A Phase III, Open-label, Randomized, Controlled, Multi-Country Study to Evaluate the Immune Response, Safety and Reactogenicity of RSVPreF3 OA Investigational Vaccine When Co Administered With PCV20 in Adults Aged 60\xa0Years and Older
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

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TITLE PAGE 
Protocol Title:  
A Phase III, Open-label, Randomized, Controlled, Multi-country Study to Evaluate the 
Immune Response, Safety and Reactogenicity of RSVPreF3 OA Investigational Vaccine 
When Co-administered with 20-Valent Pneumococcal Conjugate Vaccine (PCV20) in Adults 
Aged 60 Years and Older. 
Protocol Number: 219276 
Compound: RSVPreF3 OA 
Study Phase: III 
Sponsor Name: GlaxoSmithKline Biologicals S.A. 
Legal Registered Address: Rue De L'institut 89, 1330 Rixensart, Belgium 
EU CT Number: 2022-501988-40-00 
Date of Original Protocol: 06 January 2023 
Date of Original Protocol v2.0: 27 February 2023 
Date of Protocol Amendment v1.0: 23 June 2023 

C O N FI D E N TI A L  
2 1 9 2 7 6 (R S V O A = A DJ -0 1 9 ) 
A me n d me nt v 1. 0   
 
2 3-J u ne- 2 0 2 3 
2 of 1 1 2 
A p pr o v al D ate:  2 3-J u ne- 2 0 2 3 
S p o ns or Si g nat or y 
 
 
Na dia Me yer , M D 
Cli nical Pr oject Lea d  
R S V Ol der A d ults  
 
 
Date  
 
Me dical M o nit or n a me a n d co ntact i nf or mati o n will be pr o vi de d se paratel y.  
 
 
P P D

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Protocol Investigator Agreement 
I agree: 
• To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals SA. 
• To assume responsibility for the proper conduct of the study at this site. 
• That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 
• That I will comply with the terms of the site agreement. 
• To ensure that all individuals assisting me with the study are adequately informed 
about the GSK study intervention and other study-related duties and functions as 
described in the protocol. 
• To supervise any individual or party to whom I have delegated study-related duties and 
functions conducted at the study site. 
• To ensure that any individual or party to whom I have delegated study-related duties 
and functions conducted at the study site are qualified to perform those study-related 
duties and functions. 
• To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality Assurance 
procedure manual. 
• To ensure that no clinical samples (including blood and serum samples) are retained 
onsite or elsewhere without the approval of GSK and the express written informed 
consent of the participant. 
• To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• To co-operate with representative(s) of GSK in the monitoring 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 study. 
• That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational intervention(s), and more generally about his/her 
financial ties with the sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 
Hence, I: 
• Agree to supply GSK with any necessary information regarding ownership interest and 
financial ties (including those of my spouse and dependent children). 
• Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 

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• Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 
 
Investigator name:  
__________________________________________ 
 
Signature: 
 
 
__________________________________________ 
 
Date:  
 
 
__________________________________________ 
 
 
 
 
 

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PROTOCOL SUMMARY OF CHANGES TABLE 
 
DOCUMENT HISTORY 
 
 
Document 
Date 
Substantial 
Region 
Amendment 1.0 
23-June-2023 
Yes 
Global 
Original Protocol v2.0 
27-February-2023 
No 
Global 
Original Protocol 
06-January-2023 
- 
- 
Amendment v1.0 (23-June-2023) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for Protocol Update: 
The protocol has been amended to include the definition of Serious Adverse Reaction 
(SAR)/Suspected Unexpected Serious Adverse Reactions (SUSAR), and to clarify time period 
for collecting AE, SAE, and pIMD information as required in Request for Information from 
Belgium member state of the European Medicines Agency dated 14-June-2023. 
(Added text is bold italic, deleted text is strikethrough) 
Section # and Name 
Description of Change 
Brief Rationale 
8.3.1 Time Period and 
Frequency for Collecting 
AE, SAE, and pIMD 
Information 
Edited text: 
All AEs (regardless of the 
assessment of relatedness to the 
study vaccines), including all 
SAEs and all pIMDs will be 
collected from the first study 
intervention administration. All 
SAEs and all pIMDs will be 
collected until 6 months after the 
last study intervention 
administration at the timepoints 
specified in the SoA (Section 1.3). 
AEs (including SAEs and 
pIMDs) leading to withdrawal 
from the study will be collected 
from the time of the first study 
intervention administration until 
the participant is discharged from 
the study. 
In addition, SAEs assessed as 
related to study participation (e.g., 
Clarification 

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protocol-mandated invasive 
procedures) or related to any 
other GSK product (non-IMP) 
will be recorded from the time a 
participant consents to participate 
in the study until the participant is 
discharged from the study. 
 
Deleted text: 
All SAEs and pIMDs will be 
collected from the start of study 
intervention until 6 months after 
the last administration of study 
interventions at the time points 
specified in the SoA (Section 1.3).   
SAEs assessed as related to study 
participation (e.g., study 
intervention, protocol mandated 
procedures, invasive tests, or 
change in existing therapy) or 
related to a GSK product 
(non IMP) will be recorded from 
the time a participant consents to 
participate in the study until the 
participant is discharged from the 
study. 
All AEs/SAEs/pIMDs leading to 
withdrawal from the study will be 
collected and recorded from the 
time of the first receipt of study 
intervention until the participant is 
discharged from the study.  
 
10.4 Appendix 4: 
Abbreviations and 
Glossary of Terms 
Added to Abbreviations and 
Glossary of Terms list: 
Serious Adverse Reaction: 
Suspected Unexpected Serious 
Adverse Reactions: All noxious 
and unintended responses to an 
investigational medicinal product 
(IMP) related to any dose 
administered that result in death, 
are life-threatening, require patient 
hospitalization or prolongation of 
existing hospitalization, result in 
persistent or significant disability 
or incapacity, or are a congenital 
anomaly or birth defect.  
Suspected Unexpected Serious 
Adverse Reactions: A Suspected 
Unexpected Serious Adverse 
Required in Request for Information from 
Belgium, EMA 

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Reaction is a Serious Adverse 
Reaction whose nature, severity or 
outcome is not consistent with the 
reference safety information. 
 

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TABLE OF CONTENTS 
1.0 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1 
Synopsis .......................................................................................................... 13 
1.2 
Schema ............................................................................................................ 16 
1.3 
Schedule of Activities .................................................................................... 17 
2.0 
INTRODUCTION ..................................................................................................... 24 
2.1 
Study Rationale .............................................................................................. 24 
2.2 
Background .................................................................................................... 24 
2.3 
Benefit/Risk Assessment ............................................................................... 25 
2.3.1 
Risk Assessment ................................................................................ 25 
2.3.2 
Benefit Assessment ........................................................................... 26 
2.3.3 
Overall Benefit-Risk Conclusion ...................................................... 26 
3.0 
OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................... 27 
4.0 
STUDY DESIGN ....................................................................................................... 29 
4.1 
Overall Design ................................................................................................ 29 
4.1.1 
Overview of the Recruitment Plan .................................................... 30 
4.1.2 
Enrollment Rules ............................................................................... 30 
4.2 
Scientific Rationale for Study Design .......................................................... 30 
4.3 
Justification for Dose ..................................................................................... 31 
4.4 
End of Study Definition ................................................................................. 32 
4.5 
Study Stopping Criteria ................................................................................ 32 
4.6 
Participant Input into Design ....................................................................... 32 
5.0 
STUDY POPULATION ............................................................................................ 33 
5.1 
Inclusion Criteria ........................................................................................... 33 
5.2 
Exclusion Criteria .......................................................................................... 33 
5.2.1 
Medical Conditions ........................................................................... 33 
5.2.2 
Prior and Concomitant Therapy ........................................................ 34 
5.2.3 
Prior/Concurrent Clinical Study Experience ..................................... 35 
5.2.4 
Other Exclusions ............................................................................... 36 
5.3 
Caregiver Support ......................................................................................... 36 
5.4 
Lifestyle Considerations ................................................................................ 36 
5.5 
Screen Failures ............................................................................................... 36 
5.6 
Criteria for Temporarily Delaying .............................................................. 37 
6.0 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .................... 39 
6.1 
Study Interventions Administered ............................................................... 40 
6.1.1 
Medical Devices ................................................................................ 41 
6.2 
Preparation, Handling, Storage, and Accountability ................................. 41 

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6.3 
Measures to Minimize Bias: Randomization and Blinding ....................... 41 
6.3.1 
Participation Identification ................................................................ 41 
6.3.2 
Randomization to Study Intervention ............................................... 42 
6.3.3 
Intervention Allocation to the Participant ......................................... 42 
6.3.4 
Allocation of Participants to Assay Subsets ...................................... 42 
6.3.5 
Blinding and Unblinding ................................................................... 43 
6.4 
Study Intervention Compliance ................................................................... 43 
6.5 
Dose Modification .......................................................................................... 43 
6.6 
Treatment of Overdose ................................................................................. 43 
6.7 
Concomitant Therapy ................................................................................... 43 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................... 45 
7.1 
Discontinuation of Study Intervention ........................................................ 45 
7.1.1 
Contraindications to Subsequent Study Intervention 
Administration ................................................................................... 45 
7.2 
Participant Discontinuation/Withdrawal from the Study ......................... 46 
7.3 
Lost to Follow-up ........................................................................................... 47 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .................................................... 48 
8.1 
Immunogenicity Assessments ....................................................................... 49 
8.1.1 
Biological Samples ............................................................................ 50 
8.1.2 
Laboratory Assays ............................................................................. 50 
8.1.3 
Immunological Read-Outs ................................................................ 51 
8.1.4 
Immunological Correlates of Protection ........................................... 56 
8.2 
Safety Assessments ........................................................................................ 56 
8.2.1 
Pre-Vaccination Procedures .............................................................. 56 
8.2.2 
Safety Contact at 6 Months Post-Last Vaccination ........................... 58 
8.2.3 
Clinical Safety Laboratory Tests ....................................................... 58 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting ........................................................................................................ 58 
8.3.1 
Time Period and Frequency for Collecting AE, SAE, and 
pIMD Information ............................................................................. 59 
8.3.2 
Method of Detecting AEs, SAEs, and pIMDs .................................. 62 
8.3.3 
Follow-up of AEs, SAEs, and pIMDs ............................................... 62 
8.3.4 
Regulatory Reporting Requirements for SAEs and Other 
Events ................................................................................................ 62 
8.3.5 
Treatment of Adverse Events ............................................................ 63 
8.3.6 
Medical Device Deficiencies ............................................................ 63 
8.4 
Participant Card ............................................................................................ 64 
8.5 
Pharmacokinetics .......................................................................................... 65 
8.6 
Pharmacodynamics ....................................................................................... 65 
8.7 
Genetics .......................................................................................................... 65 
8.8 
Biomarkers ..................................................................................................... 65 
8.9 
Immunogenicity Assessments ....................................................................... 65 

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8.10 
Health Outcomes ........................................................................................... 65 
8.11 
Health Economics .......................................................................................... 65 
9.0 
STATISTICAL CONSIDERATIONS ..................................................................... 66 
9.1 
Statistical Hypotheses .................................................................................... 66 
9.2 
Populations for Analysis ............................................................................... 67 
9.2.1 
Criteria for Elimination ..................................................................... 67 
9.3 
Statistical Analyses ........................................................................................ 67 
9.3.1 
Primary Endpoint(s)/Estimand(s) Analysis ....................................... 68 
9.3.2 
Secondary Endpoint(s)/Estimand(s) Analysis ................................... 69 
9.4 
Interim Analysis ............................................................................................. 70 
9.4.1 
Sequence of Analysis ........................................................................ 70 
9.5 
Sample Size Determination ........................................................................... 70 
10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................. 73 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................... 73 
10.1.1 
Regulatory and Ethical Considerations ............................................. 73 
10.1.2 
Adequate Resources .......................................................................... 74 
10.1.3 
Financial Disclosure .......................................................................... 74 
10.1.4 
Recruitment Arrangements and Informed Consent Process ............. 74 
10.1.5 
Data Protection .................................................................................. 75 
10.1.6 
Committees Structure ........................................................................ 76 
10.1.7 
Dissemination of Clinical Study Data ............................................... 76 
10.1.8 
Data Quality Assurance ..................................................................... 77 
10.1.9 
Source Documents ............................................................................ 77 
10.1.10 Study and Site Start and Closure ....................................................... 78 
10.1.11 Publication Policy ............................................................................. 79 
10.2 
Appendix 2: Clinical Laboratory Tests ....................................................... 80 
10.3 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting for Study 
Intervention .................................................................................................... 81 
10.3.1 
Definition of AE ................................................................................ 81 
10.3.2 
Definition of SAE and Serious Adverse Device Effect 
(SADE) .............................................................................................. 84 
10.3.3 
Adverse Events of Special Interest ................................................... 85 
10.3.4 
Clinical Laboratory Parameters and Other Abnormal 
Assessments Qualifying as AEs or SAEs ......................................... 96 
10.3.5 
Recording and Follow-Up of AEs, SAEs, pIMDs, and/or 
Device Deficiencies .......................................................................... 96 
10.3.6 
Reporting of SAEs, pIMDs, Medical Device SAEs ....................... 101 
10.4 
Appendix 4: Abbreviations and Glossary of Terms ................................. 103 
10.5 
Appendix 5: Protocol Amendment History ............................................... 109 

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11.0 
REFERENCES ........................................................................................................ 111 
 

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LIST OF TABLES 
Table 1 
Schedule of Activities for the Co-ad Group ..................................................... 17 
Table 2 
Schedule of Activities for the Control Group ................................................... 20 
Table 3 
Interval Between Study Visits (Co-ad Group) ................................................. 23 
Table 4 
Interval Between Study Visits (Control Group) ............................................... 23 
Table 5 
Study Interventions Administered .................................................................... 40 
Table 6 
Biological Samples ........................................................................................... 50 
Table 7 
Laboratory Assays ............................................................................................ 50 
Table 8 
Immunological Read-outs ................................................................................ 51 
Table 9 
Timeframes for Collection and Reporting of Safety Information                           
for the Co-ad Group .......................................................................................... 60 
Table 10 
Timeframes for collection and Reporting of Safety Information                       
for the Control Group ....................................................................................... 61 
Table 11 
Timeframes for Submitting SAE and Other Events Reports to IQVIA ........... 63 
Table 12 
Study Objectives and Null Hypothesis ............................................................. 66 
Table 13 
Analysis Sets .................................................................................................... 67 
Table 14 
Overall power to demonstrate primary objectives: non-inferiority                     
of the immunogenicity of RSVPreF3 OA investigational vaccine when                     
co-administered with pneumococcal vaccine (PCV20) as compared to when 
administered alone- assuming 490 evaluable participants in each group ......... 71 
Table 15 
Solicited Administration Site Events ................................................................ 82 
Table 16 
Solicited Systemic Events ................................................................................ 82 
Table 17 
List of Potential Immune-Mediated Diseases (pIMDs) .................................... 86 
Table 18 
Intensity Scales for Solicited Events ................................................................ 98 
Table 19 
Abbreviations List .......................................................................................... 103 
Table 20 
Glossary of Terms .......................................................................................... 105 
 
LIST OF FIGURES 
Figure 1 
Study Design Overview .................................................................................. 16 
 

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1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: 
A Phase III, open-label, randomized, controlled, multi-country study to evaluate the immune 
response, safety and reactogenicity of RSVPreF3 OA investigational vaccine when 
co-administered with 20-valent pneumococcal conjugate vaccine (PCV20) in adults aged 
60 years and older. 
Rationale: 
GlaxoSmithKline Biologicals SA (GSK) is developing a new respiratory syncytial virus 
(RSV) PreFusion protein 3 Older Adult (OA) investigational vaccine (RSVPreF3 OA) against 
RSV-associated (subtypes A and B) disease in adults ≥60 years of age (YOA). The vaccine 
development is currently in Phase III, and immunogenicity, safety, and reactogenicity of the 
candidate vaccine when co-administered with other vaccines are being investigated. 
Like RSV, pneumococcal disease also presents high disease burden among older adults and 
the seasonality of RSV disease and invasive pneumococcal disease is similar.  
The present study will assess the immunogenicity, safety and reactogenicity of the RSVPreF3 
OA investigational vaccine when co-administered with the 20 valent pneumococcal conjugate 
vaccine (referred to as Prevnar 20 in USA or Apexxnar in Europe [hereafter referred to as 
PCV20]) in adults ≥60 YOA.  
Objectives, Endpoints, and Estimands: 
Objectives 
Endpoints and Estimands 
Primary* 
•
To demonstrate the non-inferiority of
PCV20 when co-administered with the
RSVPreF3 OA investigational vaccine
compared to PCV20 administered alone
•
Opsonophagocytic (OP) antibody (Ab)
titers for each of the pneumococcal
vaccine serotype (ST) expressed as
between groups geometric mean titer
(GMT) ratio, 1 month after the PCV20
dose
•
To demonstrate the non-inferiority of
RSVPreF3 OA investigational vaccine
in terms on RSV-A neutralization
antibodies when co-administered with
PCV20 compared to RSVPreF3 OA
investigational vaccine administered
alone
•
RSV-A neutralizing Ab titers expressed as
between groups GMT ratio, 1 month after
the RSVPreF3 OA investigational vaccine
dose
•
To demonstrate the non-inferiority of
RSVPreF3 OA investigational vaccine
in terms of RSV-B neutralization
antibodies when co-administered with
the PCV20 vaccine compared to
RSVPreF3 OA investigational vaccine
administered alone.
•
RSV-B neutralizing Ab titers expressed as
between groups GMT ratio, 1 month after
the RSVPreF3 OA investigational vaccine
dose

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Objectives 
Endpoints and Estimands 
Secondary 
•
To evaluate the humoral immune
response to RSVPreF3 OA
investigational vaccine when
co-administered with the PCV20 or
administered alone
•
RSV-A neutralizing Ab titers expressed as
mean geometric increase (MGI) over
baseline at 1 month after the RSVPreF3
OA investigational vaccine dose
•
RSV-B neutralizing Ab titers expressed as
MGI over baseline at 1 month after the
RSVPreF3 OA investigational vaccine
dose
•
To evaluate the safety and reactogenicity
following administration of the
RSVPreF3 OA investigational vaccine
and PCV20, co-administered or
administered alone.
•
Percentage of participants reporting each
solicited event with onset within 7 days
after vaccine administration (i.e., the day
of vaccination and 6 subsequent days)
•
Percentage of participants reporting
unsolicited AE within 30 days after
vaccine administration (i.e., the day of
vaccination and 29 subsequent days)
•
Percentage of participants reporting SAEs
after vaccine administration (Day 1) up to
EoS (6 months after last vaccination)
•
Percentage of participants reporting
pIMDs after vaccine administration (Day
1) up to EoS (6 months after last
vaccination)
Abbreviations: Ab=antibody; AE=adverse event; EoS=end of study; GMT=geometric mean titer; MGI=mean 
geometric increase; OA=older adult; OP=opsonophagocytic; PCV20=20-valent pneumococcal vaccine; 
pIMD=potential immune-mediated disease; RSV=respiratory syncytial virus; RSVPreF3 OA=respiratory 
syncytial virus PreFusion protein 3 older adult investigational vaccine; SAE=serious adverse event; 
ST=serotype.  
* PCV and RSV-A endpoint will be assessed as co-primary and following the current success RSV-B will be
demonstrated as sequential. Refer to Section 9.3.1.1 for the testing sequence of primary objectives.
Overall Design: 
Experimental design: Phase III, open-label, randomized, controlled, multi-country study with 
2 parallel groups.  
Study groups and Randomization: Approximately 1090 eligible participants will be 
randomly (1:1) assigned to 2 study groups using a centralized randomization system on 
internet at Visit 1 (Day 1). The randomization algorithm will use a minimization procedure 
accounting for age (60 to 69, 70 to 79 or ≥80 years) and center. Minimization factors will have 
equal weight in the minimization algorithm. 
Overall, participants will be enrolled in 3 age categories with a balance between males and 
females. It is intended to enroll: 

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• Approximately 40% of participants 60 to 69 YOA, approximately 30% of participants 
70 to 79 YOA and approximately 10% of participants ≥80 YOA. The remaining 20% can 
be distributed freely across the 3 age categories. 
• Approximately 40% of participants from each sex; the remaining 20% can be distributed 
freely between the 2 sexes. 
Duration of study: The total duration of the study, per participant, will be approximately 
6 months for the co-ad group, and 7 months for the control group.  
Co-administration (Co-ad) group: Study intervention administration RSVPreF3 OA 
investigational vaccine and PCV20 vaccine on Visit 1 (Day 1) and follow-up for 6 months, 
until end of study (EoS). Two site visits (Visit 1 [Day 1] and Visit 2 [Day 31]) and a phone 
contact 6 months post-last dose.  
Control group: Study intervention administrations of PCV20 vaccine on Visit 1 (Day 1) and 
RSVPreF3 OA investigational vaccine on Visit 2 (Day 31) and -follow-up for 6 months, until 
EoS. Three site visits (Visit 1 [Day 1], Visit 2 [Day 31], and Visit 3 [Day 61]) and a phone 
contact 6 months post-last dose. 
Number of Participants: 
Approximately 1090 participants aged ≥60 years will be randomly (1:1) assigned to 2 study 
groups (i.e., co-ad group or the control group). 
Safety monitoring: the study will be conducted with oversight by the project Safety Review 
Team. 

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1.2 
Schema 
Figure 1 
Study Design Overview 
 
  
AE=Adverse Event; Co-Ad group=Co-Administration group; D=Day; N=Number of participants; PCV=20-valent pneumococcal conjugate vaccine; 
pIMD=potential Immune-Mediated Disease; RSV=RSVPreF3 OA; SAE=Serious Adverse Event.  
 

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● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF. 
∆ is used to indicate a study procedure that requires documentation in the eDiary. 
a Visit 2 should preferably be done on site but if deemed necessary (during special circumstances such as the COVID-19 pandemic), this study visit can be 
replaced by a home visit conducted by authorized staff. Any information from the participant required according to study procedures and not collected during 
the home visit can be obtained by means of a phone call conducted by the site staff. 
b Six months after last vaccination. For this contact, multiple formats (e.g., email, text message, fax, or phone call) can be proposed by the study site. 
c Visit window shown in Table 3. 
d Sample collected at Day 1 will be used as baseline for RSV and PCV20 antibody titers. 
e Sample collected at Day 31 will be used for the post-vaccination RSV vaccine- and PCV20 vaccine-related testing. 
f The route for measuring body temperature can be oral or axillary. Fever is defined as temperature ≥38.0 °C/100.4 °F, regardless of the location of measurement. 
g Designated site staff should review the eDiary frequently during the active event collection period to assess participant/caregiver compliance and monitor 
reported events. 
h SAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to study vaccine 
administration) up to end of study (EoS). 

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∆ is used to indicate a study procedure that requires documentation in the individual eDiary. 
a Visit 3 should preferably be done on site but if deemed necessary (during special circumstances such as the COVID-19 pandemic), this study visit can be 
replaced by a home visit conducted by authorized staff. Any information from the participant required according to study procedures and not collected during 
the home visit can be obtained by means of a phone call conducted by the site staff. 
b Six months after last vaccination. For this contact, multiple formats (e.g., email, text message, fax, or phone call) can be proposed by the study site. 
c Visit window shown in Table 4 
d Sample collected at Day 1 will be used as baseline for PCV20 antibody titers. 
e Sample collected at Day 31 will be used for the post-vaccination PCV20 vaccine-related testing. This sample will also be used as baseline for the RSV 
vaccination in the Control group. 
f Sample collected at Day 61 will be used for the post-vaccination RSV vaccine-related testing. 
g The route for measuring body temperature can be oral or axillary. Fever is defined as temperature ≥38.0°C/100.4°F, regardless of the location of measurement. 
h Designated site staff should review the eDiary frequently during the active event collection period to assess participant/caregiver compliance and monitor 
reported events. 
iSAEs related to study participation, or to a concurrent GSK medication/vaccine should be collected from the time of consent obtained (prior to study vaccine 
administration) up to EoS. 

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Table 3 
Interval Between Study Visits (Co-ad Group) 
Interval 
Planned visit interval  Allowed interval (Visit window) 
Visit 1 (Day 1/study intervention administration) → Visit 2 (Day 31) 
30 days 
30-42 days 
Visit 1 → phone contact 
180 days 
180-210 days 
 
Table 4 
Interval Between Study Visits (Control Group) 
Interval 
Planned visit interval  Allowed interval (Visit window) 
Visit 1 (Day 1/study intervention administration) → Visit 2 (Day 31) 
30 days 
30-42 days 
Visit 2 (Day 31/study intervention administration) → Visit 3 (Day 61) 
30 days 
30-42 days 
Visit 2 → phone contact 
180 days 
180-210 days 
 
 

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2.0 INTRODUCTION 
2.1 
Study Rationale 
GlaxoSmithKline Biologicals SA (GSK) is developing a new respiratory syncytial virus 
(RSV) PreFusion protein 3 Older Adult (OA) investigational vaccine (RSVPreF3 OA) against 
RSV-associated (subtypes A and B) disease in adults ≥60 years of age (YOA). The vaccine 
development is currently in Phase III, and immunogenicity, safety, and reactogenicity of the 
candidate vaccine when co-administered with other vaccines are being investigated. 
The present study will assess the immunogenicity, safety, and reactogenicity of the 
RSVPreF3 OA investigational vaccine when co-administered with the 20-valent 
pneumococcal conjugate vaccine (referred to as Prevnar 20 in USA or Apexxnar in Europe 
[hereafter referred to as PCV20]) in adults ≥60 YOA. 
2.2 
Background 
Respiratory syncytial virus can cause severe lower respiratory tract infection in older adults 
and adults with chronic medical conditions including cardiopulmonary and 
immunocompromising conditions.  
Based on epidemiological data collected prospectively in 2008-2010 in 14 countries 
worldwide (including North America, Europe, and East Asia), the average percentage of 
documented RSV infection in older adults with influenza-like illness is 7.4%, with values 
between 0% and 17.1% across countries1. 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.2 Further information on 
RSV incidence and disease burden can be found in the Investigator’s Brochure (IB). 
There are 2 subtypes of RSV virus- RSV-A and RSV-B. RSV virus circulates with other 
respiratory viruses, and infections peak during winter period. To date, no licensed vaccine or 
prophylactic treatment is available for RSV. Currently available treatment for RSV infection 
is limited to supportive care. Like RSV, pneumococcal disease also presents high disease 
burden among older adults and the seasonality of RSV disease and invasive pneumococcal 
disease is similar.3,4  
Pneumococcal vaccines for adults are available in both conjugated and polysaccharide 
formulations. A PPSV23 is licensed, along with conjugated pneumococcal vaccines including, 
PCV15 and PCV20. Currently the recommendations for pneumococcal vaccination vary from 
country to country. Some countries recommend polysaccharide vaccine, other recommend 
conjugate vaccine, while some recommend the use of both.  

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2.3 
Benefit/Risk Assessment 
2.3.1 
Risk Assessment 
Detailed information about the known and expected benefits and potential risks and 
reasonably expected adverse events (AEs) of the RSVPreF3 OA investigational vaccine can 
be found in the Investigator’s Brochure (IB) and Development Safety Update Report (DSUR).  
Study participants must be observed closely for at least 30 minutes after the administration of 
the study interventions. Appropriate medical treatment must be readily available during the 
observation period in case of anaphylaxis and/or syncope.  
 
Important Potential/Identified Risk 
Mitigation Strategy 
RSV investigational vaccine 
Potential immune-mediated diseases (pIMDs) are 
considered a potential risk, as for all vaccines 
containing an adjuvant system. 
Refer to Section 10.3.3 for details. 
Syncope and hypersensitivity reactions (including 
anaphylaxis). 
 
All participants will remain under observation at the 
clinical center for at least 30 minutes after 
vaccination. 
Participants with a history of hypersensitivity or 
severe allergic reaction to any component of the 
vaccine are excluded from study enrollment. 
Study procedures 
Intramuscular vaccination commonly precipitates a 
transient and self-limiting local inflammatory 
reaction. This may typically include pain at injection 
site, erythema/redness, and swelling. 
As a mitigation strategy, physicians can implement 
the measures that they consider necessary. 
Pain and bruising may occur at the site where blood 
is drawn. 
As a mitigation strategy, physicians can implement 
the measures that they consider necessary. 
Syncope (fainting) can occur following or even 
before any blood draw as a psychogenic response to 
the needle insertion. 
Participants who mention experiencing previous 
episodes of fainting or dizziness before, during or 
after a blood draw, will remain under observation at 
the clinical center until deemed necessary by site 
personnel. Appropriate medical treatment must be 
readily available during this period. 
Abbreviations: PCV20=20 pneumococcal serotypes vaccine; pIMD=potential immune-mediated disease; RSV=respiratory 
syncytial virus. 
For expected adverse reactions associated with Pfizer’s PCV20 vaccine, please refer to the 
Prescribing Information. 

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2.3.2 
Benefit Assessment 
The participants may have the benefit of being protected against RSV infection during the 
active season. In a large Phase III vaccine clinical trial in adults aged 60 years and above, the 
RSVPreF3 investigational vaccine candidate demonstrated overall vaccine efficacy of 82.6% 
(96.95% confidence interval [CI], 57.9 to 94.1) against RSV lower respiratory tract disease 
(RSV-LRTD).5 The vaccine was well tolerated with a favorable safety profile.  
All participants in this study will also receive PCV20 vaccine as part of this study, which is 
one of the most recently developed pneumococcal vaccines and is recommended in US for 
adults ≥65 years of age for the prevention of pneumococcal disease.  
An indirect benefit is that the information obtained in this study will generate more knowledge 
about the RSV vaccine and the possibility to be co-administered with pneumococcal vaccine. 
Another benefit for all study participants may include gaining information about their general 
health status through the recurrent 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 recent 
data on the vaccine efficacy, and 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. 
Prevnar 20™ is a vaccine indicated for active immunization for the prevention of pneumonia 
and invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 
9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in adults 18 years of age and 
older.  

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3.0 OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
 
Objectives 
Endpoints and Estimands 
Primary* 
• 
To demonstrate the non-inferiority of 
PCV20 when co-administered with the 
RSVPreF3 OA investigational vaccine 
compared to PCV20 administered alone 
• 
Opsonophagocytic (OP) antibody (Ab) titers 
for each of the pneumococcal vaccine serotype 
(ST) expressed as between groups geometric 
mean titer (GMT) ratio, 1 month after the 
PCV20 dose 
• 
To demonstrate the non-inferiority of 
RSVPreF3 OA investigational vaccine in 
terms of RSV-A neutralization antibodies 
when co-administered with PCV20 
compared to RSVPreF3 OA investigational 
vaccine administered alone 
• 
RSV-A neutralizing Ab titers expressed as 
between groups GMT ratio, 1 month after the 
RSVPreF3 OA investigational vaccine dose 
 
• 
To demonstrate the non-inferiority of 
RSVPreF3 OA investigational vaccine in 
terms of RSV-B neutralization antibodies 
when co-administered with the PCV20 
vaccine compared to RSVPreF3 OA 
investigational vaccine administered alone 
• 
RSV-B neutralizing Ab titers expressed as 
between groups GMT ratio, 1 month after the 
RSVPreF3 OA investigational vaccine dose 
Secondary 
• 
To evaluate the humoral immune response 
to RSVPreF3 OA investigational vaccine 
when co-administered with the PCV20 or 
administered alone  
• 
RSV-A neutralizing Ab titers expressed as 
mean geometric increase (MGI) over baseline 
at 1 month after the RSVPreF3 OA 
investigational vaccine dose 
• 
RSV-B neutralizing Ab titers expressed as MGI 
over baseline at 1 month after the RSVPreF3 
OA investigational vaccine dose  
• 
To evaluate the safety and reactogenicity 
following administration of the RSVPreF3 
OA investigational vaccine and PCV20, 
co-administered or administered alone. 
• 
Percentage of participants reporting each 
solicited event with onset within 7 days after 
vaccine administration (i.e., the day of 
vaccination and 6 subsequent days) 
• 
Percentage of participants reporting unsolicited 
AE within 30 days after vaccine administration 
(i.e., the day of vaccination and 29 subsequent 
days) 
• 
Percentage of participants reporting SAEs after 
vaccine administration (Day 1) up to EoS 
(6 months after last vaccination) 
• 
Percentage of participants reporting pIMDs 
after vaccine administration (Day 1) up to EoS 
(6 months after last vaccination) 

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Footnotes for the Objectives, Endpoints, and Estimands table. 
Abbreviations: Ab=antibody; AE=adverse event; EoS=end of study; GMT=geometric mean titer; MGI=mean 
geometric increase; OA=older adult; OP=opsonophagocytic; PCV20=20-valent pneumococcal vaccine; 
pIMD=potential immune-mediated disease; RSV=respiratory syncytial virus; RSVPreF3 OA=respiratory 
syncytial virus PreFusion protein 3 older adult investigational vaccine; SAE=serious adverse event; 
ST=serotype.  
* PCV and RSV-A endpoint will be assessed as co-primary and following the current success RSV-B will be 
demonstrated as sequential. Refer to Section 9.3.1.1 for the testing sequence of primary objectives. 
 
Details related to attributes of estimand covering intercurrent events, population and treatment 
definition are provided in the Section 9.0. 

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4.0 STUDY DESIGN 
4.1 
Overall Design 
The Study Design Overview is provided in Figure 1. 
Experimental design: Phase III, open-label, randomized, controlled, multi-country study with 
2 parallel groups.  
Study groups and Randomization: Approximately 1090 eligible participants will be 
randomly (1:1) assigned to 2 study groups using a centralized randomization system on 
internet at Visit 1 (Day 1). The randomization algorithm will use a minimization procedure 
accounting for age (60 to 69, 70 to 79 or ≥80 years) and center. Minimization factors will have 
equal weight in the minimization algorithm. 
Overall, participants will be enrolled in 3 age categories with a balance between males and 
females. It is intended to enroll: 
• Approximately 40% of participants 60 to 69 YOA, approximately 30% of participants 
70 to 79 YOA, and approximately 10% of participants ≥80 YOA. The remaining 20% can 
be distributed freely across the 3 age categories. 
• Approximately 40% of participants from each sex; the remaining 20% can be distributed 
freely between the 2 sexes. 
Duration of study: The total duration of the study, per participant, will be approximately 
6 months for the co-ad group, and 7 months for the control.  
Safety monitoring: the study will be conducted with oversight by the project Safety Review 
Team (SRT). See Section 10.1.6 for SRT structure. 
Co-administration (Co-ad) group: Study intervention administration RSVPreF3 OA 
investigational vaccine and PCV20 vaccine on Visit 1 (Day 1) and follow-up for 6 months, 
until end of study (EoS). Two site visits (Visit 1 [Day 1] and Visit 2 [Day 31]) and a phone 
contact 6 months post-last dose.  
Control group: Study intervention administrations of PCV20 vaccine on Visit 1 (Day 1) and 
RSVPreF3 OA investigational vaccine on Visit 2 (Day 31) and follow-up for 6 months, until 
EoS. Three site visits (Visit 1 [Day 1], Visit 2 [Day 31] and Visit 3 [Day 61]) and a phone 
contact 6 months post-last dose. 
See Table 5 for study interventions administered.  
 

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4.1.1 
Overview of the Recruitment Plan 
No separate screening visit is planned for this study. The study is planned to be conducted at 
sites in multiple countries. The recruitment plan will be defined by each participating site. 
The recruitment plan may be adapted based on the actual number of participants enrolled in 
each country. In case a site would fall behind in participant recruitment, a redistribution of the 
enrollment target per site in the participating countries may be made. This would allow the 
other participating sites to enroll additional participants to ensure full and timely enrollment of 
the overall targeted number of participants specified in this protocol. 
The procedures for participants identification/recruitment must be approved by the 
Independent Ethics Committee (IEC)/Institutional Review Board (IRB) together with the 
material intended for participants identification/recruitment and participants use.  
4.1.2 
Enrollment Rules 
Overall, participants will be enrolled in 3 age categories reflecting an approximate age 
distribution in the general population with a balance between males and females. It is 
therefore intended to enroll: 
• Approximately 40% of participants 60 to 69 YOA, approximately 30% of participants 
70 to 79 YOA, and approximately 10% of participants ≥80 YOA. The remaining 20% can 
be distributed freely across the 3 age categories. 
• Approximately 40% of participants from each sex; the remaining 20% can be distributed 
freely between the 2 sexes. 
4.2 
Scientific Rationale for Study Design 
GlaxoSmithKline Biologicals SA (GSK) is developing a new respiratory syncytial virus 
(RSV) PreFusion protein 3 Older Adult (OA) investigational vaccine (RSVPreF3 OA) against 
RSV-associated (subtypes A and B) disease in adults ≥60 years of age (YOA). The vaccine 
development is currently in Phase III, and immunogenicity, safety, and reactogenicity of the 
candidate vaccine when co-administered with other vaccines are being investigated. 
Like RSV, pneumococcal disease also presents high disease burden among older adults. 
Moreover, the seasonality of RSV disease and invasive pneumococcal disease is similar. 
The present study will assess the immunogenicity, safety, and reactogenicity of the RSVPreF3 
OA investigational vaccine when co-administered with the pneumococcal conjugate vaccine 
(referred to as Prevnar 20 in USA or Apexxnar in Europe [hereafter referred to as PCV20]) in 
adults ≥60 YOA. 

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4.3 
Justification for Dose  
Based on the results up to 1-month post-Dose 2 from study RSV OA=ADJ-002, a single dose 
regimen (0.5 mL) and the 120 µg RSVPreF3/AS01E formulation were selected for further 
evaluation in the Phase 3 clinical program. The RSV OA=ADJ-002 study was designed to 
assess the immunogenicity of a 2-dose AS01-adjuvanted or unadjuvanted vaccine 
administered according to a 0-, 2-month schedule with the aim to maximize the immune 
response against RSV and vaccine efficacy over several seasons. Based on the data from 
clinical development programs for AS01-adjuvanted protein antigen vaccines in OA, such as 
Shingrix and the chronic obstructive pulmonary disease (COPD) investigational vaccine, it 
was expected that immunological responses would reach higher levels 1 month post-Dose 2 as 
compared with 1-month post-Dose 1. However, the RSV OA=ADJ-002 results demonstrated 
that the second dose given 2 months after the first dose had no added value in terms of 
humoral and/or cellular immune responses. The humoral response, both in terms of RSV-A 
neutralizing antibody GMTs and RSVPreF3 IgG geometric mean concentrations (GMCs), 
peaked 1 month after the first dose, and the second dose did not increase the level observed 
after first dose. 
The results from study RSV OA=ADJ-002 demonstrated statistically significant superiority of 
the 120 µg formulations in terms of RSV-A neutralizing titers over at least one of the 30 µg 
and 60 µg formulations with the same adjuvant content or unadjuvanted. The data 
demonstrated an immunologic benefit of any AS01E or AS01B formulations over 
unadjuvanted formulations in terms of frequency of RSVPreF3-specific CD4+ T cells 
expressing at least 2 markers. Importantly, despite lower baseline observed in OA, the 
AS01-containing formulations induced CD4+ T cells frequencies at a close or similar level as 
in young adults, that is not observed with the unadjuvanted formulations. 
There was no safety concern detected in unadjuvanted groups to be linked to the RSVPreF3 
antigen assessed for the first time in OA. The acceptable safety/reactogenicity profile in all 
120 µg groups, together with the immunological benefit demonstrated for the 120 µg antigen 
dose, supports the selection of a 120 µg based formulation. The results also showed that all the 
AS01-adjuvanted formulations evaluated are considered to have a clinically acceptable safety 
profile. The AS01-adjuvanted formulation with the lowest reactogenicity profile, i.e., the 
AS01E-based formulation, was selected. The immunological response observed after 1 vaccine 
dose of the AS01E-based formulation is considered adequate for a RSVPreF3 OA candidate 
vaccine. 
In the current study, the PCV20 vaccine will be administered as a 0.5 mL single-dose 
pre-filled syringe as per Prescribing Information. 

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4.4 
End of Study Definition 
A participant is considered to have completed the study if he/she returns for the last visit as 
described in the protocol. 
End of Study is the last subject last visit (LSLV) (contact at 6 months post-last dose). 
4.5 
Study Stopping Criteria 
Not applicable for this study.  
4.6 
Participant Input into Design 
Not applicable for this study. 

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5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
All participants must satisfy all the following criteria at study entry: 
• A male or female ≥60 YOA at the time of the first study intervention administration. 
• Participants who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g., completion of the eDiary, return for follow-up 
visits, ability to access and utilize a phone or other electronic communications). 
o Note: In case of physical incapacity that would preclude the self-completion of 
the eDiary, either site staff can assist the participant (for activities performed 
during site visits) or the participant may assign a caregiver* to assist him/her 
with this activity (for activities performed at home). However, at no time will 
the site staff or caregiver* evaluate the participant’s health status while 
answering diaries or make decisions on behalf of the participant. 
*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). 
• Written or witnessed informed consent obtained from the participant prior to any 
study-specific procedure being performed. 
• Participants living in the general community or in an assisted-living facility that 
provides minimal assistance, such that the participant is primarily responsible for 
self-care and activities of daily living. 
• Participants who are medically stable in the opinion of the investigator at the time of 
first study intervention administration. Participants with chronic stable medical 
conditions with or without specific treatment, such as diabetes mellitus, hypertension, 
or cardiac disease, are allowed to participate in this study if considered by the 
investigator as medically stable. 
 
5.2 
Exclusion Criteria  
The following criteria should be checked at the time of study entry. The potential 
participant MAY 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 

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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 (e.g., anaphylaxis) likely to be exacerbated 
by the study interventions, in particular any history of severe allergic reaction to any 
vaccine containing diphtheria toxoid (for example, diphtheria-tetanus-pertussis 
[DTaP]), or PPSV23. 
• Participants considered by investigator as suffering from serious or unstable chronic 
illness. 
• Any history of dementia or any medical condition that moderately or severely impairs 
cognition. 
o 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. 
• Recurrent or uncontrolled neurological disorders or seizures. Participants with 
medically -controlled chronic neurological diseases can be enrolled in the study as per 
investigator assessment, provided that their condition will allow them to comply with 
the requirements of the protocol (e.g., completion of the eDiary, 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 
up to EoS). 
• Any medical condition that in the judgment of the investigator would make 
intramuscular injection unsafe. 
5.2.2 
Prior and Concomitant Therapy 
• History of previous vaccination with any licensed or investigational pneumococcal 
conjugate vaccine, or planned receipt through study participation.  
• History of previous vaccination with any licensed or investigational pneumococcal 
polysaccharide vaccine in the last 5 years from enrollment, or planned receipt through 
study participation. 
• Previous vaccination with any licensed or investigational RSV vaccine 
• Use of any investigational or non-registered product (drug, vaccine or medical device) 
other than the study interventions during the period beginning 30 days before the first dose 
of study interventions and ending 30 days after the last study intervention administration, 
or their planned use during the study period. 
• Planned or actual administration of a vaccine not foreseen by the study protocol in the 
period starting 30 days before the first study intervention administration and ending 
30 days after the last study intervention administration.  

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o Planned or actual administration of adjuvanted quadrivalent influenza vaccine or 
live influenza vaccine not foreseen by the study protocol in the period starting 
30 days before the first study intervention administration and ending 30 days after 
the last study intervention administration. 
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 or designee is 
notified accordingly. 
• Administration of long-acting immune-modifying drugs during the period starting 
180 days before the administration of first dose of study interventions 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 administration of first dose of study 
interventions or planned administration during the study period. 
• Chronic administration (defined as more than 14 consecutive days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 90 days 
prior to the first study intervention 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). 
Note: European Economic Community (EEC) directive 93/42/EEC defines an invasive 
medical device as ‘A device which, in whole or in part, penetrates inside the body, either 
through a body orifice or through the surface of the body.’ 

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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 conduct that prohibits participation until study end. 
• Participation of any study personnel or their immediate dependents, family, or household 
members. 
5.3 
Caregiver Support 
Study participants may decide to assign a caregiver to help them fulfill 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. This should be recorded in the 
source documents. However, every effort should be made to ensure that only one caregiver 
enters the data into the eDiary to allow for timely completion. 
Caregivers may help the study participants with performing some practical study procedures 
such as receiving or making phone calls to site staff, planning study visits, transcribing 
responses to diaries, transportation to and from the study site etc. However, at no time, the 
caregiver should evaluate the participant’s health status while answering diaries or make 
decisions on behalf of the participant. At the first study visit (Visit 1 [Day 1]) the site staff 
should inform the participant of the possibility to appoint a caregiver. Then at subsequent 
study visit(s), the site staff should check again with the participant if he/she wishes to appoint 
a caregiver or if there were or will be changes of caregiver. 
 
5.4 
Lifestyle Considerations 
Not applicable for this study. 
5.5 
Screen Failures 
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently randomized to study intervention/entered in the study. 

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Limited data for screening failures (including reason for screening failure and any SAEs 
related to study participation, or to a concurrent GSK medication/vaccine from the time of 
consent obtained) will be collected and reported in the eCRF. 
Individuals who do not meet the criteria for participation in this study (screen failure) but at 
some point, in the future are expected to meet the eligibility criteria may be rescreened. 
Individuals who are rescreened will be assigned a new participant number and will undergo 
the informed consent process, and then restart a new screening phase. 
5.6 
Criteria for Temporarily Delaying  
Study intervention administration may be postponed within the permitted time interval as 
deemed appropriate by the investigator until transient conditions cited below are resolved and 
prior to the EoS enrollment period:  
• Acute disease and/or fever at the time of study intervention administration. Refer to 
Section 1.3 (Schedule of Activities [SoA]) for definition of fever and location for 
measuring body temperature in this study.  
• Participants with a minor illness (such as mild diarrhea) without fever may be dosed at the 
discretion of the investigator.  
• 
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 contact with COVID-19 positive individual may be vaccinated at 
least 14 days after the exposure, provided that the participant remains symptom-free, and 
at the discretion of the investigator.  
• In case of administration of inactivated and subunit influenza vaccines or COVID-19 
vaccines (fully licensed or with EUA): postponement of study intervention administration 
within given protocol timelines and prior to the end of the study enrollment period, to 
allow respect of at least 14 days interval between flu/COVID-19 vaccination and study 
intervention administration. 
• Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to study 
intervention administration. 
• Other issues (e.g., technical, or administrative) preventing dose administration on day of 
visit. 
• In case of delayed enrollment, all visit activities will be repeated when the participant is 
able to return for the visit. 

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For Visit 1, if the planned study intervention administration is delayed, blood sampling does 
not need to be repeated if it was obtained during enrollment visit. The following procedures 
must be repeated prior to the delayed study intervention administration: 
• Body temperature  
• Re-check contraindications, warnings, precautions to study intervention 
• Re-check inclusion/exclusion criteria   
Visit window for Visit 2 starts from day of first study intervention administration. 
For delay in the study intervention administration during Visit 2 of the control group, the 
following procedures must be repeated: 
• Body temperature  
• Re-check contraindications, warnings, precautions to study intervention 
• Re-check inclusion/exclusion criteria 

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6.0 STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol. Refer to the Glossary of Terms for the definition of study intervention. 

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6.1 
Study Interventions Administered 
Table 5 
Study Interventions Administered 
Study Intervention Name: 
RSVPreF3 OA 
Investigational Vaccine 
Prevnar 20/Apexxnar 
Study intervention formulation 
RSVPreF3 
(120 µg) 
AS01E: QS-
21* (25 µg), 
MPL (25µg), 
liposomes; 
Water for 
injection 
PS1(2.2 µg)¹ʼ²; PS3(2.2 µg)¹ʼ²; 
PS4(2.2 µg)¹ʼ²; PS5(2.2 µg)¹ʼ²; 
PS6A(2.2 µg)¹ʼ²; PS6B(4.4 µg)¹ʼ²; 
PS7F(2.2 µg)¹ʼ²; PS8(2.2 µg)¹ʼ²; 
PS9V(2.2 µg)¹ʼ²; PS10A(2.2 µg)¹ʼ²; 
PS11A(2.2 µg)¹ʼ²; PS12F(2.2 µg)¹ʼ²; 
PS14(2.2 µg)¹ʼ²; PS15B(2.2 µg)¹ʼ²; 
PS18C(2.2 µg)¹ʼ²; PS19A(2.2 µg)¹ʼ²; 
PS19F(2.2 µg)¹ʼ²; PS22F(2.2 µg)¹ʼ²; 
PS23F(2.2 µg)¹ʼ²; PS33F(2.2 µg)¹ʼ²; 
¹conjugated to CRM₁₉₇ (51 µg); 
²adsorbed on AlPO₄ (0.125 mg 
Al³⁺); Water for injections 
Presentation 
Vial; 
powder 
for 
suspension 
for 
injection 
Vial; 
suspension 
for 
suspension 
for injection 
Suspension for injection 
Route of Administration 
Intramuscular use 
Intramuscular use 
Product category 
Biologic 
Biologic 
Type 
Study 
Study 
Administration site 
 
Location 
Deltoid 
Deltoid 
Laterality 
Non-dominant 
Co-ad group: Dominant 
Control group: Non-dominant 
Number of doses to be 
administered 
1 
1 
Dose Volume** 
0.5 mL 
0.5 mL 
Packaging, labeling*** 
Refer to Pharmacy Manual 
for details 
Refer to Pharmacy Manual for 
details 
Manufacturer 
GSK 
Pfizer 
Abbreviations: Al=aluminum; AlPO4=aluminum phosphate; AS01E=Adjuvant System 01; CRM=cross-reactive 
material; PS=pneumococcal serotype; QS-21=Quillaja saponaria Molina, fraction 21; MPL=monophosphoryl 
lipid A.  
*Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of Agenus Inc., a Delaware, USA 
corporation. 
**Refer to the Pharmacy Manual for the volume after reconstitution. 
***Labeling is compliant with the requirements of applicable regulatory agencies. 

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6.1.1 
Medical Devices 
There are no GSK manufactured medical devices (or devices manufactured for GSK by a third 
party) provided for use in this study. Other medical devices (not manufactured by or for GSK) 
provided for use in this study are: thermometer, syringe, needle, and pre-filled syringe for 
PCV20. All medical devices are CE marked and will be used for their intended use. 
Instructions for medical device use are provided in the package insert. 
All device deficiencies (including malfunction, use error and inadequate labeling) shall be 
documented and reported by the investigator throughout the clinical investigation (see 
Sections 8.3.6 and 10.3) and appropriately managed by GSK.  
6.2 
Preparation, Handling, Storage, and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received, and any discrepancies are 
reported and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention, and only authorized 
study site staff may supply or administer study intervention.  
All study interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized study site staff. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s). 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records). 
The investigator, a member of the study site staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study interventions using the Drug 
Accountability Form. These forms must be available for inspection at any time. 
Further guidance and information for the final disposition of unused study interventions are 
provided in the Pharmacy Manual. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Participation Identification 
Participant identification numbers (IDs) will be assigned sequentially to the participants who 
have consented to participate in the study, according to the range of participant IDs allocated 

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to each study center. The participant IDs will be documented in the electronic Case Report 
Form (eCRF). 
The eligibility of the participant will be determined based on the inclusion and exclusion 
criteria listed in Section 5.0. The participant ID will be the participant’s unique identification 
number for all eCRFs and associated study documentation that will be used for duration of the 
study. If the participant is terminated from the study, their participant ID cannot be 
re-assigned. 
6.3.2 
Randomization to Study Intervention 
All eligible participants will be centrally randomized to the study group at a 1:1 ratio using 
Interactive Web Response System (IWRS) randomization (refer to Glossary of Terms for a 
definition of IWRS).  
The participants will receive a unique intervention number (refer to Glossary of Terms for a 
definition of a treatment number). Once a treatment number has been assigned, it cannot be 
re-assigned. 
6.3.3 
Intervention Allocation to the Participant 
Approximately 1090 eligible participants will be randomly (1:1) assigned to 2 study groups 
using a centralized randomization system on internet at Visit 1 (Day 1). The randomization 
algorithm will use a minimization procedure accounting for age (60 to 69, 70 to 79 or 
≥80 years) and center. Minimization factors will have equal weight in the minimization 
algorithm. 
After obtaining the signed and dated Informed Consent Form (ICF) from the participant and if 
the participant eligible, the delegated clinical trial staff will access IWRS. Upon entering the 
participant ID and age, the randomization system will determine the treatment group and 
provide the treatment number to be used for the trial intervention. The treatment number(s) to 
be used for subsequent dose administration(s) will be provided by the same IWRS. 
Instructions related to instances when IWRS is not available will be provide to the site. 
Refer to the IWRS user manual for additional information related to the treatment number 
allocation. 
6.3.4 
Allocation of Participants to Assay Subsets 
Immunogenicity assessments are planned as outlined in Section 8.1.  
Refer to Section 9.2 for descriptions of analysis populations. 

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6.3.5 
Blinding and Unblinding 
This is an open-label study. The participant and principal investigator will not be blind to the 
intervention administered.   
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There will be 
no link between the study intervention and the identity of the participant. 
6.4 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The mode of administration (i.e., 
intramuscularly), laterality, as well as the date and time of each dose administered in the clinic 
will be recorded in the source documents. See Section 6.1 for details in intervention 
administration.  
6.5 
Dose Modification 
Not applicable. 
6.6 
Treatment of Overdose 
Any dose of any study vaccine greater than the one required per protocol is considered an 
overdose. All cases of vaccine overdose should be reported as protocol deviations. Any signs 
or symptoms resulting from an overdose should be reported as AEs, or SAEs if SAE criteria 
are met; overdose per se should not be reported as an AE/SAE. GSK does not recommend 
specific treatment for an overdose; however, any resulting adverse reaction should be treated 
symptomatically. 
6.7 
Concomitant Therapy 
At each study visit/contact, the investigator or his/her delegate should question the participant 
and/or the participant’s caregiver about all medications/products taken, and vaccinations 
received by the participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the eCRF: 
• All concomitant medications including vaccines, except vitamins and dietary supplements, 
administered after the first dose of study intervention (Day 1 to EoS). 
• All concomitant medications leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines (Refer to Section 5.2.2 and 
Section 9.2.1). 

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• All concomitant medication which may explain/cause/be used to treat an SAE including 
vaccines/products, as defined in Sections 8.3.1 and 10.3.6. These must also be recorded in 
the Expedited Adverse Event report. 
• Any prophylactic medication (eg, analgesics, antipyretics) administered on the day of 
study vaccination in the absence of any symptom and in anticipation of a reaction to the 
vaccination. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 

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7.0 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific study sites or of the study as a whole are detailed in 
Section 10.1.10. 
7.1 
Discontinuation of Study Intervention 
Discontinuation of study intervention refers to any participant who has not received all 
planned doses of study intervention. A participant who discontinued study intervention may 
continue other study procedures (e.g., safety or immunogenicity), planned in the study 
protocol at the discretion of the investigator.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• Adverse event requiring expedited reporting to IQVIA  
• Unsolicited non-serious adverse event  
• Solicited adverse event 
• Not willing to be vaccinated 
• Other (specify) 
If a participant who does not meet enrollment criteria is inadvertently enrolled, that participant 
must be discontinued from study intervention and IQVIA must be contacted. An exception 
may be granted in rare circumstances for which there is a compelling safety reason to allow 
the participant to continue. In these rare cases, the investigator must obtain documented 
approval from GSK, or designee, to allow the participant to continue in the study. 
Participants who discontinue study intervention will not be replaced. 
7.1.1 
Contraindications to Subsequent Study Intervention Administration 
The eligibility for subsequent study intervention administration in the control group must be 
confirmed before administering any additional dose.  
Participants who meet any of the criteria listed below or criteria listed in sections 5.2.1 and 
5.2.2 should not receive additional doses of study intervention. Such participants should be 
encouraged to continue other study procedures, at the investigator’s discretion (10.3). All 
relevant criteria for discontinuation of study intervention administration must be recorded in 
the eCRF.  
• Participants who experience any SAE judged to be possibly or probably related to the first 
study intervention (PCV20 vaccine) and that, in the opinion of the investigator, may pose 

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additional risk to the participant if he/she receives the second study intervention (RSV 
investigational vaccine).  
• 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 study intervention(s) from Visit 1 onwards. 
• Any condition that in the judgment of the investigator would make intramuscular injection 
unsafe. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, or 
compliance, or administrative reasons. This is expected to be uncommon. 
A participant is considered to have withdrawn from the study if no new study procedure has 
been performed or no new information has been collected for him/her since the date of 
withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who did not return 
for the concluding visit/was not available for the concluding contact planned in the protocol.  
Investigators/site designee will attempt to contact participants who do not return for scheduled 
visits or follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact with 
the participant will be included in the study analyses. 
The primary reason for study withdrawal will be documented in the eCRF, based on the list 
below: 
• Adverse events requiring expedited reporting to IQVIA (see Appendix 3 for details 
regarding such events) 
• Unsolicited non-serious AEs 
• 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/the participant’s caregiver(s) has 
withdrawn consent and the reason for withdrawal was provided, the investigator must 
document this reason in the eCRF. 

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Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will follow 
participants who are withdrawn from the study due to an AE/SAE until the event is resolved 
(see Appendix 3 for details regarding follow-up AEs). 
7.3 
Lost to Follow-up 
A participant will be considered ‘lost to follow-up’ if he/she fails to return for scheduled visits 
and cannot be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The study site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls, and if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  
• Study site personnel, or an independent third party, will attempt to collect the vital status 
of the participant within legal and ethical boundaries for all participants randomized, 
including those who did not get study intervention. Public sources may be searched for 
vital status information. If vital status is determined as deceased, this will be documented, 
and the participant will not be considered lost to follow-up. Sponsor personnel will not be 
involved in any attempts to collect vital status information. 
• If the participant indicates he/she does not want to continue with the study, he/she will be 
contacted for a final assessment for safety reasons; he/she will be withdrawn from the 
study with reason of “withdrawal of consent. 

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8.0 STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management of 
immediate safety concerns for the participant.  
Immediate safety concerns should be discussed with IQVIA as soon as they occur or when the 
study team becomes aware of them. The purpose of this communication is to determine if the 
participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarized in the SoA (Section 1.3).  
Adherence to the study design requirements, including those specified in Section 1.3, is 
essential and required for study conduct. 
All screening evaluations must be completed, and the results reviewed before confirming that 
potential participants meet all eligibility criteria. Participants who have signed informed 
consent but are not eligible to proceed should be recorded in the eCRF with a status of ‘screen 
failure’ (Section 5.5). 
If local regulations allow and quality of study procedures is maintained, participants can be 
offered remote visits (e.g., telemedicine, home visits) for the collection of biological samples 
and/or safety data/safety assessment(s). These remote visits must be performed by qualified 
study staff/healthcare professionals (HCPs).   
Following procedures can be performed remotely/virtually (refer to the Glossary of Terms for 
the definitions of telemedicine, remote and virtual visits): 
• Safety follow-up may be performed by telemedicine which will use secure video 
conferences, phone calls, and a web portal and/or mobile application (or eDiary) as a way 
of communicating with the participant and monitoring the participant’s progress. In 
addition, qualified study staff/HCPs may also identify AEs and report them to the 
investigator for evaluation.  
• Biological samples may be collected remotely by qualified study staff/HCPs. Biological 
samples should be collected only if they can be processed in a timely manner and 
appropriately stored until the intended use. Remote collection of cell-mediated immunity 
(CMI) samples is not allowed except for in special circumstances and with the approval of 
the GSK Central study team. 
• In exceptional situations (e.g., pandemic), the following approach may be considered: 
o If despite best efforts it is not possible to administer the dose of study intervention 
as defined in the protocol, additional 30 days may be added to the Visit 2 interval 
(only for RSV investigational vaccine administration in the Control group). 

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Impact on the per protocol set (PPS) for immunogenicity will be determined on a case-by-case 
basis. 
For information on the role of a caregiver in study assessments and procedures, please refer to 
Section 5.3. 
Procedures conducted as part of routine clinical management (e.g., hematologic profiles), and 
obtained before the participant/participant’s caregiver signed the ICF, may be used for 
screening and/or for establishing a clinical baseline (provided the procedure met protocol 
specified criteria and was performed within the time frame defined in the SoA [Section 1.3]). 
8.1 
Immunogenicity Assessments 
Biological samples will be used for research planned in the protocol and for purposes related 
to the improvement, development and quality assurance of the laboratory tests described in 
this protocol.  
Findings in this or future studies may make it desirable to use samples acquired in this study 
for research not planned in this protocol. In this case, all participants in countries where this is 
allowed will be asked to give consent to allow GSK or a contracted partner, to use the samples 
for further research. The further research will be subject to prior IEC/IRB approval, if required 
by local legislation. 
More specifically, part of the blood sample collected from the participants in this study may 
be used to perform qualification, validation and/or assay maintenance of future streptococcus 
pneumonia humoral assays. 
Information on further research and its rationale can be obtained from GSK.  
Sample testing will be done in accordance with the recorded consent of the individual 
participant/participant’s caregiver.  
By default, collected samples will be stored for a maximum of 20 years. This storage period 
begins when the last participant performs the last study visit. This timeline can be adapted 
based on local laws, regulations or guidelines requiring different timeframes or procedures. In 
all cases, the storage period should be aligned with participant’s consent. These additional 
requirements must be formally communicated to, discussed and agreed with GSK or designee.  

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8.1.1 
Biological Samples 
An overall approximate volume of 15 mL per visit will be collected during the entire study 
period. Refer to Table 6 and Section 1.3 for details of volumes collected for different 
assessments. 
Table 6 
Biological Samples 
Sample type 
Quantity 
Unit 
Timepoint 
Group 
Blood for humoral response 
~15 per visit 
mL 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
All participants in the  
Co-ad group  
Blood for humoral response 
~15 per visit 
mL 
Visit 1 (Day 1) 
Visit 2 (Day 31) 
Visit 3 (Day 61) 
All participants in the 
Control group 
 
The approximate volume of blood that will be collected per participant during the entire study 
period is as follows: 
• 
Co-ad group: 2 × ~15 mL = ~30 mL 
• 
Control group: 3 × ~15 mL = ~45 mL 
8.1.2 
Laboratory Assays 
All laboratory testing will be performed at a GSK laboratory or in a laboratory designated by 
GSK. 
Table 7 
Laboratory Assays 
Assay Type 
System 
Component 
Method 
Laboratory 
Humoral 
immunity 
(antibody 
determination) 
Serum 
RSV-A Ab 
Neutralization 
GSK* 
RSV-B Ab 
Neutralization 
Streptococcus pneumoniae - serotype 1 Ab 
Streptococcus pneumoniae - serotype 3 Ab 
Streptococcus pneumoniae - serotype 4 Ab 
Streptococcus pneumoniae - serotype 5 Ab 
Streptococcus pneumoniae - serotype 6A Ab  
Streptococcus pneumoniae - serotype 6B Ab 
Streptococcus pneumoniae - serotype 7F Ab  
Streptococcus pneumoniae - serotype 8 Ab 
Streptococcus pneumoniae - serotype 9V Ab  
Streptococcus pneumoniae - serotype 10A Ab 
Streptococcus pneumoniae - serotype 11A Ab 
Streptococcus pneumoniae - serotype 12F Ab 
Multiplexed 
Opsonophagocytosis 
Assay (MOPA) 

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Blood sampling timepoint 
Subset tested 
N of 
participants 
Component 
Type of 
contact and 
timepoint 
Sampling 
timepoint 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 6B 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 7F 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 8 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 9V 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
10A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
11A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
12F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 14 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
15B Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
18C Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
19A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
19F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
22F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
23F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
33F Opsonophagocytic Antibodies 
Visit 2 (Day 
31) 
Post-dose 1  
All participants  
545 
RSV-A neutralizing antibody 
 
 
All participants 
545 
RSV-B neutralizing antibody  
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 1 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 3 
Opsonophagocytic Antiboides 

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Blood sampling timepoint 
Subset tested 
N of 
participants 
Component 
Type of 
contact and 
timepoint 
Sampling 
timepoint 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 4 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 5 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 6A 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 6B 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 7F 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 8 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 9V 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
10A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
11A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
12F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 14 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
15B Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
18C Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
19A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
19F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
22F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
23F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
33F Opsonophagocytic Antibodies 
 
 

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Blood sampling timepoint 
Subset tested 
N of 
participants 
Component 
Type of 
contact and 
timepoint 
Sampling 
timepoint 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
23F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
33F Opsonophagocytic Antibodies 
Visit 2 
(Day 31) 
Post-PCV dose All participants  
545 
Streptococcus pneumoniae - serotype 1 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 3 
Opsonophagocytic Antiboides 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 4 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 5 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 6A 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 6B 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 7F 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 8 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 9V 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
10A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
11A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
12F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 14 
Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
15B Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
18C Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
19A Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
19F Opsonophagocytic Antibodies 

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Blood sampling timepoint 
Subset tested 
N of 
participants 
Component 
Type of 
contact and 
timepoint 
Sampling 
timepoint 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
22F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
23F Opsonophagocytic Antibodies 
 
 
All participants  
545 
Streptococcus pneumoniae - serotype 
33F Opsonophagocytic Antibodies 
 
Pre-RSV dose 
All participants  
545 
RSV-A neutralizing antibody 
 
 
All participants 
545 
RSV-B neutralizing antibody  
Visit 3 
(Day 61) 
Post-RSV dose All participants  
545 
RSV-A neutralizing antibody 
 
 
All participants 
545 
RSV-B neutralizing antibody  
Abbreviations: N=number; RSV=respiratory syncytial virus; PCV=pneumococcal conjugate vaccine 
8.1.4 
Immunological Correlates of Protection 
No generally accepted immunological correlate of protection has been demonstrated so far for 
the antigen(s) used in the RSVPreF3 OA investigational vaccine.  
8.2 
Safety Assessments 
The investigator and his/her designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and designees are 
responsible for following up AEs that are serious, considered related to the study intervention 
or the study, or that caused the participant’s withdrawal from the study intervention or study. 
8.2.1 
Pre-Vaccination Procedures 
8.2.1.1 
Collection of Demographic Data 
Record demographic data according to local regulations such as year of birth, sex, race, and 
ethnicity will be collected on the eCRF. Collection of sex, race and ethnicity data is necessary 
to assess and monitor the diversity of the trial participants. 
*Differences in the safety and efficacy of certain medical products, including vaccines, have 
been observed in racially and ethnically distinct subgroups.6,7,8  These differences may be 
attributable to intrinsic factors (e.g., genetics, metabolism, elimination), extrinsic factors (e.g., 
diet, environmental exposure, sociocultural issues), or interactions between these factors. 
Therefore, both geographic ancestry (race) and ethnicity will be collected for all study 
participants. 

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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 study intervention in the eCRF. 
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. 
History of following vaccine administration should be recorded in eCRF. 
• Any vaccine administered up to 1 year before study vaccine administration (if 
possible, with the date of vaccination) 
• PPSV administration up to 5 years before first study vaccine administration 
• PCV administration any time before study vaccine administration 
• Recombinant zoster vaccine (Shingrix) administration any time before study vaccine 
administration 
8.2.1.4 
Targeted Physical Examinations 
History directed physical examination will be performed for each participant on Day 1. If the 
investigator determines that the participant’s health on the day of study intervention 
administration temporarily precludes dosing, the visit will be rescheduled. Refer to the 
Section 5.6 for the list of criteria for temporary delay of study intervention administration. 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate health 
care provider. 
Physical examination at each study visit after the study intervention administration visit, will 
be performed only if the participant/participant’s caregiver indicates during questioning that 
there might be some underlying pathology(ies) or if deemed necessary by the investigator or 
delegate. 
8.2.1.5 
Body Temperature 
The body temperature of each participant needs to be measured prior to any study intervention 
administration and recorded in the eCRF. The route for measuring temperature can be oral or 
axillary. If the participant has fever (fever is defined as temperature ≥38.0 °C (100.4 °F) 
regardless the location of measurement) on the day of vaccination, the vaccination visit will be 
rescheduled within the allowed interval for this visit.  

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8.2.2 
Safety Contact at 6 Months Post-Last Vaccination 
Six months after the last dose of study vaccine (i.e., Month 6 for participants in the co-ad 
group and Month 7 for participants of the control group), each participant should be contacted 
to check if he/she has experienced any SAEs or any pIMDs since last study intervention 
administration, and to collect information on concomitant medications/vaccinations. 
Multiple formats can be proposed by the site staff to organize these contacts. This contact may 
be done via email, text message, fax, or phone call for example. The most appropriate format 
should be agreed between site staff and the study participant. 
Text messages, email, and fax may be used as a screening to check if the participant has 
anything to report. If the participant answers "Yes" for at least one of the items of interest, a 
phone call must be made to get the details on the event(s).  
Data collected via phone calls and text messages will have to be recorded in source 
documents. E-mails and faxes can be archived in source documents. Receipt of the message 
must be confirmed by the participant or caregiver, as applicable. 
8.2.3 
Clinical Safety Laboratory Tests 
No clinical safety laboratory tests are scheduled for this study. 
8.3 
Adverse Events, Serious Adverse Events, and Other Safety Reporting 
Solicited and unsolicited AEs, SAEs and other safety reporting (potential immune-mediated 
diseases [pIMDs]) are to be reported as indicated in this protocol; Refer to Table 1 (co-ad 
group) and Table 2 (control group). The administration site solicited AEs that will be collected 
are erythema, pain, and swelling. The systemic solicited AEs that will be collected are 
arthralgia, fatigue, fever, headache, and myalgia. 
Safety monitoring is specified in Figure 1 and in the endpoints (Section 3.0). 
The definitions of AEs and SAEs can be found in Appendix 3. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up on AEs that are serious, considered related to the study intervention or study 
procedures, or that caused the participant to discontinue the study/study intervention (see 
Section 7.0). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 

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8.3.1 
Time Period and Frequency for Collecting AE, SAE, and pIMD Information 
All AEs (regardless of the assessment of relatedness to the study vaccines), including all SAEs 
and all pIMDs will be collected from the first study intervention administration. All SAEs and 
all pIMDs will be collected until 6 months after the last study intervention administration at 
the timepoints specified in the SoA (Section 1.3). 
AEs (including SAEs and pIMDs) leading to withdrawal from the study will be collected from 
the time of the first study intervention administration until the participant is discharged from 
the study. 
In addition, SAEs assessed as related to study participation (e.g., protocol-mandated invasive 
procedures) or assessed as related to any other GSK product (non-IMP) will be recorded from 
the time a participant consents to participate in the study until the participant is discharged 
from the study. 
All AEs will be collected in the timeframe showed in Table 9. 
The investigator or designee will record and immediately report all SAEs to IQVIA via the 
Expedited AE Reporting Form. Reporting should, under no circumstances, occur later than 
24 hours after the investigator becomes aware of an SAE, as indicated in Appendix 3. The 
investigator will submit any updated SAE data to IQVIA within 24 hours of it being available. 

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related to the study intervention or study participation, the investigator must promptly notify 
IQVIA. 
8.3.2 
Method of Detecting AEs, SAEs, and pIMDs 
Detecting and recording of AE/SAE/pIMDs are detailed in Appendix 3. 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting safety reports are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of participants is the preferred method of acquiring 
information related to an AE/SAE/pIMD. 
8.3.3 
Follow-up of AEs, SAEs, and pIMDs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and pIMDs as defined in Section 10.3.3.1 
will be followed until resolution, stabilization, the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is provided in Section 10.3.5. 
8.3.4 
Regulatory Reporting Requirements for SAEs and Other Events 
Once an investigator (or designee) becomes aware that a study participant has experienced an 
SAE/pIMD, it must be reported to IQVIA using the required documentation and within the 
timeframes mentioned in Table 11. This is essential for meeting GSK legal obligations and 
ethical responsibilities for participant safety and the safety of a study intervention under 
clinical investigation. 
For SAEs/pIMDs, the investigator must always provide an assessment of causality at the time 
of the initial report, as defined in the Appendix 3. 
Local regulatory requirements and sponsor policy for preparation of an investigator safety 
report of Suspected Unexpected Serious Adverse Reactions (SUSAR) must be followed. 
These reports will be forwarded to investigators as necessary. 
GSK has the legal responsibility to notify local authorities/regulatory agencies about the 
safety of an investigational study intervention. GSK will comply with country--specific 
regulatory requirements related to safety reporting to the regulatory authority, IRB/IEC, and 
investigators. 
Refer to Appendix 3 for further details regarding the reporting of SAEs/pIMDs. 

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An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from GSK will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
Table 11 
Timeframes for Submitting SAE and Other Events Reports to IQVIA 
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 
pIMD=potential immune-mediated disease; SAE=serious adverse events.  
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD. 
‡ Paper Expedited Adverse Events Report may be submitted in the case that the electronic Expedited Adverse 
Report system is not functioning. The paper form will be dated and signed by the investigator (or designee). 
‡‡ 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. 
8.3.5 
Treatment of Adverse Events 
Any medication, vaccine or products 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. 
8.3.6 
Medical Device Deficiencies 
Medical devices are being provided for use in this study as the study intervention. To fulfill 
regulatory reporting obligations worldwide, the investigator is responsible for the detection 
and documentation of events meeting the definitions of device deficiency that occur during the 
study with such devices. 
The definition of a medical device deficiency can be found in Appendix 3. 
NOTE: Device deficiencies that lead to an AE/SAE will be reported as an AE/SAE following 
the processes outlined in Appendix 3 of the protocol.  
8.3.6.1 
Time Period for Detecting Medical Device Deficiencies 
Medical device deficiencies will be detected, documented, and reported during all periods of 
the study in which the medical device is used. 
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such a device deficiency might have led to an SAE if 

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appropriate action had not been taken, intervention had not occurred, or circumstances had 
been less fortunate, the investigator will promptly notify GSK. 
The method of documenting medical device deficiencies is provided in Appendix 3. 
8.3.6.2 
Follow-up of Medical Device Deficiencies 
Follow-up applies to all participants, including those who discontinue study intervention. 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator. 
8.3.6.3 
Prompt Reporting of Device Deficiencies to the Sponsor 
Device deficiencies will be reported to the Sponsor or designee within 24 hours after the 
investigator determines that the event meets the protocol definition of a medical device 
deficiency. 
The medical device deficiency report form will be sent to GSK as described in Appendix 3.  
GSK will be the contact for the receipt of device deficiency reports. 
8.3.6.4 
Regulatory Reporting Requirements for Device Deficiencies 
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the Sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies. 
The investigator, or responsible person according to local requirements (e.g., the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/IEC. 
8.4 
Participant Card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to always 
keep the participant card in his/her/their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending physician/caregiver/family 
member that the participant is in a clinical study and that relevant information may be 
obtained by contacting the investigator or his/her backup. 

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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 this study. 
8.8 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.9 
Immunogenicity Assessments 
Immunogenicity is described in Section 8.1. 
8.10 Health Outcomes 
Not applicable for this study. 
8.11 Health Economics 
Health economics parameters are not evaluated in this study. 
 

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9.2 
Populations for Analysis  
Populations for analyses in this study are defined in Table 13. 
Table 13 
Analysis Sets 
Analysis Set 
Description 
Screened set 
All participants who were screened for eligibility. 
Enrolled set 
Participants who were randomized or received study intervention or have undergone 
an invasive procedure. 
ES 
All participants who received a study intervention. Analysis per group is based on the 
study intervention administered. 
PPS 
All eligible participants: 
• 
Who received all study interventions as per protocol 
• 
Had immunogenicity results pre- and post-dose 
• 
Complied with blood draw intervals (contribution of participants to PPS at 
specific timepoint will be defined by timepoint) 
• 
Without intercurrent medical conditions that may interfere with 
immunogenicity 
• 
Without prohibited concomitant medication/vaccination 
Abbreviations: ES=Exposed set; PPS=Per Protocol set.  
9.2.1 
Criteria for Elimination 
If the participant meets one of the criteria mentioned below or any listed in the Section 7.1.1, 
(contraindication to subsequent vaccination) or Section 5.2.1 (medical conditions) or 
Section 5.2.2 (prior and concomitant therapy), he/she may be eliminated from per protocol 
analysis. 
In case of unplanned administration of any medication mentioned in Section 5.2.2 during the 
study, this will be considered as a protocol deviation and the participant may be eliminated 
from the Per Protocol set (PPS). 
Participants may be eliminated from the PPS for immunogenicity if, during the study, they 
incur a condition that has the capability of altering their immune response (intercurrent 
medical condition) or are confirmed to have an alteration of their initial immune status. Refer 
to Glossary of Terms for the definition of intercurrent medical conditions. 
9.3 
Statistical Analyses 
The Statistical Analysis Plan (SAP) will be developed and finalized before first subject first 
visit (FSFV) and will include a more technical and detailed description of the statistical 

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analyses including the supportive analyses and demography summaries. This section is a 
summary of the planned statistical analyses of the primary and secondary endpoints. 
9.3.1 
Primary Endpoint(s)/Estimand(s) Analysis 
The primary endpoints are described in Section 3.0. The confirmatory analyses of 
non-inferiority will be based on the PPS. 
• Method for non-inferiority of the PCV20 in terms of opsonophagocytic (OP) Ab GMT 
between groups ratio for each of the pneumococcal vaccine serotypes at one month after 
the PCV20 dose (i.e., at Day 31 for both groups): 
o The 2-sided 95% CI for Group GMT ratio between the PCV20 administered alone 
(control group) over PCV20 (co-ad group) co--administered with the RSVPreF3 OA 
investigational vaccine will be derived from an analysis of covariance (ANCOVA) 
model* on log10 transformed titer. 
• Method for non-inferiority of RSV investigational vaccine in terms of RSV-A neutralizing 
antibody geometric mean titer (GMT) between groups ratio at one after the RSVPreF3 OA 
investigational vaccine dose (i.e., at Day 31 for the co-ad group and at Day 61 for the 
control group): 
o The 2-sided 95% CI for RSV-A neutralizing antibody GMT ratio between RSVPreF3 
OA investigational vaccine administered alone (control group) over RSVPreF3 OA 
investigational vaccine when co-administered with the PCV20 vaccine (co-ad group) 
will be derived from an ANCOVA model* on log10 transformed titer. 
• Method for non-inferiority of RSV investigational vaccine in terms of RSV-B neutralizing 
antibody geometric mean titer (GMT) between groups ratio at one after the RSVPreF3 OA 
investigational vaccine dose (i.e., at Day 31 for the co-ad group and at Day 61 for the 
control group): 
o The 2-sided 95% CI for RSV-B neutralizing antibody GMT ratio between RSVPreF3 
OA investigational vaccine administered alone (control group) over RSVPreF3 OA 
investigational vaccine when co-administered with the PCV20 vaccine (co-ad group) 
will be derived from an ANCOVA model* on log10 transformed titer. 

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*The model will include the intervention/treatment group and age category (age at 
vaccination: 60 to 69, 70 to 79 or ≥80 years) as fixed effects, and the pre-dose 
log10-transformed titer as covariate. Missing data will not be replaced. Titers below the 
assay cut-off will be replaced by half the assay cut-off; titers above the upper limit of 
quantification (ULOQ) will be replaced by the ULOQ. 
9.3.1.1 
Success Criteria for Non-inferiority and Testing sequence: 
1st Sequence: 
• The upper limit (UL) of the 2-sided 95% CI of the GMT ratio (control group divided by 
co-ad group) for each individual pneumococcal conjugate serotype as measured by OPA 
is ≤2. 
AND 
• The upper limit of the 2 sided 95% CI of the GMT ratio (control group divided by co-ad 
group) between the control group versus co-ad group for RSV-A neutralizing antibody 
titer one month after the RSVPreF3 OA investigational vaccine dose is ≤1.5. 
2nd sequence: 
• 
The upper limit of the 2 sided 95% CI of the GMT ratio (control group divided by co-ad 
group) between the control group versus co-ad group for RSV-B neutralizing antibody 
titer one month after the RSVPreF3 OA investigational vaccine dose is ≤1.5. 
Testing will progress in the 2nd sequence only if the 1st sequence is a success, so that no 
further adjustment of alpha is required. 
The NI margin of 2 for PCV20 is based on well documented criteria for pneumococcal 
vaccines which has been used for demonstrating the NI of PCV20 against PCV13.9 The NI 
margin of 1.5 for RSV is based on Center for Biologics Evaluation and Research (CBER) 
feedback.  
9.3.2 
Secondary Endpoint(s)/Estimand(s) Analysis 
Method for evaluation of humoral immune response to RSVPreF3 OA investigational vaccine 
when co-administered with the PCV20 or administered alone 
• Mean geometric increase for within participants ratios of the post-dose titer (at 1-month 
after the RSVPreF3 OA investigational vaccine dose) over the predose titer (at baseline) 
for RSV-A neutralizing Ab titers 
• Mean geometric increase for within participants ratios of the post-dose titer (at 1-month 
after the RSVPreF3 OA investigational vaccine dose) over the predose titer (at baseline) 
for RSV-B neutralizing Ab titers 
The other secondary endpoints, as detailed in Section 3.0, will have descriptive analyses of 
demography, immunogenicity, and safety detailed in the SAP. 

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9.4 
Interim Analysis 
9.4.1 
Sequence of Analysis 
The analyses will be performed stepwise: 
• A first analysis will be performed on all immunogenicity, reactogenicity and safety 
data available and as clean as possible, when data for at least primary and secondary 
endpoints up to Visit 2 (Day 31) (co-ad group) or Visit 3 (Day 61) (control group) are 
available for all participants. This analysis will be considered as final for those 
endpoints.  
• An End of Study analysis will include all data obtained until 6 months post-last dose.  
9.5 
Sample Size Determination 
The target enrollment will be approximately 1090 participants (545 in the group receiving the 
RSVPreF3 OA investigational vaccine co-administered with PCV20 (co-ad group) and 545 in 
the control group where RSVPreF3 OA investigational vaccine and PCV20 are administered 
in a staggered manner) to obtain at least 980 evaluable participants (490 in the co-ad group 
and 490 in the control group) for the evaluation of the primary objectives, assuming that 
approximately 10% of the enrolled participants will not be evaluable. 

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Table 14 
Overall power to demonstrate primary objectives: non-inferiority of the 
immunogenicity of RSVPreF3 OA investigational vaccine when co-administered 
with pneumococcal vaccine (PCV20) as compared to when administered alone- 
assuming 490 evaluable participants in each group 
Endpoint 
Standard 
deviation of 
log10 
concentration 
Reference 
ratio 
Non 
inferiority 
margin 
Type II 
error 
Power 
PCV Non-inferiority* (1-sided test with alpha=2.5%)  
GMTs Opsonophagocytic 
(OP) antibody (Ab)  
 
 
 
 
 
3 
0.572 
1.05 
2 
<0.01% 
>99.99% 
7F 
0.733 
1.05 
2 
0.01% 
99.99% 
19A 
0.771 
1.05 
2 
0.01% 
99.99% 
5 
0.782 
1.05 
2 
0.02% 
99.98% 
1 
0.789 
1.05 
2 
0.02% 
99.98% 
14 
0.792 
1.05 
2 
0.02% 
99.98% 
8 
0.797 
1.05 
2 
0.03% 
99.97% 
33F 
0.797 
1.05 
2 
0.03% 
99.97% 
9V 
0.825 
1.05 
2 
0.05% 
99.95% 
10A 
0.839 
1.05 
2 
0.06% 
99.94% 
11A 
0.843 
1.05 
2 
0.07% 
99.93% 
19F 
0.845 
1.05 
2 
0.07% 
99.93% 
6B 
0.882 
1.05 
2 
0.14% 
99.86% 
4 
0.902 
1.05 
2 
0.20% 
99.80% 
18C 
0.910 
1.05 
2 
0.22% 
99.78% 
6A 
0.927 
1.05 
2 
0.29% 
99.71% 
12F 
0.943 
1.05 
2 
0.37% 
99.63% 
22F 
0.966 
1.05 
2 
0.51% 
99.49% 
15B 
1.088 
1.05 
2 
1.96% 
98.04% 
23F 
1.096 
1.05 
2 
2.10% 
97.90% 
Global Type II error to show non-inferiority 
~6.2% 
 
Global power for PCV 
~93.8% 
RSV-A Non-inferiority* (1-sided test with alpha = 2.5%)  
GMTs RSV-A neutralization 
antibody 
0.45 
1.05 
1.5 
0.04% 
99.96% 

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Endpoint 
Standard 
deviation of 
log10 
concentration 
Reference 
ratio 
Non 
inferiority 
margin 
Type II 
error 
Power 
RSV-B Non-inferiority* (1-sided test with alpha = 2.5%)  
GMTs RSV-B neutralization 
antibody 
0.45 
1.05 
1.5 
0.04% 
99.96% 
Global Power for the study 
~6.28 
~93.7 
Abbreviations: Ab=antibody; GMT=geometric mean titer; OA=older adult; OP=opsonophagocytic; 
PCV=pneumococcal vaccine; RSV=respiratory syncytial virus. 
*Pass 2019 alpha=2.5%, Two-Sample T-Tests for Non-Inferiority Assuming Equal Variance and Equal mean, 
Power=100-the Type II error (Beta). The Global Type II error (Beta) has been adjusted using Bonferroni’s 
method (Global Type II error=sum of the individual Type II errors). 
For RSV: non-inferiority limit=0.176 (=log10[1.5]). 
For each PCV vaccine strain: non-inferiority limit=0.301 (=log10[2.0]). 
Reference Ratio=0.0212 (=log10[1.05]) 
Considering a slight interference of 1.05 in true GMTs in both groups with a common 
population standard error of 0.45 for the RSV-A and RSV-B neutralizing Ab and the 
respective SD’s for each of the PCV serotype in log10 transformed concentration, the study has 
at least 93.7% power to meet the primary objectives. 
 

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10.0 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
international ethical guidelines 
• Applicable International Council for Harmonisation (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 and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.  
Protocols and any substantial amendments to the protocol may require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• Notifying the IRB/IEC of SAEs, Device Deficiency or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the study site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other applicable 
local regulations. 
After reading the protocol, each investigator will sign the protocol signature page and send a 
copy of the signed page to IQVIA. The study will not start at any study site at which the 
investigator has not signed the protocol. 

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10.1.2 
Adequate Resources 
The investigator is responsible for supervising any individual or party to whom the 
investigator delegates study-related duties and functions conducted at the study site. 
If the investigator/institution retains the services of any individual or party to perform 
study-related duties and functions, the investigator/institution should ensure this individual or 
party is qualified to perform those study-related duties and functions and should implement 
procedures to ensure the integrity of the study-related duties and functions performed and any 
data generated. 
10.1.3 
Financial Disclosure 
Investigators and sub-investigators will provide GSK or designee with sufficient, accurate 
financial information as requested to allow GSK to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
10.1.4 
Recruitment Arrangements and Informed Consent Process 
Recruitment Arrangements 
• Potential participants will be invited to participate in this clinical study by the study 
personnel or clinical staff (including participants’ primary health physicians) in the clinic 
and/or through advertisement in appropriate resources such as, but not limited to, printed 
media, Internet, or social media. 
• Identification of potential participants can involve access to identifiable information such 
as medical records upon participants’ and/or caregiver’s signed authorization. Clinical 
center personnel will follow national standards and obey local regulations for protection of 
sensitive patient health information. 
• It is allowed that the investigator is also participant’s physician or treating clinician.  
Informed Consent Process 
• The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the participants and answer all questions regarding the 
study. 
• Potential participants must be informed that their participation is voluntary. They will be 
required to physically sign a statement of informed consent that meets the requirements of 
21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act requirements, privacy and data protection requirements, where 
applicable, and the IRB/IEC or study center. 

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• The medical record must include a statement that physical informed consent was obtained 
before the participant was enrolled in the study and the date the consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
• A physical copy of the ICF(s) must be provided to the participant and/or their caregiver(s). 
• The participant must provide consent by signing an ICF, which summarizes the study, 
includes a consent statement and provides documentation that the participant agrees to 
continue participating in the study.  
• Participants who are rescreened are required to sign a new ICF. 
10.1.5 
Data Protection 
Participants will be assigned a unique identifier (Section 6.3.1) by the investigator. Any 
participant records or datasets transferred to GSK will contain only the identifier. Name and 
any other information which would identify the participant will not be transferred.  
GSK will ensure protection of the personal data of the investigator and site staff which is 
collected within the framework of and for the purpose of the study.  
• The participant/participant’s caregiver(s) must be informed that their personal 
study-related data will be used by GSK in accordance with local data protection law. The 
level of disclosure must also be explained to the caregiver(s), that the participant’s data 
will be used as described in the informed consent. 
• The participant/participant’s caregiver(s) must be informed that their medical records may 
be examined by Clinical Quality Assurance auditors or other authorized personnel 
appointed by GSK, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
• The contract between Sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access. GSK 
and/or trusted third parties working on behalf of GSK and/or institutions working with 
GSK for the purposes of this study are contractually bound to protect participant coded 
data. GSK will protect participant coded data and will only share it as described in the 
ICF. 

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The participants must be notified about their rights regarding the use of their personal data in 
accordance with the data privacy section of the ICF.  
10.1.6 
Committees Structure 
Safety oversight will be provided by a SRT composed of GSK RSV OA project team 
members. An SRT is in place for each GSK product. It comprises of a global cross-functional 
team responsible for the ongoing assessment of benefit-risk for a product. The SRT 
contributes to the continual assessment of incoming new efficacy and safety information.  
GSK will obtain favorable opinion/approval to conduct the study from the appropriate 
regulatory agency, in accordance with applicable regulatory requirements, prior to a site 
initiating the study in that country. This includes IRBs/IECs for review and approval of the 
protocol and subsequent amendments, ICF and any other documentation. 
10.1.7 
Dissemination of Clinical Study Data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with applicable 
regulations/GSK policy. GSK will aim to register protocols summaries prior to study start and 
target results summaries submission within 12 months of primary/study completion date. 
Where external regulations require earlier disclosure, GSK will follow those timelines.  
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical 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, including a summary of trial results understandable to 
laypersons. The investigator is encouraged to share the plain language summary results with 
the study participants, as appropriate. The full study report will be made available upon 
request, after decision on marketing authorization by regulatory authorities. 
GSK will provide the investigator with the randomization codes and participant-level line 
listings for their site only after completion of the full statistical analysis. 
GSK intends to make anonymized 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. 

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10.1.8 
Data Quality Assurance 
All participant data related to the study will be recorded on printed or eCRF unless transmitted 
to GSK/IQVIA electronically (e.g., laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies for such review and inspection.  
GSK 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).  
GSK assumes accountability for actions delegated to other individuals (e.g., Contract 
Research Organizations). 
Quality tolerance limits (QTLs) will be pre-defined in the state location(s) to identify 
systematic issues that can impact participant safety and/or the reliability of study results. 
These pre-defined parameters will be monitored during the study. Important deviations from 
the QTLs and remedial actions taken will be summarized in the Clinical Study Report (CSR). 
Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring, involvement of central reading 
mechanism) methods, responsibilities, and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) are 
provided in the monitoring plan. 
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
Records and source documents pertaining to the conduct of this study, including signed ICFs, 
must be retained by the investigator for 25 years from issuance of the final CSR/equivalent 
summary unless local regulations or institutional policies require a longer retention period. No 
records may be destroyed during the retention period without the written approval of GSK. No 
records may be transferred to another location or party without written notification to GSK.  
10.1.9 
Source Documents 
The investigator/institution should maintain adequate and accurate source documents and 
study records that include all pertinent observations on each of the study site’s participants. 
Source data should be attributable, legible, contemporaneous, original, accurate, and 

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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).  
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Definition of what constitutes source data and its origin can be found in Glossary of Terms.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized study site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.10 
Study and Site Start and Closure 
First Act of Recruitment 
The start of study and the first act of recruitment are defined as first subject first visit (first 
ICF signature date) at a country-level.  
Study/Site Termination 
GSK or its designee reserves the right to close the study site or terminate the study at any time 
for any reason at its sole discretion, provided there is sufficient notice given to account for all 
participants safe exit from study.  
Regular closure of study sites will occur upon study completion. A study site is considered 
closed when all required data/documents and study supplies have been collected and a study 
site closure visit has been performed.  
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 

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Reasons for the early closure of a study site by GSK or investigator may include but are not 
limited to: 
For study termination: 
• Discontinuation of further study intervention development. 
For study site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, GSK’s procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants 
by the investigator 
• Discontinuation of further study intervention development 
• Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, GSK shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any Contract Research 
Organization(s) used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements. The investigator shall promptly inform the participant 
and should assure appropriate participant therapy and/or follow-up. 
10.1.11 
Publication Policy 
The results of this study may be published in peer reviewed scientific literature and/or 
presented at scientific meetings. The sponsor will comply with the requirements for 
publication of study results in accordance with standard editorial and ethical practice and as 
per the sponsor’s internal policy. Authorship will be determined by mutual agreement and in 
line with International Committee of Medical Journal Editors authorship requirements.  
 
 

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10.2 Appendix 2: Clinical Laboratory Tests 
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 Vero cells culture (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) 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 Estimated Dilution 60 (ED60) 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.10,11 For the testing of Phase III studies, 
secondary standards calibrated against the international reference12,13 will be included in every 
run to allow conversion into international units. 
 

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• 
Any device deficiency that might have led to an SAE if appropriate action had not been taken, 
intervention had not occurred, or circumstances had been less fortunate. 
10.3.3 
Adverse Events of Special Interest 
Potential immune-mediated diseases are the only adverse events of special interest (AESIs) 
collected during this study. 
10.3.3.1 
Potential Immune-Mediated Diseases 
Potential immune-mediated disease is a subset of AESIs that include autoimmune diseases 
and other inflammatory and/or neurologic disorders of interest which may or may not have an 
autoimmune etiology. AEs that need to be recorded and reported as pIMDs include those 
listed in the Table 17. Please refer to the Appendix 3 for reporting details. 
The investigator must exercise his/her medical/scientific judgment to determine whether other 
diseases have an autoimmune origin (i.e., pathophysiology involving systemic or 
organ-specific pathogenic autoantibodies) and should also be recorded as a pIMD. In addition, 
the investigator should categorize each pIMD either as a new onset condition (if it started 
following vaccination) or as an exacerbation of a preexisting chronic condition (if it 
exacerbated following vaccination) in the eCRF. In order to facilitate the documentation of 
pIMDs in the eCRF, a pIMD standard questionnaire and a list of preferred terms (PTs) and PT 
codes corresponding to the above diagnoses will be available to investigators at study start.

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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 
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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• 
Data on solicited events reported in the eDiary will be electronically transferred to the eDiary 
vendor, where it can be monitored by appropriately qualified site staff and sponsor staff 
through a web-based portal. Appropriately qualified site staff should monitor eDiary data 
online at frequent intervals for subject compliance and reported events that were of concern 
to the subject. 
• 
Refer to the eDiary Manual for more information regarding the use of eDiary.  
• 
For device deficiencies, it is very important that the investigator describes any corrective or 
remedial actions taken to prevent recurrence of the deficiency. 
o A remedial action is any action other than routine maintenance or servicing of a 
medical device where such action is necessary to prevent recurrence of a device 
deficiency. This includes any amendment to the device design to prevent 
recurrence. 
• 
If the site during the course of the study becomes aware of any serious, nonserious incident 
(including device deficiencies and malfunctions) related to any GSK non-IMP product they 
will report these events to GSK or to the concerned competent authority via the national 
spontaneous reporting system. 
10.3.5.1 
Time Period for Collecting and Recording AEs, SAEs, and pIMDs 
Time Period for Collecting and Recording AEs, SAEs, and pIMDs 
• 
All solicited events that occur during 7 days following administration of the dose of study 
intervention (Day 1 to Day 7) must be recorded into the eDiary, irrespective of intensity. All 
other AEs occurring within this time frame should be recorded onto/into the appropriate section 
of the eCRF, irrespective of their intensity or whether or not they are considered related to the 
study intervention. 
• 
All unsolicited AEs that occur during 30 days following administration of each dose/the dose of 
study intervention must be recorded onto/into the appropriate section of the eCRF, irrespective 
of their intensity or whether or not they are considered related to the study intervention. 
• 
All SAEs, and pIMDs that occur up to 6 months post last-dose of study intervention must be 
recorded onto/into the appropriate section of the eCRF, irrespective of their intensity or whether 
or not they are considered related to the study intervention. 

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10.4 Appendix 4: Abbreviations and Glossary of Terms 
 
Table 19 
Abbreviations List 
Abbreviation 
Definition 
Ab 
Antibody 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ANCOVA 
Analysis of Covariance 
C 
Celsius 
CBER 
Center for Biologics Evaluation and Research 
CD4 
Cluster of Differentiation 4 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CMI 
Cell-mediated immunity 
Co-ad 
Co-administration group 
COVID-19 
Coronavirus disease 2019 
CSR 
Clinical Study Report 
CTR 
Clinical Trial Regulation 
eCRF 
Electronic case report form 
DTaP 
Diphtheria-tetanus-pertussis 
EEC 
European Economic Community 
EoS 
End of Study 
EU 
European Union 
F 
Fahrenheit 
FSFV 
First subject first visit 
GCP 
Good Clinical Practice 
GMT 
Geometric mean titer 
GSK 
GlaxoSmithKline 
HCP 
Health care professional 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 

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Abbreviation 
Definition 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
ID 
Identification 
IEC 
Independent Ethics Committee 
IMP 
Investigational medicinal product 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
LSLV 
Last subject last visit 
MedDRA 
Medical Dictionary for Regulatory Activities 
MGI 
Mean geometric increase 
MMSE 
Mini-Mental State Examination 
MoCA 
Montreal Cognitive Assessment 
MOPA 
Multiplexed Opsonophagocytosis 
OA 
Older adult 
OP 
Opsonophagocytic 
PCV 
Pneumococcal Conjugate Vaccine 
pIMD 
Potential Immune-Medicated Disease 
PPS 
Per Protocol Set 
PPSV 
Pneumococcal polysaccharide vaccine 
RSV 
Respiratory syncytial virus 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAR 
Serious adverse reaction 
SoA 
Schedule of activities 
SRM 
Study Reference Manual 
SRT 
Safety Review Team 
ST 
Serotype 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
UADE 
Unanticipated adverse device effect 
UL 
Upper limit 
YOA 
Years of age 

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Table 20 
Glossary of Terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the use 
of a medicinal product, whether or not considered related to 
the medicinal product.  
An AE can therefore be any 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 AEs  
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).  
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. 
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 

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Enrolled participant: 
‘Enrolled’ means a participant’s agreement to participate in 
a clinical study following completion of the informed 
consent process. Potential participants who are screened for 
determining eligibility for the study, but do not participate 
in the study, are not considered enrolled, unless otherwise 
specified by the protocol.  
Refer to the Section 9.2 of the protocol for the definition of 
‘enrolled set’ applicable to the study.  
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, included 
in the per-protocol analysis. 
Immunological correlate of 
protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intercurrent medical 
condition: 
A condition that has the capability of altering the immune 
response to the study vaccine or is confirmed to have an 
alteration of the participant’s initial immune status. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
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. 
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. 
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. 
Participant: 
Term used throughout the protocol to denote an individual 
who has been contacted to participate or who participates in 

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the clinical study as a recipient of the study intervention 
(vaccine(s)/product(s)/control). 
Synonym: subject. 
Randomization: 
Process of random attribution of intervention to participants 
to reduce selection bias. 
Remote visit 
This term refers to the visit conducted in the place other 
than the study site. 
Serious Adverse Reaction 
All noxious and unintended responses to an IMP related to 
any dose administered that result in death, are life-
threatening, require patient hospitalization or prolongation 
of existing hospitalization, result in persistent or significant 
disability or incapacity, or are a congenital anomaly or birth 
defect.  
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 (eg, hospital 
records, clinical and office charts, laboratory notes, 
memoranda, participants' diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified 
after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x-
rays, participant files, and records kept at the pharmacy, 
laboratories and at medico-technical departments involved 
in the clinical trial). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Suspected Unexpected 
Serious Adverse Reaction 
A Suspected Unexpected Serious Adverse Reaction is a 
Serious Adverse Reaction whose nature, severity or 
outcome is not consistent with the reference safety 
information. 
Telemedicine 
The use of electronic information and telecommunications 
technologies (both video-based and audio-only) to facilitate 

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remote health care delivery, participant and professional 
health-related education, public health and health 
administration. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse event. 
Virtual visit 
This term refers to study visits conducted using multimedia 
or technological platforms. 
 

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10.5 Appendix 5: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the table of contents. 
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union because it neither significantly impacts the safety or physical/mental integrity of 
participants nor the scientific value of the study. 
Overall Rationale for Protocol Update: 
The Original Protocol is updated to version 2.0 to clarify the timeframe to collect adverse 
events, serious adverse events, and pIMDs in Appendix 3 of this document. Additionally, the 
Protocol Investigator Agreement has been added to this document. During this protocol update 
minor clarifications were added. 
(Added text is bold italic, deleted text is strikethrough) 
Section # and Name 
Description of Change 
Brief Rationale 
Protocol Investigator 
Agreement 
Added to the page after the 
Sponsor Signatory page. 
Included to avoid separate collection of 
signed Protocol Investigator Agreement. 
Sponsor signatory page 
Updated signatory: 
Mathieu Peeters, MD 
Maria Van Der Wielen, MD 
Original signatory on leave. 
1.1 Synopsis 
Edited text: 
Data Monitoring Committee/Other 
Committee: None 
Safety monitoring: the study will 
be conducted with oversight by the 
project Safety Review Team. 
Clarification 
1.3 Schema 
Edited text: 
AEs/SAEs leading to withdrawal 
from the study start up to study 
end 
Clarification 
2.3.1 Risk Assessment 
Added text to RSV investigational 
vaccine Mitigation Strategy: 
Participants with a history of 
hypersensitivity or severe allergic 
reaction to any component of the 
vaccine are excluded from study 
enrollment. 
Additional mitigation strategy for known 
hypersensitivity or severe allergic reaction. 
5.2.2 Prior and 
Concomitant Therapy 
Deleted bullet: 
• 
Administration of long-acting 
immune-modifying drugs or 
planned administration at any 
To minimize the interference due to 
external factors among study participants. 

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Section # and Name 
Description of Change 
Brief Rationale 
time during the study period 
(e.g., infliximab). 
Added bullet: 
• 
Administration of long-acting 
immune-modifying drugs 
during the period starting 
180 days before the 
administration of first dose of 
study interventions or 
planned administration at any 
time during the study period 
(e.g., infliximab). 
 
5.6 Criteria for 
Temporarily Delaying  
Added bullet: 
• 
Use of antipyretics and/or 
analgesics and/or antibiotics 
within 3 days prior to study 
intervention administration. 
Use of antipyretics and/or analgesics 
and/or antibiotics within 3 days may 
indicate an acute condition. 
6.1 Study Interventions 
Administered 
Edited text: 
Vial; suspension for suspension 
for injection 
Clarification 
6.6 Treatment of 
Overdose 
Added section 
To better guide investigators about what to 
do in case of an overdose. 
7.1 Discontinuation of 
Study Intervention 
Edited text: 
Adverse event requiring expedited 
reporting to IQVIA GSK 
Clarification 
10.3.5.1 Time Period for 
Collecting and Recording 
AEs, SAEs, and pIMDs 
Edited text: 
•All unsolicited AEs that occur 
during 30 days following 
administration of each dose/the 
dose of study intervention must be 
recorded onto/into the appropriate 
section of the eCRF (…) 
 
Added text: 
•All SAEs, and pIMDs that occur 
up to 6 months post last-dose of 
study intervention must be 
recorded onto/into the appropriate 
section of the eCRF, irrespective 
of their intensity or whether or not 
they are considered related to the 
study intervention. 
Clarification on timing of AE, SAE, and 
pIMD collection for this study. 
Summary of Changes 
Summary of Changes table was 
added to document updates to 
Original Protocol. 
Version control 

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11.0 REFERENCES 
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2. Shi T, Denouel A, Tiejen AK, et al. Global Disease Burden Estimates of Respiratory 
Syncytial Virus-Associated Acute Respiratory Infection in Older Adults in 2015: A 
Systematic Review and Meta-Analysis. The Journal od Infectious Diseases. 
2019;222(Supplement_7):S577-S583.doi:10.1093/infdis/jiz059. 
3. Dowell SF, Whitney CG, Wright C, et al. Seasonal patterns of invasive pneumococcal 
disease. Emerg Infect Dis., 2003; 9(5):573-9. doi: 10.3201/eid0905.020556. 
4. Weinberger DM, Harboe ZB, Viboud C, et al. Pneumococcal disease seasonality: 
incidence, severity and the role of influenza activity. Eur Respir J. 2014; 43(3):833-41. 
doi: 10.1183/09031936.00056813. 
5. GSK’s older adult respiratory syncytial virus (RSV) vaccine candidate shows 94.1% 
reduction in severe RSV disease and overall vaccine efficacy of 82.6% in pivotal trial 
(2022). GSK. Available at: https://www.gsk.com/en-gb/media/press-releases/gsk-s-
older-adult-respiratory-syncytial-virus-rsv-vaccine-candidate/ (Accessed: December 8, 
2022).  
6. Borchers AT, Chang C, Gershwin ME, et al.  Respiratory syncytial virus – a 
comprehensive review. Clin Rev Allergy Immunol. 2013;45:331-79. 
7. Pérez-Losada M, Posada D, Arenas M, et al. Ethnic differences in the adaptation rate 
of HIV gp120 from a vaccine trial. Retrovirology. 2009; 6:67. 
8. Kollmann TR. Variation between Populations in the Innate Immune Response to 
Vaccine Adjuvants. Front Immunol. 2013; 4:81. 
9. Essink B, Sabharwal C, Cannon K, et al. Pivotal Phase 3 Randomized Clinical Trial of 
the Safety, Tolerability, and Immunogenicity of 20-Valent Pneumococcal Conjugate 
Vaccine in Adults Aged ≥18 Years. Clin Infect Dis., 2022; 75(3):390-398. doi: 
10.1093/cid/ciab990. 
10. Barbas CF, Crowe JE, Cababa D, et al. Human monoclonal Fab fragments derived 
from a combinatorial library bind to respiratory syncytial virus F glycoprotein and 
neutralize infectivity. Proc Natl Acad Sci USA. 1992; 89(21):10164-8. 
11. Bates JT, Keefer CJ, Slaughter JC, et al. Escape from neutralization by the respiratory 
syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by 
changes in on-rate of binding to the fusion protein. Virology. 2014; 454-455: 139-44. 
12. McDonald JU, Rigsby P, Dougall T, et al. Establishment of the first WHO 
International Standard for antiserum to Respiratory Syncytical Virus: Report of an 
International collaborative study. Vaccine.2018; 36: 7641-7649.  
13. McDonald JU, Rigsby P, Atkinson E, et al. Expansion of the 1st WHO international 
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against RSV subtype B: An international collaborative study. Vaccine. 2020; 38: 
800-807. 

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Signature of Investigator 
PROTOCOL TITLE: A Phase III, open-label, randomized, controlled, multi-country study to 
evaluate the immune response, safety and reactogenicity of RSVPreF3 OA investigational 
vaccine when co-administered with 20 valent pneumococcal conjugate vaccine (PCV20) in 
adults aged 60 years and older.   
PROTOCOL NO: 
219276 
VERSION:  
 
Amendment v1.0  
This protocol is a confidential communication of GSK. I confirm that I have read this 
protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and 
that are consistent with Good Clinical Practices and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from GSK. 
Instructions to the investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the 
study center in which the study will be conducted. Return the signed copy to IQVIA. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator:      ___________________________            Date:  ________ 
Printed Name:                         ___________________________ 
Investigator Title:                    ___________________________ 
 
Name/Address of Center:               
___________________________ 
 
 
 
 
 
___________________________ 
 
 
 
 
 
___________________________