for details 
Check with participant if he/she will appoint 
a caregiver and distribute caregiver 
information letter, when applicable 
O 
O 
O 
O 
O 
O 
O 
O 
See Section 5.2.5 for details 
Distribution of participant card 
O 
 
 
 
 
 
 
 
See Section 8.3.5 for details 
Check inclusion/exclusion criteria 
● 
 
 
 
 
 
 
 
See Sections 5.1 and 5.2 for Inclusion and 
Exclusion criteria 
Collect demographic data 
● 
 
 
 
 
 
 
 
See Section 8.2.1.1 for more information 
Recording smoking status and smoking 
exposure history, including electronic 
smoking devices 
● 
 
 
 
 
 
 
 
See Section 8.2.1.4 for more information. Refer 
to the Glossary of terms for definitions of 
current and former smoker 
Recording medical history 
● 
 
 
 
 
 
 
 
See Section 8.2.1.2 for more information 
Recording history of any vaccine 
administration 2 
● 
 
 
 
 
 
 
 
See Section 8.2.1.3 for more information 
Vaccine 
Randomization 
● 
 
 
 
 
 
 
 
See Section 6.3 for more information 
Check criteria for temporary delay for 
enrolment and vaccination 
O 
 
 
 
 
 
 
 
See Section 7.1.1 for more information 
Recording pre-vaccination body 
temperature 
● 
 
 
 
 
 
 
 
See Section 8.2.1.6 for more information. The 
route for measuring temperature can be oral, 
axillary or tympanic. Fever is defined as 
temperature 38.0°C/100.4°F regardless the 
location of measurement 
History-directed physical examination 
O 
 
 
 
 
 
 
 
See Section 8.2.1.5 for more information 
Study group and intervention number 
allocation 
O 
 
 
 
 
 
 
 
See Sections 6.3.2 and 6.3.3 for more 
information 
Recording of administered intervention 
number 
● 
 
 
 
 
 
 
 
The number of each administered study 
intervention must be recorded in the eCRF 
Vaccine administration (including 30-
minute post-vaccination observation) 
● 
 
 
 
 
 
 
 
See Section 6.1 for more information 

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Type (V = visit)** 
V 
V 
V 
V 
V 
V 
V 
V 
Notes 
Timepoint 
D1 
D31 
M6 
M12 
M18 
M24 
M30 
M36 
Clinical specimens for laboratory assays 
Blood sampling for antibody determination, 
from all participants3 (10 mL) 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 8.1.1 for more information 
Blood sampling for CMI, from CMI subset4 
(25 mL) 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 8.1.1 for more information 
Safety assessments 
Recording any concomitant 
medication/vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 6.5 for more information 
Recording any intercurrent medical 
conditions 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 9.3.1.1 for more information 
Distribution of paper diary cards for 
solicited events and unsolicited AEs 
O 
 
 
 
 
 
 
 
See Section 8.2.1.7 for more information 
Return of paper diary cards 
 
O 
 
 
 
 
 
 
Recording of solicited events (Days 1–4 
post-vaccination) 
● 
● 
 
 
 
 
 
 
See Section 10.3.8 for more information 
Recording of unsolicited AEs (Days 1–30 
post-vaccination) 
● 
● 
 
 
 
 
 
 
See Section 10.3.8 for more information 
Recording of pIMDs and SAEs5 
● 
● 
● 
 
 
 
 
 
See Section 10.3.8 for more information 
Recording of fatal SAEs, SAEs related to 
study vaccination and pIMDs related to 
study vaccination 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording AEs/SAEs leading to withdrawal 
from the study 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Recording of SAEs related to study 
participation, or to a concurrent GSK 
medication/vaccine6 
● 
● 
● 
● 
● 
● 
● 
● 
See Section 10.3.8 for more information 
Study Conclusion 
 
 
 
 
 
 
 
● 
See Section 4.4 for more information 
Note: The double-line borders indicate analyses which will be performed on all data obtained up to these timepoints. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
V = visit, D = day; M = month; AE = adverse event; CMI = cell-mediated immunity; pIMDs = potential immune-mediated diseases; SAE = serious adverse event; eCRF = electronic 
case report form. 
*Refer to Table 7 for the description of study groups. 

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**Study visits should preferably be done on site. As of Protocol Amendment 1 implementation, if deemed necessary, local regulations allow, and quality of study procedures is 
maintained, study visits during the follow-up phases for the humoral subset can be done at home or at the LTCF, as per local regulation. Home visits are not allowed for the CMI 
subset (due to sensitivity of CMI samples) except in special circumstances and with the approval of the GSK Central study team. 
1 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. 
2 Any vaccination administered up to 1 year before administration of the first dose of study vaccine should be recorded in the eCRF. Administration of Shingrix at any timepoint (even if 
longer than 1 year before the first study dose) should be recorded in the eCRF. 
3 Blood samples for humoral immunity will be taken from all participants. Refer to Section 6.3.4 for details. 
4 CMI blood samples should only be taken from ~115 participants. Refer to Section 6.3.4 for details. 
5 Recording of any SAE or any pIMD should only be done from Day 1 to Month 6.  
6 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 Dose 1) up to study 
end. 

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Table 4 
Intervals between study visits for group RSV_annual 
Interval 
Length of interval 
Allowed interval 
Day 1 → Day 31 
30 days 
30-42 days 
Day 1 → Month 6 
180 days 
180-210 1 days 
Day 1 → Month 12 
365 days 
350-380 days 
Month 12 → Month 13 
30 days 
30-42 days 
Month 12 → Month 18 
180 days 
180-210 1 days 
Day 1 → Month 24 
730 days 
715-745 days 
Month 24 → Month 25 
30 days 
30-42 days 
Month 24 → Month 30 
180 days 
180-210 1 days 
Day 1 → Month 36 
1095 days 
1080-1110 days 
1 Visit must not be performed before the 6-month post-vaccination timepoint to allow collection of safety data up to at 
least 6 months post-vaccination for each participant. 
For the intervals, exclusion from the per-protocol set will be defined in the Statistical Analysis Plan (SAP). 
Table 5 
Intervals between study visits for groups RSV_flexible revaccination 
and RSV_1dose (Amended: 01 April 2022) 
Interval 
Length of interval 
Allowed interval 
Day 1 → Day 31 
30 days 
30-42 days 
Day 1 → Month 6 
180 days 
180-210 1 days 
Day 1 → Month 12 
365 days 
350-380 days 
Month 12 → Month 18 
180 days 
180-210 days 
Day 1 → Month 24 
730 days 
715-745 days 
Month 24 → Month 25 2 
30 days 
30-42 days 
Month 24 → Month 30 
180 days 
180-210 1 days 
Day 1 → Month 36 
1095 days 
1080-1110 days 
1 Visit must not be performed before the 6-month post-vaccination timepoint to allow collection of safety data up to at 
least 6 months post-vaccination for each participant. Note that the 6-month safety follow-up following 
revaccination at Month 24 is only applicable for the RSV_flexible revaccination group. 
2 Only applicable for the RSV_flexible revaccination group. 
For the intervals, exclusion from the per-protocol set will be defined in the SAP. 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
GlaxoSmithKline Biologicals SA (GSK) is developing a new RSV PreFusion protein 3 
Older Adult (RSVPreF3 OA) investigational vaccine against respiratory syncytial virus 
(RSV)-associated (subtypes A and B) disease in adults  60 years of age (YOA). 
The RSVPreF3 OA investigational vaccine was administered intramuscularly for the first 
time to adults 60–80 YOA according to a 0, 2-month vaccination schedule in another 
clinical study (RSV OA=ADJ-002). The vaccine formulation and schedule to be used in 
the present study was selected based on safety and immunogenicity data from the 
RSV OA=ADJ-002 study. 
The RSV OA=ADJ-004 is conducted to evaluate the safety, reactogenicity, 
immunogenicity profile and long-term persistence of the immune response up to 3 years 
following a single dose vaccination regimen of the RSVPreF3 OA investigational vaccine 
in adults ≥ 60 YOA. Considering the uncertainty on the persistence of the immune 
response, this study is also designed to evaluate the immunogenicity, safety and 
reactogenicity of additional vaccine doses according to different revaccination schedules 
(annual revaccination or revaccination at a later stage). 
The rationale for the study design is presented in Section 4.2. 
2.2. 
Background 
RSV is a ribonucleic acid virus of which 2 antigenically distinct subgroups exist, RSV-A 
and RSV-B [Borchers, 2013]. It is a highly contagious pathogen that causes respiratory 
tract infections in people of all ages. In temperate climates throughout the world, it 
predictably causes fall-winter epidemics. In (sub)tropical regions, viral activity is more 
endemic, and outbreaks are less temporally focused. 
As the global population ages, the morbidity and mortality from 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 infection in older adults 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). 
There is currently no vaccine or other prophylactic treatment available against RSV in 
older adults. Currently available treatment for RSV in this age group is generally 
supportive in nature, as detailed in the IB. 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 
2.3.1. 
Risk Assessment 
Information about the known and expected benefits and risks and reasonably expected 
adverse events (AEs) of the RSVPreF3 OA investigational vaccine (potential syncope, 
hypersensitivity) or adjuvant system (potential immune-mediated diseases [pIMDs]) can 
be found in the IB and Development Safety Update Report. 
All participants will remain under observation at the clinical center for at least 30 minutes 
after vaccination. 
Intramuscular vaccination commonly precipitates a transient and self-limiting local 
inflammatory reaction. This may typically include pain at administration 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 4.2. 
2.3.2. 
Benefit Assessment 
The participants may not directly benefit from vaccination with the RSVPreF3 OA 
investigational vaccine because vaccine efficacy has not been established yet. 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. 
Another benefit for all study participants may include gaining information about their 
general health status through the medical evaluations/assessments associated with this 
study (i.e., physical examination). 
2.3.3. 
Overall Benefit/Risk Conclusion 
The RSVPreF3 OA 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. 

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3. 
OBJECTIVES AND ENDPOINTS 
Table 6 
Study objectives and endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the humoral immune response following 
a 1-dose primary schedule of RSVPreF3 OA 
investigational vaccine up to 12 months post-Dose 1. 
Humoral immune response at pre-vaccination (Day 1), 
30 days post-Dose 1 (Day 31), and at 6 and 12 months 
post-Dose 1 (Months 6 and 12), in a subset of 
participants: 
− Neutralizing antibody titers against RSV-A 
− Neutralizing antibody titers against RSV-B. 
Secondary 
To further evaluate the humoral immune response 
following a 1-dose primary schedule of RSVPreF3 OA 
investigational vaccine up to 12 months post-Dose 1. 
Humoral immune response at pre-vaccination (Day 1), 
30 days post-Dose 1 (Day 31), and at 6 and 12 months 
post-Dose 1 (Months 6 and 12), in a subset of 
participants: 
− RSVPreF3-specific Immunoglobulin G (IgG) 
antibody concentrations. 
To evaluate the humoral immune response following 
1 dose of the RSVPreF3 OA investigational vaccine 
and following revaccination doses, up to study end. 
Humoral immune response at Months 18, 24, 30 and 36 
post-Dose 1, and at 1 month after each revaccination 
dose (Months 13 and 25), in a subset of participants: 
− Neutralizing antibody titers against RSV-A and 
RSV-B 
− RSVPreF3-specific IgG antibody concentrations. 
To evaluate the CMI response following 1 dose of the 
RSVPreF3 OA investigational vaccine and following 
revaccination doses up to study end. 
CMI response at pre-vaccination (Day 1), 30 days 
post-Dose 1 (Day 31), at Months 6, 12, 18, 24, 30 and 36 
post-Dose 1, and at 1 month after each revaccination 
dose (Months 13 and 25), in a subset of participants: 
− Frequency of RSVPreF3-specific CD4+ and/or 
CD8+ T cells expressing at least 2 activation 
markers including at least one cytokine among 
CD40L, 4-1BB, IL-2, TNF-, IFN-, IL-13, IL-17. 
To evaluate the safety and reactogenicity of each 
vaccination schedule of the RSVPreF3 OA 
investigational vaccine in all participants. 
• 
Occurrence of each solicited administration site 
and systemic event during a 4-day follow-up period 
(i.e., on the day of vaccination and 3 subsequent 
days) after each vaccination. 
• 
Occurrence of any unsolicited AE during a 30-day 
follow-up period (i.e., on the day of vaccination and 
29 subsequent days) after each vaccination. 
• 
Occurrence of all SAEs and pIMDs up to 6 months 
after each vaccination. 
• 
Occurrence of fatal SAEs, related SAEs and 
related pIMDs from first vaccination (Day 1) up to 
study end (Month 36).  
Tertiary 
To further characterize immune responses to the 
RSVPreF3 OA investigational vaccine. 
• 
Any further exploratory immunology in a subset of 
participants, such as, but not limited to:  
− Antibodies against specific protein F epitopes. 
− Potential new immunological markers for 
protection. 
− Frequency of RSVPreF3-specific CD4+ and/or 
CD8+ T cells expressing one or any 
combination of immune marker(s). 
CMI = cell-mediated immunity, AE = adverse event, SAE = serious adverse event, pIMD = potential immune-mediated 
disease. 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
Figure 1 
Study design overview (Amended: 01 April 2022) 
 

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N = number of participants; D = day; M = month; AE = adverse event; HI = humoral immunity; CMI = cell-mediated immunity; pIMD = potential immune-mediated disease; 
SAE = serious adverse event. 
= blood sample for humoral immune responses (only applicable for ~ 345 participants of the RSV_annual group; and for all participants of the RSV_flexible revaccination and 
RSV_1dose groups) 
 = blood sample for CMI (only applicable for ~345 participants of the RSV_annual group, and for ~115 participants each from the RSV_flexible revaccination and RSV_1dose 
groups). 
Note: For group RSV_annual: Revaccination Year 1 = Month 12; Revaccination Year 2 = Month 24; for group RSV_flexible revaccination: Revaccination Year 2 = Month 24. 
*Visit and follow-up of solicited events, unsolicited AEs, SAEs and pIMDs are only applicable for RSV_annual group. 
**Visit and follow-up of solicited events, unsolicited AEs, SAEs and pIMDs are only applicable for RSV_annual and RSV_flexible revaccination groups. 
***For the RSV_annual group, the same ~345 participants will be part of both the HI and CMI subsets. The remaining ~645 participants will have no blood draws and will only be 
followed up for safety and reactogenicity. 
****For those participants in the RSV_annual group without blood sample collections, visits at Months 6, 18, 30 and 36 may be held through a contact. However, contact should be 
attempted only if site visit is not possible at Months 6, 18, 30 and 36. 

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• 
Type of study: Self-contained. 
• 
Experimental design: Phase 3, randomized, open-label, multi-country study with 
3 parallel groups (see Figure 1). 
• 
Duration of the study: ~36 months for each participant. 
• 
Primary completion date: Month 12. 
• 
Control: None. 
• 
Blinding: Open-label. 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 participant Diary card (paper Diary 
card). 
• 
Safety monitoring: The study will be conducted with oversight by the project Safety 
Review Team (SRT). Please refer to Section 8.2.2 for the description of review of 
safety data by the SRT. 
• 
Study groups: refer to Figure 1 and Table 7 for an overview of the study groups. 
Table 7 
Study groups, intervention and blinding foreseen in the study 
(Amended: 01 April 2022) 
Study groups Number of 
participants 
Age 
Intervention 
Blinding 
Primary 
vaccination 
Revaccination 
Year 1 (Month 12) 
Revaccination 
Year 2 (Month 24) 
Open 
RSV_annual 
~990 
≥ 60 
years 
RSVPreF3 OA 
investigational 
vaccine 
RSVPreF3 OA 
investigational 
vaccine 
RSVPreF3 OA 
investigational 
vaccine 
X 
RSV_flexible 
revaccination 
~330 
≥ 60 
years 
RSVPreF3 OA 
investigational 
vaccine 
(none) 
RSVPreF3 OA 
investigational 
vaccine 
X 
RSV_1dose 
~330 
≥ 60 
years 
RSVPreF3 OA 
investigational 
vaccine 
(none) 
(none) 
X 
4.1.1. 
Overview of the recruitment plan 
No screening visit is planned for this study. The study is planned to be conducted at sites 
in multiple countries. Recruitment plan will be defined by each participating site. 
The recruitment plan may be adapted based on the actual number of participants enrolled 
in each country. In case a site/country would fall behind in participant recruitment, a 
redistribution of the enrolment target per site/country may be made. This would allow the 
other participating sites/countries to enroll additional participants in an effort to ensure 
full and timely enrolment 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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4.2. 
Scientific rationale for study design (Amended: 01 April 
2022) 
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. The study 
RSV OA=ADJ-004 has been designed to consider the possibility of a decline in the 
immune response through the assessment of persistence over 3 years, while also 
evaluating revaccination as early as the second year to generate data, should an annual 
revaccination be required. 
For that reason, the study is designed not only to evaluate the safety, the reactogenicity, 
the immunogenicity profile and the long-term persistence of the immune response up to 
3 years following a single dose vaccination regimen of the RSVPreF3 OA investigational 
vaccine in adults ≥60 YOA, but also to evaluate the immunogenicity, safety and 
reactogenicity of an additional vaccine dose through different revaccination schedules 
(annual revaccination or revaccination at a later stage): 
• 
RSV_annual group will receive the first dose (Dose 1) at Day 1, followed by 
revaccination doses at 12 months post-Dose 1 and at 24 months post-Dose 1. 
• 
RSV_flexible revaccination group will receive the first dose (Dose 1) at Day 1. 
A revaccination dose will be given 24 months post-Dose 1. Immunogenicity data 
from other studies using the same study intervention showed that following a 
two-dose vaccination schedule (0–2-month schedule), the immune response 
gradually declines over time but remains above baseline value up to 18 months 
post-Dose 2 and that a re-vaccination at 18 months post-Dose 2 (i.e., 20 months 
post-Dose 1) induced humoral and cellular immune responses. 
• 
RSV_1dose group will receive a single dose (Dose 1) at Day 1. 
The study will include the target population of older adults ≥ 60 YOA living in the 
community (community dwelling [CD]) or living in a LTCF and presenting with 
medically stable condition. 
The vaccine formulation was selected in a previous study, where the vaccine was 
administered intramuscularly according to a 0, 2-month vaccination schedule. Please 
refer to the IB for details. 
4.3. 
Justification for dose 
A 2-dose vaccination regimen with an interval of 2 months between doses was evaluated 
in the RSV OA=ADJ-002 study. This regimen was supported by available data from 
several clinical studies in GSK’s Herpes Zoster and chronic obstructive pulmonary 
disease vaccine development programs [Chlibek, 2013; Leroux-Roels, 2016] conducted 
with an AS01-adjuvanted protein in older adults. 
In the RSV OA=ADJ-002 study, the peak response for both IgG and neutralizing 
antibodies was observed at 1 month post-Dose 1. Comparisons of the mean responses 1 
month post-Dose 2 versus 1 month post-Dose 1, in terms of neutralizing antibodies 

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against RSV-A and in terms of frequencies of CD4+ T cells expressing at least 2 markers 
did not show any added value of the second dose. 
Based on safety, reactogenicity and immunogenicity data (humoral and cellular immune 
response) of the RSV OA=ADJ-002 study, the 120 µg RSVPreF3/AS01E formulation as a 
single dose was selected for the Phase 3 clinical development. 
4.4. 
End of Study definition 
A participant is considered to have completed the study if he/she returns for the last visit 
or is available for the last scheduled procedure as described in the protocol. 
End of Study (EoS): Last testing results released of samples collected at Month 36, i.e. 
Last Subject Last Visit (LSLV). In these cases, EoS must be achieved no later than 
8 months after LSLV. 
5. 
STUDY POPULATION 
5.1. 
Inclusion criteria for enrolment 
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 first vaccination, who live in the 
community (CD participants) or in a LTCF (LTCF participants). 
Please refer to the Glossary of terms for the definition of 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, attend regular phone 
calls/study site visits, 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, 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 
will the site staff or caregiver evaluate the participant’s health status while 
answering diaries or make decisions on behalf of the participant. Refer to the 
Glossary of terms 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. Patients 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 enrolment 
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. 
• 
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 diary cards, attend 
regular phone calls/study site visits). 
• 
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. 
• 
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 Examination (MMSE), Mini-Cog or Montreal Cognitive 
Assessment (MoCA) to determine cognition levels of the participant. 
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 dose of study vaccine, or planned use during the study period. 

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• 
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 
study vaccine administration, with the exception of inactivated, split virion 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 dose of study vaccine 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 vaccine dose 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 the 
Glossary of terms 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 participation in the trial until 
the study end. This includes: 
− 
Planned move during the study period to another LTCF that will prohibit 
participation in the trial until study end. 
− 
Planned move from the community to a LTCF that will prohibit participation in 
the trial until study end. 
• 
Participation of any study personnel or their immediate dependents, family, or 
household members. 

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5.2.5. 
Caregiver support 
Study participants may decide to assign a caregiver to help them fulfilling the study 
procedures. Please refer to the Glossary of terms for the definition of a caregiver. 
A caregiver can be appointed by the participant at any time during the study, when the 
participant feels it is necessary. Each caregiver should receive the caregiver information 
letter before providing support to the study participant. 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 settings). This should be recorded in the source documents. 
Caregivers may help the study participants with performing some practical study 
procedures such as receiving or making phone calls to site staff, planning study visits, 
transcribing responses to diaries, transportation to and from the study site etc. However, 
at no time, the caregiver should evaluate the participant’s health status while answering 
diaries or make decisions on behalf of the participant. At the time of recruitment, the site 
staff should inform the participant of the possibility to appoint a caregiver. Then at each 
study visit the site staff should check again with the participant if he/she wishes to 
appoint a caregiver or if there were or will be changes of caregiver. Please refer to the 
SPM for additional information on the appointment of a caregiver. 
5.3. 
Lifestyle considerations 
This section is not applicable. 
5.4. 
Screen failures 
This section is 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 (including vaccine reconstitution). 
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 8. 
Note that the RSVPreF3 OA investigational vaccine must be reconstituted before 
administration. Refer to the SPM for instructions on study vaccine reconstitution. 

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Table 8 
Study intervention administered (Amended: 01 April 2022) 
Study intervention name: 
RSVPreF3 OA interventional vaccine 
Vaccine/Product name*: 
RSVPreF3 (120 µg) 
AS01E 
Presentation: 
RSVPreF3 (120 µg): Vial; Powder for suspension for injection 
AS01E: Vial; Suspension for injection 
Vaccine formulation: 
RSVPreF3 (120 µg) 
AS01E: QS-21* (25 µg), MPL (25 µg), liposomes; Water for injections q.s. 0.5 mL 
Route of administration: 
Intramuscular 
Location: 
Deltoid 
Laterality**: 
Non-dominant 
Number of doses to be 
administered: 
RSV_annual: 3 doses 
RSV_flexible revaccination: 2 doses 
RSV_1dose: 1 dose 
Volume to be administered: 
0.5 mL 
Packaging, labeling and TM: Refer to SPM for more details 
Manufacturer: 
GSK Biologicals 
*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. 
SPM: Study Procedures Manual 
Refer to Section 4 for the schedule of vaccine administration. 
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. 
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 sequentially to the participants who 
have consented to take part in the study, according to the range of participant 
identification numbers allocated to each study center. 
6.3.2. 
Randomization to study intervention 
Approximately 1650 eligible participants will be randomly assigned (3:1:1) to the 3 study 
groups (RSV_annual, RSV_flexible revaccination, or RSV_1dose) at the first study visit 
(Day 1). 

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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). 
To allow GSK to take advantage of greater rates of recruitment in this multi-center study 
and thus to reduce the overall study recruitment period, an over-randomization of 
supplies will be prepared. 
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. The 
SBIR’s randomization algorithm will use minimization procedure accounting for age, 
sex, center, setting (CD and LTCF participants) and CMI subset. Minimization factors 
will have equal weight in the minimization algorithm. 
Participants will be enrolled in 3 age categories reflecting an approximate age distribution 
in the general population, with 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. 
Upon providing the participant identification number, the age category, the sex, the 
setting and the subset, the randomization system will determine the study group and will 
provide the intervention number to be used for the first vaccination. The intervention 
number(s) to be used for subsequent dose administration(s) will also be provided by 
SBIR. The site will record the study intervention assignment on the applicable case report 
form, if required. 
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 
Allocation of participants to assay subsets will be performed using SBIR. The subsets are 
detailed below. 
 
RSV_annual 
RSV_flexible revaccination 
RSV_1dose 
HI subset 
~345* 
All participants (~330) 
All participants (~330) 
CMI subset 
~345* 
~115 
~115 
*For the RSV_annual group, the same ~345 participants will be part of both the HI and CMI subsets. The remaining 
~645 participants will have no blood draws and will only be followed up for safety and reactogenicity. 
• 
HI subset: ~345 participants from the RSV_annual group, and all participants from 
the RSV_flexible revaccination and RSV_1dose groups. These participants will have 
blood samples collected for testing of humoral immunity at each visit applicable for 
their study group. 

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• 
CMI subset: ~345 participants from the RSV_annual group, and ~115 participants 
each from the RSV_flexible revaccination and RSV_1dose groups. These 
participants will have additional blood samples collected for CMI testing at each 
visit applicable for their study group. 
6.3.5. 
Blinding and unblinding 
This is an open-label study. 
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. More specifically, for each 
sample, a different randomly selected code will be used at each timepoint. This sample 
coding will prevent the testing laboratory personnel from linking the consecutive 
visits/timepoints to a specific participant. 
6.3.5.1. 
Emergency unblinding 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information is essential for the clinical 
management or welfare of the participant. 
The emergency process enables the investigator to have unrestricted, immediate and 
direct access to the participant’s individual study intervention via an automated Internet-
based system, e.g., SBIR. 
The investigator may contact a GSK Helpdesk (refer to the Table 9) if he/she needs help 
to perform the unblinding process (i.e., if the investigator is unable to access the SBIR). 
A physician other than the investigator (e.g. an emergency room physician) or 
participant/care giver/family member may also request emergency access to the 
participant’s individual study intervention either via the investigator (preferred option) or 
via the GSK Helpdesk (back-up option). The subject/participant card provides contact 
information for the investigator, his/her back-up and GSK Helpdesk. 
Table 9 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Toll-free numbers: 
Germany and Taiwan: 00 800 4344 1111 
Finland: 999 800 4344 1111 
Japan: 00 531 320 109 
United States: 1 844 446 3133 
Fax : +32 2 401 25 75 
Email: rix.ugrdehelpdesk@gsk.com 

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6.4. 
Study intervention compliance (Amended: 01 April 2022) 
Study intervention will be administered to the participants directly from the investigator 
or designee, under medical supervision. The date of each dose administered will be 
recorded in the source documents and in the eCRF. 
6.5. 
Concomitant therapy (Amended: 01 April 2022) 
At each study contact, the investigator or designee 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 including vaccines/products, except vitamins and dietary 
supplements, administered during the period of 30 days post each vaccine dose 
(Day 1 to Day 31 for all groups, Month 12 to Month 12 + 30 days for the 
RSV_annual group and Month 24 to Month 24 + 30 days for the RSV_annual and 
RSV_flexible revaccination groups). 
• 
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 10.3.8.2. These must 
also be recorded on the Expedited Adverse Event report. 
• 
Any prophylactic medication (e.g., analgesics, antipyretics) administered on the day 
of study vaccination (Day 1 for all groups; Month 12 for the RSV_annual group and 
Month 24 for the RSV_annual and RSV_flexible revaccination groups) and in the 
absence of ANY symptom and in anticipation of a reaction to the vaccination. 
• 
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). 
• 
Shingrix or any AS01-containing vaccine throughout the entire study. 
Refer to Table 10 for an overview of the timing for recording of concomitant medication 
during the study. 
The Local Medical Lead should be contacted if there are any questions regarding 
concomitant or prior therapy. 

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Table 10 
Timing of collection of concomitant medication (Amended: 01 April 2022) 
 
Day 1 
Day 30 
 
Month 12 
Month 12 + 
30 days 
 
Month 24 
Month 24 + 
30 days 
Study 
conclusion 
All concomitant medication including vaccines/products, 
except vitamins and dietary supplements 
 
 
 
RSV_annual 
only 
RSV_annual 
only 
 
RSV_annual and 
RSV_flexible 
revaccination only 
RSV_annual and 
RSV_flexible 
revaccination only 
 
All concomitant medication including vaccines/products 
which may explain/cause/be used to treat an SAE/pIMD 
 
 
 
 
 
 
 
 
 
Any prophylactic medication 
 
 
 
RSV_annual 
only 
 
 
RSV_annual and 
RSV_flexible 
revaccination only 
 
 
All concomitant medications including vaccines/products 
leading to discontinuation of the study intervention or an 
elimination from the analysis 
 
 
 
 
 
 
 
 
 
Shingrix or any AS01-containing vaccine 
 
 
 
 
 
 
 
 
 
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 
 
 
 
 
 
 
 
 
 
Note: The collection period for the concomitant medications to be recorded in eCRF for all groups is indicated in grey. 

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6.6. 
Dose modification 
This section is not applicable. 
6.7. 
Intervention after the end of the study 
During the study conclusion visit, the investigator might ask each participant if they are 
interested in participating in an additional extension study on longer term follow-up. If a 
participant is not interested in joining an additional extension study, 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 
‘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 or revaccination, 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: 
• 
AE 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 the 
Glossary of terms for the definition of intervention. 
7.1.1. 
Criteria for temporary delay for enrolment and/or vaccination 
Vaccination may be postponed within the permitted time interval until transient 
circumstances cited below are resolved: 
• 
Acute disease and/or fever at the time of vaccination. Refer to the Schedule of 
Activities for fever definition and preferred location for measuring temperature in 
this study. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be vaccinated at the discretion of the investigator. 

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• 
Participants with symptoms suggestive of active Coronavirus Disease 2019 
(COVID-19) infection (e.g., fever, cough, etc.). The return of the participant to the 
site will follow the specific guidance from local public health and other competent 
authorities (e.g., free of symptoms, COVID-19 negative testing, etc.). 
• 
Participants with known COVID-19 positive contacts within the past 14 days should 
be delayed for at least 14 days since the exposure, and if the participant remains 
symptom free. 
Refer to Table 4 for the permitted time intervals. 
7.1.2. 
Contraindications to subsequent vaccine administration 
(Amended: 01 April 2022) 
Participants in the RSV_annual and RSV_flexible revaccination groups must be 
evaluated to confirm they are eligible 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 
and 5.2.2 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 
study vaccine or non-study 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. 
• 
Anaphylaxis following the administration of vaccine. 
• 
Any condition that in the judgment of the investigator would make intramuscular 
injection unsafe. 
• 
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 
for the definition of pIMDs. 
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.  

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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 (please 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 
Study procedures and their timing are summarized in the Schedule of Activities 
(Section 1.3). 
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. 
The investigator is not allowed to do testing on samples outside of what has been agreed 
upon by the IEC/IRB. 
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. 
Procedures conducted as part of routine clinical management (e.g. hematologic profiles) 
and obtained before the participant signed the Informed Consent Form (ICF) may be used 
for establishing a clinical baseline, provided the procedure met protocol-specified criteria 
and was performed within the timeframe defined in the Schedule of Activities 
(Section 1.3). 
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 means and/or 
conventional mail. 
• 
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. 
*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 site 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 site staff at a site other than the designated study site. Refer to 
European Medicines Agency (EMA) Guidance on the Management of Clinical Trials during the 
COVID-19 (Coronavirus) pandemic (version 5, 10 February 2022) and to the Food and Drug 
Administration Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 
Public Health Emergency (updated 30 August 2021) for more details. (Amended: 01 April 2022) 
Refer to the SPM for further details on decentralized clinical trial solutions. 
Impact on the per-protocol set for immunogenicity will be determined on a case by case 
basis. 

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8.1. 
Efficacy and/or immunogenicity assessments 
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. 
8.1.1. 
Biological samples (Amended: 01 April 2022) 
Table 11 
Biological samples (Amended: 01 April 2022) 
Sample type 
Quantity 
Unit 
Timepoint 
Subset name* 
Blood for humoral 
immune response 
10 
mL 
Day 1 
Day 31 
Month 6 
Month 12 
Month 13** 
Month 18 
Month 24 
Month 25*** 
Month 30 
Month 36 
HI subset 
Blood for CMI 
25 
mL 
Day 1 
Day 31 
Month 6 
Month 12 
Month 13** 
Month 18 
Month 24 
Month 25*** 
Month 30 
Month 36 
CMI subset 
CMI: cell-mediated immunity 
*Refer to Section 6.3.4 for subset description. 
**Only applicable for the RSV_annual group 
***Only applicable for the RSV_annual and RSV_flexible revaccination groups 

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The approximate overall volume that will be collected per participant during the entire 
3-year study period is as follows: 
Group 
Participant 
subset 
Number of 
participants 
Total volume of 
blood 
Notes 
RSV_annual group 
HI subset 
~345 
10x10 mL = ~100 mL 
The same ~345 participants will 
be part of both the HI and CMI 
subsets. The participants from 
this group who are not part of the 
subset will not have blood draws 
CMI subset 
~345 
10x25 mL = ~250 mL 
RSV_flexible 
revaccination group 
All participants 
~330 
9x10 mL = ~90 mL 
 
CMI subset 
~115 
9x25 mL = ~225 mL 
RSV_1dose 
All participants 
~330 
8x10 mL = ~80 mL 
 
CMI subset 
~115 
8x25 mL = ~200 mL 
Refer to the Table 11 and Schedule of Activities for details of volumes collected for 
different assessments. 
8.1.2. 
Laboratory assays 
Table 12 
Laboratory assays 
Assay type 
System 
Component 
Challenge 
Method 
Laboratory* 
Cell-mediated 
Immunity  
PBMC 
IL-2, CD40L, TNF-, 
IFN-, IL-13, IL-17 or 
4-1BB secreting CD4+ 
and CD8+ T cells 
Peptide pool 
covering 
RSVPreF3 
ICS 
GSK** 
Humoral Immunity 
(antibody 
determination) 
Serum 
Respiratory Syncytial 
Virus A antibody 
 
Neutralization 
GSK** 
Serum 
Respiratory Syncytial 
Virus B antibody 
Neutralization 
GSK** 
Serum 
RSVPreF3-specific IgG 
antibody 
ELISA 
GSK** 
PBMC = peripheral blood mononuclear cells; ICS = intracellular cytokine staining; ELISA = enzyme-linked 
immunosorbent assay 
*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 
Contract Research Organization 
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. 

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8.1.3. 
Immunological read-outs 
Table 13 
Immunological read-outs (Amended: 01 April 2022) 
Blood sampling timepoint 
Subset 
name 
No. 
participants 
Component 
Components 
priority rank 
Type of contact and 
timepoint 
Sampling 
timepoint 
Humoral immunity (on serum samples) 
Day 1 
Pre-Vacc 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Day 31 
Day 31 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Month 6 
Month 6 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Month 12 
Month 12 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Month 131 
Month 131 
Humoral 
immunity 
subset 
~345 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Month 18 
Month 18 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Month 24 
Month 24 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Month 25 2 
Month 25 2 
Humoral 
immunity 
subset 
~675 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody 
2 
RSVPreF3-specific IgG antibody 
3 
Month 30 
Month 30 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody 
2 
RSVPreF3-specific IgG antibody 
3 
Month 36 
Month 36 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody 
2 
RSVPreF3-specific IgG antibody 
3 
Cell-mediated immunity (on PBMC samples) 
Day 1 
Pre-Vacc 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Day 31 
Day 31 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Month 6 
Month 6 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Month 12 
Month 12 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Month 131 
Month 131 
CMI subset 
~345 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 

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Blood sampling timepoint 
Subset 
name 
No. 
participants 
Component 
Components 
priority rank 
Type of contact and 
timepoint 
Sampling 
timepoint 
Month 18 
Month 18 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Month 24 
Month 24 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Month 25 2 
Month 25 2 
CMI subset 
~460 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Month 30 
Month 30 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
Month 36 
Month 36 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
PBMC = peripheral blood mononuclear cells; CMI = cell-mediated immunity. 
1 Only applicable for the RSV_annual group. 
2 Only applicable for the RSV_annual and RSV_flexible revaccination groups. 
8.1.4. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen used in the RSVPreF3 OA investigational vaccine. 
8.2. 
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 
intervention or study. 
8.2.1. 
Pre-vaccination procedures 
8.2.1.1. 
Collection of demographic data 
Record demographic data such as year of birth, sex, race, ethnicity and type of residence 
(CD/LTCF) in the participant’s eCRF. 
8.2.1.2. 
Medical history 
Obtain the participant’s medical history by interviewing the participant and/or review of 
the participant’s medical records. Record any relevant pre-existing conditions, signs 
and/or symptoms present prior to the first study vaccination in the eCRF. 

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8.2.1.3. 
Vaccination history 
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 administration of the first dose of study 
vaccine should be recorded in the eCRF. For history of influenza vaccination, 
information about the vaccine formulation (e.g., adjuvanted or non-adjuvanted, or 
high-dose) should be recorded if known. 
Administration of Shingrix at any timepoint (even if longer than 1 year before the first 
study dose) should be recorded in the eCRF. The date of vaccination should be collected 
and recorded in the eCRF. 
8.2.1.4. 
Smoking status and smoking exposure history 
Obtain the participant’s smoking status and smoking history by interviewing the 
participant, differentiating tobacco use (cigarettes, cigars, cigarillos, pipes …) and use of 
electronic smoking devices (e-cigarettes). Refer to the Glossary of terms for 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. 
8.2.1.5. 
History-directed physical examination 
Perform a history-directed physical examination. If the investigator determines that the 
participant’s health on the day of vaccination temporarily precludes vaccination, the visit 
will be rescheduled within the allowed interval for this visit (refer to Table 4 for the 
allowed intervals). 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. 
8.2.1.6. 
Pre-vaccination body temperature 
The axillary, oral or tympanic body temperature of each participant needs to be measured 
prior to any study vaccine administration and recorded in the eCRF. If the participant has 
fever (fever is defined as temperature  38.0°C/100.4°F regardless the location of 
measurement) on the day of vaccination, the vaccination visit will be rescheduled within 
the allowed interval for this visit (see Table 4). 

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8.2.1.7. 
Distribution of paper diary cards 
Paper diary cards will be distributed at each vaccination visit for the participants to record 
any solicited event in the 4-day period following each vaccination, and any unsolicited 
AE they may have experienced as well as any medication taken in the 30-day period 
following each vaccination. Refer to Section 10.3.8 for guidelines. 
8.2.2. 
Safety monitoring 
The project’s SRT will perform the safety monitoring in this study. 
As the RSVPreF3 OA investigational vaccine will be administered for the first time in 
adults older than 80 years, an initial safety assessment will be performed by the SRT on 
the 30 days post-Dose1 data of the first 50 participants aged 80 years and above who 
received one dose of study intervention. 
8.3. 
AEs, SAEs and other events of interest 
8.3.1. 
Time period and frequency for collecting AE, SAE and other 
safety information 
An overview of the protocol-required reporting periods for AEs, SAEs and pIMDs is 
given in Table 14. 

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Table 14 
Timeframes for collecting and reporting of safety information 
 
Pre-
Dose 1*  Dose 
1** 
 
 
6 months 
after 
vaccination 
(M6) 
 Revaccination Year 1 (Month 12)** 
 
 Revaccination Year 2 (Month 24)** 
 
Study 
Conclusion 
(M36) 
D1 
 
D1 
D4 
D30 
 
M12  
M12 + D4 
M13  
M18 
 
M24  
M24 + D4 
M25 
M30 
Solicited 
administration site 
and systemic events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SAEs/pIMDs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs/pIMDs related 
to study vaccination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation or 
concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatal SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to 
withdrawal from the 
study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intercurrent medical 
conditions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D = day; M = month; Vacc = vaccination; AE = adverse event; SAE = serious adverse event; pIMD = potential immune-mediated disease 
*i.e. consent obtained on Day 1 (prior to vaccination). 
**Solicited administration site and systemic events up to 4 days, unsolicited AEs up to 30 days and SAEs/pIMDs up to 6 months will be collected only after vaccination. 
Note: COVID-19 cases will be collected during the same timeframes as those used for collecting and reporting the other safety information (unsolicited AEs/SAEs, etc.). 

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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 14. 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 the Table 16. 
8.3.2. 
Method of detecting AEs, SAEs and other events 
Methods of detecting and recording AEs/SAEs/pIMDs are detailed in the Section 10.3.8. 
The assessment of AEs/SAEs intensity, causality and outcome are provided in the 
Section 10.3.9. 
Open-ended and non-leading verbal questioning of the participant is the preferred method 
of acquiring information related to an AE/SAE/pIMD. 
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/pIMD, he/she must report it to GSK using the required 
documentation, and within the timeframes, mentioned in the Table 15. 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/pIMDs, the investigator will always provide an assessment of causality at the 
time of the initial report, as defined in the 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/pIMDs. 

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Table 15 
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 
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 an 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. 
8.3.3.1. 
Contact information for reporting of SAEs and pIMDs 
Table 16 
Contact information for reporting of SAEs and pIMDs (Amended: 
01 April 2022) 
Study contact for questions regarding SAEs and pIMDs 
Refer to the local study contact information document 
Back-up study contact for reporting SAEs and pIMDs 
Available 24/24 hours and 7/7 days: 
GSK Clinical Safety & Pharmacovigilance 
Outside US sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: ogm28723@gsk.com 
US sites only: 
Fax: 1-610-787-7053 
8.3.4. 
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). 
8.3.5. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
keep the participant card in his/her/their possession at all times throughout the study. In 
an emergency, this card serves to inform the responsible attending 
physician/caregiver/family member that the participant is in a clinical study and that 
relevant information may be obtained by contacting the investigator. 

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8.4. 
Treatment of overdose 
This section is not applicable. 
8.5. 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7. 
Genetics 
Genetics are not evaluated in the current study. For participants who consent to 
participate in genetic research in future studies, the obtained blood samples may be used 
at a later stage in future studies for research such as B cell receptor repertoire analysis 
(B cell receptor sequencing). 
8.8. 
Biomarkers 
Biomarkers for pharmacogenetics are not evaluated in this study. 
8.9. 
Health outcomes 
Economic outcome measures such as health care resource utilization data associated with 
healthcare encounters are not evaluated in this study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
Not applicable as this study is descriptive. 
9.2. 
Sample size determination (Amended: 01 April 2022) 
This study is planned to enroll ~1650 participants randomized according to 3:1:1 ratio to 
1 of the 3 study groups: RSV_annual, RSV_flexible revaccination, and RSV_1dose 
respectively. 
The proposed sample size is based on the following considerations: 
• 
Ensure a sufficient number of participants to evaluate with adequate precision the 
immunogenicity after a single dose regimen up to 12 months post-vaccination (based 
on the 3 pooled RSV_annual, RSV_flexible revaccination and RSV_1dose groups) but 
also the immunogenicity after revaccination (based on RSV_annual and 
RSV_flexible revaccination groups). 

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• 
Ensure adequate description of the antibody kinetics after a single dose keeping the 
flexibility to give a revaccination to a part of the participants. 
• 
Ensure an adequate sample size for evaluation of reactogenicity and safety profile 
following revaccination. 
Approximately 345 participants will be enrolled in the humoral subset in the RSV_annual 
group and approximately 330 participants per group in the RSV_flexible revaccination 
and RSV_1dose groups. Approximately 345, 115 and 115 participants will be enrolled in 
the CMI subset in the RSV_annual, RSV_flexible revaccination, and RSV_1dose groups, 
respectively. A total of 990 and 330 participants will be enrolled in the RSV_annual and 
RSV_flexible revaccination groups, respectively, for evaluation of reactogenicity and 
safety profile following revaccination. A 20% rate of non-evaluable participants every 
year will be considered. 
Withdrawals will not be replaced. 
9.2.1. 
Evaluation of humoral immune response up to Month 12 (primary 
objective and first secondary objective) 
At Month 12, the effect of a 1-dose primary schedule will be evaluated in terms of 
RSV-A/B neutralizing antibody titers and RSVPreF3-specific IgG concentrations. 
Approximately 804 participants in the (RSV_annual, RSV_flexible revaccination, and 
RSV_1dose) pooled group receiving a single dose of RSVPreF3 OA investigational 
vaccine will be evaluable for the humoral immune response at Month 12. 
Table 17 shows the precision that can be obtained based on different values of standard 
deviations in terms of RSV-A/B neutralizing antibody titers, and RSVPreF3-specific IgG 
antibody concentrations. 
Table 17 
Precision and 95% confidence interval on the geometric mean 
antibody titers and concentrations at Month 12 based on different 
values of standard deviations for 804 evaluable participants in the 
(RSV_annual, RSV_flexible revaccination and RSV_1dose) pooled 
groups 
Number of enrolled 
participants in the 
humoral subset 
(3 groups pooled*) 
Number of evaluable 
participants in the humoral 
subset up to Month 12 
(3 groups pooled*) 
Standard 
deviation in 
log10 
Width ½ 
95% CI in 
log10 
Ratio 
upper 
limit 95% 
CI/GM 
Ratio 
upper limit/ 
lower limit 
95% CI 
1005 
804 
0.30 
0.021 
1.05 
1.10 
1005 
804 
0.35 
0.024 
1.06 
1.12 
1005 
804 
0.40 
0.028 
1.07 
1.14 
1005 
804 
0.45 
0.031 
1.07 
1.15 
1005 
804 
0.50 
0.035 
1.08 
1.17 
*At the time of the analysis at Month 12 (RSV_annual, RSV_flexible revaccination and RSV_1dose groups) will be 
pooled. 
Precision estimated using PASS 12.0.10: Confidence interval of a mean, alpha = 5%. 
CI = Confidence Interval, LL = Lower Limit, UL = Upper Limit 
GM = Geometric Mean 

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9.2.2. 
Evaluation of the cellular immune response up to Month 12 
(secondary objective) 
At Month 12, the effect of a 1-dose primary schedule dose will be evaluated in terms of 
RSVPreF3-specific CD4+ T cells frequency. Approximately, 460 participants in the 
pooled groups (RSV_annual, RSV_flexible revaccination, and RSV_1dose groups) 
receiving a single dose of RSVPreF3 OA investigational vaccine will be evaluable for the 
CMI response at study Month 12. 
Table 18 shows the precision that can be obtained based on different values of standard 
deviations in terms of the frequency of RSVPreF3-specific CD4+ T cells. 
Table 18 
Precision and 95% confidence interval on the geometric mean of the 
frequency of RSVPreF3-Specific CD4+ T cells at Month 12 based on 
different values of standard deviations for 460 evaluable participants 
in the (RSV_annual, RSV_flexible revaccination and RSV_1dose) 
pooled groups 
Number of enrolled 
participants in the 
CMI subset 
(3 groups pooled*) 
Number of evaluable 
participants in the CMI 
subset up to Month 12 
(pooled 3 groups pooled*) 
Standard 
deviation in 
log10 
Width ½ 
95% CI in 
log10 
Ratio 
upper 
limit 95% 
CI/GM 
Ratio 
upper limit/ 
lower limit 
95% CI 
575 
460 
0.30 
0.027 
1.06 
1.13 
575 
460 
0.35 
0.032 
1.08 
1.16 
575 
460 
0.40 
0.037 
1.09 
1.19 
575 
460 
0.45 
0.041 
1.10 
1.21 
575 
460 
0.50 
0.046 
1.11 
1.24 
*At the time of the analysis at Month 12 (RSV_annual, RSV_flexible revaccination and RSV_1dose groups) will be 
pooled. 
Precision estimated using PASS 12.0.10: Confidence interval of a mean, alpha = 5%. 
CI = Confidence Interval, LL=Lower Limit, UL=Upper Limit 
GM = Geometric Mean 
9.2.3. 
Evaluation of humoral and cellular immune response at Month 13 
(secondary objective) 
At Month 13 (one month post-revaccination at Month 12), the effect of a revaccination 
dose will be evaluated. As such ~ 276 participants in the RSV_annual group receiving a 
revaccination dose of RSVPreF3 OA investigational vaccine will be evaluable for the 
humoral and cellular immune response at study Month 13. 
Table 19 shows the precision that can be obtained based on different values of standard 
deviations in terms of RSV-A/B neutralizing antibody titers, RSVPreF3-specific IgG 
antibody concentrations and the frequency of RSVPreF3-specific CD4+ T cells. 

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Table 19 
Precision and 95% confidence interval on the geometric mean 
antibody titers/concentrations and of the frequency of RSVPreF3-
Specific CD4+ T cells at Month 13 based on different values of 
standard deviations for 276 evaluable participants in the 
RSV_annual group 
Number of enrolled 
participants in the 
humoral and CMI subsets 
in the RSV_annual 
Number of evaluable 
participants in the 
humoral and CMI 
subsets at Month 13 
Standard 
deviation in 
log10 
Width ½ 
95% CI in 
log10 
Ratio 
upper 
limit 95% 
CI/ GM 
Ratio 
upper limit/ 
lower limit 
95% CI 
345 
276 
0.30 
0.036 
1.09 
1.18 
345 
276 
0.35 
0.041 
1.10 
1.21 
345 
276 
0.40 
0.047 
1.11 
1.24 
345 
276 
0.45 
0.053 
1.13 
1.28 
345 
276 
0.50 
0.059 
1.15 
1.31 
Precision estimated using PASS 12.0.10: Confidence interval of a mean, alpha = 5%. 
CI = Confidence Interval, LL = Lower Limit, UL = Upper Limit 
GM = Geometric Mean 
9.2.4. 
Evaluation of humoral and cellular immune response at Month 25 
in the RSV_annual and RSV_flexible revaccination groups 
(secondary objective) (Amended: 01 April 2022) 
At Month 25 (one month post-revaccination at Month 24), the effect of revaccination 
dose will be evaluated. 
As such ~220 participants in the RSV_annual group receiving a revaccination dose of 
RSVPreF3 OA investigational vaccine will be evaluable for the humoral and cellular 
immune response at study Month 25. 
Table 20 shows the precision that can be obtained based on different values of standard 
deviations in terms of RSV-A/B neutralizing antibody titers, RSVPreF3-specific IgG 
antibody concentrations and the frequency of RSVPreF3-specific CD4+ T cells. 
Approximately 211 participants in the RSV_flexible revaccination group receiving a 
revaccination dose of RSVPreF3 OA investigational vaccine will be evaluable for the 
humoral immune response at study Month 25. Table 21 shows the precision that can be 
obtained based on different values of standard deviations in terms of RSV-A/B 
neutralizing antibody titers, RSVPreF3-specific IgG antibody concentrations. 
Approximately 74 participants in the RSV_flexible revaccination group receiving a 
revaccination dose of RSVPreF3 OA investigational vaccine will be evaluable for the 
cellular immune response at study Month 25. Table 22 shows the precision that can be 
obtained based on different values of standard deviations in terms of the frequency of 
RSVPreF3-specific CD4+ T cells. 

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Table 20 
Precision and 95% confidence interval on the geometric mean 
antibody titers/concentrations and of the frequency of 
RSVPreF3-specific CD4+ T cells at Month 25 based on different 
values of standard deviations for 220 evaluable participants in the 
RSV_annual group 
Number of enrolled 
participants in the humoral and 
CMI subsets in the RSV_annual 
Number of evaluable 
participants in the 
humoral and CMI 
subsets at Month 25 
Standard 
deviation 
in log10 
Width ½ 
95% CI in 
log10 
Ratio 
upper 
limit 95% 
CI/GM 
Ratio 
upper limit/ 
lower limit 
95% CI 
276 
220 
0.30 
0.040 
1.10 
1.20 
276 
220 
0.35 
0.047 
1.11 
1.24 
276 
220 
0.40 
0.053 
1.13 
1.28 
276 
220 
0.45 
0.060 
1.15 
1.32 
276 
220 
0.50 
0.066 
1.16 
1.36 
Precision estimated using PASS 12.0.10: Confidence interval of a mean, alpha = 5%. 
CI = Confidence Interval, LL = Lower Limit, UL = Upper Limit 
GM = Geometric Mean 
Table 21 
Precision and 95% confidence interval on the geometric mean 
antibody titers/concentrations at Month 25 based on different values 
of standard deviations for 211 evaluable participants in the 
RSV_flexible revaccination group 
Number of enrolled 
participants in the 
humoral subset in 
the RSV_flexible 
revaccination 
Number of 
evaluable 
participants in the 
humoral subset at 
Month 13 
Number of 
evaluable 
participants in the 
humoral subset at 
Month 25 
Standard 
deviation 
in log10 
Width ½ 
95% CI in 
log10 
Ratio UL 
95% CI / 
GM 
Ratio UL / LL 
95% CI 
330 
264 
211 
0.30 
0.041 
1.10 
1.21 
330 
264 
211 
0.35 
0.047 
1.11 
1.24 
330 
264 
211 
0.40 
0.054 
1.13 
1.28 
330 
264 
211 
0.45 
0.061 
1.15 
1.32 
330 
264 
211 
0.50 
0.068 
1.17 
1.37 
Precision estimated using PASS 2019: Confidence interval for one mean, alpha = 5%. 
CI = Confidence Interval, LL = Lower Limit, UL = Upper Limit; GM = Geometric Mean 
Table 22 
Precision and 95% confidence interval of the frequency of 
RSVPreF3-specific CD4+ T cells at Month 25 based on different 
values of standard deviations for 74 evaluable participants in the 
RSV_flexible revaccination group 
Number of enrolled 
participants in the 
CMI subset in the 
RSV_flexible 
revaccination group 
Number of 
evaluable 
participants in the 
CMI subset at 
Month 13 
Number of 
evaluable 
participants in 
the CMI subset 
at Month 25 
Standard 
deviation 
in log10 
Width ½ 
95% CI in 
log10 
Ratio UL 
95% CI / 
GM 
Ratio UL / LL 
95% CI 
115 
92 
74 
0.30 
0.070 
1.17 
1.38 
115 
92 
74 
0.35 
0.081 
1.21 
1.45 
115 
92 
74 
0.40 
0.093 
1.24 
1.53 
115 
92 
74 
0.45 
0.105 
1.27 
1.62 
115 
92 
74 
0.50 
0.116 
1.31 
1.71 
Precision estimated using PASS 2019: Confidence interval of a mean, alpha = 5%. 
CI = Confidence Interval, LL = Lower Limit, UL = Upper Limit; GM = Geometric Mean 

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9.2.5. 
Evaluation of reactogenicity and safety profile following 
revaccination in the RSV_annual and RSV_flexible revaccination 
groups (Amended: 01 April 2022) 
As indicated in Table 23, the proposed sample sizes of 990 participants in the 
RSV_annual group receiving revaccination on an annual basis and 330 participants in 
the RSV_flexible revaccination group receiving revaccination at Year 2 (Month 24), 
give 99.3% and 80.9% probabilities, respectively, of observing at least one AE if a true 
incidence rate equals 0.5%. This probability increases to 100% for true incidence rates 
0.8% for the RSV_annual group. Although lower, the probability remains above 62% 
to detect at least one AE that would occur at a frequency of 0.1% (1/1000) and 0.3% 
(3/1000) in the RSV_annual and RSV_flexible revaccination groups, respectively. 
Table 23 
Probability (%) to observe at least one AE depending on the AE true 
incidence rate with 990 and 330 participants in the RSV_annual and 
RSV_flexible revaccination groups, respectively 
Incidence rate 
Probability to observe at least one AE in 
the RSV_annual 
Probability to observe at least one AE 
in the RSV_flexible revaccination 
0.01% 
9.4% 
3.2% 
0.05% 
39.1% 
15.2% 
0.10% 
62.9% 
28.1% 
0.15% 
77.4% 
39.1% 
0.20% 
86.2% 
48.3% 
0.25% 
91.6% 
56.2% 
0.30% 
94.9% 
62.9% 
0.35% 
96.9% 
68.6% 
0.40% 
98.1% 
73.4% 
0.50% 
99.3% 
80.9% 
0.60% 
99.7% 
86.3% 
0.70% 
99.9% 
90.2% 
0.80% 
100.0% 
92.9% 
0.90% 
100.0% 
94.9% 
1.00% 
100.0% 
96.4% 
9.3. 
Populations for analyses (Amended: 01 April 2022) 
Table 24 
Populations for analyses (Amended: 01 April 2022) 
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 1 dose of the study intervention. The 
allocation in a group is done in function of the administered intervention. 
Per-Protocol set (PPS) 
All participants who received at least 1 dose of the study intervention to which they 
are randomized and have post-vaccination immunogenicity data, minus 
participants with protocol deviations that lead to exclusion. 
The primary analysis for immunogenicity will be performed on the PPS. If in any study 
group and for at least one visit, the percentage of vaccinated participants with serological 
results excluded from the PPS for immunogenicity is at least 5%, a second analysis will 
be performed on the ES. The immunogenicity analysis will be performed, overall, by sex, 

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by age category (age at Dose 1: ≥ 65 YOA, ≥ 70 YOA, ≥ 80 YOA, 60-69 YOA and 70-
79 YOA), and by region. 
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 the Sections 7.1.2 
(contraindication to subsequent vaccination) or 5.2.1 (medical conditions) or 5.2.2 
(concomitant therapy), he/she may be eliminated from per-protocol analysis. 
Participants may be eliminated from the PPS for immunogenicity if, during the study, 
they incur a condition that has the capability of altering their immune response 
(intercurrent medical condition) or are confirmed to have an alteration of their initial 
immune status. 
9.4. 
Statistical analyses 
The statistical analysis plan (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. 
9.4.1. 
General considerations (Amended: 01 April 2022) 
Analysis of data up to Month 12 will be performed by group (RSV_annual, RSV_flexible 
revaccination and RSV_1dose), and for the 3 groups pooled. For Month 13 and 
Month 18, the analysis will be tabulated for RSV_annual group versus the pooled 
RSV_flexible revaccination and RSV_1dose groups. From Month 25 up to study end, 
the analysis will be performed by group. 
9.4.1.1. 
Demography 
For a given participant and a given demographic variable, missing measurements will not 
be replaced. 
9.4.1.2. 
Immunogenicity (Amended: 01 April 2022) 
• 
Any missing or non-evaluable immunogenicity measurement will not be replaced. 
The descriptive analysis performed for each assay at each timepoint will exclude 
participants with a missing or non-evaluable measurement. This is applicable to the 
standard way of computing geometric mean titers/concentrations (GMTs/GMCs). 
• 
During the computation of GMTs/GMCs from the mixed model, multiple 
imputation (MI) technique will not be applied for any missing immunogenicity 
measurement. This is because the mixed model inherently accounts for the 
missingness, under the assumption that the missing data are missing at random 

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(MAR). Thus, considering that “missing data are MAR” is a reasonable assump-
tion for this descriptive clinical trial, then it is not necessary to perform MI [Rubin, 
1995]. More details about the mixed-effects model have been described in the SAP. 
• 
The 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. 
• 
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) 
value will be given the ULOQ value for the purpose of GMT/GMC calculation. 
• 
The mean geometric increase (MGI) is calculated by the geometric mean of ratios of 
antibody titer/concentrations of each post-primary vaccination timepoint over 
pre-primary vaccination (Day 1). 
More details regarding the handling of numerical serology results will be described in the 
SAP. 
9.4.1.3. 
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, pIMDs 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. 
9.4.2. 
Demographics and participants’ disposition (Amended: 01 April 
2022) 
Descriptive summaries will be performed for each group (RSV_annual, RSV_flexible 
revaccination and RSV_1dose) and overall. The same will be performed in each subset 
(humoral immune subset and CMI subset). 
Demographic/baseline characteristics (age at vaccination in years, sex, race, ethnicity, 
type of residence [CD/LTCF] and smoking status) will be summarized 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 
such as age. 

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The distribution of participants will be tabulated as a whole and per group, for each age 
category, sex, region, and for each subset. 
The number of doses of the study vaccine administered will be tabulated by group and by 
visit. 
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 Per-Protocol (PP) analyses will be tabulated.  
• 
The numbers of participants withdrawn from the study will be tabulated according to 
the reason for withdrawal. 
Participant disposition in the ES and PPS will be reported as a whole and per group. 
The number and percentage of participants using concomitant medication (any 
medication, any antipyretic and any antipyretic taken prophylactically, respectively) 
during the 4-day follow-up period (i.e., on the day of vaccination and 3 subsequent days) 
and during the 30-day follow-up period (i.e., on the day of vaccination and 29 subsequent 
days) will be summarized by group after each vaccine dose and overall, and after the 
revaccination. 
9.4.3. 
Primary endpoints 
9.4.3.1. 
Humoral immune response – up to Month 12 (Amended: 01 April 2022) 
The analysis of the primary vaccination timepoints up to Month 12 will be performed for 
each group and for the 3 groups pooled. For each timepoint with blood sample collection 
for humoral immune response up to Month 12 and for each assay (RSV-A/-B 
neutralization), unless otherwise specified, the following analyses will be performed: 
Within groups evaluation: 
• 
Percentage of participants with antibody titers/concentrations above a positivity 
cut-off and their exact 95% confidence interval (CI) will be tabulated. 
• 
GMTs/GMCs and their 95% CI will be tabulated and represented graphically. 
Furthermore, to account for all the timepoints at which the blood samples are 
collected, a mixed effects model will be fitted, from which the GMTs/GMCs will be 
computed. More details about the mixed model have been defined in the SAP. 
• 
Antibody titers/concentrations will be displayed using reverse cumulative curves. 
• 
The MGI will be tabulated with 95% CI. 

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9.4.4. 
Secondary endpoints 
9.4.4.1. 
Humoral immune response (Amended: 01 April 2022) 
The same analyses as described above for the primary endpoint will be performed for 
ELISA up to Month 12 and for each timepoint with blood sample collection for humoral 
immune response from study Month 13 up to study end and for each assay (ELISA and 
RSV-A/-B neutralization). For Month 13 and Month 18, the analysis will be tabulated 
for RSV_annual group versus the pooled RSV_flexible revaccination and RSV_1dose 
groups. From Month 25 up to study end, the analysis will be performed by group. 
Only the analyses requiring further clarification of the exact timepoints analyzed are 
summarized below: 
Within groups evaluation: 
• 
The MGI, i.e. geometric mean of ratios of antibody titer/concentrations, will be 
tabulated with 95% CI: 
− 
For each post-primary vaccination timepoint (at Months 18, 24, 30 and 36 when 
applicable) over pre-primary vaccination (Day 1), 
− 
For each post-revaccination timepoint over corresponding pre-revaccination 
(Months 12/24) in the RSV_annual group, 
− 
For each post-revaccination timepoint over corresponding pre-revaccination 
(Month 24) in the RSV_flexible revaccination group, 
− 
For 1 month post-revaccination at Month 12 (Month 13) over 1 month 
post-Dose 1 vaccination (Day 31) in RSV_annual group, 
− 
For 1 month post-revaccination at Month 24 (Month 25) over 1 month 
post-revaccination at Month 12 (Month 13) in RSV_annual group. 
− 
For 1 month post-revaccination at Month 24 (Month 25) over 1 month 
post-Dose 1 vaccination (Day 31) in RSV_flexible revaccination group. 
In addition, the following evaluations will be performed: 
• 
The kinetics of GMTs/GMCs will be plotted as a function of time for participants 
with results available at all post-primary vaccination timepoints. 
The immunogenicity analysis will also be performed by age category (age at Dose 1: 
≥65 YOA, ≥70 YOA, ≥80 YOA, 60-69 YOA and 70-79 YOA), by sex and by region. 
9.4.4.2. 
Cell-mediated immune response (Amended: 01 April 2022) 
Within groups evaluation: 
The following parameters will be summarized by group at each timepoint for which 
blood samples are collected, for the 3 groups pooled for timepoints up to study Month 12. 
For Month 13 and Month 18, the analysis will be tabulated for RSV_annual group 
versus the pooled RSV_flexible revaccination and RSV_1dose groups. From Month 25 
up to study end, the analysis will be performed by group using descriptive statistics (N, 
geometric mean, min, Q1, median, Q3, max) in the CMI subset: 

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• 
Frequency of RSVPreF3-specific CD4+ and/or CD8+ T cells expressing at least 
2 activation markers including at least one cytokine among CD40L, 4-1BB, IL-2, 
TNF-, IFN-, IL-13, IL-17, measured by intracellular cytokine staining (ICS) 
using peripheral blood mononuclear cells (PBMCs). 
• 
The kinetics of RSVPreF3-specific CD4+ T cells frequencies will be plotted as a 
function of time for participants with results available at all timepoints. 
• 
Fold increase of the frequency of RSVPreF3-specific CD4+ T cells expressing at 
least 2 activation markers including at least one cytokine among CD40L, 4-1BB, IL-
2, TNF-, IFN-, IL-13, IL-17, measured by ICS, at each post-primary vaccination 
timepoint over pre-vaccination (Day 1), at each post-revaccination over the 
corresponding pre-revaccination (Month 12/Month 24 in the RSV_annual group 
and Month 24 in the RSV_flexible revaccination group) and at one month post-
revaccination over 1 month post-previous dose in the RSV_annual group [one month 
post-revaccination at Month 12 (Month 13) over one month post-Dose 1 
vaccination (Day 31) and one month post-revaccination at Month 24 (Month 25) 
over one month post-revaccination at Month 12 (Month 13)] and in the 
RSV_flexible revaccination group [one month post-revaccination at Month 24 
(Month 25) over one month post-Dose 1 vaccination (Day 31)]. 
The descriptive immunogenicity analysis will also be performed by age category (age at 
Dose 1: ≥ 65 YOA, ≥ 70 YOA, ≥ 80 YOA, 60-69 YOA and 70-79 YOA), by sex and by 
region. 
9.4.4.3. 
Safety analysis (Amended: 01 April 2022) 
Primary vaccination and revaccination dose: 
The safety analysis will be performed on the ES. A descriptive analysis by group, for the 
3 groups pooled up to Month 12, for the RSV_flexible revaccination and RSV_1dose 
groups pooled versus RSV_annual group for Month 13 and Month 18, and by group 
from Month 25 up to study end, will present a summary of: 
• 
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 during the 4-day or 30-day follow-up period will be 
tabulated with exact 95% CI after each dose. The same computations will be done 
for Grade 3 AEs, and for Grade 3 non-serious AEs and for AEs resulting in 
medically attended visit. 
• 
The number and percentage of participants reporting each individual solicited 
administration site event (any grade, Grade 3 and resulting in medically attended 
visit) and solicited systemic event (any grade, Grade 3 and resulting in medically 
attended visit) during the 4-day follow-up period (i.e., on the day of vaccination and 
3 subsequent days) will be tabulated for each group after each dose. 
• 
For fever, the number and percentage of participants reporting fever by half degree 
(°C) cumulative increments during the 4-day follow-up period (i.e., on the day of 
vaccination and 3 subsequent days) will be tabulated for each group after each dose. 

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• 
The incidence of each solicited administration site event and solicited systemic event 
(any grade and Grade 3) will be represented graphically for each group after each 
dose. 
• 
The number and percentage of participants with any unsolicited AEs during the 
30-day follow-up period (i.e., on the day of vaccination and 29 subsequent days) 
with its exact 95% CI will be tabulated for each dose by group and by Medical 
Dictionary for Regulatory Activities (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 verbatim reports of unsolicited AEs 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 the MedDRA Primary SOC, HLT and PTs and reported from Dose 1 up to 6 
months post-Dose 1 and from revaccination dose up to 6 months post-revaccination 
will be tabulated with exact 95% CI. 
• 
The number and percentage of participants with at least one report of causally related 
SAE classified by the MedDRA Primary SOC, HLT and PTs and reported during 
the entire study period will be tabulated with exact 95% CI. 
• 
The same tabulation will be presented for fatal SAEs. 
• 
All SAEs will also be described in detail in a tabular listing. 
• 
All AEs/SAEs leading to study/intervention discontinuation from Dose 1 up to 
study end will be tabulated. 
• 
The number and percentage of participants with at least one report of pIMD 
classified by the MedDRA Primary SOC, HLT and PTs and reported from Dose 1 
up to 6 months post-primary and from revaccination dose up to 6 months 
post-revaccination will be tabulated with exact 95% CI. 
• 
The number and percentage of participants with at least one causally related pIMD 
classified by the MedDRA Primary SOC, HLT and PTs and reported during the 
entire study period will be tabulated with exact 95% CI. 
• 
All pIMDs will also be described in detail in a tabular listing. 
• 
The analyses of unsolicited AEs will include SAEs (unless otherwise specified). 
The analysis of safety will also be performed by age category (age at Dose 1: ≥ 65 YOA, 
≥ 70 YOA, ≥ 80 YOA, 60-69 YOA and 70-79 YOA) and region (North America, 
Europe, Asia). 
9.4.5. 
Tertiary/exploratory endpoints (Amended: 01 April 2022) 
Please refer to the SAP for statistical analyses concerning tertiary endpoints and 
modeling of long-term persistence of post-primary vaccination antibodies (using mixed 
effects models for repeated measurements). 

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9.5. 
Interim analyses 
All analyses will be conducted on final data, as clean as possible. 
9.5.1. 
Sequence of analyses 
9.5.1.1. 
Analyses for objectives and endpoints (Amended: 01 April 2022) 
Analyses to evaluate objectives and endpoints will be performed stepwise: 
• 
Month 6: A first analysis will be performed on all reactogenicity, safety and 
immunogenicity data available and as clean as possible, when data for at least 
primary and secondary endpoints up to Month 6 are available. This analysis will be 
considered as final for those endpoints.  
• 
Month 13: A second analysis will be performed on all reactogenicity, safety and 
immunogenicity data available and as clean as possible, when data for at least 
primary and secondary endpoints up to Month 12 are available for all participants, as 
well as data up to 1 month after the first revaccination (Month 13) in the 
RSV_annual group. This analysis will be considered as final for those endpoints. 
• 
Month 18: A third analysis will be performed on all safety and/or immunogenicity 
data available and as clean as possible, when data for secondary endpoints up to 
Month 18 are available for all participants. This analysis will be considered as final 
for those endpoints. Safety and immunogenicity analysis may be performed at 
different time depending on data availability.  
• 
Month 25: A fourth analysis will be performed on all safety, reactogenicity and 
immunogenicity data available and as clean as possible, when data for at least 
primary and secondary endpoints up to Month 24 are available for all participants, as 
well as data up to 1 month after the second revaccination (Month 25) in the 
RSV_annual group and up to 1 month after the first revaccination (Month 25) in 
the RSV_flexible revaccination group. This analysis will be considered as final for 
those endpoints. 
• 
The final End of Study analysis will be performed when all reactogenicity, safety 
and immunogenicity data for at least primary and secondary endpoints up to study 
conclusion are available (Month 36). 
• 
If the data for tertiary endpoints become available at a later stage, (an) additional 
analysis/analyses will be performed. 
9.5.2. 
Statistical consideration for interim analysis 
All analyses will be conducted on final data (all planned results available for the time-
points of interest) and therefore no statistical adjustment for interim analyses is required. 
9.6. 
Data Monitoring Committee (DMC) 
Not applicable. 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations 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/IEC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 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. 

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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. In 
addition, in case a caregiver is assigned by the participant to help him/her with the study 
procedures, the caregiver must receive an information letter prior to supporting the 
participant, that describes the role and data that will be collected from the caregiver. 
The content of ICF 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.  
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.  

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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. 
Safety oversight will be provided by an unblinded SRT composed of GSK RSV OA 
project team members. 
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 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 (see Glossary of terms for the exact definition of 
essential and 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, eCRF), the copy should fulfill the 
requirements for certified copies (see Glossary of terms for the exact definition of 
certified copies).  

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All participant data relating to the study will be recorded on 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 (see Glossary 
of terms for the exact definition of source documents) that supports information entered 
in the eCRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies. 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data (see Glossary of terms for the exact definition of 
source data).  
Study monitors will perform ongoing source data verification to confirm that data entered 
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.  
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 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 the 
Glossary of terms. 

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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. 
At study or site closure, 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 LSLV for interventional studies and follows 
the guidance from the International Committee of Medical Journal Editors. 
10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
Laboratory assays (Amended: 01 April 2020) 
RSV-A and RSV-B neutralization assays 
The serum neutralization assay is a functional assay that measures the ability of serum 
antibodies to neutralize RSV entry and replication in a host cell line.  
Virus neutralization is performed by incubating a fixed amount of RSV-A strain (Long, 
ATCC No. VR-26) or RSV-B strain (18537, ATCC No. VR-1580) with serial dilutions of 
the test serum. The serum-virus mixture is then transferred onto a monolayer 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 monolayer. Following a fixation step, RSV-infected cells are 
detected using a primary antibody directed against RSV (Polyclonal anti-RSV-A/B IgG) 

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and a secondary antibody conjugated to horse-radish 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 or equivalent). For each serum dilution, a ratio, expressed 
as a percentage, is calculated between the number of plaques at each serum dilution and 
the number of plaques in the virus control wells (no serum added). The serum neutralizing 
antibody 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]. For the testing of phase 3 studies, secondary standards calibrated against the 
international reference (NIBSC 16/284) [McDonald, 2018; McDonald, 2020] will be 
included in every run to allow conversion into international units.  
RSVPreF3 protein IgG ELISA 
Responses to the RSVPreF3 antigen will be evaluated by an indirect ELISA allowing the 
detection and the quantification of antigen-specific IgG 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). 
Intracellular cytokine staining (ICS) 
The ICS is used to assess RSVPreF3-specific CD4+ and/or CD8+ T cells expressing at 
least 2 activation markers including at least one cytokine among CD40L, 4-1BB, IL-2, 
TNF-, IFN-, IL-13, IL-17 (secondary endpoint).  
As previously described [Moris, 2011], thawed peripheral blood mononuclear cells 
(PBMCs) are stimulated in vitro in the presence of anti-CD28 and anti-CD49d antibodies 
either with pools of 15-mer peptides overlapping by 11 amino acids and spanning the 
sequence of the RSVPreF3 protein, or with medium. After 2 hours of incubation at 37C, 
Brefeldin A is added to inhibit cytokine secretion during an additional overnight 
incubation at 37C. Cells are subsequently harvested, stained for surface markers (CD4+ 
and CD8+) and then fixed. Fixed cells are then permeabilized and stained with labeled 
antibodies specific for the following immune markers:  
• 
CD3+: phenotyping T cells; 

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• 
CD40L (CD154), expressed on activated CD4+ T cells, [Chattopadhyay, 2005; 
Frentsch, 2005; Samten, 2000; Stubbe, 2006]; 
• 
IL-2: key for the development, survival and function of T cells [Boyman, 2012]; 
• 
TNF-α: anti-viral/intracellular factor, pro-inflammatory cytokine, cytotoxicity 
[Sedger, 2014]; 
• 
IFN-γ: anti-viral factor, associated with the Th1-like profile [Schoenborn, 2007]; 
• 
4-1BB (CD137), expressed on activated CD4+ and CD8+ T cells [Wölfl, 2008]; 
• 
IL-13: associated with the Th2-like profile [Bao, 2015]; 
• 
IL-17: associated with the Th17-like profile [Korn, 2009]. 
After staining with the markers above, the cellular samples are analyzed by flow-
cytometry allowing to determine the frequency of CD4+ and/or CD8+ T cells expressing 
the marker(s) of interest per million of CD4+ and/or CD8+ T cells. 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting AEs 
10.3.1. 
Definition of an 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). 

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• 
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. 
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 an SAE 
An SAE is any untoward medical occurrence that: 
a. 
Results in death 
b. Is life-threatening 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the participant was at risk of death at the time of the event. It does not refer 
to an event, which hypothetically might have caused death, had it been more 
severe. 
c. 
Requires 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. 

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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  
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: 
Table 25 
Solicited administration site events 
Pain  
Erythema  
Swelling  
b. Solicited systemic events 
The following systemic events will be solicited: 
Table 26 
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 diary card. 

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10.3.4. 
Unsolicited AEs 
An unsolicited AE is an AE 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 
medically attended event(s) during the reporting period for safety information, as well as 
any events that, though not medically attended, are of participant’s concern. Detailed 
information about reported unsolicited AEs will be collected by qualified site personnel 
and documented in the participant’s records. 
Unsolicited AEs that are not medically attended nor perceived as a concern by 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 
10.3.5.1. 
Potential immune-mediated diseases 
pIMDs are a subset of AEs of special interest that include autoimmune diseases and other 
inflammatory and/or neurologic disorders of interest which may or may not have an 
autoimmune etiology. AEs that need to be recorded and reported as pIMDs include those 
listed in the Table 27 (please refer to the 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. 

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Table 27 
List of potential immune-mediated diseases (pIMDs) (Amended: 01 April 2022) 
Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid syndrome 
 
Autoimmune aplastic anemia 
 
Autoimmune hemolytic anemia 
• 
Includes warm antibody hemolytic anemia and cold antibody hemolytic anemia 
Autoimmune lymphoproliferative syndrome (ALPS) 
 
Autoimmune neutropenia  
 
Autoimmune pancytopenia 
 
Autoimmune thrombocytopenia 
• 
Frequently used related terms include: “autoimmune thrombocytopenic purpura”, “idiopathic 
thrombocytopenic purpura (ITP)”, “idiopathic immune thrombocytopenia”, “primary immune 
thrombocytopenia”. 
Evans syndrome 
 
Pernicious anemia 
 
Thrombosis with thrombocytopenia syndrome (TTS) 
 
Thrombotic thrombocytopenic purpura 
• 
Also known as “Moschcowitz-syndrome” or “microangiopathic hemolytic anemia” 
Cardio-pulmonary inflammatory disorders 
Idiopathic Myocarditis/Pericarditis 
Including but not limited to: 
• 
Autoimmune / Immune-mediated myocarditis 
• 
Autoimmune / Immune-mediated pericarditis 
• 
Giant cell myocarditis 
Idiopathic pulmonary fibrosis 
Including but not limited to: 
• 
Idiopathic interstitial pneumonia (frequently used related terms include “Interstitial lung disease”, 
“Pulmonary fibrosis”, “Immune-mediated pneumonitis”) 
• 
Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar proteinosis (PAP) 
• 
Frequently used related terms include: “pulmonary alveolar lipoproteinosis”, “phospholipidosis” 

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Medical Concept 
Additional Notes 
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 

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Medical Concept 
Additional Notes 
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 
 
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 
 

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Medical Concept 
Additional Notes 
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) 

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Medical Concept 
Additional Notes 
Idiopathic cranial nerve palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• 
Cranial nerve neuritis (e.g. Optic neuritis) 
• 
Idiopathic nerve palsies/paresis (e.g. Bell’s palsy) 
• 
Melkersson-Rosenthal syndrome 
• 
Multiple cranial nerve palsies/paresis  
Multiple Sclerosis (MS) 
Includes the following: 
• 
Clinically isolated syndrome (CIS)  
• 
Malignant MS (the Marburg type of MS)  
• 
Primary-progressive MS (PPMS) 
• 
Radiologically isolated syndrome (RIS) 
• 
Relapsing-remitting MS (RRMS) 
• 
Secondary-progressive MS (SPMS) 
• 
Uhthoff's phenomenon  
Myasthenia gravis 
• 
Includes ocular myasthenia and Lambert-Eaton myasthenic syndrome 
Narcolepsy 
• 
Includes narcolepsy with or without presence of unambiguous cataplexy 
Peripheral inflammatory demyelinating neuropathies 
and plexopathies 
Including but not limited to: 
• 
Acute Brachial Radiculitis (also known as Parsonage-Turner Syndrome or neuralgic amyotrophy) 
• 
Antibody-mediated demyelinating neuropathy 
• 
Chronic idiopathic axonal polyneuropathy (CIAP) 
• 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), including atypical CIDP variants 
(e.g. multifocal acquired demyelinating sensory and motor neuropathy also known as Lewis-Sumner 
syndrome) 
• 
Multifocal motor neuropathy (MMN)  
Transverse myelitis (TM) 
• 
Includes acute partial transverse myelitis (APTM) and acute complete transverse myelitis (ACTM) 

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Medical Concept 
Additional Notes 
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 
 

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Medical Concept 
Additional Notes 
Stevens-Johnson Syndrome (SJS) 
Including but not limited to:  
• 
Toxic Epidermal Necrolysis (TEN)  
• 
SJS-TEN overlap 
Sweet’s syndrome 
• 
Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• 
Arteritic anterior ischemic optic neuropathy (AAION or arteritic AION) 
• 
Giant cell arteritis (also called temporal arteritis)  
• 
Takayasu's arteritis  
Medium sized and/or small vessels vasculitis  
Including but not limited to: 
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis (type unspecified)  
• 
Behcet's syndrome  
• 
Buerger’s disease (thromboangiitis obliterans) 
• 
Churg–Strauss syndrome (allergic granulomatous angiitis)  
• 
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)” 

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Medical Concept 
Additional Notes 
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 
 
 

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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 10.3.1 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 
This section is not applicable for the study population. 
10.3.8. 
Recording and follow-up of AEs, SAEs and pIMDs (Amended: 
01 April 2022) 
The participants will be instructed to contact the investigator immediately should they 
manifest any signs or symptoms they perceive as serious.  
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
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 and not the individual signs/symptoms. 
A Paper Diary, hereafter referred to as Participant Diary will be used in this study to 
capture solicited administration site or systemic events and unsolicited AEs. The 
participant should be trained on how and when to complete each field of the Participant 
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 the Glossary of terms for the definition of 
caregiver). 

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Any individual(s) who performs the measurements of administration site or systemic 
events and who will enter the information into the Participant Diary should be trained on 
the use of the Diary; for example, the study caregiver should have received a caregiver 
information letter explaining the role of the caregiver prior to completing the diary card. 
This training must be documented in the participant’s source record. If any other 
individual than the participant is making entries in the Participant Diary (i.e., caregiver), 
their identity should be documented in the participant’s source record. 
• 
Collect and verify completed diary cards during discussion with the participant at 
Day 31 for all groups, and at Month 13 for the RSV_annual group only and 
Month 25 for the RSV_annual and RSV_flexible revaccination groups. 
• 
Any unreturned diary cards will be sought from the participant through telephone 
call(s) or any other convenient procedure. 
The investigator or designee will transcribe the required information into the eCRF in 
English. Refer to the SPM for more information regarding the completion of the paper 
diary. 
10.3.8.1. 
Time period for collecting and recording AEs, SAEs and pIMDs 
All solicited administration site and systemic events that occur during 4 days following 
administration of each dose of study vaccine must be recorded into the appropriate 
section of the eCRF, irrespective of intensity. All unsolicited AEs that occur during 
30 days following administration of each dose of study vaccine must be recorded into the 
appropriate section of the eCRF, irrespective of intensity or whether or not they are 
considered vaccination-related. 
The time period for collecting and recording SAEs and pIMDs will begin at the first 
receipt of study vaccine and will end 6 months after study vaccine administration. 
All SAEs and pIMDs considered related to study vaccination, any fatal SAEs and 
AEs/SAEs leading to withdrawal from the study will be collected and recorded from the 
time of the first receipt of study vaccine until the participant is discharged from the study. 
SAEs related to study participation or to a concurrent GSK medication/vaccine will be 
collected from the time consent is obtained until the participant is discharged from the 
study. 
10.3.8.2. 
Follow-up of AEs, SAEs, pIMDs or any other events of interest 
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 and pIMDs (as defined in the 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. 

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10.3.8.2.1. Follow-up during the study 
AEs (serious or non-serious) or pIMDs documented at a previous visit/contact and 
defined as not recovered/not resolved or recovering/resolving will be reviewed at 
subsequent visits/contact 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. 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 and pIMD information after removal of write access to 
the participant’s eCRF 
When additional SAE or pIMD 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 8.3.3.1 or to GSK Clinical Safety and Pharmacovigilance department within the 
defined reporting timeframes specified in the Table 15. 

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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 28 
Intensity scales for solicited events in adults 
Adults 
Event 
Intensity grade 
Parameter 
Pain at administration site 
0 
None 
1 
Mild: Any pain neither interfering with nor preventing 
normal everyday activities. 
2 
Moderate: Painful when limb is moved and interferes with 
everyday activities. 
3 
Severe: Significant pain at rest. Prevents normal 
everyday activities. 
Erythema at administration site  
Record greatest surface diameter in mm 
Swelling at administration site 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C/°F (with 1 decimal) 
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 
* Refer to Section 1.3 for the definition of fever and the preferred location for temperature measurement. 
The maximum intensity of local administration site erythema/swelling and fever will be 
scored at GSK as follows: 
 
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. 
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 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 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. 

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Possible contributing factors include: 
• 
Medical history. 
• 
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 and unsolicited adverse event 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). 

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10.3.10. 
Reporting of SAEs, pIMDs 
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. 
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 15 for the details on timeframes for reporting of SAEs/pIMD. 
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 (refer to Section 
8.3.3.1 for contact information). 
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. 

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10.4. 
Appendix 4: Country-specific requirements 
10.4.1. 
Requirements for 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 27th 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. 
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. 

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10.4.2. 
Requirements for Germany (Amended: 01 April 2022) 
Explanatory statement concerning gender distribution (Article 7, Paragraph 2 (12) 
of the German GCP order) 
There is no intention to conduct specific analyses investigating the relationship between 
the sex of the participants and the immunogenicity and safety of GSK’s RSVPreF3 OA 
investigational vaccine. The ratio of male to female participants recruited into the study 
RSV OA=ADJ-004 is expected to be in line with the demographics of the population 
aged 60 years and above in the Member state. 
Remote Source Data Verification (rSDV) during exceptional situations in Germany 
Frequent in-stream monitoring of safety data by the central study team at GSK is 
required for this study. In-stream review of study data items and processes should be 
considered during exceptional situations/circumstances, such as with pandemics like 
COVID-19, focusing on key data points, patient assessments and processes that are 
critical to ensure the rights, safety and well-being of study participants and the 
integrity of the study and data. Prior to any rSDV activity, a written agreement by the 
investigator will be obtained. The agreement includes the extent and the method of 
rSDV activities. Monitoring Plan and Study-Specific Risk Register will be updated to 
include rSDV activities and Clinical Research Associates (CRAs) will be guided for the 
conduct of rSDV. 
Option 1: Transfer of redacted source documentation 
Process for transfer and review of redacted source documentation provided by the site: 
• 
The CRA instructs study site on the source data needed for the rSDV activities. 
• 
The CRA instructs site staff that they must pseudonymize the requested 
documentation, do a quality check that anonymized (redacted) areas cannot be 
read, and then delivers the documentation to the CRA in an encrypted form of 
communication (the site should have a documented process). 
• 
The minimum requirements regarding quality of the copies will be agreed with the 
site upfront: 
− 
For the scanning of paper documents resolution will be a minimum of 300 
dots per inch (dpi). 
− 
For the scanning of photographs and images resolution will be 600 dpi 
minimum. 
− 
Color scanners must be able to produce copies that match the original. 
− 
A4 format as final size without loss of information. 
− 
Documents will be saved as portable document format (PDF). 
− 
In order to maintain quality standards, a captured image will not be subjected 
to non-uniform scaling (i.e., sizing) or re-sampling to a lower resolution. 

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• 
Redacted source document scans will be sent to the CRA via email using one of the 
following secure options: 
a. Transport Layer Security (TLS) connection: 
TLS connections are intended to support significant mail flow between GSK and 
external partners in a secure manner. 
b. GSK Secure 
In cases where only a handful of users are communicating or the volume of emails 
is low, the use of GSK secure, the GSK ad hoc message encryption solution is 
recommended. 
c. 
Password-protected PDF attachment 
A password protected scan (PDF) will be attached to an email. The password to 
open the attachment will be send in a separate email. 
• 
The CRA may use the secure email website to assess whether the sites email 
address is secure (i.e., encrypted). 
• 
Prior to starting rSDV, the CRA ensures that the provided documents is complete 
and does not contain any Personal Information (PI). 
− 
In case the CRA detects any PI that has not been redacted, the CRA informs 
the study site and deletes the files (including the Recycle bin). 
− 
A Data Breach must be reported Data Breach Web Report Form. 
• 
Use of an external PC screen is recommended. The CRA will not generate any 
copies from the source data received. 
• 
Source data verification/review will be conducted according to the process outlined 
in the GSK Monitoring Standard Operating Procedure (SOP). 
• 
After completion of SDV activities, the CRA deletes all copies/images of 
participant data received from the site. This includes the deletion of the recycle bin 
and any temporary files. 
• 
A statement confirming that all documents were destroyed will be provided by the 
CRA via email to the site. 
• 
Details of what was monitored remotely will be documented in the appropriate 
section of the Monitoring Visit Report (MVR). 
Option 2: Review of participant’s source documentation remotely 
Process for use of Webcams, WebEx, MS Teams for viewing participant’s source 
documentation remotely: 
• 
The CRA ensures that the site personnel sharing information with GSK have 
authority to do so. 
• 
rSDV activities will be performed exclusively by the assigned site monitor. 

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• 
Prior to conducting any rSDV activities, the CRA ensures that a written informed 
consent, covering the proposed SDV activities, has been signed by the participant. 
• 
For CRAs using GSK laptops, only use GSK-approved video conferencing tools 
(e.g., MS Teams or GSK WebEx). Live image transmission is fully encrypted and 
protected for authorized user. By using these systems, it will be assured that data 
will be viewed only but not transmitted/stored. 
• 
Functional Service Provider (FSP)/local Clinical Research Organization (CRO) 
CRAs not using GSK laptops, only MS Teams via Remote Access Application 
(RAA) may be used for meetings between the CRA and the site. WebEx is not 
permitted from non-GSK laptops. Other tools like FaceTime, WhatsApp or Zoom 
are not permitted since they do not have sufficient encryption features. GSK does 
not have enterprise contract/privacy agreement with these providers. 
• 
Prior to the remote monitoring visit, the CRA instructs study site on the specific 
data needed for the rSDV. 
• 
Source data verification will be conducted according to the process outlined in the 
Monitoring SOP. 
• 
The use of a headset is required; do not use computer audio. 
• 
The CRA does not capture screens or take pictures of screens to ensure we are not 
transferring content outside of clinical sites. 
• 
WebEx or Teams do not store or have access to any data, GSK staff is not allowed 
to make or store any screenshots or save any data which has been shared. 
• 
Details of what was monitored remotely will be documented in the appropriate 
section of the MVR. 
• 
In case of technical malfunctions or if the security of the transmission is no longer 
ensured, we will pause rSDV activities. GSK Issue Management Procedures will be 
initiated. 

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10.5. 
Appendix 5: Abbreviations and glossary of terms 
10.5.1. 
List of abbreviations (Amended: 01 April 2022) 
AE: 
Adverse Event 
AS01E: 
Adjuvant System containing MPL, QS-21 and liposome (25 g MPL 
and 25 g QS-21) 
CD: 
Community Dwelling 
CD40L:  
Cluster of Differentiation 40 Ligand 
CI: 
Confidence Interval 
CLS: 
Clinical Laboratory Sciences 
CMI: 
Cell-Mediated Immunity 
COVID-19: 
Coronavirus Disease 2019 
CRA: 
Clinical Research Associate 
eCRF: 
electronic Case Report Form 
ELISA: 
Enzyme-Linked Immunosorbent Assay 
EoS: 
End of Study 
ES: 
Exposed Set 
GCP: 
Good Clinical Practice 
GMC: 
Geometric Mean Concentration 
GMT: 
Geometric Mean Titer 
GSK: 
GlaxoSmithKline  
HLT: 
High Level Term 
HRP: 
Horse-Radish Peroxidase 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
ICH: 
International Council on Harmonization 
ICS: 
Intracellular Cytokine Staining 
IEC: 
Independent Ethics Committee 

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IFN-: 
Interferon-gamma 
IgG: 
Immunoglobulin G 
IL-2/13/17: 
Interleukin-2/13/17 
IRB: 
Institutional Review Board 
LSLV: 
Last Subject Last Visit 
LTCF: 
Long-Term Care Facility 
MedDRA: 
Medical Dictionary for Regulatory Activities 
MGI: 
Mean Geometric Increase 
PBMC: 
Peripheral Blood Mononuclear Cells 
PI: 
Personal Information 
pIMD: 
Potential Immune-Mediated Disease 
PP: 
Per-Protocol 
PPS: 
Per-Protocol Set 
PT: 
Preferred Term 
QS-21: 
Quillaja saponaria Molina, fraction 21 (Licensed by GSK from 
Antigenics Inc, a wholly owned subsidiary of Agenus Inc., a 
Delaware, USA corporation) 
rSDV: 
remote Source Data Verification 
RSV: 
Respiratory Syncytial Virus 
SAE: 
Serious Adverse Event 
SAP: 
Statistical Analysis Plan 
SBIR: 
Source data Base for Internet Randomization  
SOP: 
Standard Operating Procedure 
SPM: 
Study Procedures Manual 
SRT: 
Safety Review Team 
TNF-: 
Tumor Necrosis Factor-alpha 
US: 
United States 
YOA: 
Years Of Age 

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10.5.2. 
Glossary of terms (Amended: 01 April 2022) 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product.  
An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, 
or disease (new or exacerbated) temporally associated with 
the use of a medicinal product. For marketed medicinal 
products, this also includes failure to produce expected 
benefits (i.e. lack of efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial are kept 
unaware of the intervention assignment in order to reduce 
the risk of biased study outcomes. The level of blinding is 
maintained throughout the conduct of the trial, and only 
when the data are cleaned to an acceptable level of quality 
will appropriate personnel be unblinded or when required 
in case of a serious adverse event. In an open-label study, 
no blind is used. Both the investigator and the participant 
know the identity of the intervention assigned. 
Caregiver: 
A ‘caregiver’ is 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 
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 diaries, receiving phone calls, 
planning study visits, etc.). However, at no time, the 
caregiver should evaluate the participant’s health status 
while answering diaries or make decisions on behalf of the 
participant. 
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. 

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Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrolled participant: 
‘Enrolled’ means a participant’s agreement to participate in 
a clinical study following completion of the informed 
consent process. Potential participants who are screened for 
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. 
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.  
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 
(LTCF): 
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 Harmonization (ICH) 
defines a protocol amendment as: “A written description 
of a change(s) to or formal clarification of a protocol”. 
GSK further details this to include a change to an 
approved protocol that affects the safety of participants, 
scope of the investigation, study design, or scientific 
integrity of the study. 
Randomization: 
Process of random attribution of intervention to 
participants to reduce selection bias. 

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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 1 or more 
investigational sites. 
Site staff: 
Site staff refers to qualified personnel who are trained on 
the study protocol and to whom the investigator has 
delegated significant study-related duties. 
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 (non-serious and serious) reported in addition to 
those solicited during the clinical study. Also, any 
‘solicited’ event with onset outside the specified period of 
follow-up for solicited events will be reported as an 
unsolicited AE. 

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TRADEMARKS 
The following trademarked products are referenced in the present protocol. 
Trademarks of the GSK group of companies 
 
Generic description 
Shingrix 
 
Zoster vaccine (Recombinant, adjuvanted) 
Trademarks not owned by the GSK group of 
companies 
 
Generic description 
TrueBlue peroxidase substrate (SeraCare) 
 
Chromagenic substrate for visualization of horse-
radish peroxidase-labeled reporter reagents 

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10.6. 
Appendix 8: 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 
Protocol 
28 October 2020 
Amendment 1 
01 April 2022 
Detailed description of Protocol Amendment: 
Section 1.3 
Schedule of Activities 
Study visits should preferably be done on site. As of Protocol Amendment 1 
implementation, if deemed necessary, local regulations allow, and quality of study 
procedures is maintained, study visits during the follow-up phases can be done at home 
or at the long-term care facility (LTCF) […]. 
Table 1 
Schedule of activities: RSV_annual 
Type (V = visit, C = contact)** 
V 
[…] 
V/C(7) 
V 
V 
V/C(7) 
V/C 
Notes 
Timepoint 
D1 
[…] 
M18(7) 
M24 
M25 
M30(7) 
M36 
Study participant informed 
consent1 
● 
 
 
 
 
 
 
See Section 10.1.3 for 
details 
Check with participant if he/she will 
appoint a caregiver […] 
O 
 
 
O 
O 
O 
 
See Section 10.1.3 5.2.5 
for details 
[…] 
 
 
 
 
 
 
 
Clinical specimens for laboratory assays 
Blood sampling for antibody 
determination, from HI subset3 
(10 mL) 
● 
 
 
●6 
● 
 
 
 
Blood sampling for CMI, from CMI 
subset3 (25 mL) 
● 
 
 
●6 
● 
 
 
 
[…] 
**Study visits should preferably be done on site. As of Protocol Amendment 1 implementation, if deemed 
necessary, local regulations allow, and quality of study procedures is maintained, study visits during the 
follow-up phases can be done at home or at the LTCF, […] 
[…] 
6 Blood sampling should be performed prior to vaccination (this has been clarified for the vaccination visit 
occurring after implementation of Protocol Amendment 1). 
7 Visits/contacts at Month 18 and Month 30 must not be performed before the 6-month post-vaccination 
timepoint to allow collection of safety data up to at least 6 months after each vaccination for each participant 
(this has been clarified for the vaccination visit occurring after implementation of Protocol Amendment 1). 

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Table 2 
Schedule of activities: RSV_flexible revaccination 
Type (V = visit)** 
V 
[…] 
V 
V 
V(8) 
V 
Notes 
Timepoint 
D1 
[…] M24 M25 M30(8) M36 
Study participant informed consent1 
● 
 
 
 
 
 
See Section 10.1.3 for details 
Check with participant if he/she will 
appoint a caregiver […] 
O 
 
O 
O 
O 
O 
See Section 10.1.3 5.2.5 for details 
[…] 
 
 
 
 
 
 
Check criteria for temporary delay for 
enrolment and vaccination 
O 
 
O 
 
 
 
See Section 7.1.1 for more 
information 
Check contraindications to 
vaccination 
 
 
O 
 
 
 
See Section 7.1.2 for more 
information 
Recording pre-vaccination body 
temperature 
● 
 
● 
 
 
 
See Section 8.2.1.6 for more 
information. The route […] 
History-directed physical examination 
O 
 
O 
 
 
 
See Section 8.2.1.5 for more 
information 
Study group and intervention number 
allocation 
O 
 
 
 
 
 
See Sections 6.3.2 and 6.3.3 for 
more information 
Intervention number allocation for 
subsequent dose 
 
 
O 
 
 
 
See Section 6.3.3 for more 
information 
Recording of administered intervention 
number 
● 
 
● 
 
 
 
The number of each administered 
study intervention must be […] 
Vaccine administration (including 30-
minute […]) 
● 
 
● 
 
 
 
See Section 6.1 for more information 
Blood sampling for antibody 
determination, from all […] 
● 
 
● 
●7 
● 
● 
See Section 8.1.1 for more 
information 
Blood sampling for CMI, from CMI 
subset4 (25 mL) 
● 
 
● 
●7 
● 
● 
See Section 8.1.1 for more 
information 
Recording any concomitant 
medication/vaccination 
● 
 
● 
● 
● 
● 
See Section 6.5 for more information 
Recording any intercurrent medical 
conditions 
● 
 
● 
● 
● 
● 
See Section 9.3.1.1 for more 
information 
Distribution of paper diary cards for 
solicited events […] 
O 
 
O 
 
 
 
See Section 8.2.1.7 for more 
information 
Return of paper diary cards 
 
 
 
O 
 
 
Recording of solicited events (Days 1–4 
post-vaccination) 
● 
 
● 
● 
 
 
See Section 10.3.8 for more 
information 
Recording of unsolicited AEs (Days 1–
30 post-vaccination) 
● 
 
● 
● 
 
 
See Section 10.3.8 for more 
information 
Recording of pIMDs and SAEs5 
● 
 
● 
● 
● 
 
See Section 10.3.8 for more 
information 
Recording of fatal SAEs, SAEs related 
to study vaccination […] 
● 
 
● 
● 
● 
● 
See Section 10.3.8 for more 
information 
Recording AEs/SAEs leading to 
withdrawal from the study 
● 
 
● 
● 
● 
● 
See Section 10.3.8 for more 
information 
Recording of SAEs related to study 
participation, or to […] 
● 
 
● 
● 
● 
● 
See Section 10.3.8 for more 
information 
Study Conclusion 
 
 
 
 
 
● 
See Section 4.4 for more information 
[…] 
**Study visits should preferably be done on site. As of Protocol Amendment 1 implementation, if deemed 
necessary, local regulations allow, and quality of study procedures is maintained, study visits during the 
follow-up phases for the humoral subset can be done at home or at the LTCF, […] 
[…] 
5 Recording of any SAE or any pIMD should only be done in the 6-month post-vaccination period, i.e., from Day 1 to 
Month 6 and from Month 24 to Month 30. 
[…] 

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7 Blood sampling should be performed prior to vaccination (this has been clarified for the revaccination visit 
occurring after implementation of Protocol Amendment 1). 
8 Visits at Month 30 must not be performed before the 6-month post-vaccination timepoint to allow collection 
of safety data up to at least 6 months after each vaccination for each participant (this has been clarified for the 
revaccination visit occurring after implementation of Protocol Amendment 1). 
Table 3 
Schedule of activities: RSV_1dose* 
Type (V = visit)** 
V 
[…] 
Notes 
Timepoint 
D1 
[…] 
Study participant informed consent1 
● 
 
See Section 10.1.3 for details 
Check with participant if he/she will 
appoint a caregiver […] 
 
 
See Section 10.1.3 5.2.5 for details 
[…] 
**Study visits should preferably be done on site. As of Protocol Amendment 1 implementation, if deemed 
necessary, local regulations allow, and quality of study procedures is maintained, study visits during the 
follow-up phases for the humoral subset can be done at home or at the LTCF, […] 
Table 5 
Intervals between study visits for groups RSV_flexible revaccination and 
RSV_1dose 
Interval 
Length of interval 
Allowed interval 
Day 1 → Day 31 
30 days 
30-42 days 
[…] 
[…] 
[…] 
Month 24 → Month 25 2 
30 days 
30-42 days 
Month 24 → Month 30 
180 days 
180-210 1 days 
1 Visit must not be performed before the 6-month post-vaccination timepoint to allow collection of safety data up to at 
least 6 months post-vaccination for each participant. Note that the 6-month safety follow-up following 
revaccination at Month 24 is only applicable for the RSV_flexible revaccination group. 
2 Only applicable for the RSV_flexible revaccination group. 
[…] 

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Section 4.1 
Overall Design 
Figure 1 
Study design overview 
Old figure: 
 

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New figure: 
 
[…] 
Note: For group RSV_annual: Revaccination Year 1 = Month 12; Revaccination Year 2 = Month 24; for group RSV_flexible revaccination: Revaccination Year 2 = Month 24. 
[…] 
**Visit and follow-up of solicited events, unsolicited AEs, SAEs and pIMDs are only applicable for RSV_annual and RSV_flexible revaccination groups. 
***For the RSV_annual group, the same ~345 participants will be part of both the HI and CMI subsets. The remaining ~645 participants […]. 
****For those participants in the RSV_annual group without blood sample collections, visits at Months 6, 18, 30 and 36 may be held through a contact. However, […]. 

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Table 7 
Study groups, intervention and blinding foreseen in the study 
Study 
groups 
Number of 
participants 
Age 
Intervention 
Blinding 
Primary 
vaccination 
Revaccination 
Year 1 (Month 12) 
Revaccination 
Year 2 (Month 24) 
Open 
RSV_annual 
~990 
≥ 60 
years 
RSVPreF3 OA 
investigational 
vaccine 
RSVPreF3 OA 
investigational 
vaccine 
RSVPreF3 OA 
investigational 
vaccine 
X 
RSV_flexible 
revaccination-*- 
~330 
≥ 60 
years 
RSVPreF3 OA 
investigational 
vaccine 
(none) 
RSVPreF3 OA 
investigational 
vaccine 
X 
[…] 
[…] 
[…] 
[…] 
[…] 
[…] 
[…] 
*Based on immunogenicity data from this study and efficacy results from the Phase 3 study RSV OA=ADJ-006, a 
revaccination might be decided for this group. 
Section 4.2 
Scientific rationale for study design 
[…] 
For that reason, the study is designed not only to evaluate the safety, the reactogenicity, 
the immunogenicity profile and the long-term persistence of the immune response […]: 
• 
RSV_flexible revaccination group will receive the first dose (Dose 1) at Day 1. 
A revaccination dose will be given whenever a revaccination would be needed, based 
on immunogenicity data from this study and efficacy results from the Phase 3 study 
RSV OA=ADJ-006, which will assess the efficacy, immunogenicity and safety of a 
single dose of the RSVPreF3 OA investigational vaccine in adults aged 60 years and 
above 24 months post-Dose 1. Immunogenicity data from other studies using the 
same study intervention showed that following a two-dose vaccination schedule 
(0-2-month schedule), the immune response gradually declines over time but 
remains above baseline value up to 18 months post-Dose 2 and that a 
re-vaccination at 18 months post-Dose 2 (i.e., 20 months post-Dose 1) induced 
humoral and cellular immune responses. 
Section 6.1 
Study interventions administered 
Table 8 
Study intervention administered 
Study intervention name: 
RSVPreF3 OA interventional vaccine 
[…] 
[…] 
Number of doses to be 
administered: 
RSV_annual: 3 doses 
RSV_flexible revaccination: 1 2 doses 
RSV_1dose: 1 dose 
Section 6.4 
Study intervention compliance 
When participants are dosed, they will receive Study intervention will be administered to 
the participants directly from the investigator or designee, […] 

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Section 6.5 
Concomitant therapy 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medication including vaccines/products, except vitamins and dietary 
supplements, administered during the period of 30 days post each vaccine dose 
(Day 1 to Day 31 for all groups, Month 12 to Month 12 + 30 days for the 
RSV_annual group and Month 24 to Month 24 + 30 days for the RSV_annual and 
RSV_flexible revaccination groups). 
• 
[…] 
• 
Any prophylactic medication (e.g., analgesics, antipyretics) administered on the day 
of study vaccination (Day 1 for all groups; Month 12 for the RSV_annual group and 
Month 24 for the RSV_annual and RSV_flexible revaccination groups) and in the 
absence of ANY symptom and in anticipation of a reaction to the vaccination. 
Table 10 
Timing of collection of concomitant medication 
 
Day 1 
 
Month 24 
Month 24 + 
30 days 
Study 
conclusion 
All concomitant medication including 
vaccines/products, except vitamins and dietary 
supplements 
 
 
RSV_annual and 
RSV_flexible 
revaccination only 
RSV_annual and 
RSV_flexible 
revaccination only
 
All concomitant medication […] SAE/pIMD 
 
 
 
 
 
Any prophylactic medication 
 
 
RSV_annual and 
RSV_flexible 
revaccination only 
 
 
All concomitant medications including 
vaccines/products leading to discontinuation […] 
 
 
 
 
 
Section 7.1.2 Contraindications to subsequent vaccine administration 
Participants in the RSV_annual and RSV_flexible revaccination groups must be 
evaluated to confirm they are eligible for subsequent vaccination before administering 
each additional study vaccine dose. 
Section 8 
Study assessments and procedures 
[…] 
• 
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 […]. 
*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 […] at a site other than the 
designated study site. Refer to European Medicines Agency (EMA) Guidance on the Management of 
Clinical Trials during the COVID-19 (Coronavirus) pandemic (version 2 5, 27 March, 2020 10 
February 2022) and to the Food and Drug Administration Guidance on Conduct of Clinical Trials 
of Medical Products During the COVID-19 Public Health Emergency (updated 30 August 2021) 
for more details. 

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Section 8.1.1 Biological samples 
Table 11 
Biological samples 
Sample type 
Quantity 
Unit 
Timepoint 
Subset name* 
Blood for humoral 
immune response 
10 
mL 
Day 1 
[…] 
Month 25*** 
HI subset 
Blood for CMI 
25 
mL 
Day 1 
[…] 
Month 25*** 
CMI subset 
[…] 
***Only applicable for the RSV_annual and RSV_flexible revaccination groups 
The approximate overall volume that will be collected per participant during the entire 
3-year study period is as follows: 
Group 
Participant 
subset 
Number of 
participants 
Total volume of blood 
Notes 
RSV_annual group 
HI subset 
~345 
10x10 mL = ~100 mL 
The same ~345 participants 
will be part of both […] 
CMI subset 
~345 
10x25 mL = ~250 mL 
RSV_flexible 
revaccination group 
All participants 
~330 
8 9x10 mL = ~80 90 mL 
 
CMI subset 
~115 
8 9x25 mL = ~200 225 mL 
RSV_1dose 
[…] 
[…] 
[…] 
 
Section 8.1.3 Immunological read-outs 
Table 13 
Immunological read-outs 
Blood sampling timepoint 
Subset 
name 
No. 
participants 
Component 
Components 
priority rank 
Type of contact and 
timepoint 
Sampling 
timepoint 
Humoral immunity (on serum samples) 
Day 1 
Pre-Vacc 
Humoral 
immunity 
subset 
~1005 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
[…] 
[…] 
[…] 
[…] 
[…] 
[…] 
Month 25-1- 2 
Month 25-1- 2 
Humoral 
immunity 
subset 
~345 675 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody 
2 
RSVPreF3-specific IgG antibody 
3 
Cell-mediated immunity (on PBMC samples) 
Day 1 
Pre-Vacc 
CMI subset 
~575 
IL-2, CD40L, TNF-, IFN-, […] 
- 
[…] 
[…] 
[…] 
[…] 
[…] 
[…] 
Month 25-1- 2 
Month 25-1- 2 
CMI subset 
~345 460 
IL-2, CD40L, TNF-, IFN-, IL-13, 
IL-17 or 4-1BB secreting CD4+ 
and CD8+ T cells 
- 
[…] 
2 Only applicable for the RSV_annual and RSV_flexible revaccination groups. 

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Section 8.3.3.1 
Contact information for reporting of SAEs and pIMDs 
Table 16 
Contact information for reporting of SAEs and pIMDs 
Study contact for questions regarding SAEs and pIMDs 
Refer to the local study contact information document 
GSK Clinical Safety & Pharmacovigilance 
[…] 
Email address: Rix.CT-safety-vac@gsk.com ogm28723@gsk.com 
Section 9.2 
Sample size determination 
[…] 
The proposed sample size is based on the following considerations: 
• 
Ensure a sufficient number of participants to evaluate with adequate precision […] 
but also the immunogenicity after revaccination (based on RSV_annual and 
RSV_flexible revaccination groups only). 
• 
[…] 
Approximately 345 participants will be enrolled in the humoral subset in the RSV_annual 
group and approximately 330 participants per group in the RSV_flexible revaccination 
and RSV_1dose groups. […]. A total of 990 and 330 participants will be enrolled in the 
RSV_annual and RSV_flexible revaccination groups, respectively, for evaluation of 
reactogenicity and safety profile following revaccination. 
Section 9.2.4 Evaluation of humoral and cellular immune response at Month 25 in 
the RSV_annual and RSV_flexible revaccination groups (secondary objective) 
[…] 
Approximately 211 participants in the RSV_flexible revaccination group receiving a 
revaccination dose of RSVPreF3 OA investigational vaccine will be evaluable for the 
humoral immune response at study Month 25. Table 21 shows the precision that can be 
obtained based on different values of standard deviations in terms of RSV-A/B 
neutralizing antibody titers, RSVPreF3-specific IgG antibody concentrations. 
Approximately 74 participants in the RSV_flexible revaccination group receiving a 
revaccination dose of RSVPreF3 OA investigational vaccine will be evaluable for the 
cellular immune response at study Month 25. Table 22 shows the precision that can be 
obtained based on different values of standard deviations in terms of the frequency of 
RSVPreF3-specific CD4+ T cells. 
[…] 

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Table 21 
Precision and 95% confidence interval on the geometric mean antibody 
titers/concentrations at Month 25 based on different values of standard deviations for 
211 evaluable participants in the RSV_flexible revaccination group 
Number of enrolled 
participants in the 
humoral subset in 
the RSV_flexible 
revaccination 
Number of 
evaluable 
participants in the 
humoral subset at 
Month 13 
Number of 
evaluable 
participants in the 
humoral subset at 
Month 25 
Standard 
deviation 
in log10 
Width ½ 
95% CI in 
log10 
Ratio 
upper limit 
95% CI / 
GM 
Ratio upper 
limit / lower 
limit 95% CI 
330 
264 
211 
0.30 
0.041 
1.10 
1.21 
330 
264 
211 
0.35 
0.047 
1.11 
1.24 
330 
264 
211 
0.40 
0.054 
1.13 
1.28 
330 
264 
211 
0.45 
0.061 
1.15 
1.32 
330 
264 
211 
0.50 
0.068 
1.17 
1.37 
Precision estimated using PASS 2019: Confidence interval for one mean, alpha = 5%. 
CI = Confidence Interval, LL = Lower Limit, UL = Upper Limit; GM = Geometric Mean 
Table 22 
Precision and 95% confidence interval of the frequency of 
RSVPreF3-specific CD4+ T cells at Month 25 based on different values of standard 
deviations for 74 evaluable participants in the RSV_flexible revaccination group 
Number of enrolled 
participants in the 
CMI subset in the 
RSV_flexible 
revaccination group 
Number of 
evaluable 
participants in the 
CMI subset at 
Month 13 
Number of 
evaluable 
participants in 
the CMI subset 
at Month 25 
Standard 
deviation 
in log10 
Width ½ 
95% CI in 
log10 
Ratio 
upper limit 
95% CI / 
GM 
Ratio upper 
limit / lower 
limit 95% CI 
115 
92 
74 
0.30 
0.070 
1.17 
1.38 
115 
92 
74 
0.35 
0.081 
1.21 
1.45 
115 
92 
74 
0.40 
0.093 
1.24 
1.53 
115 
92 
74 
0.45 
0.105 
1.27 
1.62 
115 
92 
74 
0.50 
0.116 
1.31 
1.71 
Precision estimated using PASS 2019: Confidence interval of a mean, alpha = 5%. 
CI = Confidence Interval, LL = Lower Limit, UL = Upper Limit; GM = Geometric Mean 
Section 9.2.5 Evaluation of reactogenicity and safety profile following revaccination 
in the RSV_annual and RSV_flexible revaccination groups 
As indicated in Table 23, the proposed sample sizes of 990 participants in the 
RSV_annual group receiving revaccination on an annual basis and 330 participants in 
the RSV_flexible revaccination group receiving revaccination at Year 2 (Month 24), 
gives 99.3% and 80.9% probabilities, respectively, of observing at least one AE if a true 
incidence rate equals 0.5%. This probability increases to 100% for true incidence rates 
0.8% for the RSV_annual group. Although lower, the probability remains above 62% 
to detect at least one AE that would occur at a frequency of 0.1% (1/1000) and 0.3% 
(3/1000) in the RSV_annual and RSV_flexible revaccination groups, respectively. 

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Table 23 
Probability (%) to observe at least one AE depending on the AE true 
incidence rate with 990 and 330 participants in the RSV_annual and RSV_flexible 
revaccination groups, respectively 
Incidence rate 
Probability to observe at least one AE in 
the RSV_annual 
Probability to observe at least one AE 
in the RSV_flexible revaccination 
0.01% 
9.4% 
3.2% 
0.05% 
39.1% 
15.2% 
0.10% 
62.9% 
28.1% 
0.15% 
77.4% 
39.1% 
0.20% 
86.2% 
48.3% 
0.25% 
91.6% 
56.2% 
0.30% 
94.9% 
62.9% 
0.35% 
96.9% 
68.6% 
0.40% 
98.1% 
73.4% 
0.50% 
99.3% 
80.9% 
0.60% 
99.7% 
86.3% 
0.70% 
99.9% 
90.2% 
0.80% 
100.0% 
92.9% 
0.90% 
100.0% 
94.9% 
1.00% 
100.0% 
96.4% 
Section 9.3 
Population for analyses 
Table 24 
Populations for analyses 
Analysis set 
Description 
[…] 
[…] 
Per-Protocol set (PPS) 
All participants who received at least 1 dose of the study intervention to which they 
are randomized and have post-vaccination immunogenicity data, minus […] 
The primary analysis for immunogenicity will be performed on the PPS. If in any study 
group and for at least one visit, the percentage of vaccinated participants with serological 
results excluded from the PPS for immunogenicity is at least 10 5%, a second analysis 
will be performed […]. 
Section 9.4.1 General considerations 
Analysis of data up to Month 12 will be performed by group (RSV_annual, RSV_flexible 
revaccination and RSV_1dose), and for the 3 groups pooled. From For Month 13 and 
Month 18, the analysis will be tabulated for RSV_annual group versus the pooled 
RSV_flexible revaccination and RSV_1dose groups. From Month 25 up to study end, 
the analysis will be performed by group, at applicable timepoints. 

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Section 9.4.1.2 
Immunogenicity 
• 
Any missing or non-evaluable immunogenicity […]. This is applicable to the 
standard way of computing geometric mean titers/concentrations (GMTs/GMCs). 
• 
During the computation of GMTs/GMCs from the mixed model, multiple 
imputation (MI) technique will not be applied for any missing immunogenicity 
measurement. This is because the mixed model inherently accounts for the 
missingness, under the assumption that the missing data are missing at random 
(MAR). Thus, considering that “missing data are MAR” is a reasonable assump-
tion for this descriptive clinical trial, then it is not necessary to perform MI [Rubin, 
1995]. More details about the mixed-effects model have been described in the SAP. 
Section 9.4.2 Demographics and participants’ disposition 
[…] 
The distribution of participants will be tabulated as a whole and per group, for each age 
category, sex, region, and for each subset. 
The number of doses of the study vaccine administered will be tabulated by group and by 
visit. 
Withdrawal status will be summarized by group using descriptive statistics: 
• 
[…] 
• 
The numbers of withdrawn participants withdrawn from the study will be tabulated 
according to the reason for withdrawal. 
Participant disposition in the ES and PPS will be reported as a whole and per group, and 
for each age category. 
Section 9.4.3.1 
Humoral immune response – up to Month 12 
[…] 
Within groups evaluation: 
• 
[…] 
• 
GMTs/GMCs and their 95% CI will be tabulated and represented graphically. 
Furthermore, to account for all the timepoints at which the blood samples are 
collected, a mixed effects model will be fitted, from which the GMTs/GMCs will be 
computed. More details about the mixed model have been defined in the SAP. 
• 
[…] 
• 
Individual post-vaccination results (at Days 31 and at Months 6 and 12) versus 
pre-vaccination results (Day 1) will be plotted using scatter plots.  
• 
Distribution of the fold increase of the antibody titers/concentrations (post- over 
pre-primary vaccination titers) will be tabulated. 

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Section 9.4.4.1 
Humoral immune response 
The same analyses as described above for the primary endpoint […] (ELISA and 
RSV-A/-B neutralization). The analysis of the post-primary vaccination timepoints from 
study Month 13 up to study end will be performed for each group and for the pooled 
RSV_flexible revaccination and RSV_1dose groups. For Month 13 and Month 18, the 
analysis will be tabulated for RSV_annual group versus the pooled RSV_flexible 
revaccination and RSV_1dose groups. From Month 25 up to study end, the analysis 
will be performed by group. 
Within groups evaluation: 
• 
The MGI, i.e. geometric mean of ratios of antibody titer/concentrations, […]: 
− 
[…], 
− 
For each post-revaccination timepoint over corresponding pre-revaccination 
(Month 24) in the RSV_flexible revaccination group, 
− For 1 month post-revaccination at Month 24 (Month 25) over 1 month post 
Dose 1 vaccination (Day 31) in RSV_flexible revaccination group. 
• 
Individual post-primary vaccination results (at Months 18, 24, 30 and 36 when 
applicable) versus pre-vaccination results (Day 1) by group and individual 
post-revaccination results versus the corresponding pre-revaccination results 
(Months 12/24) in the RSV_annual group will be provided using scatter plots. 
• 
Distribution of the fold increase of the antibody titers/concentrations (post- over pre-
primary vaccination dose, post- over the corresponding pre-revaccination and 1 
month post-revaccination over 1 month post-previous dose) will be tabulated when 
applicable. 
• 
The ratio of fold increase (pre to post-vaccination) of anti-RSVPreF3-specific 
antibody concentrations over the fold increase (pre to post-vaccination) of anti-RSV-
A/-B neutralizing antibody titers will be tabulated using descriptive statistics and 
displayed graphically using scatter plots. 
Section 9.4.4.2 
Cell-mediated immune response 
Within groups evaluation: 
The following parameters will be summarized by […] up to study Month 12,. For Month 
13 and Month 18, the analysis will be tabulated for RSV_annual group versus the 
pooled RSV_flexible revaccination and RSV_1dose groups. From Month 25 up to 
study end, the analysis will be performed by group for the pooled RSV_flexible 
revaccination and RSV_1dose from study Month 13 up to study end using descriptive 
statistics (N, geometric mean, min, Q1, median, Q3, max) in the CMI subset: 
• 
Frequency of RSVPreF3-specific CD4+ […], IL-17, measured by intracellular 
cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs). 
• 
The kinetics of RSVPreF3-specific CD4+ and/or CD8+ T cells frequencies will be 
plotted as a function of time for participants with results available at all primary 
vaccination timepoints. 

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• 
Fold increase of the frequency of RSVPreF3-specific CD4+ and/or CD8+ T cells 
expressing at least 2 activation markers […] IL-17, measured by ICS, at each post-
primary vaccination timepoint over pre-vaccination (Day 1) by group, at each post-
revaccination over the corresponding pre-revaccination (Month 12/Month 24) in the 
RSV_annual group and Month 24 in the RSV_flexible revaccination group) and at 
one month post-revaccination over 1 month post-previous dose in the RSV_annual 
group [one month post-revaccination at Month 12 (Month 13) over one month 
post-Dose 1 vaccination (Day 31) and one month post-revaccination at Month 24 
(Month 25) over one month post-revaccination at Month 12 (Month 13)] and in 
the RSV_flexible revaccination group [one month post-revaccination at Month 24 
(Month 25) over one month post-Dose 1 vaccination (Day 31)]. 
Section 9.4.4.3 
Safety analysis 
Primary vaccination and revaccination dose: 
The safety analysis will be performed on the ES. A descriptive analysis by group, […] 
versus RSV_annual group for Month 13 and Month 18, and by group from Month 25 
up to study end, from study Month 13 up to study end will present a summary of: 
• 
[…] 
• 
In addition, the prevalence of each solicited administration site event and solicited 
systemic event (any grade and Grade 3) will be represented graphically over time for 
each group after each dose. 
• 
[…] 
• 
The number and percentage of participants with any unsolicited AEs […] 
(MedDRA) Primary System Organ Class (SOC), High Level Term (HLT) and 
Preferred Term (PT). Similar tabulation […]. 
• 
The number and percentage of participants with at least one report of SAE classified 
by the MedDRA Primary SOC, HLT and PTs and reported from Dose 1 […]. 
• 
The number and percentage of participants with at least one report of causally related 
SAE classified by the MedDRA Primary SOC, HLT and PTs and reported […]. 
• 
All SAEs will also be described in detail in a tabular listing. 
• 
All AEs/SAEs leading to study/intervention discontinuation from Dose 1 up to 
study end will be tabulated. 
• 
The number and percentage of participants with at least one report of pIMD 
classified by the MedDRA Primary SOC, HLT and PTs and reported […]. 
• 
The number and percentage of participants with at least one causally related pIMD 
classified by the MedDRA Primary SOC, HLT and PTs and reported […]. 
• 
All pIMDs will also be described in detail in a tabular listing. 
• 
The analyses of unsolicited AEs will include SAEs (unless otherwise specified). 

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The analysis of safety will also be performed by age category (age at Dose 1: ≥ 65 YOA, 
≥ 70 YOA, ≥ 80 YOA, 60-69 YOA and 70-79 YOA) and region (North America, 
Europe, Asia). 
9.4.5 Tertiary/exploratory endpoints 
Please refer to the SAP for statistical analyses concerning tertiary endpoints and 
modeling of long-term persistence of post-primary vaccination antibodies (using mixed 
effects models for repeated measurements). 
Section 9.5.1.1 
Analyses for objectives and endpoints 
Analyses to evaluate objectives and endpoints will be performed stepwise: 
• 
Month 6: A first analysis* will be performed on all reactogenicity, […]. 
*Note: the analysis at Month 6 may be merged with the analysis at the subsequent 
timepoint. 
• 
Month 25: A fourth analysis will be performed on all safety, […], as well as data up 
to 1 month after the second revaccination (Month 25) in the RSV_annual group and 
up to 1 month after the first revaccination (Month 25) in the RSV_flexible 
revaccination group. This analysis will be considered as final for those endpoints. 
Section 10.2.1  
Laboratory assays 
RSV-A and RSV-B neutralization assays 
The serum neutralization assay is a functional assay that measures the ability of serum 
antibodies to neutralize RSV entry and replication in a host cell line. 
Virus neutralization is performed by incubating a fixed amount of RSV-A strain (Long, 
ATCC No. VR-26) or RSV-B strain (18537, ATCC No. VR-1580) with serial dilutions of 
[…]. For the testing of phase 3 studies, secondary standards calibrated against the 
international reference (NIBSC 16/284) [McDonald, 2018; McDonald, 2020] will be 
included in every run to allow conversion into international units. 

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Section 10.3.5.1 
Potential immune-mediated diseases 
Table 27 
List of potential immune-mediated diseases (pIMDs) 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• 
Cranial nerve neuropathy, including paralysis and 
paresis (e.g. Bell’s palsy). 
• 
Optic neuritis. 
• 
Multiple sclerosis. 
• 
Transverse myelitis. 
• 
Guillain-Barré syndrome, including Miller Fisher 
syndrome and other variants. 
• 
Acute disseminated encephalomyelitis, including 
site specific variants e.g.: non-infectious 
encephalitis, encephalomyelitis, myelitis, 
myeloradiculoneuritis. 
• 
Myasthenia gravis, including Lambert-Eaton 
myasthenic syndrome. 
• 
Demyelinating peripheral neuropathies including: 
• 
Chronic inflammatory demyelinating 
polyneuropathy,  
• 
Multifocal motor neuropathy  
• 
Polyneuropathies associated with monoclonal 
gammopathy. 
• 
Narcolepsy. 
• 
Systemic lupus erythematosus and associated 
conditions 
• 
Systemic scleroderma (Systemic sclerosis), 
including: 
• 
Diffuse Scleroderma 
• 
CREST syndrome 
• 
Idiopathic inflammatory myopathies, including: 
• 
Dermatomyositis  
• 
Polymyositis  
• 
Anti-synthetase syndrome. 
• 
Rheumatoid Arthritis and associated conditions 
including:  
• 
Juvenile Idiopathic Arthritis 
• 
Still’s disease. 
• 
Polymyalgia rheumatica. 
• 
Spondyloarthropathies, including:  
• 
Ankylosing Spondylitis,  
• 
Reactive Arthritis (Reiter’s Syndrome), 
• 
Undifferentiated Spondyloarthritis, 
• 
Psoriatic Arthritis, 
• 
Enteropathic arthritis. 
• 
Relapsing Polychondritis. 
• 
Mixed Connective Tissue disorder. 
• 
Gout. 
• 
Psoriasis. 
• 
Vitiligo. 
• 
Erythema nodosum. 
• 
Autoimmune bullous skin diseases 
(including pemphigus, pemphigoid and 
dermatitis herpetiformis). 
• 
Lichen planus. 
• 
Sweet’s syndrome. 
• 
Localized Scleroderma (Morphea). 

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Vasculitis 
Blood disorders 
Others 
• 
Large vessels vasculitis including:  
• 
Giant Cell Arteritis (Temporal Arteritis), 
• 
Takayasu’s Arteritis.  
• 
Medium sized and/or small vessels vasculitis 
including:  
• 
Polyarteritis nodosa, 
• 
Kawasaki’s disease,  
• 
Microscopic Polyangiitis,  
• 
Wegener’s Granulomatosis (granulomatosis with 
polyangiitis),  
• 
Churg–Strauss syndrome (allergic granulomatous 
angiitis or eosinophilic granulomatosis with 
polyangiitis),  
• 
Buerger’s disease (thromboangiitis obliterans),  
• 
Necrotizing vasculitis (cutaneous or systemic),  
• 
Anti-neutrophil cytoplasmic antibody (ANCA) 
positive vasculitis (type unspecified), 
• 
Henoch-Schonlein purpura (IgA vasculitis),  
• 
Behcet’s syndrome, 
• 
Leukocytoclastic vasculitis. 
• 
Autoimmune hemolytic anemia. 
• 
Autoimmune thrombocytopenia. 
• 
Antiphospholipid syndrome. 
• 
Pernicious anemia. 
• 
Autoimmune aplastic anemia. 
• 
Autoimmune neutropenia. 
• 
Autoimmune pancytopenia. 
• 
Autoimmune glomerulonephritis including: 
• 
IgA nephropathy,  
• 
Glomerulonephritis rapidly progressive,  
• 
Membranous glomerulonephritis,  
• 
Membranoproliferative glomerulonephritis,  
• 
Mesangioproliferative glomerulonephritis.  
• 
Tubulointerstitial nephritis and uveitis 
syndrome. 
• 
Ocular autoimmune diseases including: 
• 
Autoimmune uveitis  
• 
Autoimmune retinitis. 
• 
Autoimmune myocarditis. 
• 
Sarcoidosis. 
• 
Stevens-Johnson syndrome. 
• 
Sjögren’s syndrome. 
• 
Alopecia areata. 
• 
Idiopathic pulmonary fibrosis. 
• 
Goodpasture syndrome. 
• 
Raynaud’s phenomenon. 
Liver disorders 
Gastrointestinal disorders 
Endocrine disorders 
• 
Autoimmune hepatitis. 
• 
Primary biliary cirrhosis. 
• 
Primary sclerosing cholangitis. 
• 
Autoimmune cholangitis. 
• 
Inflammatory Bowel disease, including: 
• 
Crohn’s disease,  
• 
Ulcerative colitis,  
• 
Microscopic colitis,  
• 
Ulcerative proctitis. 
• 
Celiac disease. 
• 
Autoimmune pancreatitis. 
• 
Autoimmune thyroiditis (Hashimoto 
thyroiditis). 
• 
Grave’s or Basedow’s disease. 
• 
Diabetes mellitus type I. 
• 
Addison’s disease. 
• 
Polyglandular autoimmune syndrome. 
• 
Autoimmune hypophysitis. 
 

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Medical Concept 
Additional Notes 
Blood disorders and coagulopathies 
Antiphospholipid syndrome 
 
Autoimmune aplastic anemia 
 
Autoimmune hemolytic anemia 
• 
Includes warm antibody hemolytic anemia and cold antibody hemolytic anemia 
Autoimmune lymphoproliferative syndrome (ALPS) 
 
Autoimmune neutropenia  
 
Autoimmune pancytopenia 
 
Autoimmune thrombocytopenia 
• 
Frequently used related terms include: “autoimmune thrombocytopenic purpura”, “idiopathic 
thrombocytopenic purpura (ITP)”, “idiopathic immune thrombocytopenia”, “primary immune 
thrombocytopenia”. 
Evans syndrome 
 
Pernicious anemia 
 
Thrombosis with thrombocytopenia syndrome (TTS) 
 
Thrombotic thrombocytopenic purpura 
• 
Also known as “Moschcowitz-syndrome” or “microangiopathic hemolytic anemia” 
Cardio-pulmonary inflammatory disorders 
Idiopathic Myocarditis/Pericarditis 
Including but not limited to: 
• 
Autoimmune / Immune-mediated myocarditis 
• 
Autoimmune / Immune-mediated pericarditis 
• 
Giant cell myocarditis 
Idiopathic pulmonary fibrosis 
Including but not limited to: 
• 
Idiopathic interstitial pneumonia (frequently used related terms include “Interstitial lung disease”, 
“Pulmonary fibrosis”, “Immune-mediated pneumonitis”) 
• 
Pleuroparenchymal fibroelastosis (PPFE) 
Pulmonary alveolar proteinosis (PAP) 
• 
Frequently used related terms include: “pulmonary alveolar lipoproteinosis”, “phospholipidosis” 

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Additional Notes 
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 

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Additional Notes 
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 
 
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 
 

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Additional Notes 
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) 

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Additional Notes 
Idiopathic cranial nerve palsies/paresis and 
inflammations (neuritis) 
Including but not limited to: 
• 
Cranial nerve neuritis (e.g. Optic neuritis) 
• 
Idiopathic nerve palsies/paresis (e.g. Bell’s palsy) 
• 
Melkersson-Rosenthal syndrome 
• 
Multiple cranial nerve palsies/paresis  
Multiple Sclerosis (MS) 
Includes the following: 
• 
Clinically isolated syndrome (CIS)  
• 
Malignant MS (the Marburg type of MS)  
• 
Primary-progressive MS (PPMS) 
• 
Radiologically isolated syndrome (RIS) 
• 
Relapsing-remitting MS (RRMS) 
• 
Secondary-progressive MS (SPMS) 
• 
Uhthoff's phenomenon  
Myasthenia gravis 
• 
Includes ocular myasthenia and Lambert-Eaton myasthenic syndrome 
Narcolepsy 
• 
Includes narcolepsy with or without presence of unambiguous cataplexy 
Peripheral inflammatory demyelinating neuropathies 
and plexopathies 
Including but not limited to: 
• 
Acute Brachial Radiculitis (also known as Parsonage-Turner Syndrome or neuralgic amyotrophy) 
• 
Antibody-mediated demyelinating neuropathy 
• 
Chronic idiopathic axonal polyneuropathy (CIAP) 
• 
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), including atypical CIDP variants 
(e.g. multifocal acquired demyelinating sensory and motor neuropathy also known as Lewis-Sumner 
syndrome) 
• 
Multifocal motor neuropathy (MMN)  
Transverse myelitis (TM) 
• 
Includes acute partial transverse myelitis (APTM) and acute complete transverse myelitis (ACTM) 

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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 
 

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Stevens-Johnson Syndrome (SJS) 
Including but not limited to:  
• 
Toxic Epidermal Necrolysis (TEN)  
• 
SJS-TEN overlap 
Sweet’s syndrome 
• 
Includes Acute febrile neutrophilic dermatosis 
Vitiligo 
 
Vasculitis 
Large vessels vasculitis  
Including but not limited to: 
• 
Arteritic anterior ischemic optic neuropathy (AAION or arteritic AION) 
• 
Giant cell arteritis (also called temporal arteritis)  
• 
Takayasu's arteritis  
Medium sized and/or small vessels vasculitis  
Including but not limited to: 
• 
Anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis (type unspecified)  
• 
Behcet's syndrome  
• 
Buerger’s disease (thromboangiitis obliterans) 
• 
Churg–Strauss syndrome (allergic granulomatous angiitis)  
• 
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)” 

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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 
 
 

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Section 10.3.8  
Recording and follow-up of AEs, SAEs and pIMDs 
[…] 
• 
Collect and verify completed diary cards during discussion with the participant at 
Day 31 for all groups, and at Month 13 for the RSV_annual group only and 
Month 25 for the RSV_annual and RSV_flexible revaccination groups. 
Section 10.4.2  
Requirements for Germany 
[…] 
Remote Source Data Verification (rSDV) during exceptional situations in Germany 
Frequent in-stream monitoring of safety data by the central study team at GSK is 
required for this study. In-stream review of study data items and processes should be 
considered during exceptional situations/circumstances, such as with pandemics like 
COVID-19, focusing on key data points, patient assessments and processes that are 
critical to ensure the rights, safety and well-being of study participants and the 
integrity of the study and data. Prior to any rSDV activity, a written agreement by the 
investigator will be obtained. The agreement includes the extent and the method of 
rSDV activities. Monitoring Plan and Study-Specific Risk Register will be updated to 
include rSDV activities and Clinical Research Associates (CRAs) will be guided for the 
conduct of rSDV. 
Option 1: Transfer of redacted source documentation 
Process for transfer and review of redacted source documentation provided by the site: 
• 
The CRA instructs study site on the source data needed for the rSDV activities. 
• 
The CRA instructs site staff that they must pseudonymize the requested 
documentation, do a quality check that anonymized (redacted) areas cannot be 
read, and then delivers the documentation to the CRA in an encrypted form of 
communication (the site should have a documented process). 
• 
The minimum requirements regarding quality of the copies will be agreed with the 
site upfront: 
− 
For the scanning of paper documents resolution will be a minimum of 300 
dots per inch (dpi). 
− 
For the scanning of photographs and images resolution will be 600 dpi 
minimum. 
− 
Color scanners must be able to produce copies that match the original. 
− 
A4 format as final size without loss of information. 
− 
Documents will be saved as portable document format (PDF). 
− 
In order to maintain quality standards, a captured image will not be subjected 
to non-uniform scaling (i.e., sizing) or re-sampling to a lower resolution. 

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• 
Redacted source document scans will be sent to the CRA via email using one of the 
following secure options: 
a. Transport Layer Security (TLS) connection: 
TLS connections are intended to support significant mail flow between GSK and 
external partners in a secure manner. 
b. GSK Secure 
In cases where only a handful of users are communicating or the volume of emails 
is low, the use of GSK secure, the GSK ad hoc message encryption solution is 
recommended. 
c. 
Password-protected PDF attachment 
A password protected scan (PDF) will be attached to an email. The password to 
open the attachment will be send in a separate email. 
• 
The CRA may use the secure email website to assess whether the sites email 
address is secure (i.e., encrypted). 
• 
Prior to starting rSDV, the CRA ensures that the provided documents is complete 
and does not contain any Personal Information (PI). 
− 
In case the CRA detects any PI that has not been redacted, the CRA informs 
the study site and deletes the files (including the Recycle bin). 
− 
A Data Breach must be reported Data Breach Web Report Form. 
• 
Use of an external PC screen is recommended. The CRA will not generate any 
copies from the source data received. 
• 
Source data verification/review will be conducted according to the process outlined 
in the GSK Monitoring Standard Operating Procedure (SOP). 
• 
After completion of SDV activities, the CRA deletes all copies/images of 
participant data received from the site. This includes the deletion of the recycle bin 
and any temporary files. 
• 
A statement confirming that all documents were destroyed will be provided by the 
CRA via email to the site. 
• 
Details of what was monitored remotely will be documented in the appropriate 
section of the Monitoring Visit Report (MVR). 
Option 2: Review of participant’s source documentation remotely 
Process for use of Webcams, WebEx, MS Teams for viewing participant’s source 
documentation remotely: 
• 
The CRA ensures that the site personnel sharing information with GSK have 
authority to do so. 
• 
rSDV activities will be performed exclusively by the assigned site monitor. 
• 
Prior to conducting any rSDV activities, the CRA ensures that a written informed 
consent, covering the proposed SDV activities, has been signed by the participant. 

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• 
For CRAs using GSK laptops, only use GSK-approved video conferencing tools 
(e.g., MS Teams or GSK WebEx). Live image transmission is fully encrypted and 
protected for authorized user. By using these systems, it will be assured that data 
will be viewed only but not transmitted/stored. 
• 
Functional Service Provider (FSP)/local Clinical Research Organization (CRO) 
CRAs not using GSK laptops, only MS Teams via Remote Access Application 
(RAA) may be used for meetings between the CRA and the site. WebEx is not 
permitted from non-GSK laptops. Other tools like FaceTime, WhatsApp or Zoom 
are not permitted since they do not have sufficient encryption features. GSK does 
not have enterprise contract/privacy agreement with these providers. 
• 
Prior to the remote monitoring visit, the CRA instructs study site on the specific 
data needed for the rSDV. 
• 
Source data verification will be conducted according to the process outlined in the 
Monitoring SOP. 
• 
The use of a headset is required; do not use computer audio. 
• 
The CRA does not capture screens or take pictures of screens to ensure we are not 
transferring content outside of clinical sites. 
• 
WebEx or Teams do not store or have access to any data, GSK staff is not allowed 
to make or store any screenshots or save any data which has been shared. 
• 
Details of what was monitored remotely will be documented in the appropriate 
section of the MVR. 
• 
In case of technical malfunctions or if the security of the transmission is no longer 
ensured, we will pause rSDV activities. GSK Issue Management Procedures will be 
initiated. 
Section 10.5.1  
List of abbreviations 
CRA: 
Clinical Research Associate 
HLT: 
High Level Term 
PI: 
Personal Information 
PT: 
Preferred Term 
rSDV: 
remote Source Data Verification 
SOP: 
Standard Operating Procedure 

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Section 10.5.2  
Glossary of terms 
Protocol 
amendment: 
The International Council on Harmonization (ICH) defines a protocol 
amendment as: “A written description of a change(s) to or formal 
clarification of a protocol”. GSK further details this to include a change 
to an approved protocol that affects the safety of participants, scope of 
the investigation, study design, or scientific integrity of the study. 
Section 11 
References 
[…] 
McDonald JU, Rigsby P et al. Establishment of the first WHO International Standard 
for antiserum to Respiratory Syncytial Virus: Report of an International collaborative 
study. Vaccine 2018; 36: 7641-7649. 
McDonald JU, Rigsby P et al. Expansion of the 1st WHO international standard for 
antiserum to respiratory syncytial virus to include neutralisation titres against RSV 
subtype B: An international collaborative study. Vaccine 2020; 38: 800-807. 
[…] 
Rubin, DB, Stern H and Vehovar V. Handling “don’t know” survey responses: the 
case of the Slovenian plebiscite. Journal of the American Statistical Association 90, 
1995, 822–828. 

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11. 
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Bates JT, Keefer CJ, Slaughter JC, et al. Escape from neutralization by the respiratory 
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Binder W, Thorsen J, Borczuk P. RSV in adult ED patients: Do emergency providers 
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Leroux-Roels G, Van Damme P, Haazen W, et al. Phase I, randomized, observer-blind, 
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McDonald JU, Rigsby P et al. Establishment of the first WHO International Standard 
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Samten B, Thomas EK, Gong J, Barnes PF. Depressed CD40 ligand expression 
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Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive 
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Sedger LM, McDermott MF. TNF and TNF-receptors: From mediators of cell death and 
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Stubbe M, Vanderheyde N, Goldman M et al. Antigen-specific central memory CD4+ T 
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