A Phase 2b, Open-label, Multi-center, Extension Study to Evaluate the Safety and Immunogenicity of a Revaccination Dose of the RSVPreF3 Older Adults (OA) Investigational Vaccine Administered Intramuscularly 18 Months Post-Dose 2 in Adults 60 Years and Older Who Participated in the RSV OA=ADJ-002 Study
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

 
 
 
 
Protocol Amendment 1 
 
Study ID:  213569 
 
Official Title of Study: A phase 2b, open-label, multi-center, extension 
study to evaluate the safety and immunogenicity of 
a revaccination dose of the RSVPreF3 older adults 
(OA) investigational vaccine administered 
intramuscularly 18 months post-Dose 2 in adults 60 
years and older who participated in the 
RSV OA=ADJ-002 study 
 
 
EudraCT number: 2020-000692-21 
 
Date of Document: 04-11-2020 
 
 

CONFIDENTIAL 
213569 (RSV OA=ADJ-011 EXT:002 MTH20) 
Protocol Amendment 1 Final 
4 November 2020 
1 
 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut, 89 
1330 Rixensart, Belgium 
Primary Study vaccines and 
numbers 
GlaxoSmithKline (GSK) Biologicals’ 
investigational respiratory syncytial virus (RSV) 
vaccine BIO RSV OA=ADJ (GSK3844766A) 
Other Study 
vaccine(s)/product(s) 
Not applicable 
eTrack study number and 
abbreviated title 
213569 (RSV OA=ADJ-011 EXT:002 MTH20) 
EudraCT number 
2020-000692-21 
Date of protocol 
Final: 2 July 2020 
Date of protocol amendment 
Amendment 1 Final: 4 November 2020 
Title 
A phase 2b, open-label, multi-center, extension 
study to evaluate the safety and immunogenicity of 
a revaccination dose of the RSVPreF3 older adults 
(OA) investigational vaccine administered 
intramuscularly 18 months post-Dose 2 in adults 60 
years and older who participated in the 
RSV OA=ADJ-002 study. 
Short title 
Extension study to evaluate the safety and 
immunogenicity of a revaccination dose of the 
RSVPreF3 OA investigational vaccine in adults 60 
years and older who participated in the RSV 
OA=ADJ-002 study.  
Based on GSK Biologicals’ Protocol WS v17.0 
© 2020 GSK group of companies or its licensor. 
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Protocol Amendment 1 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
213569 (RSV OA=ADJ-011 EXT:002 MTH20) 
EudraCT number 
2020-000692-21 
Date of protocol 
Final: 2 July 2020 
Date of protocol amendment 
Amendment 1 Final: 4 November 2020 
Title  
A phase 2b, open-label, multi-center, extension 
study to evaluate the safety and immunogenicity of a 
revaccination dose of the RSVPreF3 older adults 
(OA) investigational vaccine administered 
intramuscularly 18 months post-Dose 2 in adults 60 
years and older who participated in the 
RSV OA=ADJ-002 study.  
Sponsor signatory 
(Amended 4 November 2020) 
Marie Van Der Wielen, MD 
Clinical and Epidemiology R&D Project Lead, 
Older Adults project 
 
 
Signature 
 
 
 
Date 
 
 
 
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Protocol Amendment 1 Final 
4 November 2020 
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Protocol Amendment 1 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals SA. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.  
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study vaccines and other study-related duties and functions as described in 
the protocol. 
• 
To supervise any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site. 
• 
To ensure that any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site are qualified to perform those trial-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the participant and/or the participant’s legally acceptable representative.  
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).  
• 
To co-operate with a representatives of GSK Biologicals in the monitoring process 
of the study and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccines, and more generally about his/her 
financial ties with the sponsor. GSK Biologicals will use and disclose the 
information for the solely for the purpose of complying with regulatory 
requirements. 
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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
course of the study and for 1 year following completion of the study.  
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and other documents 
required by regulatory agencies for this study. 
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4 November 2020 
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eTrack study number and 
Abbreviated Title 
213569 (RSV OA=ADJ-011 EXT:002 MTH20) 
EudraCT number 
2020-000692-21 
Date of protocol 
Final: 2 July 2020 
Date of protocol amendment 
Amendment 1 Final: 4 November 2020 
Title 
A phase 2b, open-label, multi-center, extension 
study to evaluate the safety and immunogenicity of a 
revaccination dose of the RSVPreF3 older adults 
(OA) investigational vaccine administered 
intramuscularly 18 months post-Dose 2 in adults 60 
years and older who participated in the RSV 
OA=ADJ-002 study. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
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SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA  
Rue de l’Institut, 89 
1330 Rixensart, Belgium 
2. Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
3. Sponsor Study Monitor 
Refer to the local study contact information document. 
4. Sponsor Study Contact for Reporting of a Serious Adverse Event 
GSK Central Back-up Study Contact for Reporting SAEs: refer to the protocol section 
8.3.3.1. 
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
5. GSK Helpdesk for Emergency Unblinding 
Refer to the protocol Section 6.3.3.1. 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document history 
Document 
Date 
Original Protocol 
2 July 2020 
Amendment 1: 4 November 2020 
Overall Rationale for the Amendment:  
The protocol is amended to address the comments from the United States Food and Drug 
Administration (US FDA). Specifically, instructions to delay enrolment or vaccination of 
participants with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) 
infection or with known COVID-19 positive contacts have been updated. In addition, the 
requirement to obtain written approval from the Sponsor for a participant to receive a 
vaccine as part of mass vaccination for an unforeseen public health threat (e.g., 
pandemic) if the vaccine to be used according to the local governmental 
recommendations has been amended. Other changes have been made to align the protocol 
with the parent RSV OA=ADJ-002 study and other phase 3 studies in the project.  
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Section 5.2.2 Prior/ 
Concomitant therapy 
Wording for mass vaccination 
during a pandemic is updated. 
This change is made to acknowledge the FDA’s 
request to remove the requirement to obtain written 
approval from the Sponsor for a participant to receive 
a vaccine as part of mass vaccination for an 
unforeseen public health threat (e.g., pandemic) if the 
vaccine to be used according to the local 
governmental recommendations.  
Section 7.1.1 Criteria 
for temporary delay 
for enrolment and/or 
vaccination 
Wording for COVID-19-related 
delay of vaccination is updated. 
This change is made to acknowledge the FDA’s 
recommendation about the temporary delay of 
enrolment of vaccination of participants with 
symptoms suggestive of COVID-19 infection or 
known COVID-19 positive contacts. 
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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
Document history ..................................................................................................... 7 
List of main changes in the protocol and their rationale ............................................ 7 
1. 
PROTOCOL SUMMARY ........................................................................................ 14 
1.1. 
Synopsis ..................................................................................................... 14 
1.2. 
Schema ...................................................................................................... 14 
1.3. 
Schedule of Activities (SoA) ........................................................................ 15 
2. 
INTRODUCTION .................................................................................................... 18 
2.1. 
Study rationale ............................................................................................ 18 
2.2. 
Background ................................................................................................ 18 
2.3. 
Benefit/Risk assessment ............................................................................. 19 
2.3.1. 
Risk Assessment ......................................................................... 19 
2.3.2. 
Benefit Assessment ..................................................................... 20 
2.3.3. 
Overall Benefit/Risk Conclusion ................................................... 20 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 21 
4. 
STUDY DESIGN .................................................................................................... 22 
4.1. 
Overall design ............................................................................................. 22 
4.2. 
Scientific rationale for study design ............................................................. 23 
4.2.1. 
Rationale for study design ........................................................... 23 
4.3. 
Justification for dose ................................................................................... 24 
4.4. 
End of Study definition ................................................................................ 24 
5. 
STUDY POPULATION ........................................................................................... 25 
5.1. 
Inclusion criteria for enrolment .................................................................... 25 
5.2. 
Exclusion criteria for enrolment ................................................................... 25 
5.2.1. 
Medical conditions ....................................................................... 25 
5.2.2. 
Prior/Concomitant therapy (Amended 4 November 2020) ............ 26 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 27 
5.2.4. 
Other exclusions .......................................................................... 27 
5.3. 
Lifestyle considerations ............................................................................... 27 
5.4. 
Screen failures ............................................................................................ 27 
6. 
STUDY INTERVENTION ........................................................................................ 28 
6.1. 
Study intervention administered .................................................................. 28 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 28 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 29 
6.3.1. 
Participant identification ............................................................... 29 
6.3.2. 
Intervention allocation to the participant ....................................... 29 
6.3.3. 
Blinding and unblinding ................................................................ 29 
6.3.3.1. 
Emergency unblinding ................................................ 29 
6.4. 
Study intervention compliance .................................................................... 30 
6.5. 
Concomitant therapy ................................................................................... 30 
6.6. 
Dose modification ....................................................................................... 31 
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6.7. 
Intervention after the end of the study ......................................................... 31 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 31 
7.1. 
Discontinuation of study intervention ........................................................... 31 
7.1.1. 
Criteria for temporary delay for enrolment and/or 
vaccination (Amended 4 November 2020) ................................... 31 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 32 
7.3. 
Lost to follow-up.......................................................................................... 32 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 33 
8.1. 
Efficacy and/or immunogenicity assessments ............................................. 34 
8.1.1. 
Biological samples ....................................................................... 34 
8.1.2. 
Laboratory assays ....................................................................... 35 
8.1.3. 
Immunological read-outs .............................................................. 36 
8.1.4. 
Immunological correlates of protection ......................................... 36 
8.2. 
Safety Assessments ................................................................................... 36 
8.2.1. 
Pre-vaccination procedures ......................................................... 36 
8.2.1.1. 
Collection of demographic data .................................. 36 
8.2.1.2. 
Medical/vaccination history ......................................... 37 
8.2.1.3. 
Physical examination (Amended 4 November 
2020) .......................................................................... 37 
8.2.1.4. 
Warnings and precautions to vaccination ................... 37 
8.2.1.5. 
Pre-vaccination body temperature .............................. 37 
8.2.1.6. 
Distribution of paper diary cards ................................. 38 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and other 
events of interest ........................................................................................ 38 
8.3.1. 
Time period and frequency for collecting AEs, SAEs and 
other safety information (Amended 4 November 2020) ................ 38 
8.3.2. 
Method of detecting AEs and SAEs, and other events ................. 39 
8.3.3. 
Regulatory reporting requirements for SAEs and other 
events .......................................................................................... 39 
8.3.3.1. 
Contact information for reporting of SAEs and 
pIMDs ......................................................................... 40 
8.3.4. 
Treatment of adverse events ....................................................... 40 
8.3.5. 
Participant card ............................................................................ 40 
8.4. 
Treatment of overdose ................................................................................ 41 
8.5. 
Pharmacokinetics ....................................................................................... 41 
8.6. 
Pharmacodynamics .................................................................................... 41 
8.7. 
Genetics ..................................................................................................... 41 
8.8. 
Biomarkers ................................................................................................. 41 
8.9. 
Health outcomes ......................................................................................... 41 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 41 
9.1. 
Statistical hypotheses ................................................................................. 41 
9.2. 
Sample size determination .......................................................................... 41 
9.3. 
Populations for analyses ............................................................................. 42 
9.3.1. 
Criteria for elimination from analysis ............................................ 42 
9.3.1.1. 
Intercurrent medical conditions and 
concomitant medications/products/vaccines 
that may lead to elimination of a participant 
from per-protocol analyses ......................................... 42 
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9.4. 
Statistical analyses ..................................................................................... 42 
9.4.1. 
General considerations ................................................................ 42 
9.4.1.1. 
Demography ............................................................... 42 
9.4.1.2. 
Immunogenicity .......................................................... 42 
9.4.1.3. 
Reactogenicity/Safety ................................................. 43 
9.4.2. 
Demographics and participants disposition .................................. 43 
9.4.3. 
Primary endpoint .......................................................................... 44 
9.4.3.1. 
Safety analysis ........................................................... 44 
9.4.3.2. 
Humoral immune response up to 1 month post-
Dose 3 ........................................................................ 45 
9.4.4. 
Secondary endpoints ................................................................... 45 
9.4.4.1. 
Humoral immune response up to 1 month post-
Dose 3 ........................................................................ 45 
9.4.4.2. 
CMI response up to 1 month post-Dose 3 .................. 45 
9.4.4.3. 
SAEs and pIMDs up to 6 months post-Dose 3 ............ 46 
9.4.5. 
Tertiary endpoints ........................................................................ 46 
9.5. 
Interim analyses .......................................................................................... 46 
9.5.1. 
Sequence of analyses.................................................................. 46 
9.5.2. 
Statistical consideration for interim analysis ................................. 46 
9.6. 
Data Monitoring Committee (DMC) ............................................................. 46 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 47 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 47 
10.1.1. 
Regulatory and ethical considerations ......................................... 47 
10.1.2. 
Financial disclosure ..................................................................... 48 
10.1.3. 
Informed consent process ............................................................ 48 
10.1.4. 
Data protection ............................................................................ 48 
10.1.5. 
Committees structure ................................................................... 49 
10.1.6. 
Dissemination of clinical study data ............................................. 49 
10.1.7. 
Data quality assurance ................................................................ 49 
10.1.8. 
Source documents ....................................................................... 50 
10.1.9. 
Study and site start and closure ................................................... 51 
10.1.10. Publication policy ......................................................................... 51 
10.2. 
Appendix 2: Clinical laboratory tests ........................................................... 52 
10.2.1. 
Laboratory assays ....................................................................... 52 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of AE .................. 54 
10.3.1. 
Definition of an Adverse Event (AE) ............................................. 54 
10.3.1.1. Events Meeting the AE Definition ............................... 54 
10.3.1.2. Events NOT Meeting the AE Definition ....................... 55 
10.3.2. 
Definition of a Serious Adverse Event (SAE) ............................... 55 
10.3.3. 
Solicited events............................................................................ 56 
10.3.4. 
Unsolicited AEs............................................................................ 57 
10.3.5. 
Adverse events of special interest (AESIs) .................................. 57 
10.3.5.1. Potential immune-mediated diseases ......................... 57 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 60 
10.3.7. 
Recording and follow-up of AEs, SAEs, pIMDs ............................ 60 
10.3.7.1. Time period for collecting and recording AEs, 
SAEs, and pIMDs ....................................................... 60 
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10.3.7.2. Follow-up of AEs, SAEs, pIMDs ................................. 61 
10.3.7.2.1. Follow-up during the study ...................... 61 
10.3.7.2.2. Follow-up after the participant is 
discharged from the study 
(Amended 4 November 2020) ................. 61 
10.3.7.3. Updating of SAE, pIMD information after 
removal of write access to the participant’s 
eCRF .......................................................................... 61 
10.3.8. 
Assessment of intensity and toxicity ............................................. 62 
10.3.8.1. Assessment of intensity .............................................. 62 
10.3.8.2. Assessment of causality (Amended 4 
November 2020) ......................................................... 63 
10.3.8.3. Assessment of outcomes............................................ 64 
10.3.9. 
Reporting of SAEs, pIMDs ........................................................... 64 
10.3.9.1. Events requiring expedited reporting to GSK 
(Amended 4 November 2020) .................................... 64 
10.3.9.2. Back-up system in case facsimile or electronic 
reporting system does not work (Amended 4 
November 2020) ......................................................... 65 
10.4. 
Appendix 4: Abbreviations and glossary of terms ........................................ 66 
10.4.1. 
List of abbreviations ..................................................................... 66 
10.4.2. 
Glossary of terms ......................................................................... 68 
10.5. 
Appendix 5: Protocol Amendment history ................................................... 72 
11. REFERENCES (AMENDED 4 NOVEMBER 2020) ................................................. 74 
TRADEMARKS ............................................................................................................. 76 
 
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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities ............................................................................. 15 
Table 2 
Intervals between study visits ................................................................. 17 
Table 3 
Study objectives and endpoints .............................................................. 21 
Table 4 
Study groups, intervention and blinding foreseen in the study ................ 23 
Table 5 
Study intervention administered ............................................................. 28 
Table 6 
Contact information for emergency unblinding ....................................... 30 
Table 7 
Biological samples* ................................................................................ 35 
Table 8 
Laboratory assays .................................................................................. 35 
Table 9 
Immunological read-outs ........................................................................ 36 
Table 10 
Timeframes for collecting and reporting of safety information ................. 38 
Table 11 
Timeframes for submitting serious adverse events and other 
events reports to GSK (Amended 4 November 2020) ............................ 40 
Table 12 
Contact information for reporting of SAEs and pIMDs ............................ 40 
Table 13 
Populations for analyses ........................................................................ 42 
Table 14 
Solicited administration site events......................................................... 56 
Table 15 
Solicited systemic events ....................................................................... 57 
Table 16 
List of potential immune-mediated diseases (pIMDs) ............................. 58 
 
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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 22 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Rationale: 
GlaxoSmithKline Biologicals SA (GSK) is developing an RSV Prefusion protein 3 Older 
Adult (RSVPreF3 OA) investigational vaccine against respiratory syncytial virus (RSV)  
-associated (subtypes A and B) disease in adults aged  60 years.  
Different formulations of the RSVPreF3 OA investigational vaccine were administered 
intramuscularly for the first time to adults aged 60 – 80 years according to a 0, 2 months 
schedule in the parent study, RSV OA=ADJ-002 (208851). Based on safety and 
immunogenicity data from the parent study, the selected vaccine formulation is composed 
of RSVPreF3 recombinant antigen dose 120 µg adjuvanted with AS01E (hereafter 
referred to as 120 µg RSVPreF3/AS01E). The participants who received 2 doses of the 
selected formulation, as well as the participants who received vaccine formulations with 
the same adjuvant (RSVPreF3 recombinant antigen doses 30 µg and 60 µg adjuvanted 
with AS01E) in the parent study will be invited to participate in this study. 
All participants enrolled in the current study will receive a single dose of the selected 
RSVPreF3 OA investigational vaccine (120 µg RSVPreF3/AS01E) at approximately 
18 months after they received Dose 2 in the parent study, RSV OA=ADJ-002 (208851).  
The purpose of this study is to:  
i. 
evaluate the safety and reactogenicity of the third dose of the RSVPreF3 OA 
investigational vaccine in adults previously vaccinated in RSV OA=ADJ-002, Part B 
with formulations containing the same, selected adjuvant, and  
ii. evaluate the immunological response (boostability) of the third dose of the 
RSVPreF3 OA investigational vaccine in adults previously vaccinated with the same 
antigen (120 µg RSVPreF3/AS01E recipients in parent study receiving a third dose of 
the same vaccine). In addition, this study will also evaluate the immunogenicity of 
the vaccine in adults previously vaccinated in RSV OA=ADJ-002, Part B with the 
same, selected formulation of the RSVPreF3 OA investigational vaccine.  
Objectives and Endpoints: Please refer to Table 3. 
1.2. 
Schema 
Please refer to Figure 1 for a schematic presentation of the study design. 
 
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1.3. 
Schedule of Activities (SoA) 
Table 1 
Schedule of Activities  
Type of contact 
Visit 1 
Visit 2 
Contact 
Notes 
Timepoints 
Day 1*  
Day 31  
Month 6  
Informed consent  
● 
 
 
See Section 10.1.3 for details 
Check inclusion/exclusion criteria  
● 
 
 
See Sections 5.1 and 5.2 for Inclusion and Exclusion criteria 
Collect demographic data 
● 
 
 
See Section 8.2.1.1 for more information 
Medical and vaccination history** 
● 
 
 
See Section 8.2.1.2 for more information 
Physical examination  
● 
O 
 
See Section 8.2.1.3 for more information 
Vaccine(s)/product(s) 
Check contraindications, warnings and precautions to 
vaccination 
O 
 
 
See Section 8.2.1.4 for more information 
Check criteria for temporary delay for enrolment and 
vaccination 
O 
 
 
See Section 7.1.1 for more information 
Study group and intervention number allocation 
O 
 
 
See Section 6.3.2 for more information 
Pre-vaccination body temperature 
● 
 
 
The preferred location for measuring temperature will be the oral 
cavity. Fever is defined as temperature  38.0°C/100.4°F 
regardless the location of measurement. 
Recording of administered intervention number 
● 
 
 
 
Vaccine(s)/product(s) administration 
● 
 
 
See Section 6.1 for more information 
Distribution of diary cards  
O 
 
 
 
Laboratory assessments 
Blood sampling for antibody determination (20 mL)*** 
● 
● 
 
See Section 8.1.1 for more information 
Blood sampling for CMI response (25 mL)*** 
● 
● 
 
See Section 8.1.1 for more information 
Safety assessments 
Record concomitant medication/vaccination 
● 
● 
● 
See Section 6.5 for more information 
Record any intercurrent medical conditions 
● 
● 
● 
See Section 9.3.1.1 for more information 
Recording of solicited events (Days 1–4 post-vaccination)  
● 
● 
 
See Section 10.3.7 for more information 
Return of diary cards  
 
O 
 
 
Diary card transcription by investigator  
 
O 
 
 
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Type of contact 
Visit 1 
Visit 2 
Contact 
Notes 
Timepoints 
Day 1*  
Day 31  
Month 6  
Recording of unsolicited adverse events (Days 1-30 post-
vaccination)  
● 
● 
 
See Section 10.3.7 for more information 
Recording of SAEs, pIMDs  
● 
● 
● 
See Section 10.3.7 for more information 
Recording of SAEs related to study participation, or to a 
concurrent GSK medication/vaccine 
● 
● 
● 
See Section 10.3.7 for more information 
AEs/SAEs leading to withdrawal from the study 
● 
● 
● 
See Section 10.3.7 for more information 
Contact for safety follow-up 
 
 
● 
See Section 10.3.7.2 for more information 
Study Conclusion  
 
 
● 
See Section 4.4 for more information 
Note: The double-line borders indicate analyses which will be performed on all data obtained up to those time points. 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
O is used to indicate a study procedure that does not require documentation in the individual eCRF. 
CMI = Cell- Mediated Immunity; pIMDs = potential Immune-Mediated Diseases 
AE = Adverse Event; SAE = Serious Adverse Event 
*Visit 1 (Day 1) = 18 months post-Dose 2 in RSV OA=ADJ-002 study  
** Only for the transition period between the RSV OA=ADJ-002 parent study and the current extension study. Note that administration of Shingrix during the transition period and 
throughout the duration of the current study should be recorded in the eCRF (refer to Section 8.2.1.2).  
***Only for the group 120-AS01E_B: Selected formulation revaccinated with the same formulation 
 
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Table 2 
Intervals between study visits 
Interval 
Length of interval  
Recommended 
interval 
Allowed interval*** 
RSV OA=ADJ 002 Visit 4 (Month 2*) → Visit 1 
(Day 1**) 
540 days 
525-555 days  
510-570 days 
Visit 1 → Visit 2  
30 days 
30-42 days 
30-42 days 
Visit 1 → Contact  
180 days 
165-195 days  
165-195 days 
*Dose 2 in parent study RSV OA=ADJ-002 
**Dose 3 in current study RSV OA=ADJ-011 EXT:002 MTH20; 18 months post-Dose 2 in RSV OA=ADJ-002 study 
***During special circumstances if site visits are restricted (e.g., COVID-19 pandemic-related national restrictions) 
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2. 
INTRODUCTION 
2.1. 
Study rationale 
GlaxoSmithKline Biologicals SA (GSK) is developing an RSV Prefusion Protein F3 
Older Adult (RSVPreF3 OA) investigational vaccine against respiratory syncytial virus 
(RSV) -associated (subtypes A and B) disease in adults aged  60 years.  
Different formulations of the RSVPreF3 OA investigational vaccine were administered 
intramuscularly for the first time to adults aged 60 – 80 years according to a 0, 2 months 
schedule in the parent study, RSV OA=ADJ-002 (208851). Based on safety and 
immunogenicity data from the parent study, the selected vaccine formulation is composed 
of RSVPreF3 recombinant antigen dose 120 µg adjuvanted with AS01E (hereafter 
referred to as 120 µg RSVPreF3/AS01E). The participants who received 2 doses of the 
selected formulation, as well as the participants who received vaccine formulations with 
the same adjuvant (RSVPreF3 recombinant antigen doses 30 µg and 60 µg adjuvanted 
with AS01E) in the parent study will be invited to participate in this study.  
All participants enrolled in the current study will receive a single dose of the selected 
RSVPreF3 OA investigational vaccine (120 µg RSVPreF3/AS01E) at approximately 
18 months after they received Dose 2 in the parent study, RSV OA=ADJ-002 (208851).  
The purpose of this study is to: 
i. 
evaluate the safety and reactogenicity of the third dose of the RSVPreF3 OA 
investigational vaccine in adults previously vaccinated in RSV OA=ADJ-002, Part B 
with formulations containing the same, selected adjuvant, and  
ii. evaluate the immunological response (boostability) of the third dose of the 
RSVPreF3 OA investigational vaccine in adults previously vaccinated with the same 
antigen (120 µg RSVPreF3/AS01E recipients in parent study receiving a third dose of 
the same vaccine). In addition, this study will also evaluate the immunogenicity of 
the vaccine in adults previously vaccinated in RSV OA=ADJ-002, Part B with the 
same, selected formulation of the RSVPreF3 OA investigational vaccine.  
2.2. 
Background 
RSV is a ribonucleic acid virus of the Pneumoviridae family of which 2 antigenically 
distinct subgroups, referred to as RSV A and RSV B, exist [Rima, 2017]. RSV is a highly 
contagious human pathogen that causes respiratory tract infections in people of all ages. 
In temperate climates throughout the world, RSV predictably causes fall-winter 
epidemics [Simões, 2008], whereas viral activity is more endemic in (sub-) tropical 
regions and outbreaks are less temporally focused [Borchers, 2013]. 
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According to the ‘Centers for Disease Control and Prevention’ (CDC) website [CDC], 
RSV leads to 177 000 hospitalizations and 14 000 deaths on average each year among 
adults  65 YOA in the United States (US). As the global population ages, the morbidity 
and mortality of respiratory infections appear to be steadily increasing. In the US, the 
burden of the disease has been shown to be significant and data indicate that RSV is 
comparable to influenza (in an influenza vaccinated population) in terms of number of 
infections, hospitalization and deaths. 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 OA (  65 years) 
with influenza-like illness is 7.4%, with values between 0% and 17.1% across countries 
[Falsey, 2014]. 
Previous infection with RSV does not prevent subsequent infections. Therefore, re-
infection with RSV occurs throughout an individual’s lifetime and is common in all age 
groups [Simões, 1999; Krilov, 2011]. Generally, these re-infections go undiagnosed 
because they usually manifest as common acute upper respiratory tract infections. 
However, in more vulnerable individuals (e.g. immunocompromised persons or OA), re-
infections can also lead to severe disease despite the presence of serum RSV neutralizing 
antibodies, as very similar levels of RSV antibody response can be found in both OA and 
young adults [Graham, 2011; Cherukuri, 2013]. 
Despite the significant medical need in OA aged 60 years or above, there is currently no 
prophylactic vaccine approved for the prevention of lower respiratory tract disease 
(LRTD) caused by RSV. Additionally, no prophylactic treatments against RSV are 
available for this age population. Several attempts have been made to develop an RSV 
vaccine but to date all have been unsuccessful.  
Currently available treatment for RSV in OA is generally supportive in nature, consisting 
of supplemental oxygen, intravenous fluids and bronchodilators. Inhaled and systemic 
corticosteroids are often prescribed in patients with asthma or chronic obstructive 
pulmonary disease (COPD) [Falsey, 2000].  
Please refer to the current Investigator’s Brochure (IB) for information regarding pre-
clinical and clinical studies of RSVPreF3 OA investigational vaccine. 
2.3. 
Benefit/Risk assessment 
2.3.1. 
Risk Assessment 
Information about the known and expected benefits and risks and reasonably expected 
adverse events (AEs) of the RSVPreF3 OA investigational vaccine (potential syncope, 
hypersensitivity) or adjuvant system (potential immune-mediated diseases [pIMDs]) can 
be found in the IB and Development Safety Update Report.  
All participants will remain under observation at the clinical center for at least 30 minutes 
after vaccination. 
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Intramuscular vaccination commonly precipitates a transient and self-limiting local 
inflammatory reaction. This may typically include pain at injection site, erythema, and 
swelling. 
In addition to risks related to the vaccine, there may be risks related to the blood 
sampling planned in the study: 
• 
Pain and bruising may occur at the site where blood is drawn; as a mitigation 
strategy, a topical analgesic may be applied to the site where blood will be taken. 
• 
Syncope (fainting) can occur following or even before any blood draw as a 
psychogenic response to the needle insertion. 
For details of study procedures, dose and study design justification, refer to Sections 1.3 
and 4.2, respectively. 
2.3.2. 
Benefit Assessment 
The participants may not directly benefit from vaccination with the RSVPreF3 OA 
investigational vaccine because vaccine efficacy has not been assessed yet. Hence it is 
not known whether the RSVPreF3 OA investigational vaccine is effective in protecting 
against RSV disease. 
An indirect benefit is that the information obtained in this study will aid the development 
of an RSV vaccine, which is intended to prevent disease associated with RSV infection in 
older adults. 
Another benefit for all study participants may include gaining information about their 
general health status through the medical evaluations/assessments associated with this 
study (i.e., physical examination). 
2.3.3. 
Overall Benefit/Risk Conclusion 
The RSVPreF3 OA investigational vaccine is in clinical development. 
Considering the measures taken to minimize risk to participants in this study, the 
potential risks are justified by the potential benefits linked to the development of this 
vaccine. 
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 = Vaccination with one of 9 RSVPreF3 OA investigational vaccine formulations or placebo, in RSV OA=ADJ-002 study 
 = Vaccination of all study participants with RSVPreF3 OA investigational vaccine in current study 
N = number of participants; BS S = Blood sample for safety (hematology/biochemistry); BS H = blood sample for humoral immune responses; BS C = blood sample for CMI response 
AE = adverse event; SAE = serious adverse event; pIMD = potential immune mediated disease 
*Visit 1 (Day 1) = 18 months post-Dose 2 in RSV OA=ADJ-002 study  
**Only for the 120-AS01E_B group that received the same, selected formulation of RSVPreF3 OA investigational vaccine in RSV OA=ADJ-002 study 
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At the time of initiation of this extension study, the investigator will contact ONLY those 
participants who received the vaccine formulations with RSVPreF3 recombinant antigen 
doses 120 g, 30 g and 60 g adjuvanted with AS01E in the parent study 
RSV OA=ADJ-002 and who expressed a willingness to participate when questioned 
during the primary study. The reason for non-participation in the extension study will be 
documented in the site’s screening log, provided that the participant is willing to specify 
a reason.  
• 
Type of study: Extension of study RSV OA=ADJ-002 (208851) 
• 
Experimental design: Phase 2b, open-label, multi-center study with 3 parallel 
groups (Table 4). 
• 
Duration: Approximately 6 months per participant.  
• 
Primary completion date: One month post vaccination , i.e., Day 31 (Visit 2) 
• 
Control: None 
• 
Blinding: Open-label study  
• 
Data collection: electronic case report form (eCRF) 
Table 4 
Study groups, intervention and blinding foreseen in the study 
Study 
Groups 
Number of 
participants 
Age* 
(Min-Max) 
Intervention  
Blinding 
120-
AS01E_B 
~100 
60-80 years 
RSVPreF3 OA investigational 
vaccine  
Open 
30-
AS01E_B 
~100 
60-80 years 
RSVPreF3 OA investigational 
vaccine  
Open 
60-
AS01E_B 
~100 
60-80 years 
RSVPreF3 OA investigational 
vaccine  
Open 
*Age at the time of Dose 1 in the parent study RSV OA=ADJ-002 
Overview of the recruitment plan 
The study is planned to be conducted at sites in the US and Belgium.  
The participants who received RSVPreF3 recombinant vaccine formulations containing 
different doses of the same antigen (120 g, 30 g and 60 g) adjuvanted with AS01E in 
the parent study will be invited to participate in the current extension study. 
4.2. 
Scientific rationale for study design 
4.2.1. 
Rationale for study design 
The study has been designed as a phase 2b extension study to assess the safety and 
reactogenicity of a revaccination dose of the RSVPreF3 OA investigational vaccine in 
adults aged 60 years and above previously vaccinated in RSV OA=ADJ-002, Part B. 
There are 3 groups in this study: 
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• 
Participants in group 120-AS01E_B had received the RSVPreF3 OA investigational 
vaccine (120 µg RSVPreF3/AS01E) in the parent study RSV OA=ADJ-002  
• 
Participants in group 30-AS01E_B had received the vaccine formulation RSVPreF3 
recombinant antigen dose 30 g adjuvanted with AS01E in the parent study 
RSV OA=ADJ-002 
• 
Participants in group 60-AS01E_B had received the vaccine formulation RSVPreF3 
recombinant antigen dose 60 g adjuvanted with AS01E in the parent study 
RSV OA=ADJ-002 
In addition, this study will also evaluate the immunogenicity of a revaccination dose of 
the RSVPreF3 OA investigational vaccine in participants previously vaccinated in RSV 
OA=ADJ-002, Part B with the same, selected formulation of the RSVPreF3 OA 
investigational vaccine (i.e. group 120-AS01E_B). 
4.3. 
Justification for dose 
Different formulations and a 2-dose vaccination regimen with an interval of 2 months 
between doses of the RSVPreF3 OA investigational vaccine were administered 
intramuscularly for the first time to adults aged 60 – 80 years according to a 0, 2 months 
schedule in the parent study, RSV OA=ADJ-002 (208851). Based on 
safety/reactogenicity and immunogenicity data (humoral and cellular immune responses) 
from the RSV OA=ADJ-002 study, the 120 µg RSVPreF3/AS01E vaccine formulation 
was selected for further clinical development. All participants in the current study will 
receive this selected formulation of the vaccine. 
4.4. 
End of Study definition 
A participant is considered to have completed the study if he/she returns for the last visit 
or is available for the last scheduled contact as described in the protocol. 
End of Study (EoS): Last subject last visit (LSLV) (i.e. contact at Month 6). 
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5. 
STUDY POPULATION 
5.1. 
Inclusion criteria for enrolment 
Adherence to these criteria as specified in the protocol is essential. Inclusion criteria 
deviations are not allowed because they can jeopardize the scientific integrity or 
regulatory acceptability of the study or participant safety. 
All participants must satisfy ALL of the following criteria at study entry: 
• 
Male or female participants, who received 2 doses of RSVPreF3 OA investigational 
vaccine and formulations with matched adjuvant in part B of the parent study 
RSV OA=ADJ-002: recombinant RSVPreF3 antigen doses 120 g, 30 g and 60 g 
adjuvanted with AS01E  
• 
Participants who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary cards, return for the 
follow-up visit, be available for contact) 
• 
Written informed consent obtained from the participant prior to performance of any 
study specific procedure. 
5.2. 
Exclusion criteria for enrolment 
Adherence to criteria specified in the protocol is essential. Exclusion criteria deviations 
are not allowed because they can potentially jeopardize the scientific integrity or 
regulatory acceptability of the study or safety of the participant. 
The following criteria should be checked at the time of study entry. The potential 
participant MUST NOT be included in the study if ANY exclusion criterion applies: 
5.2.1. 
Medical conditions 
• 
Significant underlying illness or administered therapy that in the opinion of the 
investigator would be expected to prevent participation in the study.  
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition 
based on information on concomitant medication/vaccination collected prior to the 
study start and physical examination (no laboratory testing required). 
• 
Serious or unstable chronic illness that developed during or after the parent study. 
Patients with chronic stable medical conditions with or without specific treatment, 
such as diabetes, hypertension or cardiac disease, are allowed to participate in this 
study if considered by the investigator as clinically stable.  
• 
Recurrent or un-controlled neurological disorders or seizures that developed during 
or after the parent study. Participants with medically-controlled active or chronic 
neurological diseases can be enrolled in the study as per investigator assessment, 
provided that their condition will allow them to comply with the requirements of the 
protocol (e.g. completion of diary cards, attend phone calls/study site visits).  
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• 
Significant underlying illness that developed during or after the parent study, that in 
the opinion of the investigator would be expected to prevent completion of the study 
(e.g., life-threatening disease likely to limit survival to less than 6 months).  
• 
Lymphoproliferative disorder and malignancy developed during or after the parent 
study. 
• 
Any medical condition that developed during or after the parent study, that in the 
judgment of the investigator would make intramuscular injection unsafe.  
• 
Previous vaccination with RSV vaccine, other than the one in the parent study. 
5.2.2. 
Prior/Concomitant therapy (Amended 4 November 2020) 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study vaccine during the period beginning 30 days before the 
dose of study vaccine, or planned use during the study period. 
• 
Planned or actual administration of a vaccine not foreseen by the study protocol in 
the period starting 30 days before and ending 30 days after the dose of study vaccine 
administration, with the exception of inactivated, split virion and subunit influenza 
vaccines which can be administered up to 14 days before or from 30 days after the 
study vaccination.  
Note: In case an emergency mass vaccination for an unforeseen public health threat 
(e.g.: a pandemic) is recommended and/or organized by the public health 
authorities, outside the routine immunization program, the time period described 
above can be reduced if necessary for that vaccine provided it is used according to 
the local governmental recommendations and provided that the Sponsor is notified 
accordingly.. 
• 
Administration of long-acting immune-modifying drugs or planned administration at 
any time during the study period (e.g. infliximab).  
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 90 days before the dose of study vaccine or planned 
administration during the study period.  
• 
Chronic administration (defined as more than 14 consecutive days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 90 
days prior to the vaccine dose or planned administration during the study period. For 
corticosteroids, this will mean prednisone  20 mg/day, or equivalent. Inhaled and 
topical steroids are allowed.  
• 
Confirmed use or anticipated use of immunosuppressive/cytotoxic therapy (e.g., 
medication used during cancer chemotherapy, organ transplantation, or to treat 
autoimmune disorders). 
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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 (pharmaceutical product or invasive medical 
device). Refer to the Glossary of terms for the definition of invasive medical device. 
5.2.4. 
Other exclusions 
• 
Bedridden participants.  
• 
Planned move to a location that will prohibit participating in the trial. 
• 
History of chronic alcohol consumption and/or drug abuse that developed during or 
after the parent study as deemed by the investigator to render the potential participant 
unable/unlikely to provide accurate safety reports or comply with study procedures.  
5.3. 
Lifestyle considerations 
Not applicable. 
5.4. 
Screen failures 
Not applicable. 
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6. 
STUDY INTERVENTION 
A ‘study intervention’ is defined as a set of investigational or marketed product(s) or 
placebo intended to be administered to a participant during the study. 
Refer to the Study Procedures Manual (SPM) for additional details (including vaccine 
reconstitution). 
6.1. 
Study intervention administered  
Table 5 
Study intervention administered 
Study intervention name: 
RSVPreF3 OA interventional vaccine 
Vaccine(s)/Product(s) name * 
RSVPreF3 (120 µg)  
AS01E  
Presentation 
RSVPreF3 (120 µg): Vial; Powder for suspension for injection 
AS01E: Vial; Suspension for injection  
Vaccine formulation: 
RSVPreF3 (120 µg) 
AS01E: QS-21* (25 µg), MPL (25 µg), liposomes; Water for 
injection q.s. 0.5 mL 
Route of administration  
Intramuscular 
Location 
Deltoid 
Laterality ** 
Non-dominant 
Number of doses to be administered: 
1 dose 
Volume to be administered 
0.5 mL 
Packaging, labelling and TM 
Refer to SPM for more details 
Manufacturer 
GSK Biologicals 
* QS-21: Quillaja saponaria Molina, fraction 21 (Licensed by GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation)  
** The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the vaccine in the 
non-dominant arm, an injection in the dominant arm may be performed. 
SPM: Study Procedures Manual 
The participants must be observed closely for at least 30 minutes after the administration 
of the vaccine. Appropriate medical treatment must be readily available during the 
observation period in case of anaphylaxis and/or syncope. 
Refer to Section 4 for the schedule of vaccine administration. 
6.2. 
Preparation/Handling/Storage/Accountability 
The study vaccine must be stored in a safe, locked place at the temperature specified on 
the vaccine label. The storage temperature should be continuously monitored with 
calibrated (if not validated) temperature monitoring device(s) and recorded. Only 
authorized study personnel should be allowed access to the study vaccine. Storage 
conditions will be assessed by a sponsor study contact during pre-study activities. Refer 
to the section on Study Supplies in the SPM for more details on storage and handling of 
the study vaccine.  
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6.3. 
Measures to minimize bias: randomization and blinding 
6.3.1. 
Participant identification 
Participants will receive the same identification number as in the parent study 
RSV OA=ADJ-002. 
6.3.2. 
Intervention allocation to the participant 
Intervention allocation to the participants will be performed using an automated, Internet-
based system (SBIR). After obtaining the signed and dated ICF from the participant and 
having checked the eligibility of the participant, the site staff in charge of the intervention 
administration will access SBIR. Upon providing the participant identification number, 
the system will provide the treatment number to be used. The number of each 
administered intervention must be recorded in the eCRF. 
When an automated, Internet-based system (e.g. SBIR) is not available, please refer to 
the SBIR user guide or SPM for specific instructions. 
Refer to the SPM for additional information relative to the intervention number 
allocation. 
6.3.3. 
Blinding and unblinding 
This is an open-label study, as all participants will receive the same RSVPreF3 OA 
investigational vaccine.  
6.3.3.1. 
Emergency unblinding 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention via an 
automated Internet-based system e.g. SBIR.  
The investigator may contact a GSK Helpdesk (refer to the Table 6) if he/she needs help 
to perform the unblinding process (i.e., if the investigator is unable to access the SBIR). 
A physician other than the investigator (e.g. an emergency room physician) or 
participant/care giver/family member may also request emergency unblinding either via 
the investigator (preferred option) or via the GSK Helpdesk (back up option). The 
subject/participant card provides contact information for the investigator, his/her back up 
and GSK Helpdesk. 
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Table 6 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Toll-free numbers:  
Belgium: 
 
United States: 
 
Fax: 
 
Email: 
 
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 date of the dose 
administered in the clinic will be recorded in the source documents and in the eCRF. The 
study participant identification will be confirmed at the time of dosing by a member of 
the study site staff other than the person administering the study intervention. 
6.5. 
Concomitant therapy 
At each study visit/contact, the investigator or delegate should question the participant 
about any medications/products taken and vaccinations received by the participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medications/products/vaccines, except vitamins and dietary 
supplements, administered during the 30-day period following vaccination (Day 1 to 
Day 31). 
• 
Any concomitant medications/products/vaccines leading to study 
participation/intervention non-eligibility, or an elimination from the analysis (refer to 
Section 5.2.2 for details). 
• 
Any prophylactic medication (e.g. analgesics, antipyretics) administered on the day 
of study vaccination (Day 1) and in the absence of ANY symptom and in 
anticipation of a reaction to the vaccination. 
• 
Any concomitant medications/products/vaccines relevant to an SAE/pIMD to be 
reported as per protocol or administered at any time during the study period for the 
treatment of an SAE/pIMD. Concomitant medications relevant to SAEs and pIMDs 
must be recorded on the Expedited Adverse Event Report. 
• 
Shingrix or any AS01-containing vaccine throughout the entire study.  
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PPD
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The Local Medical Lead (LML) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.6. 
Dose modification 
Not applicable. 
6.7. 
Intervention after the end of the study 
During the study conclusion contact, the investigator will ask each participant if they are 
interested in participating in a long-term study. If a participant is not interested in joining 
the long-term study the reason for refusal will be documented, when available, in the 
participant’s eCRF. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
Not applicable, as only one dose of the RSVPreF3 OA investigational vaccine will be 
administered in the study. 
7.1.1. 
Criteria for temporary delay for enrolment and/or vaccination 
(Amended 4 November 2020) 
Enrolment/vaccination may be postponed within the permitted time interval until 
transient circumstances cited below are resolved:  
• 
Acute disease and/or fever at the time of enrolment and/or vaccination. Refer to the 
SoA (Section 1.3) for fever definition and preferred location for measuring 
temperature in this study. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be enrolled and/or vaccinated at the discretion of the 
investigator. 
• 
Participants with symptoms suggestive of active Coronavirus Disease 2019 (COVID-
19) infection (i.e. fever, cough, etc.). The return of the participant to the site will 
follow the specific guidance from local public health and other competent 
authorities (e.g. free of symptoms, COVID-19 negative testing, etc.).  
• 
Participants with known COVID-19 positive contacts within the past 14 days may 
be vaccinated at the discretion of the investigator at least 14 days after the 
exposure if the participant remains symptom free. 
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7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this participant from the date of withdrawal/last contact. 
From an analysis perspective, a ‘withdrawal’ from the study refers to any participant who 
was not available for the concluding contact foreseen in the protocol.  
Investigators will attempt to contact those participants who do not return for scheduled 
visits or follow-up. 
All data and samples collected until the date of withdrawal/last contact of the participant 
will be used for the analysis. 
The primary reason for study withdrawal will be documented in the eCRF based on the 
list below: 
• 
Adverse events requiring expedited reporting to GSK (please refer to Section 
10.3.9.1 for the details) 
• 
Unsolicited non-serious adverse event 
• 
Solicited adverse event 
• 
Withdrawal by participant, not due to an adverse event* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
*If a participant is withdrawn from the study because he/she has withdrawn consent and 
provided the reason for its withdrawal, the investigator must document this reason in the 
eCRF. 
Participants who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigators will 
follow participants who are withdrawn from the study as result of an SAE/AE until the 
event is resolved. (see Section 10.3.7.2). 
7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if he or she fails to return for 
scheduled visits and is unable to be contacted by the study site.  
Please refer to the SPM for a description of the actions to be taken before considering the 
participant as lost to follow-up.  
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.3). 
Adherence to the protocol is required for study conduct. 
Protocol waivers or exemptions are not allowed unless necessary for the management of 
an immediate safety concern.  
The investigator is not allowed to do testing on samples outside of what has been agreed 
upon by the IEC/IRB. 
Immediate safety concerns should be discussed with the sponsor as soon as they occur or 
when the study team is aware of them. 
Participants who received 2 doses of RSVPreF3 OA investigational vaccine and 
formulations with matched adjuvant in part B of the parent study RSV OA=ADJ-002: 
recombinant RSVPreF3 antigen doses 120 g, 30 g and 60 g adjuvanted with AS01E 
will be invited to participate in this extension study. 
The SPM provides the investigator and site personnel with administrative and detailed 
technical information that does not impact participant safety. 
During special circumstances (e.g., COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be applied. For the duration of such special circumstances, the 
following measures may be implemented for enrolled participants: 
• 
Safety follow-up may be made by a telephone call, other means of virtual contact or 
home visit, if appropriate. 
• 
Diary cards may be transmitted from and to the site by electronic means and/ or 
conventional mail. 
• 
Biological samples may be collected at a different location* other than the study site 
or at participant’s home. Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use.  
• 
If despite best efforts it is not possible to vaccinate the participants within the 
recommended interval predefined in the protocol (see Table 2, recommended 
interval), then the interval may be extended up to a maximum length of 30 days only 
for vaccination (see Table 2, allowed interval). 
*It is the investigator’s responsibility to identify an alternate location. The investigator 
should ensure that this alternate location meets ICH GCP requirements, such as adequate 
facilities to perform study procedures, appropriate training of the staff and documented 
delegation of responsibilities in this location. This alternate location should be covered by 
proper insurance for the conduct of study on participants by investigator and staff at a site 
other than the designated study site. Refer to EMA Guidance on the Management of 
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Clinical Trials during the COVID-19 (Coronavirus) pandemic (version 2, 27 March, 
2020) for more details. 
Impact on the per protocol set for immunogenicity will be determined on a case by case 
basis. 
Before implementing any study procedures, the investigator should confirm strict 
adherence to all inclusion/exclusion criteria (refer to Table 1). The criteria for temporary 
delay for enrolment and/or vaccination to ensure participants are still qualified for 
enrolment in the study should be checked, but this does not need to be recorded in the 
participant’s eCRF. 
8.1. 
Efficacy and/or immunogenicity assessments 
Collected biological samples will be used for protocol mandated research and purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol.  
Future findings may make it desirable to use the samples acquired in this study for future 
research not described in this protocol. Therefore, all participants in countries where this 
is allowed will be asked to give a specific consent to allow GSK or a contracted partner 
to use the samples for future research. Future research will be subject to prior IEC/IRB 
approval if required per local legislation. 
Information on further investigations and their rationale can be obtained from GSK.  
Sample testing will be done in accordance with the recorded consent of the individual 
participant.  
If additional testing is performed, the marker priority ranking given in the Section 8.1.3 
may be changed. 
Collected samples will be stored for a maximum of 20 years. This storage period begins 
when the last participant performed the last study visit, unless local rules, regulations or 
guidelines require different timeframes or procedures, which would then be in line with 
participant consent. These extra requirements need to be communicated formally to, and 
discussed and agreed with GSK. 
8.1.1. 
Biological samples 
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment). 
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8.1.3. 
Immunological read-outs  
Table 9 
Immunological read-outs 
Blood sampling timepoint 
No. 
participants* 
Component 
Components priority 
rank  
Type of contact and timepoint 
Humoral immunity (serum samples) 
Visit 1 (Day 1**) 
~100 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Visit 2 (Day 31) 
 
~100 
RSV-A neutralizing antibody 
1 
RSV-B neutralizing antibody  
2 
RSVPreF3-specific IgG antibody  
3 
Cell-mediated immunity (on PBMC samples) 
Visit 1 (Day 1) 
~100 
IL-2, CD40L, TNF-, IFN-, IL-13, IL-
17, 4-1BB secreting CD4+ and CD8+ T-
cells 
- 
Visit 2 (Day 31) 
 
~100 
IL-2, CD40L, TNF-, IFN-, IL-13, IL-
17, 4-1BB secreting CD4+ and CD8+ T-
cells 
- 
*Samples taken only from the group 120-AS01E_B: Selected formulation revaccinated with the same formulation 
**Visit 1 (Day 1) = 18 months post-Dose 2 in RSV OA=ADJ-002 study 
PBMC = peripheral blood mononuclear cells; CD40L: cluster of differentiation 40 ligand; IFN-  : interferon gamma, IL 
(IL-2, IL-13, IL-17): interleukin; TNF-  : tumor necrosis factor alpha; 4-1BB (CD137). 
8.1.4. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen used in the RSVPreF3 OA investigational vaccine. 
8.2. 
Safety Assessments 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and any 
designees remain responsible for following up AEs that are serious, considered related to 
the study intervention or the study, or that caused the participant to discontinue the study. 
8.2.1. 
Pre-vaccination procedures 
8.2.1.1. 
Collection of demographic data 
Record demographic data such as year of birth and sex in the participant’s eCRF. 
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8.2.1.2. 
Medical/vaccination history 
Obtain the participant’s medical/vaccination history for the transition period between the 
parent study RSV OA=ADJ-002 and the current study by interviewing the participant 
and/or review of the participant’s medical records. Record any pre-existing participant 
conditions, signs and/or symptoms present during the transition period between the parent 
study RSV OA=ADJ-002 and the current study, or that worsened from the parent study, 
in the eCRF. 
Administration of Shingrix during the transition period between the parent study 
RSV OA=ADJ-002 and the current study, and throughout the duration of the current 
study should be recorded in the eCRF. The date of vaccination should be collected and 
recorded in the eCRF. 
8.2.1.3. 
Physical examination (Amended 4 November 2020) 
At minimum, vital signs (e.g., heart rate, respiratory rate, blood pressure) must be 
collected. 
Vital signs are to be taken before blood collection for laboratory tests and/or vaccination. 
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
If the investigator determines that the participant’s health on the day of vaccination 
temporarily precludes vaccination, the visit will be rescheduled. 
Physical examination at each study visit subsequent to the vaccination visit, will be 
performed only if the participant indicates during questioning that there might be some 
underlying pathology(ies) or if deemed necessary by the investigator or delegate. 
Treatment of any abnormality observed during physical examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. 
8.2.1.4. 
Warnings and precautions to vaccination 
Warnings and precautions to vaccination must be checked at the beginning of the 
vaccination visit.  
8.2.1.5. 
Pre-vaccination body temperature 
The oral body temperature of each participant needs to be measured prior to any study 
vaccine administration and recorded in the eCRF. If the participant has fever (fever is 
defined as temperature  38.0°C/100.4°F regardless the location of measurement) on the 
day of vaccination, the vaccination visit will be rescheduled within the allowed interval 
for this visit (see Table 2). 
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A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting periods defined in Table 10. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
he/she considers the event to be reasonably related to vaccination, the investigator will 
promptly notify the Study Contact for Reporting SAEs mentioned in the Table 12. 
8.3.2. 
Method of detecting AEs and SAEs, and other events  
Methods of detecting and recording AEs/SAEs/pIMDs are detailed in the Section 10.3.7. 
The assessment of AE/SAE intensity, causality and outcome are provided in the Section 
10.3.8.  
Open-ended and non-leading verbal questioning of the participants is the preferred 
method of acquiring information related to an AE/SAE/pIMD. 
8.3.3. 
Regulatory reporting requirements for SAEs and other events  
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/pIMD, he/she must report it to GSK using the required 
documentation, and within the timeframes, mentioned in the Table 11. This is essential 
for meeting legal obligations and ethical responsibilities for participant safety and the 
safety of a study intervention under clinical investigation. 
For SAEs/pIMDs, the investigator will always provide an assessment of causality at the 
time of the initial report, as defined in the Section 10.3.8.2. 
Local regulatory requirements and sponsor policy for the preparation of an investigator 
safety report for Suspected Unexpected Serious Adverse Reactions (SUSAR) must be 
followed. These reports will be forwarded to investigators as necessary. 
The sponsor has a legal responsibility to notify local authorities and other regulatory 
agencies about the safety of a study intervention under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements related to safety reporting to 
the regulatory authority, IRB/IEC, and investigators. 
Please refer to Section 10.3.9 for further details regarding the reporting of SAEs/pIMDs. 
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Table 11 
Timeframes for submitting serious adverse events and other events 
reports to GSK (Amended 4 November 2020) 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡‡ 
electronic Adverse 
Events Form and 
corresponding 
Expedited Adverse Event 
Form 
24 hours* 
electronic Adverse Events 
Form and corresponding 
Expedited Adverse Event Form 
pIMDs  
24 hours**  ‡‡  
electronic Adverse 
Events Form and 
corresponding 
Expedited Adverse Event 
Form 
24 hours* 
electronic Adverse Events 
Form and corresponding 
Expedited Adverse Event Form 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of a pIMD. 
‡‡ The investigator will be required to review the SAE/pIMD causality within 72 hours of submission of the SAE/pIMD. 
Date/time of the causality review should be entered in the eCRF. 
8.3.3.1. 
Contact information for reporting of SAEs and pIMDs 
Table 12 
Contact information for reporting of SAEs and pIMDs 
Study contact for questions regarding SAEs and pIMDs 
Refer to the local study contact information document 
Back-up study contact for reporting SAEs and pIMDs 
Available 24/24 hours and 7/7 days: 
GSK Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: 
 or 
 
Email address: 
 
US sites only: 
Fax: 
 
8.3.4. 
Treatment of adverse events 
Any medication administered for the treatment of an SAE/pIMD should be recorded in 
the Expedited Adverse Event Report of the participant’s eCRF screen (refer to the 
Section 10.3.9.1). 
8.3.5. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
keep the participant card in his/her/their possession at all times throughout the study. In 
an emergency, this card serves to inform the responsible attending physician/care 
giver/family member that the participant is in a clinical study and that relevant 
information may be obtained by contacting the investigator. 
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PPD
PPD
PPD

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8.4. 
Treatment of overdose 
This section is not applicable. 
8.5. 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this study. 
8.6. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.7. 
Genetics 
Genetics are not evaluated in the current study. 
8.8. 
Biomarkers 
Biomarkers for pharmacogenetics are not evaluated in this study. 
8.9. 
Health outcomes 
Economic outcome measures such as health care resource utilization data associated with 
healthcare encounters are not evaluated in this study. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
Not applicable as this study is descriptive. 
9.2. 
Sample size determination 
No sample size is calculated for this study. Potentially eligible participants who received 
2 doses of the RSVPreF3 OA investigational vaccine and formulations with matched 
adjuvant in part B of the parent study RSV OA=ADJ-002: recombinant antigen doses 120 
g , 30 g and 60 g adjuvanted with AS01E will be invited to participate in this 
extension study. An estimate of the maximum number of participants to be potentially 
enrolled can therefore be obtained by considering all currently enrolled participants in 
study RSV OA=ADJ-002 who received both doses in the groups considered for this 
extension study. 
Withdrawals will not be replaced. 
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9.3. 
Populations for analyses 
Table 13 
Populations for analyses 
Analysis Set 
Description 
Enrolled  
Participants who agreed to participate in the clinical study after completion of the informed 
consent process. 
Exposed  
All participants who received Dose 3 of the study intervention. 
Per Protocol  
All participants who received Dose 3 of the study intervention and have post-vaccination data 
minus participants with protocol deviations that lead to exclusion. 
The primary analysis for immunogenicity will be performed on the Per Protocol set (PPS) for immunogenicity. If in any 
study group the percentage of participants with serological results excluded from the PPS for immunogenicity is at 
least 10%, a second analysis will be performed on the Exposed Set (ES). 
9.3.1. 
Criteria for elimination from analysis  
9.3.1.1. 
Intercurrent medical conditions and concomitant 
medications/products/vaccines that may lead to elimination of a 
participant from per-protocol analyses  
If the participant meets one of the criteria mentioned in the Sections 5.2.1 (medical 
conditions) or 5.2.2 (prior/concomitant therapy), he/she may be eliminated from per 
protocol analysis. Refer to Glossary of terms for the definition of intercurrent medical 
conditions. 
9.4. 
Statistical analyses 
The statistical analysis plan (SAP) will be finalized prior to First Participant First Visit 
and it will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of 
the most important endpoints including primary and key secondary endpoints. 
9.4.1. 
General considerations 
9.4.1.1. 
Demography 
For a given participant and a given demographic variable, missing measurements will not 
be replaced. 
9.4.1.2. 
Immunogenicity 
• 
Any missing or non-evaluable immunogenicity measurement will not be replaced. 
The descriptive analysis performed for each assay at each time point will exclude 
participants with a missing or non-evaluable measurement.  
• 
The geometric mean titers/concentrations (GMTs/GMCs) will be computed by 
taking the anti-logarithm of the arithmetic mean of the log10 transformed 
titers/concentrations.  
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• 
A seronegative participant will be defined as a participant whose antibody 
titer/concentration is below the cut-off value of the assay. A seropositive participant 
is a participant whose antibody titer/concentration is greater than or equal to the cut-
off value of the assay. 
• 
Antibody titers/concentrations below the assay cut-off will be given an arbitrary 
value of half the assay cut-off for the purpose of GMT/GMC calculation. 
• 
Antibody titers/concentrations above the assay upper limit of quantification (ULOQ) 
will be given the value of the ULOQ for the purpose of GMT/GMC calculation. 
9.4.1.3. 
Reactogenicity/Safety 
• 
For a given participant and the analysis of solicited events within 4 days post-
vaccination, missing or non-evaluable measurements will not be replaced. Therefore, 
the analysis of solicited events will include only vaccinated participants with 
documented solicited safety data (i.e., paper diary completed). 
• 
For analysis of unsolicited AEs, SAEs, pIMDs and concomitant medications, all 
vaccinated participants will be considered. Participants who did not report an event 
or concomitant medication will be considered as participants without the event or the 
concomitant medication, respectively. 
9.4.2. 
Demographics and participants disposition 
Demographic characteristics (age in years, sex) will be summarized by group using 
descriptive statistics: 
• 
Frequency tables will be generated for categorical variables such as sex. 
• 
Mean, median, standard deviation and range will be provided for continuous data 
such as age. 
The distribution of participants will be tabulated overall, per group and for each age 
category (60-69 years and 70-80 years). 
Withdrawal status will be summarized by group using descriptive statistics: 
• 
The number of participants enrolled into the study as well as the number of 
participants excluded from PP analyses will be tabulated.  
• 
The numbers of withdrawn participants will be tabulated according to the reason for 
withdrawal. 
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9.4.3. 
Primary endpoint 
9.4.3.1. 
Safety analysis 
The safety analysis will be performed on the ES. A descriptive analysis by group and 
overall will present a summary of: 
• 
The number and percentage of participants with at least one administration site event 
(solicited and unsolicited), with at least one systemic event (solicited and 
unsolicited) and with any AE during the 4-day or 30-day follow-up period will be 
tabulated with exact 95% CI after Dose 3. The same computations will be done for 
Grade 3 and related AEs. 
• 
The number and percentage of participants with any AE (solicited and unsolicited) 
resulting in a medically attended visit during the 30-day follow-up period will be 
tabulated after Dose 3. 
• 
The number and percentage of participants reporting each individual solicited 
administration site event (any grade, Grade 3) and solicited systemic event (any 
grade, Grade 3) during the 4-day follow-up period (i.e., on the day of vaccination 
and 3 subsequent days) will be tabulated for each group after Dose 3.  
• 
For fever, the number and percentage of participants reporting fever by half degree 
(°C) cumulative increments during the 4-day follow-up period (i.e., on the day of 
vaccination and 3 subsequent days) will be tabulated for each group after Dose 3. 
• 
The number and percentage of participants with any unsolicited AEs during the 30-
day follow-up period (i.e., on the day of vaccination and 29 subsequent days) with its 
exact 95% CI will be tabulated by group and by Medical Dictionary for Regulatory 
Activities (MedDRA) preferred term. The same tabulation will be done for Grade 3 
unsolicited AEs, for any causally related unsolicited AEs, for Grade 3 causally 
related unsolicited AEs and for unsolicited AEs resulting in a medically attended 
visit. The verbatim reports of unsolicited AEs will be reviewed by a qualified person 
and the signs and symptoms will be coded according to the MedDRA Dictionary for 
Adverse Reaction Terminology. Every verbatim term will be matched with the 
appropriate Preferred Term. 
• 
The number and percentage of participants with at least one report of SAE/pIMD 
classified by the MedDRA Preferred Terms and reported during the 30-day follow-
up period (i.e., on the day of vaccination and 29 subsequent days) will be tabulated 
with exact 95% CI. The same tabulation will be done for related SAEs/pIMDs. 
• 
The number and percentage of participants using concomitant medication (any 
medication, any antipyretic and any antipyretic taken prophylactically, respectively) 
during the 4-day follow-up period (i.e., on the day of vaccination and 3 subsequent 
days) and during the 30-day follow-up period (i.e., on the day of vaccination and 29 
subsequent days) will be summarized by group. 
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9.4.3.2. 
Humoral immune response up to 1 month post-Dose 3 
At each time point that blood samples are collected for humoral immune response and for 
each assay (unless otherwise specified), the analyses below will be performed: 
• 
Percentage of participants with antibody titers/concentrations above the positivity 
cut-off and their exact 95% CI will be tabulated.  
• 
GMTs/GMCs and their 95% CI will be tabulated and represented graphically. 
Antibody titers/concentrations will be displayed using reverse cumulative curves.  
• 
Distributions of antibody titers/concentrations will be tabulated. 
• 
The mean geometric increase (MGI) i.e. geometric mean of ratios of antibody 
titers/concentrations of each post-vaccination time point over pre-vaccination, will 
be tabulated with 95% CI.  
• 
Individual post-vaccination results versus pre-vaccination results will be plotted 
using scatter plots.  
• 
Distribution of the fold increase of the antibody titers/concentrations (post- over pre-
vaccination titers/concentrations) will be tabulated. 
• 
The ratio of fold increase (pre to post) of anti-RSVPreF3-specific antibody 
concentrations over the fold increase (pre to post) of anti-RSV-A neutralizing 
antibody titers will be tabulated using descriptive statistics and displayed graphically 
using scatter plots. 
• 
The fold increase of post-dose 3 (in RSV OA=ADJ-011 EXT:002 MTH20 study) 
over post-dose 1 (in RSV OA=ADJ-002 study) antibody titers/concentrations will be 
tabulated using descriptive statistics. 
As pre-vaccination will be considered both pre-Dose 1 in RSV OA=ADJ-002 and pre-
Dose 3 in RSV OA=ADJ-011 EXT:002 MTH20. 
The immunogenicity analysis might also be performed by age category (60-69 years and 
70-80 years, age according to the parent study).  
9.4.4. 
Secondary endpoints 
9.4.4.1. 
Humoral immune response up to 1 month post-Dose 3  
See Section 9.4.3.2. 
9.4.4.2. 
CMI response up to 1 month post-Dose 3  
The following parameters will be summarized by group using descriptive statistics (N, 
geometric mean, min, Q1, median, Q3, max) at each time point for which blood samples 
are collected for CMI:  
• 
Frequency of RSVPreF3-specific CD4+ T-cells identified as expressing at least 2 
activation markers among IL-2, CD40L, TNF-α, IFN-γ. 
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• 
Fold increase of the frequency of RSVPreF3-specific CD4+ T-cells identified as 
expressing at least 2 activation markers among IL-2, CD40L, TNF-α, IFN-γ, at each 
post-vaccination time point over pre-vaccination.  
• 
Distribution of the fold increase: the percentage of participants with at least a 2-fold, 
4-fold, 6-fold, 8-fold, 10-fold increase post-vaccination as compared to pre-
vaccination (Post over Pre) will be tabulated by timepoint and by group. 
The immunogenicity analysis might also be performed by age category (60-69 years and 
70-80 years, age according to the parent study).  
9.4.4.3. 
SAEs and pIMDs up to 6 months post-Dose 3 
• 
The number and percentage of participants with at least one report of SAE classified 
by the MedDRA Preferred Terms and reported during the entire study period will be 
tabulated with exact 95% CI. The same tabulation will be done for causally related 
and fatal SAEs. SAEs will also be described in detail. 
• 
The number and percentage of participants with at least one pIMD classified by the 
MedDRA Preferred Terms and reported during the entire study period will be 
tabulated with exact 95% CI. The same tabulation will be done for causally related 
pIMDs. pIMDs will also be described in detail. 
9.4.5. 
Tertiary endpoints 
The statistical analyses concerning tertiary endpoints will be described in the SAP. 
9.5. 
Interim analyses  
All analyses will be conducted on final data, as clean as possible. 
9.5.1. 
Sequence of analyses 
The analyses will be performed stepwise: 
• 
A first analysis will be performed when all data as clean as possible are available for 
at least primary and secondary endpoints up to Visit 2 (Day 31). 
• 
The final end-of-study analysis will be performed when all data for at least primary 
and secondary endpoints up to study conclusion (Month 6) are available. All 
available tertiary endpoints will also be analyzed in this step. Individual listings will 
only be provided at this stage.  
If data for tertiary endpoints become available at a later stage, (an) additional 
analysis/analyses will be performed. 
9.5.2. 
Statistical consideration for interim analysis 
All analyses will be conducted on final data (all planned results available for the time 
points of interest) and therefore no statistical adjustment for interim analyses is required. 
9.6. 
Data Monitoring Committee (DMC) 
Not applicable. 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, Informed Consent Form (ICF), Investigator 
Brochure, and other relevant documents (e.g. advertisements) must be submitted, to 
an IRB/IEC by the investigator for review and approval. These documents will be 
signed and dated by the investigator before the study is initiated.  
• 
Any protocol amendments will require IEC/IRB approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants.  
• 
GSK will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
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10.1.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. Investigators are 
responsible for providing a Financial Disclosure update if their financial interests change 
at any point during their participation in a study and for 1 year after completion of the 
study. 
10.1.3. 
Informed consent process 
The investigator or his/her representative will explain the nature of the study to the 
participant and answer all questions regarding the study.  
Participants must be informed that their participation is voluntary.  
Freely given and written informed consent must be obtained from each participant, as 
appropriate, prior to participation in the study. In addition, the signed informed consent of 
the designate must be obtained, in case a designate is assigned by the participant. 
The content of informed consent form must meet the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF.  
Participants must be re-consented to the most current version of the ICF(s) or an ICF 
addendum during their participation in the study.  
A copy of the ICF(s) must be provided to the participants.  
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred.  
The participants must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law.  
The participants must be informed of their rights regarding the use of their personal data 
in accordance with the data privacy section of the ICF. 
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The participants must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
GSK will also ensure protection of the personal data of the investigator and site staff 
which will be collected within the framework and for the purpose of the study in 
accordance with the Data Privacy Notice that will be sent to the site staff.  
10.1.5. 
Committees structure 
10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study register in compliance with the 
applicable regulations/GSK policy. GSK will aim to register protocols summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines.  
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical trial registers. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the investigator 
with the full summary of the study results. The investigator is encouraged to share the 
summary results with the study participants, as appropriate. 
GSK intends to make anonymized patient-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by trial 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents including source documents. The storage system used during the trial and for 
archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, CRF), the copy should fulfil the 
requirements for certified copies.  
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All participant data relating to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee electronically (e.g. laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF.  
The investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial participants (see Glossary 
of terms for the exact definition of source documents) that supports information entered 
in the eCRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data.  
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data should be traceable, should not 
obscure the original entry, and should be explained if necessary (e.g. via an audit trail). 
The safety and rights of participants must be protected and study be conducted in 
accordance with the currently approved protocol and any other study agreements, ICH 
GCP, and all applicable regulatory requirements.  
Trial records and source documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (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 the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor.  
10.1.8. 
Source documents 
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Investigator should maintain a record of the location(s) 
of their source documents.  
Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available. 
Definition of what constitutes source data and source documents can be found in the 
Glossary of terms. 
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10.1.9. 
Study and site start and closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure will 
occur upon study completion. A study site is considered closed when all required 
data/documents and study supplies have been collected and a study-site closure visit has 
been performed.  
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
10.1.10. 
Publication policy 
GSK aims to submit for publication the results of the study in searchable, peer reviewed 
scientific literature within 18 months from LSLV for interventional studies and follows 
the guidance from the International Committee of Medical Journal Editors. 
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10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
Laboratory assays 
RSV-A and RSV-B neutralization assays 
The serum neutralization assay is a functional assay that measures the ability of serum 
antibodies to neutralize RSV entry and replication in a host cell line.  
Virus neutralization is performed by incubating a fixed amount of RSV-A strain (Long, 
ATCC No. VR-26) or RSV-B strain (18537, ATCC No. VR-1580) with serial dilutions of 
the test serum. The serum-virus mixture is then transferred onto a monolayer of Vero 
cells (African Green Monkey, kidney, Cercopitheus aethiops, ATCC CCL 81) and 
incubated for 2 days to allow infection of the Vero cells by non-neutralized virus and the 
formation of plaques in the cell monolayer. Following a fixation step, RSV-infected cells 
are detected using a primary antibody directed against RSV (Polyclonal anti-RSV A/B 
IgG) and a secondary antibody conjugated to horse-radish peroxidase (HRP), allowing 
the visualization of plaques after coloration with TrueBlue peroxidase substrate. Viral 
plaques are counted using an automated microscope coupled to an image analyzer 
(Scanlab system with a Reading software or equivalent). For each serum dilution, a ratio, 
expressed as a percentage, is calculated between the number of plaques at each serum 
dilution and the number of plaques in the virus control wells (no serum added). The 
serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and 
corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction 
in the number of plaques compared to the virus control wells, as described by others 
[Barbas, 1992; Bates, 2014]. For the testing of phase 2/3 studies, secondary standards 
calibrated against the international reference (NIBSC 16/284) will be included in every 
run to allow conversion into international units.  
RSVPreF3 protein IgG ELISA 
Responses to the RSVPreF3 antigen will be evaluated by an indirect ELISA allowing the 
detection and the quantification of antigen-specific IgG antibodies in human serum 
samples. 
The principle of these assays is as follows: RSVPreF3 protein antigen will be adsorbed 
onto a 96-well polystyrene microplate. After washing and blocking steps, dilutions of 
serum samples, controls and standards will be added to the coated microplate. A 
reference standard curve will be prepared using a pool of commercial human serum 
containing anti- RSV antibodies. After incubation, the microplate will be washed to 
remove unbound primary antibodies. Bound IgG will be detected by the addition of a 
secondary anti-human antibody (total IgG specific), conjugated to HRP. Bound 
antibodies are quantified by the addition of the HRP substrate, tetramethylbenzidine 
(TMB) and hydrogen peroxide, whereby a colored product develops proportionally to the 
amount of anti-RSVPreF3 protein total IgG antibodies present in the serum sample. The 
optical density of each sample dilution is then interpolated on the reference standard. The 
corresponding antibody concentration, corrected for the dilution factor, is expressed in 
arbitrary ELISA Laboratory Units per milliliter (ELU/mL). 
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Intracellular cytokine staining (ICS) 
The ICS is used to assess RSVPreF3-specific CD4+ and/or CD8+   T-cells expressing 
CD40L and/or IL2 and/or IFN-γ and/or TNF-α (secondary endpoint). Additional markers 
might be used to further characterize the cellular immune response (exploration analysis 
in tertiary endpoint): 4-1BB, IL-13, IL-17. 
As previously described [Moris, 2011], thawed peripheral blood mononuclear cells 
(PBMCs) are stimulated in vitro in the presence of anti-CD28 and anti-CD49d antibodies 
either with pools of 15-mer peptides overlapping by 11 amino acids and spanning the 
sequence of the RSVPreF3 protein, or with medium. After 2 hours of incubation at 37C, 
Brefeldin A is added to inhibit cytokine secretion during an additional overnight 
incubation at 37C. Cells are subsequently harvested, stained for surface markers (CD4+ 
and CD8+) and then fixed. Fixed cells are then permeabilized and stained with labeled 
antibodies specific for the following immune markers (7 parameters assay):  
• 
CD3+: phenotyping T-cells; 
• 
CD40L (CD154), expressed on activated CD4+ T-cells, [Chattopadhyay, 2005; 
Frentsch, 2005; Samten, 2000; Stubbe, 2006]; 
• 
IL-2: key for the development, survival and function of T-cells [Boyman, 2012]; 
• 
TNF-α: anti-viral/intracellular factor, pro-inflammatory cytokine, cytotoxicity 
[Sedger, 2014]; 
• 
IFN-γ: anti-viral factor, associated with the Th1-like profile [Schoenborn, 2007]; 
And potentially integrating as well (10 parameters assay):  
• 
4-1BB (CD137), expressed on activated CD4+ and CD8+ T-cells [Wölfl, 2008]; 
• 
IL-13: associated with the Th2-like profile [Bao, 2015]; 
• 
IL-17: associated with the Th17-like profile [Korn, 2009]. 
After staining with the markers above, the cellular samples are analyzed by flow-
cytometry allowing to determine the frequency of CD4+ T-cells expressing the marker(s) 
of interest per million of CD4+ T-cells. 
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c. 
Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the participant has been admitted at 
the hospital or emergency ward for observation and/or treatment that would not 
have been appropriate in the physician’s office or in an out-patient setting. 
Complications that occur during hospitalization are also considered as AEs. If a 
complication prolongs hospitalization or fulfils any other serious criteria, the event 
will also be considered serious. When in doubt as to whether ‘hospitalization’ 
occurred, or was necessary, the AE should be considered serious. 
d. Results in disability/incapacity  
Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza like illness, and accidental trauma 
(e.g. sprained ankle) which may interfere or prevent everyday life functions but do 
not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant  
f. 
Other situations 
Medical or scientific judgement should be exercised in deciding whether reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These should also 
be considered serious. Examples of such events are invasive or malignant cancers, 
intensive treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization. 
10.3.3. 
Solicited events 
a. Solicited administration site events 
The following administration site events will be solicited: 
Table 14 
Solicited administration site events 
Pain at the injection site 
Erythema at the injection site 
Swelling at the injection site 
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b. Solicited systemic events 
The following systemic events will be solicited: 
Table 15 
Solicited systemic events 
Fever 
Note: participants will be instructed to measure and record the oral body temperature in 
the evening. Should additional temperature measurements be performed at other times of 
day, participants will be instructed to record the highest temperature in the diary card. 
10.3.4. 
Unsolicited AEs 
An unsolicited AE is an AE that was not solicited using a Participant Diary and that was 
spontaneously communicated by a participant who has signed the informed consent. 
Unsolicited AEs include serious and non-serious AEs. 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or emergency room visit, or visit to/by a health care provider). 
The participants will be instructed to contact the site as soon as possible to report 
medically attended event(s), as well as any events that, though not medically attended, 
are of participant’s concern. Detailed information about reported unsolicited AEs will be 
collected by qualified site personnel and documented in the participant’s records. 
Unsolicited AEs that are not medically attended nor perceived as a concern by participant 
will be collected during interview with the participants and by review of available 
medical records at the next visit. 
10.3.5. 
Adverse events of special interest (AESIs) 
10.3.5.1. 
Potential immune-mediated diseases 
pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory 
and/or neurologic disorders of interest which may or may not have an autoimmune 
etiology. AEs that need to be recorded and reported as pIMDs include those listed in the 
Table 16.  
However, the investigator will exercise his/her medical and scientific judgement to 
determine whether other diseases have an autoimmune origin (i.e. pathophysiology 
involving systemic or organ-specific pathogenic autoantibodies) and should also be 
recorded as a pIMD. 
 
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10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs  
Not applicable. 
10.3.7. 
Recording and follow-up of AEs, SAEs, pIMDs 
The participants will be instructed to contact the investigator immediately should the 
participants manifest any signs or symptoms they perceive as serious.  
When an AE/SAE/pIMD occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE/pIMD in the eCRF. The investigator is not allowed to send photocopies of the 
participant’s medical records to GSK instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all participant identifiers will be blinded on the copies 
of the medical records prior to submission to GSK. 
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE/pIMD and not the individual signs/symptoms. 
A Paper Diary (pDiary), hereafter referred to as Participant Diary will be used in this 
study to capture solicited administration site or systemic events. The participant should 
be trained on how and when to complete each field of the Participant Diary. 
Any individual(s) (including the designate; refer to the Glossary of terms for the 
definition of the term “designate”) who performs the measurements of administration site 
or systemic events and who will enter the information into the Participant Diary should 
be trained on the use of the Diary. This training must be documented in the participant’s 
source record. If any other individual than the participant is making entries in the 
Participant Diary, their identity should be documented in the participant’s source record. 
• 
Collect and verify completed diary cards during discussion with the participant on 
Visit 2. 
• 
Any unreturned diary cards will be sought from the participant through telephone 
call(s) or any other convenient procedure.  
The investigator or delegate will transcribe the required information into the eCRF in 
English.  
10.3.7.1. 
Time period for collecting and recording AEs, SAEs, and pIMDs 
All AEs that occur during 30 days following administration of the dose of study vaccine 
(Day 1 to Day 31) must be recorded into the appropriate section of the eCRF, irrespective 
of intensity or whether or not they are considered vaccination-related. 
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10.3.7.2. 
Follow-up of AEs, SAEs, pIMDs 
After the initial AE/SAE/pIMD or any other event of interest for the study, the 
investigator is required to proactively follow each participant at subsequent 
visits/contacts. All SAEs and non-serious AEs of special interest as defined in the Section 
10.3.5.1, will be followed until the event is resolved, stabilized, otherwise explained, or 
the participant is lost to follow-up. 
Other non-serious AEs must be followed until 30 days after the last vaccination or until 
the participant is lost to follow-up. 
10.3.7.2.1. Follow-up during the study 
AEs (serious or non-serious) /pIMDs documented at a previous visit/contact and defined 
as not recovered/not resolved or recovering/resolving will be reviewed at subsequent 
visits/contacts until the end of the study. 
If participant dies during participation in the study or during a recognized follow-up 
period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.7.2.2. Follow-up after the participant is discharged from the study (Amended 
4 November 2020) 
The investigator will provide any new or updated relevant information on previously 
reported SAE/pIMD to GSK using  the electronic Adverse Events Form and/or 
corresponding Expedited Adverse Event Form or the paper Expedited Adverse Event 
Report as applicable. The investigator is obliged to perform or arrange for the conduct of 
supplemental clinical examinations/tests and/or evaluations to elucidate the nature and/or 
causality of the AE or SAE as fully as possible. 
10.3.7.3. 
Updating of SAE, pIMD information after removal of write access to the 
participant’s eCRF 
When additional SAE, pIMD information is received after removal of write access to the 
participant’s eCRF, new or updated information should be recorded on the appropriate 
paper report, with all changes signed and dated by the investigator. The updated report 
should be faxed to the Study Contact for Reporting SAEs (refer to the Section 8.3.3.1 or 
to GSK Clinical Safety and Pharmacovigilance department within the defined reporting 
time frames specified in the Table 11). 
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10.3.8. 
Assessment of intensity and toxicity 
10.3.8.1. 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Adults 
Event 
Intensity grade 
Parameter 
Pain at the injection site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal every day activities. 
 
2 
Moderate: Painful when limb is moved and interferes with 
every day activities. 
 
3 
Severe: Significant pain at rest. Prevents normal every 
day activities. 
Erythema at the injection site 
Record greatest surface diameter in mm 
Swelling at the injections site 
Record greatest surface diameter in mm 
Temperature* 
 
Record temperature in °C/°F  
* Refer to the Section 1.3 (SoA) for the definition of fever and the preferred location for temperature measurement. 
The maximum intensity of local injection site erythema/swelling and fever will be scored 
at GSK as follows: 
 
Erythema/swelling 
Fever 
0: 
 20 mm 
< 38.0°C (100.4°F) 
1: 
> 20 -   50 mm 
≥ 38.0°C (100.4°F) -   38.5°C (101.3°F) 
2: 
> 50 -   100 mm 
> 38.5°C (101.3°F) -   39.0°C (102.2°F) 
3: 
> 100 mm 
> 39.0°C (102.2°F) 
The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgement. 
The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the participant, causing 
minimal discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities  
In adults such an AE would, for example, prevent attendance at 
work/school and would necessitate the administration of 
corrective therapy. 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. Grade 3 
is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets 1 of the pre-defined 
outcomes as described in the Section 10.3.2. 
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10.3.8.2. 
Assessment of causality (Amended 4 November 2020) 
All solicited administration-site and systemic events will be considered causally related 
to vaccination. The complete list of these events is provided in the Table 14 and Table 15.  
The investigator must assess the relationship between the study vaccine and the 
occurrence of each unsolicited AE/SAE using clinical judgement. Where several different 
vaccines/products were administered, the investigator should specify, when possible, if 
the unsolicited AE/SAE could be causally related to a specific vaccine/product (i.e. 
investigational, control/placebo or co-administered vaccine). When causal relationship to 
a specific vaccine cannot be determined, the investigator should indicate the unsolicited 
AE/SAE to be related to all products. 
Alternative plausible causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study vaccine will be considered and investigated. The investigator will also consult the 
IB to determine his/her assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study vaccine? 
YES 
: 
There is a reasonable possibility that the study vaccine contributed 
to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to 
the administration of the study vaccine. There are other, more 
likely causes and administration of the study vaccine is not 
suspected to have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible 
contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the vaccine, if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify). 
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There may be situations when an SAE/pIMD has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very important 
to record an assessment of causality for every event before submitting the Adverse 
Events Form and corresponding Expedited Adverse Event Form to GSK. 
The causality assessment is ONE of the criteria used when determining regulatory 
reporting requirements. The investigator may change his/her opinion of causality after 
receiving additional information and update the SAE information accordingly. 
10.3.8.3. 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
10.3.9. 
Reporting of SAEs, pIMDs 
10.3.9.1. 
Events requiring expedited reporting to GSK (Amended 4 November 
2020) 
Once an investigator becomes aware that an SAE/pIMD has occurred in a study 
participant, the investigator (or designee) must report the SAE/pIMD WITHIN 24 
HOURS by completing an Adverse Events Form and a corresponding Expedited 
Adverse Event Form. These forms will always be completed as thoroughly as possible 
with all available details of the event.  
Even if the investigator does not have all information regarding an SAE/pIMD, the forms 
should still be completed within 24 hours. Once additional relevant information is 
received, the report should be updated WITHIN 24 HOURS. The investigator will always 
provide an assessment of causality at the time of the initial report. 
Refer to the Table 11 for the details on timeframes for reporting of SAEs/pIMDs.  
The investigator will be required to review the SAE/pIMD causality within 72 hours of 
submission of the SAE/pIMD. Date/time of the causality review should be entered in the 
eCRF. 
Refer to the Section 10.3.9.2 for the back-up system in case the electronic reporting 
system does not work. 
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10.3.9.2. 
Back-up system in case facsimile or electronic reporting system does 
not work (Amended 4 November 2020) 
In rare circumstances if the electronic reporting system does not work, the investigator 
(or designee) must fax completed, dated and signed paper Expedited Adverse Event 
Report to the Study Contact for Reporting SAEs/pIMDs (refer to the Sponsor 
Information) or to GSK Clinical Safety and Pharmacovigilance department within 24 
hours.  
Investigator (or designee) must complete the electronic Adverse Events Form and the 
corresponding Expedited Adverse Event Form within 24 hours upon electronic reporting 
system is resumed. The information reported through the electronic SAE reporting 
system will be considered valid for regulatory reporting purposes. 
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10.4. 
Appendix 4: Abbreviations and glossary of terms 
10.4.1. 
List of abbreviations  
AE: 
Adverse Event 
AESI: 
Adverse Event of Specific Interest 
AS01E: 
Adjuvant System containing MPL, QS-21 and liposome 
(25 g MPL and 25 µg QS-21) 
CDC: 
Centers for Disease Control and Prevention 
CI: 
Confidence Interval 
CLS: 
Clinical Laboratory Sciences 
COPD: 
Chronic Obstructive Pulmonary Disease 
COVID-19: 
Coronavirus Disease 2019 
CMI: 
Cell Mediated Immunity 
DRE: 
Disease-related event 
eCRF: 
electronic Case Report Form 
ELISA: 
Enzyme-Linked Immunosorbent Assay 
EoS: 
End of Study 
GCP: 
Good Clinical Practice 
GMC: 
Geometric Mean Concentration 
GMT: 
Geometric Mean Titer 
GSK: 
GlaxoSmithKline 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
ICH: 
International Council on Harmonisation 
ICS: 
Intracellular Cytokine Staining 
IEC: 
Independent Ethics Committee 
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IgG: 
Immunoglobulin G 
IRB: 
Institutional Review Board 
LML: 
Local Medical Lead 
LRTD: 
Lower Respiratory Tract Disease 
LSLV: 
Last Subject Last Visit 
MedDRA: 
Medical Dictionary for Regulatory Activities 
MGI: 
Mean Geometric Increase 
OA: 
Older Adults 
PBMC: 
Peripheral Blood Mononuclear Cells 
pIMD: 
Potential Immune-Mediated Disease 
PP: 
Per protocol 
PRE: 
Population-related event 
PT: 
Preferred Term 
QS-21: 
Quillaja saponaria Molina, fraction 21 (Licensed by 
GSK from Antigenics Inc, a wholly owned subsidiary of 
Agenus Inc., a Delaware, USA corporation) 
RSV: 
Respiratory Syncytial Virus 
SAE: 
Serious Adverse Event 
SAP: 
Statistical Analysis Plan  
SBIR: 
Source data Base for Internet Randomisation  
SoA: 
Schedule of Activities 
SPM: 
Study Procedures Manual 
US: 
United States 
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10.4.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product.  
An adverse event (AE) can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal 
product. For marketed medicinal products, this also 
includes failure to produce expected benefits (i.e. lack of 
efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
trial, and only when the data are cleaned to an acceptable 
level of quality will appropriate personnel be unblinded 
or when required in case of a serious adverse event. In 
an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned.  
Certified copy: 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e. by a dated 
signature or by generation through a validated process) 
to have the same information, including data that 
describe the context, content, and structure, as the 
original. 
Designate: 
A person who helps the subject with performing some of 
the study procedures if the subject has difficulties to 
perform them alone (such as completion of the Diary, 
receiving phone calls and planning of the study visits), 
e.g. a relative of the subject, a field worker who is linked 
to this study. Designates are appointed by the subject for 
help with the study procedures solely and cannot make 
decisions on behalf of the subject. 
Eligible: 
Qualified for enrolment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
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Enrolled: 
‘Enrolled’ means a participant’s agreement to participate 
in a clinical study following completion of the informed 
consent process. Potential participants who are screened 
for the purpose of determining eligibility for the study, 
but do not participate in the study, are not considered 
enrolled, unless otherwise specified by the protocol. 
Refer to the Section 9.3 for the definition of ‘enrolled’ 
applicable to the study. 
Essential documents: 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis (see Section 9.3 for 
details on criteria for evaluability). 
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 subject’s initial immune status. 
Intervention: 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Invasive medical device: 
A device which, in whole or in part, penetrates inside the 
body, either through a body orifice or through the 
surface of the body. 
Investigational vaccine: 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorization when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use.  
Synonym: Investigational Medicinal Product 
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Investigator: 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator.  
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
and functions. 
Participant: 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or 
participates in the clinical study, either as a recipient of 
the vaccine or as a control. 
Synonym: subject 
Participant number: 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Primary completion date: 
The date that the final participant was examined or 
received an intervention for the purpose of final 
collection of data for all primary outcomes, whether the 
clinical trial was concluded according to the pre-
specified protocol or was terminated. 
Protocol amendment: 
The International Council on Harmonisation (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK Biologicals further details this to include a change 
to an approved protocol that affects the safety of 
participants, scope of the investigation, study design, or 
scientific integrity of the study. 
Protocol administrative 
change: 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study.  
Randomization: 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Site Monitor: 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
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Solicited event: 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified post-vaccination follow-up period. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data 
are contained in source documents (original records or 
certified copies). 
Source documents: 
Original legible documents, data, and records (e.g. 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participants' diaries or evaluation 
checklists, pharmacy dispensing records, recorded data 
from automated instruments, copies or transcriptions 
certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, participant files, and records 
kept at the pharmacy, at the laboratories and at medico-
technical departments involved in the clinical trial). 
Study vaccine/product: 
Any investigational vaccine/product being tested and/or 
any authorized use of a vaccine/product/placebo as a 
reference or administered concomitantly, in a clinical 
trial that evaluates the use of an investigational 
vaccine/product. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event. 
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10.5. 
Appendix 5: Protocol Amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
DOCUMENT HISTORY 
Document 
Date of Issue 
Original Protocol 
2 July 2020 
Overall Rationale for the Amendment 
The protocol is amended to address the comments from the United States Food and Drug 
Administration (US FDA). Specifically, instructions to delay enrolment or vaccination of 
participants with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) 
infection or with known COVID-19 positive contacts have been updated. In addition, the 
requirement to obtain written approval from the Sponsor for a participant to receive a 
vaccine as part of mass vaccination for an unforeseen public health threat (e.g., 
pandemic) if the vaccine to be used according to the local governmental 
recommendations has been amended. Other changes have been made to align the protocol 
with the parent RSV OA=ADJ-002 study and other phase 3 studies in the project.  
Detailed description of Protocol Amendment: 
Sponsor Approval: The name of the Sponsor Signatory has been updated. 
Narcisa Mesaros Marie Van Der Wielen, MD. 
Clinical and Epidemiology R&D Project Lead, Older Adults project 
Section 5.2.2: Prior/ Concomitant therapy: Updated to acknowledge the FDA’s request 
to remove the requirement to obtain written approval from the Sponsor for mass 
vaccination.   
Note: In case an emergency mass vaccination for an unforeseen public health threat (e.g.: 
a pandemic) is recommended and/or organized by the public health authorities, outside 
the routine immunization program, the time period described above can be reduced if 
necessary for that vaccine provided it is licensed and used according to the local 
governmental recommendations and provided a written approval of the Sponsor is 
obtained that the Sponsor is notified accordingly. 
Section 7.1.1 Criteria for temporary delay for enrolment and/or vaccination: 
Updated to acknowledge FDA feedback. 
Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to vaccination. 
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Participants with symptoms suggestive of active Coronavirus Disease 2019 (COVID-19) 
infection (i.e. fever, cough, etc.) until they are free of symptoms for at least 14 days. 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.). until they are free of symptoms for at least 14 days. 
Enrolment and/or vaccination of subjects with known COVID 19 positive contacts within 
the past 14 days should be delayed for at least 14 days since the exposure and if the 
subject remains symptom free. Participants with known COVID-19 positive contacts 
within the past 14 days may be vaccinated at the discretion of the investigator at least 
14 days after the exposure if the participant remains symptom free. 
Section 8.2.1.3 Physical examination: Updated to avoid duplication of temperature 
measurement. 
At minimum, temperature, vital signs (e.g., heart rate, respiratory rate, blood pressure) 
must be collected. 
Sections 8.3.1, 8.3.3 (Table 11), 10.3.7.2.2, 10.3.8.2, 10.3.9.1, 10.3.9.2: Throughout the 
document, in applicable sections, the wording is updated to account for both Adverse 
Events Form and the Expedited Adverse Event Form. 
…Adverse Events Form and the corresponding Expedited Adverse Events Report 
Form. 
Sections 8.3.3 (Table 11), 10.3.9.1: Wording is updated to align with the eCRF. 
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. Date/time of the causality review should be 
entered in the eCRF. 
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11. 
REFERENCES (AMENDED 4 NOVEMBER 2020) 
Bao K, Reinhardt RL. The differential expression of IL-4 and IL-13 and its impact on 
type-2 immunity. Cytokine 2015;75(1):25-37. 
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. 
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. 
Borchers AT, Chang C, Gershwin ME, et al. Respiratory syncytial virus – a 
comprehensive review. Clin Rev Allergy Immunol. 2013;45:331-79. 
Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the 
immune system. Nat Rev Immunol. 2012;12(3):180-90. 
Centers for Disease Control and Prevention. Respiratory Syncytial Virus Infection 
(RSV): Trends and Surveillance. RSV | Trends and Surveillance | Respiratory Syncytial 
Virus | CDC 2018, Accessed November 2020. [CDC website]. (Amended 4 November 
2020) 
Chattopadhyay PK, Yu J, Roederer M. A live-cell assay to detect antigen-specific CD4+ 
T cells with diverse cytokine profiles. Nat Med. 2005;11(10):1113-7. 
Cherukuri A, Patton K, Gasser Jr RA, et al. Adults 65 years old and older have reduced 
numbers of functional memory T-cells to respiratory syncytial virus fusion protein. Clin 
Vaccine Immunol. 2013;20:239-47. 
Falsey AR and Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol 
Rev. 2000;13:371–84.  
Falsey AR, McElhaney JE, Beran J, et al. Respiratory syncytial virus and other 
respiratory viral infections in older adults with moderate to severe influenza-like illness. J 
Infect Dis. 2014;209:1873-81.  
Frentsch M, Arbach O, Kirchhoff D, et al. Direct access to CD4+ T cells specific for 
defined antigens according to CD154 expression. Nat Med/ 2005;11(10):1118-24. 
Graham BS. Biological challenges and technological opportunities for respiratory 
syncytial virus vaccine development. Immunol Rev. 2011;239:149-66. 
Korn T, Bettelli E, Oukka M et al. IL-17 and Th17 Cells. Annu Rev Immunol. 
2009;27:485-517. 
Krilov LR. Respiratory syncytial virus disease: update on treatment and prevention. 
Expert Rev. Anti. Infect. Ther. 2011;9:27–32. 
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Moris P, Van Der Most R, Leroux-Roels I et al. H5N1 influenza vaccine formulated with 
AS03 A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin 
Immunol. 2011; 31(3):443-54. 
Rima B, Collins P, Easton A, et al. ICTV Virus Taxonomy Profile: Pneumoviridae. J Gen 
Virol. 2017;98:2912-3. 
Samten B, Thomas EK, Gong J, Barnes PF. Depressed CD40 ligand expression 
contributes to reduced gamma interferon production in human tuberculosis. Infect Immun 
2000;68(5):3002-6. 
Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive 
immune responses. Adv Immunol. 2007; 96:41-101. 
Sedger LM, McDermott MF. TNF and TNF-receptors: From mediators of cell death and 
inflammation to therapeutic giants - past, present and future. Cytokine Growth Factor 
Rev. 2014;25(4):453-72. 
Simões EA. Respiratory syncytial virus infection. Lancet. 1999;354:847–52. 
Simões EA. RSV disease in the pediatric population: epidemiology, seasonal variability, 
and long-term outcomes. Manag Care. 2008;17(11 Suppl 12):3-6, discussion 18-9. 
Stubbe M, Vanderheyde N, Goldman M et al. Antigen-specific central memory CD4+ T 
lymphocytes produce multiple cytokines and proliferate in vivo in humans. J Immunol. 
2006;177(11):8185-90. 
Wölfl M, Kuball J, Eyrich M, Schlegel PG, Greenberg PD. Use of CD137 to study the 
full repertoire of CD8+ T cells without the need to know epitope specificities. Cytometry 
A. 2008 Nov;73(11):1043-9. 
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TRADEMARKS 
The following trademarked products are referenced in the present protocol. 
Trademarks of the GSK group of companies 
 
Generic description 
Shingrix 
 
Zoster vaccine (Recombinant, adjuvanted) 
 
Trademarks not owned by the GSK group of 
companies 
 
Generic description 
TrueBlue peroxidase substrate (SeraCare) 
 
Chromagenic substrate for visualization of 
horseradish peroxidase-labeled reporter reagents 
 
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