A Phase III, Randomized, Multi-country Study to Evaluate the Lot-to-lot Consistency of GSK's Investigational RSV Maternal Vaccine and the Immune Response, Safety and Reactogenicity of RSV Maternal Vaccine When Co-administered With GSK's Quadrivalent Influenza D-QIV Vaccine in Healthy Non-pregnant Women 18-49 Years of Age.
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

 
 
 
 
 
 
Protocol 
A Phase III, observer-blind, randomized, multi-country study to evaluate the lot-to-lot consistency of 
GSK’s investigational RSV maternal vaccine and the immune response, safety and reactogenicity of RSV 
maternal vaccine when co-administered with GSK’s quadrivalent influenza D-QIV vaccine in healthy 
non-pregnant women 18-49 years of age. 
26-MAY-2022 

CONFIDENTIAL 
214709 (RSV MAT-010) 
Protocol Amendment 3 Final  
26 May 2022 
1 
 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Primary study intervention(s) 
and number(s) 
GlaxoSmithKline (GSK) Respiratory Syncytial Virus 
(RSV) Maternal (RSVPreF3) Vaccine 
[GSK3888550A] 
Other study intervention(s) 
• 
Placebo (Saline solution [NaCl]) 
• 
Flu D-QIV vaccine 
eTrack study number and 
abbreviated title 
214709 (RSV MAT-010) 
EudraCT number 
2021-000357-26 
Date of protocol 
Final: 21 April 2021 
Date of protocol amendment 
Amendment 1 Final: 24 May 2021 
Amendment 2 Final: 17 November 2021 
Amendment 3 Final: 26 May 2022 
Title 
A Phase III, randomized, multi-country study to 
evaluate the lot-to-lot consistency of GSK’s 
investigational RSV maternal vaccine and the 
immune response, safety and reactogenicity of RSV 
maternal vaccine when co-administered with GSK’s 
quadrivalent influenza D-QIV vaccine in healthy 
non-pregnant women 18-49 years of age. 
Brief title 
A Phase III study to assess the lot-to-lot consistency 
of GSK’s investigational RSV maternal vaccine and 
the immune response and safety of RSV maternal 
vaccine when given alone or co-administered with 
GSK’s influenza D-QIV vaccine in healthy non-
pregnant women. 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.1 
©2022 GSK group of companies or its licensor. 

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214709 (RSV MAT-010) 
Protocol Amendment 3 Final  
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Protocol Amendment 3 Sponsor Signatory Approval 
eTrack study number and 
abbreviated title 
214709 (RSV MAT-010) 
EudraCT number 
2021-000357-26 
Date of protocol amendment 
Amendment 1 Final: 24 May 2021 
Amendment 2 Final: 17 November 2021 
Amendment 3 Final: 26 May 2022 
Title  
A Phase III, randomized, multi-country study to 
evaluate the lot-to-lot consistency of GSK’s 
investigational RSV maternal vaccine and the 
immune response, safety and reactogenicity of RSV 
maternal vaccine when co-administered with GSK’s 
quadrivalent influenza D-QIV vaccine in healthy 
non-pregnant women 18-49 years of age 
Sponsor signatory 
Joon Hyung Kim, Clinical Epidemiology Project 
Lead, RSV Maternal, Clinical R&D 
Signature 
 
 
 
Date 
 
Note: Not applicable if an alternative signature process (e.g. electronic signature or 
email approval) is used to get the sponsor approval. 

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214709 (RSV MAT-010) 
Protocol Amendment 3 Final  
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Protocol Amendment 3 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 intervention 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. 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• 
To co-operate with representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the 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 intervention(s), and more generally about his/her 
financial ties with the sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 

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214709 (RSV MAT-010) 
Protocol Amendment 3 Final  
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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 

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214709 (RSV MAT-010) 
Protocol Amendment 3 Final  
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eTrack study number and 
abbreviated title 
214709 (RSV MAT-010) 
EudraCT number 
2021-000357-26 
Date of protocol amendment 
Amendment 1 Final: 24 May 2021 
Amendment 2 Final: 17 November 2021 
Amendment 3 Final: 26 May 2022 
Title 
A Phase III, randomized, multi-country study to 
evaluate the lot-to-lot consistency of GSK’s 
investigational RSV maternal vaccine and to 
evaluate the immune response, safety and 
reactogenicity of RSV maternal vaccine when co-
administered with GSK Biologicals’ quadrivalent 
influenza D-QIV vaccine in healthy non-pregnant 
women 18-49 years of age  
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 

CONFIDENTIAL 
214709 (RSV MAT-010) 
Protocol Amendment 3 Final  
26 May 2022 
6 
SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA (GSK) 
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 Events (SAEs) 
GSK central back up study contact for reporting SAEs: refer to the protocol Section 
8.3.3.1. 
Study contact for reporting SAEs: refer to the local study contact information 
document. 
5. GSK Helpdesk for emergency unblinding 
Refer to the protocol section 6.3.5.1 

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Protocol Amendment 3 Final  
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Amendment 3 (26 May 2022) 
This amendment is considered substantial based on the criteria defined in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it impacts the scientific value of the study. 
Overall rationale for the current Amendment:  
This protocol has been amended to reflect the following: 
• 
Following review of data collected so far from the RSV MAT-009 study in pregnant 
women, safety signals have been identified. An imbalance in the proportion of 
preterm births and neonatal deaths have been observed in infants born to mothers 
who received RSV maternal vaccine versus those who received a placebo. The safety 
signals are being investigated, and although at this time a cause has not been 
determined, based on the above observations, GSK has nevertheless decided to stop 
enrolment and vaccination for active enrolment in all RSV MAT studies. When this 
decision was taken, the enrollment had been completed in RSV MAT-010 study.  
• 
Due to issues in validation of A/Victoria/2570/2019 (H1N1) influenza strain, the 
primary and secondary objectives were modified to evaluate only 3 influenza strains 
(A/Tasmania/503/2020 (H3N2), B/Washington/02/2019, B/Phuket/3073/2013). The 
A/Victoria/2570/2019 (H1N1) will be evaluated as part of the tertiary objectives. 
• 
The secondary safety objective and its corresponding endpoint related to assessment 
of safety of RSV maternal vaccine when given alone and co-administered with Flu 
D-QIV from vaccination up to study end was recategorized as a primary objective. 
• 
The interim analysis was removed following GSK’s decision to stop enrollment and 
vaccination for active enrollment in all RSV MAT studies. 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Section 2.3 
Benefit/Risk 
assessment 
Updated to provide details on the 
current status on expected benefits 
and risks from receiving the RSV 
MAT (RSVPreF3) vaccine 
Updated to reflect potential changes in the 
benefit-risk profile.  
Section 3 
Objective(s), 
Endpoints, and 
Estimands 
• 
Categorized primary and 
secondary objectives related 
the assessment of the 
A/Victoria/2570/2019 (H1N1) 
influenza strain as tertiary 
objectives. 
• 
Categorised secondary safety 
objective related to the 
assessment of safety of 
RSVPreF3 when given alone 
Updated due to issues in validating the 
A/Victoria/2570/2019 (H1N1) influenza strain. 
Updated to reflect the change to study’s safety 
assessment plan. 

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Section # and title 
Description of change 
Brief rationale 
and co-administered with Flu 
D-QIV as a primary objective. 
9.4.1 Primary 
endpoints/estimands 
analysis 
9.4.2 Secondary 
endpoints/estimands 
analysis 
• 
Categorized primary and 
secondary endpoints related 
the assessment of the 
A/Victoria/2570/2019 (H1N1) 
influenza strain as tertiary 
endpoints. 
• 
Categorised secondary safety 
endpoint related to the 
assessment of safety of 
RSVPreF3 when given alone 
and co-administered with Flu 
D-QIV as a primary endpoint. 
Updated due to issues in validating the 
A/Victoria/2570/2019 (H1N1) influenza strain.  
 
 
Updated to reflect the change to study’s safety 
assessment plan. 
9.5.1 Sequence of 
analysis  
9.5.2 Statistical 
considerations for 
analysis 
Updated to remove the interim 
analysis to evaluate all participant 
safety, reactogenicity, and 
immunogenicity data collected up to 
Day 31 (Visit 2). 
Updated to reflect the change to study’s statistical 
analysis plan from the decision to stop further 
enrollment and vaccination.  

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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
List of main changes in the protocol and their rationale: ........................................... 7 
1. 
PROTOCOL SUMMARY ........................................................................................ 17 
1.1. 
Synopsis (Amended 26 May 2022) ............................................................. 17 
1.2. 
Schema ...................................................................................................... 17 
1.3. 
Schedule of Activities (SoA) ........................................................................ 19 
2. 
INTRODUCTION .................................................................................................... 22 
2.1. 
Study rationale (Amended 26 May 2022) .................................................... 22 
2.2. 
Background ................................................................................................ 23 
2.3. 
Benefit/Risk assessment (Amended 26 May 2022) ..................................... 23 
3. 
OBJECTIVE(S), ENDPOINTS, AND ESTIMANDS (AMENDED 26 MAY 
2022) ...................................................................................................................... 25 
4. 
STUDY DESIGN .................................................................................................... 28 
4.1. 
Overall design ............................................................................................. 28 
4.2. 
Scientific rationale for study design ............................................................. 30 
4.3. 
Justification for dose ................................................................................... 30 
4.4. 
End of Study definition ................................................................................ 30 
5. 
STUDY POPULATION ........................................................................................... 31 
5.1. 
Inclusion criteria .......................................................................................... 31 
5.2. 
Exclusion criteria ......................................................................................... 31 
5.2.1. 
Medical conditions ....................................................................... 32 
5.2.2. 
Prior/Concomitant therapy ........................................................... 32 
5.2.3. 
Prior/Concurrent clinical study experience ................................... 33 
5.2.4. 
Other exclusions .......................................................................... 33 
5.3. 
Lifestyle considerations ............................................................................... 33 
5.3.1. 
Demographic data ....................................................................... 33 
5.4. 
Screen failures ............................................................................................ 34 
5.5. 
Criteria for temporarily delaying enrollment ................................................. 34 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 34 
6.1. 
Study intervention(s) administered .............................................................. 35 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 36 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 36 
6.3.1. 
Participant identification ............................................................... 36 
6.3.2. 
Randomization to study intervention ............................................ 37 
6.3.3. 
Intervention allocation to the participant ....................................... 37 
6.3.4. 
Allocation of participants to assay subsets ................................... 37 
6.3.5. 
Blinding and unblinding ................................................................ 37 
6.3.5.1. 
Emergency unblinding ................................................ 38 
6.3.5.2. 
Unblinding prior to regulatory reporting of SAEs ......... 38 
6.4. 
Study intervention compliance .................................................................... 39 
6.5. 
Dose modification ....................................................................................... 39 

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6.6. 
Continued access to study intervention after the end of the study ............... 39 
6.7. 
Treatment of overdose ................................................................................ 39 
6.8. 
Concomitant therapy ................................................................................... 39 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 40 
7.1. 
Discontinuation of study intervention ........................................................... 40 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration .............................................................................. 40 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 40 
7.3. 
Lost to follow-up.......................................................................................... 41 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 41 
Study Procedures During Special Circumstances................................................... 42 
8.1. 
Immunogenicity assessments ..................................................................... 43 
8.1.1. 
Biological samples ....................................................................... 44 
8.1.2. 
Laboratory assays ....................................................................... 44 
8.1.3. 
Immunological read-outs .............................................................. 46 
8.1.4. 
Immunological correlates of protection ......................................... 46 
8.2. 
Safety Assessments ................................................................................... 46 
8.2.1. 
Pre-vaccination procedures ......................................................... 47 
8.2.1.1. 
Informed consent agreement ...................................... 47 
8.2.1.2. 
Collection of demographic data .................................. 47 
8.2.1.3. 
Medical/vaccination history ......................................... 47 
8.2.1.4. 
Physical examination .................................................. 47 
8.2.1.5. 
Pregnancy test ........................................................... 47 
8.2.1.6. 
Warnings and precautions to vaccination ................... 48 
8.2.2. 
Study holding rules and safety monitoring.................................... 48 
8.3. 
AEs, SAEs and other safety reporting ......................................................... 48 
8.3.1. 
Time period and frequency for collecting AE, SAE, and 
other safety information ............................................................... 48 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and 
other events ................................................................................. 49 
8.3.2.1. 
Clinically significant abnormal laboratory 
findings ....................................................................... 49 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies 
and other events .......................................................................... 49 
8.3.3.1. 
Contact information for reporting SAEs, AESIs, 
pregnancies and study holding rules .......................... 50 
8.3.4. 
Treatment of adverse events ....................................................... 50 
8.3.5. 
COVID-19 Infection ...................................................................... 51 
8.3.6. 
Participant card ............................................................................ 51 
8.3.7. 
Medical device deficiencies ......................................................... 51 
8.3.7.1. 
Detection, follow-up and prompt reporting of 
medical device deficiency ........................................... 51 
8.3.7.2. 
Regulatory reporting of medical device 
deficiency when used as combination product ............ 52 
8.4. 
Pharmacokinetics ....................................................................................... 52 
8.5. 
Genetics ..................................................................................................... 52 
8.6. 
Biomarkers ................................................................................................. 52 
8.7. 
Immunogenicity........................................................................................... 52 
8.8. 
Health outcomes ......................................................................................... 52 

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9. 
STATISTICAL CONSIDERATIONS ........................................................................ 53 
9.1. 
Statistical hypotheses ................................................................................. 53 
9.2. 
Sample size determination .......................................................................... 53 
9.2.1. 
Primary objective for Lot-to-Lot consistency ................................. 53 
9.2.2. 
Primary objective: To demonstrate Non-inferiority of 
immune response of Flu D-QIV vaccine when co-
administered with RSVPreF3 vaccine or administered 
alone at Day 31 post dose vaccination (Amended 26 May 
2022) ........................................................................................... 54 
9.2.3. 
Secondary objectives ................................................................... 55 
9.2.3.1. 
To demonstrate the non-inferiority of immune 
response between RSVPreF3 co-administered 
with Flu D-QIV and RSVPreF3 alone in term of 
RSV A Neutralizing antibody titers at Day 31 
post administration ..................................................... 55 
9.2.3.2. 
To demonstrate the non-inferiority of immune 
response between RSVPreF3 co-administered 
with Flu D-QIV and Flu D-QIV alone in term of 
SCR at Day 31 post 1st dose administration 
(Amended 26 May 2022) ............................................ 56 
9.2.4. 
Safety consideration .................................................................... 56 
9.3. 
Analysis sets ............................................................................................... 57 
9.3.1. 
Criteria for elimination from analysis ............................................ 57 
9.4. 
Statistical analyses(Amended 26 May 2022) .............................................. 58 
9.4.1. 
Primary endpoints/estimands analysis ......................................... 58 
9.4.2. 
Secondary endpoints/estimands analysis .................................... 59 
9.4.3. 
Tertiary endpoints/estimands analysis ......................................... 60 
9.5. 
Conduct of analyses ................................................................................... 60 
9.5.1. 
Sequence of analyses (Amended 26 May 2022) .......................... 60 
9.5.2. 
Statistical consideration for analysis (Amended 26 May 
2022) ........................................................................................... 60 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 61 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 61 
10.1.1. 
Regulatory and ethical considerations ......................................... 61 
10.1.2. 
Financial disclosure ..................................................................... 61 
10.1.3. 
Informed consent process ............................................................ 62 
10.1.4. 
Data protection ............................................................................ 62 
10.1.5. 
Committees structure ................................................................... 63 
10.1.6. 
Dissemination of clinical study data ............................................. 63 
10.1.7. 
Data quality assurance ................................................................ 63 
10.1.8. 
Source documents ....................................................................... 64 
10.1.9. 
Study and site start and closure ................................................... 65 
10.1.10. Publication policy ......................................................................... 65 
10.2. 
Appendix 2: Clinical laboratory tests (Amended 26 May 2022) ................... 66 
10.2.1. 
Protocol required safety laboratory assessments ......................... 66 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of AE .................. 67 
10.3.1. 
Definition of an AE ....................................................................... 67 
10.3.1.1. Events Meeting the AE Definition ............................... 67 

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10.3.1.2. Events NOT Meeting the AE Definition ....................... 68 
10.3.2. 
Definition of an SAE ..................................................................... 69 
10.3.3. 
Solicited events............................................................................ 69 
10.3.4. 
Unsolicited adverse events .......................................................... 70 
10.3.5. 
Adverse events of special interest (AESIs) .................................. 70 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs ...................................... 71 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs ..................... 71 
10.3.7.1. Pregnancy .................................................................. 71 
10.3.8. 
Recording and follow-up of AEs, SAEs, and pregnancies ............ 71 
10.3.8.1. Time period for collecting and recording AEs, 
SAEs, and pregnancies .............................................. 72 
10.3.8.2. Follow-up of AEs, SAEs, pregnancies or any 
other events of interest ............................................... 72 
10.3.8.2.1. Follow-up during the study ...................... 72 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study ...................... 72 
10.3.8.2.3. Follow-up of pregnancies ........................ 73 
10.3.8.3. Updating of SAE and pregnancy information 
after removal of write access to the 
participant’s eCRF ...................................................... 73 
10.3.9. 
Assessment of intensity and toxicity ............................................. 74 
10.3.9.1. Assessment of intensity .............................................. 74 
10.3.9.2. Assessment of causality ............................................. 75 
10.3.9.3. Medically attended visits ............................................. 76 
10.3.9.4. Assessment of outcomes............................................ 76 
10.3.10. Reporting of SAEs and pregnancies and other events ................. 76 
10.3.10.1. Events requiring expedited reporting to GSK .............. 76 
10.3.10.2. Backup system in case the electronic reporting 
system does not work ................................................. 77 
10.4. 
Appendix 4: Contraceptive guidance and collection of pregnancy 
information .................................................................................................. 77 
10.4.1. 
Definitions .................................................................................... 77 
10.4.1.1. Woman of Childbearing Potential (WOCBP) ............... 77 
10.4.1.1.1. Women not considered as women 
of childbearing potential .......................... 77 
10.4.2. 
Contraception guidance ............................................................... 78 
10.4.3. 
Collection of pregnancy information ............................................. 79 
10.4.3.1. Female participants who become pregnant ................ 79 
10.5. 
Appendix 5: Genetics .................................................................................. 79 
10.6. 
Appendix 6: Definition of medical device AE, adverse device effect 
(ADE), serious adverse device effect (SADE) and unanticipated 
SADE (USADE) .......................................................................................... 79 
10.6.1. 
Definition of medical device AE and adverse device effect 
(ADE) ........................................................................................... 79 
10.6.2. 
Definition of medical device SAE, SADE and USADE .................. 79 
10.6.3. 
Recording and reporting of medical device AE, ADEs, 
SADEs and USADE ..................................................................... 80 
10.7. 
Appendix 7: Country-specific requirements ................................................. 80 
10.7.1. 
South Korea ................................................................................. 81 
10.8. 
Appendix 8: Abbreviations and glossary of terms ........................................ 81 
10.8.1. 
List of abbreviations ..................................................................... 81 

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10.8.2. 
Glossary of terms ......................................................................... 82 
10.9. 
Appendix 9: Protocol Amendment ............................................................... 87 
11. REFERENCES ..................................................................................................... 105 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities ............................................................................. 19 
Table 2 
Intervals between study visits ................................................................. 22 
Table 3 
Study objectives, endpoints and estimands ............................................ 25 
Table 4 
Study groups and intervention ................................................................ 29 
Table 5 
Study intervention(s) administered ......................................................... 35 
Table 6 
Study intervention administered (Part 2) ................................................ 36 
Table 7 
Contact information for emergency unblinding ....................................... 38 
Table 8 
Biological samples ................................................................................. 44 
Table 9 
Laboratory assays .................................................................................. 44 
Table 10 
Immunological read-outs ........................................................................ 46 
Table 11 
Reporting periods for collecting safety information ................................. 48 
Table 12 
Timeframes for submitting SAE, pregnancy and other events 
reports to GSK ....................................................................................... 50 
Table 13 
Contact information for reporting SAEs and pregnancies ....................... 50 
Table 14 
Power to demonstrate Lot-to-Lot consistency on immune 
responses of RSVPreF3 IgG ELISA concentration at Day 31 post 
vaccination ............................................................................................. 53 
Table 15 
Power to demonstrate non-inferiority of immune response 
between Flu D-QIV vaccine co-administered with RSVPreF3 or 
administered alone in term of GMT for Flu D-QIV strains at Day 
31 post 1st vaccination with assumed GMT ratio 1 (Amended 26 
May 2022) .............................................................................................. 54 
Table 16 
Power to demonstrate non-inferiority of immune response of 
RSVPreF3 vaccine when co-administered with Flu D-QIV 
vaccine or administered alone at Day 31 post vaccination ..................... 55 
Table 17 
Powers to demonstrate non-inferiority in terms of HI antibody 
SCR for Flu D-QIV strains between Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and administered alone at 
Day 31 post vaccination (Amended 26 May 2022) ................................. 56 
Table 18 
Exact 95% confidence interval (CI) on the percentage of 
participants with AEs following vaccination from 660 participants 

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with 3 lots pooled, and 440 participants from RSVPreF3 co-
administration group ............................................................................... 57 
Table 19 
Analysis sets .......................................................................................... 57 
Table 20 
Protocol required safety laboratory assessments ................................... 67 
Table 21 
Solicited administration site events......................................................... 70 
Table 22 
Solicited systemic events ....................................................................... 70 
Table 23 
Intensity scales for solicited events ........................................................ 74 
Table 24 
Highly effective contraceptive methods .................................................. 78 
 

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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 28 
 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis (Amended 26 May 2022) 
Rationale 
GSK is developing an investigational respiratory syncytial virus (RSV) maternal vaccine 
(RSVPreF3) against RSV disease in infants through maternal immunization. This study 
will be a Phase III study to evaluate clinical lot-to-lot consistency in healthy 
non-pregnant women 18-49 years of age (YOA) by comparing safety and 
immunogenicity results. In addition, this study will evaluate safety and immunogenicity 
of the RSVPreF3 vaccine when co-administered with GSK’s quadrivalent seasonal 
influenza (Flu D-QIV) vaccine. 
A Phase I/II, observer-blind study (RSV MAT-001; NCT 03674177) in healthy non-
pregnant women 18-45 YOA, to determine the safety and immunogenicity of 3 dose 
levels of the RSVPreF3 vaccine (30, 60, and 120 µg) compared to placebo, has been 
completed. No safety concerns have been identified. 
Based on preliminary results of RSV MAT-001 study, the 60 and 120 µg dose levels 
were selected for further evaluation in the following 2 additional studies, which are 
completed: 
• 
RSV MAT-004 (NCT 04126213): A Phase II, observer-blind study to assess safety, 
reactogenicity, and immunogenicity of 2 dose levels of the RSVPreF3 vaccine in 
healthy pregnant women and infants born to vaccinated mothers. 
• 
RSV MAT-011 (NCT 04138056): A Phase II, observer-blind study of 2 dose levels 
of the RSVPreF3 vaccine, given alone or with Boostrix, to healthy non-pregnant 
women to assess safety, reactogenicity and immunogenicity. 
Based on the final results of RSV MAT-001, on the Day 31 results of RSV MAT-004 and 
RSV MAT-011 studies, the 120µg dose level was selected for evaluation in RSV MAT-
010 study. In addition, the 120µg dose level was also administered in pregnant women 
participating in the Phase III study RSV MAT-009.  
Objectives and endpoints/estimands of the RSV MAT-010 study are presented in Table 3. 
1.2. 
Schema 
This Phase III, randomized, multi-country study is observer-blinded to evaluate the 
lot-to-lot consistency of GSK RSVPreF3 vaccine, and single-blinded to evaluate the 
immune response, safety and reactogenicity when co-administered with Flu D-QIV 
vaccine. A total of 1541 healthy non-pregnant women 18 to 49 YOA will be enrolled in 
the study. 

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Approximately 660 non-pregnant women 18 to 49 YOA (inclusive, at the time of the 
study intervention administration) will be evenly enrolled. The RSV1, RSV2, and RSV3 
groups will receive RSVPreF3 (120 µg of RSVPreF3 vaccine), each group receiving a 
different lot of RSVPreF3 vaccine. Study participants from RSV1, RSV2, and RSV3 
groups will be provided with an option of receiving Flu D-QIV vaccine at Day 31 to 
allow the participants to receive the standard of care. 
In addition, approximately 881 non-pregnant women will be enrolled for the co-
administration of RSVPreF3 with Flu D-QIV or Flu D-QIV with placebo at their first 
vaccination in additional 2 groups. The participants in the co-administration (RSVPreF3 
with Flu D-QIV) group will receive the RSVPreF3 vaccine from lots 1, 2, or 3 evenly. 
Approximately 1541 participants will be randomized with randomization ratio of 
3:3:3:2:2:2:6. 
• 
Approximately 220 participants in the RSV1 group (Lot 1) 
• 
Approximately 220 participants in the RSV2 group (Lot 2) 
• 
Approximately 220 participants in the RSV3 group (Lot 3) 
• 
Approximately 441 participants in the RSV + Flu pooled group (split into 3 groups) 
− 
Approximately 147 participants in the RSV1 (Lot 1) + Flu group 
− 
Approximately 147 participants in the RSV2 (Lot 2) + Flu group 
− 
Approximately 147 participants in the RSV3 (Lot 3) + Flu group 
• 
Approximately 440 participants in the Flu + placebo group 
Section 4.1 provides an overview of the study design. 
Blood samples for humoral immunogenicity will be collected from all participants at 
Visit 1 and Visit 2 (pre-vaccination at Day 1 and Day 31 post study vaccination). 
All participants who receive the study intervention will be followed for safety and 
reactogenicity and evaluated for solicited administration site and systemic adverse events 
(AEs) within 7 days of vaccination, unsolicited AEs within 30 days of vaccination, and 
SAEs throughout the study period and pregnancy outcomes. 
All safety data will be reviewed by a Safety Review Team (SRT) on an ongoing basis. 
 

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1.3. 
Schedule of Activities (SoA) 
Table 1 presents the Schedule of Activities (SoA). 
Table 1 
Schedule of Activities 
Type of contact 
Visit 1 
TC 1 
Visit 2 
TC 2 
Comments 
Time points 
Day 1 
Day 8 
Day 31 
Day 181 
 
Sampling time points 
Pre-Vaccination 
Post-
Vaccination  
Post-
Vaccination 
Post-
Vaccination 
 
Informed consent  
● 
 
 
 
[See Section 10.1.3 for details]  
Assign participant number 
● 
 
 
 
 
Check inclusion/exclusion criteria 
● 
 
 
 
See Sections 5.1 and 5.2 for 
Inclusion and Exclusion criteria] 
Check contraindications to subsequent vaccine(s) administration  
 
 
O 
 
See Sections 7.1.1 and 8.2 for 
more information 
Collect demographic data1 
● 
 
 
 
See Section 8.2 for more 
information 
Medical and vaccination history  
● 
 
O 
 
[See Section 8.2 for more 
information] 
Physical examination2,4 
● 
 
 
 
See Section 8.2 for more 
information 
Vital signs2,4 
● 
 
O 
 
 
Urine pregnancy test 3 
● 
 
 
 
See Section 8.2 for more 
information 
Pre-vaccination body temperature  
● 
 
● 
 
 
Randomization 
● 
 
 
 
 
Blood sampling for humoral immune response (~10 mL)5 
● 
 
● 
 
See Section 8.1.1 for more 
information 
Study group and treatment number allocation (SBIR)  
O 
 
 
 
 
Vaccine administration  
● 
 
●8 
 
 
Recording of administered treatment number  
● 
 
●8 
 
 
30 minutes post-vaccination observation period  
O 
 
O 
 
 
Distribution of participant card 
O 
 
 
 
 
Training on use of e-diary  
O 
 
 
 
 

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Type of contact 
Visit 1 
TC 1 
Visit 2 
TC 2 
Comments 
Time points 
Day 1 
Day 8 
Day 31 
Day 181 
 
Sampling time points 
Pre-Vaccination 
Post-
Vaccination  
Post-
Vaccination 
Post-
Vaccination 
 
Distribution of e-diary device6 
O 
 
 
 
 
Review of e-diary 
O 
O 
O 
 
 
Return of e-diary device 
 
 
O 
 
 
Collection of solicited adverse events (Days 1 to 7 post-vaccination) 6 
O 
O 
 
 
[See Section 10.3.8 for more 
information] 
Recording of unsolicited adverse events for 30 days (days 1 to 30 post 
vaccination) 
● 
● 
● 
 
[See Section 10.3.8 for more 
information] 
Recording of AEs/SAEs leading to withdrawal 
● 
● 
● 
● 
[See Section 10.3.8 for more 
information] 
Recording of SAEs7  
● 
● 
● 
● 
[See Section 10.3.8 for more 
information] 
Recording of pregnancies  
 
● 
● 
● 
[See Section 10.3.8 for more 
information] 
Recording of concomitant medications/vaccinations 
● 
● 
● 
 
[See Section 6.8 for more 
information] 
Record any intercurrent medical conditions  
● 
● 
● 
 
[See Section 9.3.1 for more 
information] 
Phone contact 
 
● 
 
● 
 
Investigator sign-off on eCRF before analysis 
 
 
● 
● 
 
COVID-19 eCRFs log page 
● 
● 
● 
● 
 
Screening Conclusion 
● 
 
 
 
 
Study conclusion 
 
 
 
● 
[See Section 4.4 for more 
information] 
TC= Telephone contact 
● is used to indicate a study procedure that requires documentation in the individual eCRF. 
○ is used to indicate a study procedure that does not require documentation in the individual eCRF 
1 Date of birth (month and year or year only, as per local regulations), race, ethnicity and childbearing potential (if participant not of childbearing potential, the specific reason should be 
documented in the eCRF). 
2 Physical examination including (height and weight) BMI as well as resting vital signs (blood pressure, heart rate and respiratory rate, temperature) after at least 10 minutes of rest. 
At Day 1 (Visit 1) both physical exam and vital signs will be measured. At Day 31 (Visit 2) medical and vaccination history and vital signs may be measured. 
3 Only for women of childbearing potential. Urine pregnancy test is sufficient to determine the eligibility to enter the study. Serum pregnancy test (instead of urine test) may be 
performed if required by country, local or ethics committee regulations. 

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4 Fever is defined as temperature ≥38.0°C. The preferred location for measuring temperature in this study is the oral cavity. 
5 Subgroups, method, cut-off, and laboratory locations will be defined in Section 8. 
6 The e-diary device will be distributed at the day of vaccination and will be used for recording solicited AEs for 6 subsequent days (7 days total including day of vaccination).  
7SAEs related to study participation or concurrent GSK intervention product will be monitored from the time of screening to the time of the immunization. Both will be conducted on the 
same visit. 
8 Vaccination at Day 31 (Visit 2) is only for RSV 1, 2, 3 groups and optional. 
 

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Table 2 
Intervals between study visits 
Interval 
Optimal timing  
Allowed interval (Study day) 
Visit 1*→ Phone Contact 1 
Day 8  
Day 7 - 10 
Visit 1→ Visit 2 
Day 31 
Day 31 -38 
Visit 1 → Phone Contact 2 
Day 181 
Day 165 - 195  
*The interval between study visits begins at the time of vaccination during Visit 1 timepoint. 
2. 
INTRODUCTION 
2.1. 
Study rationale (Amended 26 May 2022) 
GSK is developing an investigational RSV maternal vaccine (RSVPreF3) against RSV 
disease in infants through maternal immunization. This will be a Phase III study to 
evaluate clinical lot consistency in 660 healthy non-pregnant women 18-49 YOA. Three 
different lots of RSVPreF3 (120µg) vaccine will be administered and examined for both 
immunogenicity and safety outcomes. In addition, this study will evaluate 
immunogenicity, safety and reactogenicity from co-administration of RSVPreF3 and Flu 
D-QIV in healthy non-pregnant women 18-49 YOA. 
A Phase I/II study (study RSV MAT-001; NCT 03674177) in healthy non-pregnant 
women 18-45 YOA to determine the safety and immunogenicity of 3 dose levels of 
RSVPreF3 (30, 60 and 120µg) vaccine compared to placebo is now complete. The results 
from this study demonstrated that the RSV maternal (RSVPreF3) vaccine is highly 
immunogenic and no safety concerns have been identified. Study results for safety and 
immunogenicity are now available in the Investigator Brochure. 
In another completed Phase II randomized, observer-blinded study (RSV MAT-011) in 
non-pregnant women 18 to 45 YOA, two dose levels of the RSV maternal vaccine, 60 
µg, and 120 µg, are being evaluated. The primary objectives are to evaluate the effects of 
Boostrix co-administration in terms of reactogenicity, safety and immune response to the 
RSV maternal vaccine at 1-month post study intervention (considering the US and 
outside the US data pooled). The effects of RSV maternal vaccine co-administration on 
the safety and immune response to Boostrix were evaluated as secondary objectives. 
Additional secondary objectives included safety assessment up to 6 months post-
intervention, and evaluations of the safety and immune response considering the US and 
outside the US data both separately and pooled. Enrollment is complete and participant’s 
follow-up is ongoing to examine the persistence of antibody 12-18 months post-1st dose 
and safety of a 2nd dose of RSV PreF3 vaccine given from 12 up to 18 months post 1st 
dose. Preliminary results are now available in the IB. Briefly, both formulations and both 
dose levels of the investigational RSV maternal vaccine elicited an immune response, no 
safety concern was observed in the study population of non-pregnant women. The 
safety and immunogenicity profile were also similar in another study (RSV MAT 004) 
examining RSV maternal vaccine in pregnant women. 

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Pregnant women are at increased risk for serious consequences of influenza infection. 
Influenza illness may also pose risks to fetal development, which can lead to adverse 
pregnancy outcomes such as stillbirth, preterm delivery, and decreased neonatal birth 
weight [WHO, 2012]. Consequently, many recommending bodies, including the World 
Health Organisation (WHO), US Centers for Disease Control and Prevention (CDC), the 
Advisory Committee on Immunisation Practices, the European Medicines Agency, the 
UK National Health Service, and the Australian Technical Advisory group on 
Immunisation recommend the use of Seasonal Inactivated Influenza Vaccine (sIIVs) 
during pregnancy. 
GSK manufactures a quadrivalent, inactivated, split virion, seasonal influenza vaccine 
(FLU-D-QIV) / (Fluarix Quadrivalent, Fluarix Tetra, FluarixTetra, α-RIX-Tetra and 
Influsplit Tetra), hereafter referred to as FLU-D-QIV. Flu D-QIV is a quadrivalent 
vaccine indicated for active immunization of adults and children from 6 months of age 
for the prevention of influenza disease caused by influenza virus types A and B contained 
in the vaccine. 
This study (RSV MAT-010) will be the first to evaluate co-administration of 120 µg of 
the RSVPreF3 (RSV MAT) vaccine with Flu D-QIV in healthy non-pregnant women (see 
Figure 1). Selection of the RSVPreF3 antigen dose was based on preliminary results of 
the completed studies (RSV MAT-001, RSV MAT-011 and RSV MAT-004). 
2.2. 
Background 
Please refer to the current Investigator’s Brochure (IB) for background information on 
RSV infection, the rationale for the maternal immunization approach described in this 
protocol, and information regarding pre-clinical and clinical studies of the RSVPreF3 
vaccine. 
2.3. 
Benefit/Risk assessment (Amended 26 May 2022) 
Detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of the RSVPreF3 (RSV MAT) vaccine can be found in the IB. 
GSK has included provisions in this trial to ensure participant’s safety. Participants will 
remain under observation for 30 minutes after administration of the study intervention to 
ensure that immediate treatment may be provided in the event of a hypersensitivity 
reaction, or syncope. Safety monitoring will be conducted throughout this study by a 
Safety Review Team. 
Measures to suspend the study should a potential safety issue be identified, are described 
in Section 8.2. 
Following a recommendation from the Independent Data Monitoring Committee 
(IDMC), the Sponsor made the decision to pause the enrollment, randomization and 
vaccination of pregnant study participants in our active studies based on an 
observation of imbalance of the proportion of preterm births between the vaccine group 
and the placebo group in the RSV MAT-009 study in pregnant women. This pause was 

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to allow for an evaluation of the available data in RSV MAT-009 to better understand 
the safety signal observed. Following a review of additional unblinded data from RSV 
MAT-009 trial in which a higher proportion of neonatal deaths reported in the 
treatment group compared to the placebo group was also observed, the Sponsor decided 
to STOP enrollment and vaccination in these studies.  
The safety signals are being investigated and, although at this time a cause has not 
been determined, as a precautionary measure GSK stopped active enrollment and 
further vaccination of participants in the RSV MAT studies enrolling both pregnant 
women on February 25, 2022. We also considered it not appropriate to enroll any 
additional participants in studies for the RSV maternal program and therefore also 
stopped active enrollment and further vaccination of participants in the RSV MAT 
studies enrolling non-pregnant women on March 1, 2022. The studies remain ongoing 
for safety follow-up. Participants already vaccinated will continue to be monitored until 
the end of the study. At this time, the safety observation has been observed only among 
pregnant trial participants. 

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3. 
OBJECTIVE(S), ENDPOINTS, AND ESTIMANDS 
(Amended 26 May 2022) 
Table 3 
Study objectives, endpoints and estimands 
Objectives 
Endpoints/Estimands 
Primary 
Safety 
• 
To evaluate the safety and reactogenicity of 
RSVPreF3 when given alone (pooled lots) or co-
administered with Flu D-QIV up to study end. 
The number and percentage of participants in each group 
reporting 
• 
Each solicited administration site AE collected 
during the 7 days follow-up period (Day 1 to Day 7) 
• 
Each solicited systemic events in the 7 days follow-
up period 
• 
Unsolicited AEs collected during the 30 days follow-
up period (Day 1 to Day 30) 
• 
SAEs in the 30 days follow-up period (Day 1 to Day 
30) 
• 
SAEs in the 180 days follow-up period (Day 1 to 
Day 181)  
Immunogenicity 
• 
To demonstrate the lot-to-lot consistency of 3 lots of 
the investigational RSVPreF3 vaccine based on 
GMC of RSVPreF3 IgG ELISA at Day 31 
RSVPreF3 IgG ELISA concentration at Day 31 (30 days 
post administration) 
Measured by ratio of Geometric mean concentration 
(GMC) between lots in terms of RSVPreF3 IgG ELISA 
titers at Day 31 (30 days post administration) 
• 
To demonstrate non-inferiority of Flu D-QIV vaccine 
when co-administered with RSVPreF3 vaccine 
compared to Flu D-QIV given alone based on 
Geometric mean titer (GMT) of Flu D-QIV antibody 
titers against 3 influenza strains at Day 31 post 
administration 
Flu D-QIV antibody titers against 3 influenza strains at 
Day 31 (30 days post administration) 
Measured by ratio of Haemagglutinin inhibition (HI) GMT 
between group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and Flu D-QIV vaccine alone group 
against 3 strains at Day 31 (30 days post administration)  
Secondary 
Confirmatory Immunogenicity*** 
• 
To demonstrate the non-inferiority of RSVPreF3 
vaccine co-administered with Flu D-QIV compared 
to given alone based on GMT of RSV A neutralizing 
antibody at Day 31 post administration 
RSV A neutralizing antibody titers at Day 31 (30 days post 
administration) 
Measured by ratio of GMT between group of RSVPreF3 
vaccine co-administered with Flu D-QIV and RSVPreF3 
vaccine alone (pooled lot 1,2,3) group in term of RSV A 
neutralizing antibody titers at Day 31 (30 days 
administration) 
• 
To demonstrate the non-inferiority of Flu D-QIV 
vaccine co-administered with RSVPreF3 compared 
to given alone based on Seroconversion rate (SCR) 
of Flu D-QIV HI antibody titers against 3 influenza 
strains at Day 31 post study intervention 
• 
Seroconversion rate to Flu D-QIV HI antibody titers 
against the 3 influenza strains at Day 31 
Measured by the difference of proportion of participants 
achieving seroconversion for HI antibody at Day 31 in the 
group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and the group of Flu D-QIV vaccine 
alone 

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Objectives 
Endpoints/Estimands 
Descriptive Immunogenicity 
• 
To evaluate the humoral immune response of 
RSVPreF3 vaccine when given alone and co-
administered with Flu D-QIV in terms of RSV A, 
RSV B neutralizing antibody and RSVPreF3 IgG 
concentration at Day 1 (prior to the vaccination) and 
Day 31 (post study intervention). 
• 
RSV A, RSV B neutralizing antibody titers and RSV 
PreF3 IgG concentration at Day 1 and Day 31 
GMT of RSV A and RSV B neutralizing antibody, GMC of 
RSVPreF3 IgG at Day 1 and Day 31, in the group of 
RSVPreF3 vaccine co-administered with Flu D-QIV and 
the group of RSVPreF3 vaccine alone  
• 
To evaluate the humoral immune response to the 
Flu D-QIV vaccine when given alone and co-
administered with RSVPreF3 vaccine in terms of 
antibody titers against 3 influenza strains at Day 1 
and Day 31 
Flu D-QIV HI antibody titers against the 3 influenza strains 
at Day 1 and Day 31 
HI GMT in the 3 influenza strains at Day 1 and Day 31 in 
the group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and the group of Flu D-QIV vaccine 
alone 
• 
To evaluate seroprotection rate (SPR)and 
Seroconversion rate (SCR)* of the Flu D-QIV 
vaccine when given alone and co-administered with 
RSVPreF3 vaccine 
Seroprotection rate to Flu D-QIV HI antibody titers against 
the 3 influenza strains at Day 1 and Day 31 
Measured by the proportion of participants achieving an HI 
antibody titer ≥1:40 at Day 1 and Day 31 in the group of 
Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine alone 
• 
Seroconversion rate to Flu D-QIV HI antibody titers 
against the 3 influenza strains at Day 31 
Measured by the proportion of participants achieving 
seroconversion for HI antibody at Day 31 in the group of 
Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine alone 
• 
To evaluate the humoral immune response in 3 
individual lots of RSVPreF3  
• 
RSV A, RSV B neutralizing antibody titers and 
RSVPreF3 IgG antibody concentrations at pre-
vaccination and Day 31 
Geometric mean titer/concentration (GMT/GMC) in term of 
RSV A, RSV B neutralizing antibody and RSVPreF3 IgG 
antibody at Day 1 (pre-vaccination) and Day 31 in each of 
3 lots of the investigational PreF3 vaccine.  
Tertiary  
To demonstrate non-inferiority of Flu D-QIV vaccine 
when co-administered with RSVPreF3 vaccine 
compared to Flu D-QIV given alone based on 
Geometric mean titer (GMT) of Flu D-QIV antibody 
titers against the A/Victoria/2570/2019 (H1N1) 
influenza strain at Day 31 post administration 
Flu D-QIV* antibody titers against the 
A/Victoria/2570/2019 (H1N1) influenza strain at Day 31 
(30 days post administration) 
Measured by ratio of Haemagglutinin inhibition (HI) 
GMT between group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and Flu D-QIV 
vaccine alone group against the A/Victoria/2570/2019 
(H1N1) strain at Day 31 (30 days post administration)  
To demonstrate the non-inferiority of Flu D-QIV 
vaccine co-administered with RSVPreF3 compared to 
given alone based on Seroconversion rate (SCR) of 
Flu D-QIV HI antibody titers against the 
A/Victoria/2570/2019 (H1N1) influenza strain at Day 31 
post study intervention 
• 
Seroconversion rate to Flu D-QIV* HI antibody 
titers against the A/Victoria/2570/2019 (H1N1) 
influenza strain at Day 31 
Measured by the difference of proportion of 
participants achieving seroconversion for HI antibody 
at Day 31 in the group of Flu D-QIV vaccine co-

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Objectives 
Endpoints/Estimands 
administered with RSVPreF3 vaccine and the group of 
Flu D-QIV vaccine alone 
To evaluate the humoral immune response to the Flu 
D-QIV vaccine when given alone and co-administered 
with RSVPreF3 vaccine in terms of antibody titers 
against the A/Victoria/2570/2019 (H1N1) influenza 
strain at Day 1 and Day 31 
Flu D-QIVHI antibody titers against the 
A/Victoria/2570/2019 (H1N1) influenza strain at Day 1 
and Day 31 
HI GMT in the A/Victoria/2570/2019 (H1N1) influenza 
strain at Day 1 and Day 31 in the group of Flu D-QIV 
vaccine co-administered with RSVPreF3 vaccine and 
the group of Flu D-QIV vaccine alone 
To evaluate seroprotection rate (SPR) and 
Seroconversion rate (SCR)* of the Flu D-QIV vaccine 
when given alone and co-administered with RSVPreF3 
vaccine 
Seroprotection rate to Flu D-QIV HI antibody titers 
against the A/Victoria/2570/2019 (H1N1) influenza 
strain at Day 1 and Day 31 
Measured by the proportion of participants achieving 
an HI antibody titer ≥1:40 at Day 1 and Day 31 in the 
group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and the group of Flu D-QIV vaccine 
alone 
x
Seroconversion rate to Flu D-QIV HI antibody 
titers against the A/Victoria/2570/2019 (H1N1) 
influenza strain at Day 31 
Measured by the proportion of participants achieving 
seroconversion for HI antibody at Day 31 in the group 
of Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine alone 
*The SCR is defined as the proportion of participants with: 
A Day 1 (pre-vaccination) serum anti-HI titer <1:10 and a Day 31 (post-vaccination) serum anti-HI titer ≥1:40, or 
A Day 1 (pre-vaccination) serum anti-HI titer ≥ 1:10 and a fold increase (post/pre) ≥ 4 at Day 31 
*** Two confirmatory objectives will be tested sequentially. 
C
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4. 
STUDY DESIGN 
4.1. 
Overall design  
This Phase III, randomized, multi-country study in healthy non-pregnant women 18-49 
YOA, is observer-blind to evaluate the lot-to-lot consistency of GSK RSVPreF3 vaccine 
and single-blinded to evaluate the immune response, safety and reactogenicity of GSK 
RSVPreF3 vaccine when co-administered with Flu D-QIV vaccine. 
Approximately 660 non-pregnant women age 18 to 49 YOA (inclusive, at the time of the 
study intervention administration) will be evenly enrolled. The RSV1, RSV2, and RSV3 
groups will receive RSVPreF3 vaccine (120 µg of RSVPreF3), each group receiving a 
different lot of RSVPreF3 vaccine. Study participants from RSV1, RSV2, and RSV3 
groups will be provided with an option of receiving Flu D-QIV vaccine at Day 31 to 
allow the participants receive the standard of care. 
In addition, approximately 881 non-pregnant women will be enrolled to the co-
administration of RSVPreF3 with Flu D-QIV (RSV+Flu groups) or the co-administration 
of Flu D-QIV with placebo (Flu+P group) at their first vaccination. The co-administration 
of RSVPreF3 with Flu D-QIV group will all receive the RSVPreF3 vaccine from lots 1, 
2, or 3 evenly. See section 6.3.2 for more detail on the randomization strategy. 
Figure 1 
Study design overview 
 
SOC=Standard of Care 
* Screening and vaccination will happen on Visit 1(Day 1). The blood sample collection must be collected before 
administering the vaccine(s). 

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** Visit 2 Flu D-QIV vaccinations are not part of experimental design. It serves as an optional vaccination for the 
participant to decide if they would like to get the vaccination as part of their standard of care. The blood sample 
collection must be collected before administering the Flu D-QIV vaccine. 
• 
Study Type: self-contained. 
• 
Study duration: The study vaccine will be administered at Visit 1 and the participant 
will be followed for 6 months until the study conclusion. 
• 
Blinding: This study will utilize an observer blind design to evaluate the lot-to-lot 
consistency of GSK RSVPreF3 vaccine; and single-blinding design to evaluate the 
immune response, safety and reactogenicity of RSV maternal vaccine when co-
administered with GSK quadrivalent influenza that is described in Section 6.3.5.  
• 
Placebo used: Saline (NaCl) solution. 
• 
Vaccination schedules are described in Table 6 
• 
Randomized intervention allocation is described in Table 4 and Section 6.3. 
• 
Study (intervention) groups are described in Table 4. 
• 
Data collection: standardized Electronic Case Report Form (eCRF) and e-Diaries 
will be used to collect solicited and unsolicited event data up to Day 30 (Day 30 
inclusive). Serious Adverse event data from Day 31 until the end of the study will be 
collected through questioning at concluding phone contacts and reported into the 
eCRF, as appropriate. 
• 
Safety monitoring will be conducted by a Safety Review Team. 
Table 4 
Study groups and intervention 
Study groups** 
Approximate 
number of 
participants 
Age 
(Min-Max) 
Study intervention  
Standard of Care 
Vaccination* 
RSV1 
220 
18 – 49 years 
RSV MAT 120 (Lot1) 
Flu D-QIV 
RSV2 
220 
18 – 49 years 
RSV MAT 120 (Lot2) 
Flu D-QIV 
RSV3 
220 
18 – 49 years 
RSV MAT 120 (Lot3) 
Flu D-QIV 
RSV1+Flu 
147 
18 – 49 years 
RSV MAT 120 (Lot 1) 
Flu D-QIV 
 
RSV2+Flu 
147 
18 – 49 years 
RSV MAT 120 (Lot 2) 
Flu D-QIV 
 
RSV3+Flu 
147 
18 – 49 years 
RSV MAT 120 (Lot 3) 
Flu D-QIV 
 
Flu+P 
440 
18 – 49 years 
Flu D-QIV 
placebo 
 
RSV MAT 120 =RSVPreF3 vaccine 
*Standard of care vaccine administered only to ensure the participants receive the standard of care. 
For more information about blinding, refer to Section 6.3.5. 

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Approximately 1541 participants will be randomized into 7 study groups (5 main study 
groups including 1 pooled group [RSV1+Flu, RSV2+Flu, RSV3+Flu]) with 
randomization ratio of RSV1:RSV2:RSV3: RSV1+Flu: RSV2+Flu: RSV3+Flu: Flu+P as 
3:3:3:2:2:2:6. An automated internet based system (SBIR) will be used to randomly 
allocate a study group and treatment number to each participant. Age (18-32 vs. 33-49) 
and center will be minimization factors. Minimization factors will have equal weight in 
the algorithm. 
4.2. 
Scientific rationale for study design 
This study is part of a clinical development plan of the RSVPreF3 vaccine for the 
protection of infants from RSV lower respiratory tract infections through maternal 
immunization. This study will evaluate the safety and immunogenicity of the RSVPreF3 
vaccine from 3 lots as well as when co-administered with GSK quadrivalent influenza 
(Flu D-QIV) vaccine in healthy non-pregnant women 18-49 YOA. 
To evaluate lot-to-lot consistency, 3 groups will be vaccinated with 3 different lots. 
RSV1 vs. RSV2, RSV 2 vs. RSV 3, and RSV3 vs. RSV1 will be compared. An optional 
Flu D-QIV will be provided to these three groups during Visit 2 as part of the standard of 
care. To evaluate the impact of co-administration on the flu immunogenicity, the safety 
and immunogenicity of the Flu + P and Flu + RSV groups will be compared. The study 
will also evaluate the impact of co-administration on RSVPreF3 immunogenicity; by 
comparing the immunogenicity of pooled RSV1,2,3 group versus RSV+Flu group. Blood 
samples for humoral immune response will be collected on Day 1(Vaccination day) and 
Day 31 (Visit 2). 
4.3. 
Justification for dose 
A single formulation of the investigational RSV maternal vaccine (containing 120 µg of 
the RSVPreF3 antigen) is planned. Currently available data suggest that the 120 µg 
formulation has an acceptable safety profile and tends to elicit stronger immune 
responses in non-pregnant (RSV MAT-001 and RSV MAT-011) and pregnant (RSV 
MAT-004) women, which is likely to result in higher placental transfer of antibodies to 
the fetus than formulations containing 30 or 60 µg of the RSVPreF3 antigen. Available 
results from these studies are included in the Investigator Brochure. 
Results of study RSV MAT-001 in non-pregnant women indicate that a single dose of the 
study vaccine is sufficient to boost the neutralizing antibodies induced by previous 
natural infections. 
4.4. 
End of Study definition 
A participant is considered to have completed the study if she is available for the 
concluding phone contact 2 (Day 181) as described in the protocol. 
End of Study (EoS): Last subject last visit (LSLV) (Day 181/phone contact 2) or Date of 
the last testing/reading released of the Human Biological Samples or imaging data, 

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related to primary and secondary endpoints. EoS must be achieved no later than 8 months 
after LSLV.  
Refer to Section 10.8.2 for the definition of EoS. 
5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardize the scientific 
integrity, regulatory acceptability of the study or safety of the participant. 
5.1. 
Inclusion criteria 
All participants must satisfy ALL the following criteria at study entry: 
• 
Participants who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the e-Diary, return for follow-up 
visits). 
• 
Written or witnessed/thumb printed informed consent obtained from the participant 
prior to performance of any study specific procedure. 
• 
Healthy female participants; as established by medical history and clinical 
examination, aged 18 to 49 years at the time of the first study intervention 
administration. 
− 
Female participants of childbearing potential may be enrolled in the study, if the 
participant: 
− 
has practiced adequate contraception for 1 month prior to study intervention 
administration, and 
− 
has a negative pregnancy test on the day of study intervention administration, 
and 
− 
has agreed to continue adequate contraception during the entire treatment period 
and for 1 month after completion of the study intervention administration. 
− 
Refer to Section 10.4.1 for definitions of woman of childbearing potential and 
adequate contraception 
• 
No local condition precluding injection in both left and right deltoid muscles. 
5.2. 
Exclusion criteria 
The following criteria should be checked at the time of study entry. The potential 
participant MAY NOT be included in the study if ANY exclusion criterion applies: 

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5.2.1. 
Medical conditions 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study interventions 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required). 
• 
Current autoimmune disorder (based on medical history and physical examination;), 
for which the participant has received immune-modifying therapy within 6 months, 
before study vaccination 
• 
Hypersensitivity to latex 
• 
Acute or chronic clinically significant abnormality or poorly controlled pre-existent 
co-morbidities or any other clinical conditions, as determined by physical 
examination or medical history that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study 
• 
Significant or uncontrolled psychiatric illness 
• 
Recurrent history or uncontrolled neurological disorders or seizures 
• 
Documented HIV-positive participant 
• 
Body mass index> 40 kg/m2 
• 
Any clinically significant* hematological parameter and/or biochemical laboratory 
abnormality. 
*The investigator should use his/her clinical judgment to decide which abnormalities are clinically significant. 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study. 
5.2.2. 
Prior/Concomitant therapy 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study intervention(s) during the period starting 30 days before 
study intervention (Day -29 to Day 1), or planned use during the study period; 
− 
See Section 10.7.1 for additional country-specific considerations 
• 
Administration of long-acting immune-modifying drugs 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 3 months before the study intervention or planned 
administration during the study period; 
• 
Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 3 
months prior to the first study intervention dose(s). For corticosteroids, this will 
mean prednisone 5 mg/day, or equivalent. Inhaled and topical steroids are allowed; 

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• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol within the period starting 30 days before and ending 30 days after the 
vaccination dose*; 
* In case emergency mass vaccination for an unforeseen public health threat (e.g. a 
pandemic) is organised by public health authorities outside the routine immunisation 
programme, the time period described above can be reduced if, necessary for that 
vaccine, provided it is licensed and used according to its Product Information.  
See Section 5.5 for more details on Criteria for Temporary Delaying Enrolment). 
• 
Administration of a seasonal influenza vaccine during the 6 months preceding entry 
into the study; 
• 
Previous experimental vaccination against RSV. 
5.2.3. 
Prior/Concurrent clinical study experience 
Concurrently participating in another clinical study, at any time during the study period, 
in which the participant has been or will be exposed to an investigational or a non-
investigational vaccine/product (drug or medical device); 
5.2.4. 
Other exclusions 
• 
Pregnant or lactating female; 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions; 
• 
Alcoholism or substance use disorder within the past 24 months based on the 
presence of two or more of the following abuse criteria: hazardous use, 
social/interpersonal problems related to use, neglected major roles to use, withdrawal 
tolerance, use of larger amounts or longer, repeated attempts to quit or control use, 
much time spent using, physical or psychological problems related to use, activities 
given up to use, craving (based on the DSM-5 criteria, [Hasin, 2013]); 
• 
Any study personnel or their immediate dependents, family, or household members. 
5.3. 
Lifestyle considerations 
Lifestyle characteristics may include highest level of education, smoking 
status/exposures, household environment, and other factors that could place study 
participants at risk of adverse study outcomes. 
5.3.1. 
Demographic data 
Demographic data for participants includes geographic ancestry (race)*, ethnicity*, 
month of birth (if allowed per local regulation) and year of birth. 
*Differences in the safety and efficacy of certain medical products, including vaccines 
[Haralambieva, 2013; Pérez-Losada, 2009; Kollmann, 2013] have been observed in 

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racially and ethnically distinct subgroups. These differences may be attributable to 
intrinsic factors (e.g., genetics, metabolism, elimination), extrinsic factors (e.g., diet, 
environmental exposure, sociocultural issues), or interactions between these factors. 
Therefore, both geographic ancestry (race) and ethnicity will be collected for all study 
participants. 
5.4. 
Screen failures  
Screen failures are participants who consent to take part in this study but are determined 
ineligible and subsequently not assigned to a study intervention. 
Limited data for screening failures (including reason for screening failure and any SAEs 
that occurred at the visit) will be collected and reported in the eCRF. 
Note: Demography and required forms at Visit 1 should be completed for screening 
failures. 
5.5. 
Criteria for temporarily delaying enrollment  
Enrollment may be postponed until transient conditions cited below are resolved. 
Participants must be rescreened: 
• 
Participants with abnormal hematological/biochemical values at screening, if 
expected to be temporary at the discretion of the investigator. 
• 
Acute disease and/or fever at the time of enrollment. Refer to the Schedule of 
Activities (SoA) for definition of fever and preferred location for measuring 
temperature in this study. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be enrolled and/or vaccinated at the discretion of the 
investigator. 
• 
Use of systemic antibiotic or antiviral treatment within 48 hours prior to study 
vaccination. 
The standard time window for planned administration/administration of a vaccine not 
foreseen by the study protocol is 30 days before and after the day of vaccination with 
RSV vaccine. There may be an exception that can shorten the time window based on the 
local guidance, but it will not be less than 15 days before or after Visit 1.  
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Refer to the Glossary of terms for the definition of study intervention. Refer to the Study 
Procedures Manual (SPM) for additional details. 

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6.1. 
Study intervention(s) administered  
Table 5 
Study intervention(s) administered 
Study intervention name: 
RSV MAT 120 
Flu D-QIV* 
Placebo  
Interventional Products 
RSVPreF3 high dose 
Flu Quadrivalent influenza 
vaccine,15 µg hemagglutinin 
(HA) per strain/dose* 
NaCl Solution 
NaCl Solution 
Study intervention 
formulation: 
RSVPreF3(120 µg) 
Sodium Chloride (NaCl) 
(0.9%); Water for 
injections 
A/Victoria/2570/2019 (H1N1), 
IVR-215 (15 µg HA); 
A/Tasmania/503/2020 
(H3N2)*****, IVR-221 (15 µg 
HA); B/Washington/02/2019 
(15 µg HA); 
B/Phuket/3073/2013 (15 µg 
HA); Water for injections q.s. 
0.5 mL 
Sodium Chloride 
(NaCl) (0.9%); 
Water for injections 
Presentation: 
Powder for solution for 
injection 
Suspension for injection 
(syringe) 
Solution for injection 
(syringe) 
Solution for solution for 
injection 
Type 
Study 
Co-administration 
Control 
Product Category 
Combination Product  
Combination Product  
Combination 
Product 
Route of administration:  
Intramuscular use 
Intramuscular use 
Intramuscular use 
Administration site: 
• 
Location 
Deltoid 
Deltoid 
Deltoid 
• 
Laterality* 
See Table 6 
See Table 6 
See Table 6 
Number of doses to be 
administered: 
1 
1 
1 
Volume to be 
administered**: 
whole content 
0.5mL***  
whole content**** 
Packaging, labeling and 
TM: 
Refer to the Study 
Procedure Manual  
Refer to the Study Procedure 
Manual 
Refer to the Study 
Procedure Manual 
Manufacturer: 
RSVPreF3: GSK 
NaCl: GSK 
GSK 
GSK  
RSV MAT 120=RSVPreF3 vaccine 
*Flu D-QIV strains will depend on the World Health Organisation recommendation for the 2021/2022 season. 
**Refer to the SPM for the volume after reconstitution. 
**Full volume (0.5mL) to be administered. 
**** The volume of the saline syringe may be between 0.6ml and 0.8 ml. The full volume is to be injected. 
*****A/Tasmania/503/2020 (H3N2) IVR-221 (an A/Cambodia/e0826360/2020 (H3N2)-like virus). 

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Table 6 
Study intervention administered (Part 2) 
Day 1 Vaccination 
Interventional 
Groups 
N 
Intervention 
Laterality 
Intervention Laterality 
RSV1 
220 
RSVMAT 120 (Lot 1) Left Arm 
 
 
RSV2 
220 
RSVMAT 120 (Lot 2) Left Arm 
 
 
RSV3 
220 
RSVMAT 120 (Lot 3) Left Arm 
 
 
RSV1+Flu 
147 
RSVMAT 120 (Lot 1) Left Arm 
Flu D-QIV 
Right Arm 
RSV2+Flu 
147 
RSVMAT 120 (Lot 2) Left Arm 
Flu D-QIV 
Right Arm 
RSV3+Flu 
147 
RSVMAT 120 (Lot 3) Left Arm 
Flu D-QIV 
Right Arm 
Flu+ P 
440 
Flu D-QIV 
Left Arm 
Placebo  
Right Arm 
Day 31 Standard of Care Vaccination* 
Interventional 
Groups  
N 
Intervention 
Laterality 
RSV1 
220 
Flu D-QIV 
Non-dominant arm  
RSV2 
220 
Flu D-QIV 
Non-dominant arm 
RSV3 
220 
Flu D-QIV 
Non-dominant arm  
RSVMAT120=RSV PreF3 vaccine 
*Visit 2 Flu D-QIV vaccinations are not part of experimental design and serve as an optional vaccination for participants 
to provide standard of care. 
Study participants must be observed closely for at least 30 minutes after the 
administration of the study intervention(s). Appropriate medical treatment must be 
readily available during the observation period in case of anaphylaxis, syncope. 
6.2. 
Preparation/Handling/Storage/Accountability 
The study intervention(s) must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s). 
Only authorized study personnel should be allowed access to the study interventions. 
Storage conditions will be assessed by a sponsor study contact during pre-study activities. 
Refer to the SPM for more details on storage and handling of the study interventions. 
6.3. 
Measures to minimize bias: randomization and blinding 
6.3.1. 
Participant identification 
Participant identification numbers will be assigned sequentially to women who have 
consented to participate in the study, according to the range of participant identification 
numbers allocated to each study center. 

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6.3.2. 
Randomization to study intervention 
6.3.3. 
Intervention allocation to the participant 
The randomization algorithm will use a minimization procedure accounting age at the 
time of vaccination (18-32 vs. 33-49) and center. Minimization factors will have equal 
weight in the algorithm. 
Once a participant identification number is allocated, the randomization system will 
determine study group and will provide the study intervention number to be used for the 
first dose. 
When an automated, Internet based system (SBIR) is not available, please refer to the 
SBIR user guide or SPM for specific instructions. 
Refer to the SPM for additional information about the study intervention number 
allocation. 
6.3.4. 
Allocation of participants to assay subsets 
N/A 
6.3.5. 
Blinding and unblinding 
Data will be collected in an observer-blind manner to evaluate the lot-to-lot consistency 
of GSK RSVPreF3 vaccine and single-blind manner to evaluate the immune response, 
safety and reactogenicity of RSV maternal vaccine when co-administered with GSK 
quadrivalent influenza. To do so, study interventions will be prepared and administered 
by qualified study personnel who will NOT participate in data collection, evaluation, 
review or the entry of any study endpoint (i.e. reactogenicity, safety, immunogenicity). 
• 
This study will utilize an observer-blind design as described below: 
− 
For the Lot-to-Lot consistency groups (RSV1, RSV2, and RSV3), both the 
participant and investigator will be blinded to the lot received. However, they 
will both know that the participant is not part of the co-administration study 
groups. 
• 
This study will utilize a single blind design as described below: 
− 
For the co-administration groups (Flu+RSV or Flu+P), the investigator and 
participant will both know that the participant is part of the co-administration 
study groups. However, the participant will be blinded to the vaccine 
administration activities. Participant will be administered with either RSVPreF3 
or Flu D-QIV on the left arm. On the right arm, participant will be administered 
with either Flu D-QIV or the placebo. 
• 
This blinding strategy will apply from Visit 1 to study end (Day 181) (Amended 26 
May 2022). 

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The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no link between the study intervention and the identity of the participant. 
6.3.5.1. 
Emergency unblinding 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information is essential for the clinical 
management or welfare of the participant. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention via an 
automated (SBIR). 
The investigator may contact a GSK Helpdesk (refer to the Table 7) 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. 
Table 7 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Phone: +32 2 656 68 04 
Fax: +32 2 401 25 75 
Email: rix.ugrdehelpdesk@gsk.com 
Toll free numbers are available for the following countries.  
Country 
Toll free number 
Canada 
877.870.0019 or 1 833 541 0263 
United States 
877.870.0019 or 1 844 446 3133 
South Korea 
001 800 4344 1111 
Spain 
00 800 4344 1111 
Finland 
999 800 4344 1111 
6.3.5.2. 
Unblinding prior to regulatory reporting of SAEs 
GSK policy requires unblinding of any unexpected SAE which is attributable/suspected 
to be attributable to the study interventions, prior to regulatory reporting. Vaccines 
Clinical Safety and Pharmacovigilance (VCSP) is responsible for unblinding the study 

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intervention assignment within the timeframes defined for expedited reporting of SAEs 
(refer to the Section 10.3.10.1). 
In addition, GSK VCSP staff may unblind the intervention assignment for any participant 
with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or a SAE that is fatal 
or life-threatening. For SAEs requiring expedited reporting to 1 or more regulatory 
agencies, a copy of the report containing participant’s intervention assignment may be 
sent to investigators in accordance with local regulations and/or GSK policy. 
6.4. 
Study intervention compliance 
When the study intervention is administered at the site, participants will receive it directly 
from the investigator or designee, under medical supervision. The date of administration 
of each study intervention dose in the clinic will be recorded in the source documents. 
Before dosing, a qualified member of the site staff other than the person administering 
the dose will confirm that the intervention number is correct. The intervention number 
administered, and the administration date and time will be recorded in the source 
documents. 
6.5. 
Dose modification 
Not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study 
During the conclusion study contact, the investigator will ask each participant if they are 
interested in participating to join a booster study/long-term study. If a participant is not 
interested in joining the booster study/long-term study the reason for refusal will be 
documented, when available, in the participant’s eCRF. 
6.7. 
Treatment of overdose 
Not applicable 
6.8. 
Concomitant therapy  
At each study visit/contact, the investigator or his/her delegate should question the 
participant about all medications/products taken, and vaccinations received by the 
participant. 

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The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medication associated with an adverse event, including 
vaccines/products, except vitamins and dietary supplements, administered after the 
first dose of study intervention (Day 1 to Day 30). 
• 
All antibiotics, analgesics, and anti-pyretics taken within 7 days before dose 
administration. 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines. 
• 
All concomitant medication which may explain/cause/be used to treat an SAE 
including vaccines/products, as defined in Sections 8.3.1 and 10.3.8.2. These must 
also be recorded in the Expedited Adverse Event report. 
• 
Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination) up to the first 30 days 
after vaccination. 
The Local Medical Lead (LML) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
Criteria for discontinuation of study vaccines / products do not apply since this is a single 
dose study. However, administration of the study’s single dose may be delayed if the 
criteria presented in Section 5.5 are met. 
7.1.1. 
Contraindications to subsequent study intervention(s) 
administration 
Contraindications of study interventions do not apply since this is a single dose study. 
However, a history of severe allergic reactions (e.g., anaphylaxis) to any component of 
the Flu D-QIV vaccine, including egg protein, or following a previous dose of any 
influenza vaccine should be noted when given as standard of care during Visit 2. 
7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for him/her since the date 
of withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who was not 
available for the concluding contact planned in the protocol. 

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Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
All data and samples collected up to and including the date of withdrawal of/last contact 
with the participant will be included in the study analyses. 
The primary reason for study withdrawal will be documented in the eCRF, based on the 
list below: 
• 
Adverse events requiring expedited reporting to GSK 
• 
Unsolicited non-serious adverse events 
• 
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 she has withdrawn consent and the 
reason for withdrawal was provided, the investigator must document this reason in the 
eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.8.2). 
7.3. 
Lost to follow-up 
A participant will be considered ‘lost to follow-up’ if she fails to return for scheduled 
visits and cannot be contacted by the study site. 
Please refer to the SPM for a description of actions to be taken before considering the 
participant lost to follow-up. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant. 
Immediate safety concerns should be discussed with the sponsor as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarized in the SoA (Section 1.3). 

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All screening evaluations must be completed, and the results reviewed before confirming 
that potential participants meet all eligibility criteria. 
The investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for screening failure will be mentioned in 
this screening log. 
Procedures conducted as part of routine clinical management (e.g. hematologic profiles), 
and obtained before the participant signed the Informed Consent Form (ICF), may be 
used for screening and/or for establishing a clinical baseline provided the procedure met 
protocol-specified criteria and was performed within the time frame defined in the SoA 
(Section 1.3). 
The SPM provides the investigator and site personnel with detailed administrative and 
technical information that does not impact participant safety. 
Study Procedures During Special Circumstances 
During special circumstances (e.g., the 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: 
• 
Enrollment of additional participants may be placed on hold. Decisions on re-starting 
enrollment to achieve the planned sample size will be made in a manner consistent 
with guidance from public health and other competent authorities. 
• 
For guidance regarding the temporary delay of participants enrollment because of 
exposure to COVID-19, please refer to the SPM for details. 
• 
The following measures may be implemented for enrolled participants: 
− 
If it is not possible to conduct a protocol-specified, scheduled or event-driven 
visit as described in Section 1.3, the visit may be replaced with a contact 
conducted by SMS, email, telephone, videotelephony or telemedicine. In such 
cases: 
− 
Protocol-specified clinical data that 
− 
cannot be collected by study staff during the contact (e.g., physical 
examination results) BUT 
− 
are available within the allowed interval (Table 2) in the participant’s 
medical records and can be obtained by site staff (as allowed by local 
law), may be recorded in the participant’s source document and entered 
into the eCRF. 
− 
Whenever possible, as appropriate per the judgment of the investigator and as 
allowed by local law, arrangements should be made for qualified personnel to 
collect any protocol-specified safety data, safety assessment(s), and/or biological 
samples at an alternate location* within the visit interval (Table 2). 

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− 
Samples should not be collected if they cannot be processed in a timely 
manner and / or appropriately stored until the intended use. 
− 
Blood samples for central assessment must be collected using GSK-
provided supplies. 
Additional details of how these visits can be conducted are outlined in the SPM. 
Impact on the analysis sets for efficacy and immunogenicity will be determined on a case 
by case basis. 
*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. 
8.1. 
Immunogenicity assessments 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. 
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
IEC/IRB approval, if required by local legislation. 
Information on further research and its rationale can be obtained from GSK. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant. 
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed and agreed 
with GSK. 

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8.1.1. 
Biological samples 
Table 8 
Biological samples 
Sample type 
Collected to Evaluate 
Minimum 
Quantity 
per 
participant 
Unit 
Time point 
Additional Information 
Whole blood for 
immune response 
10 
ml 
Visit 1 (Day 1) 
Immune response: 10 mL (~ 4 mL 
serum). 
Whole blood for 
immune response  
10  
ml 
Visit 2 (Day 31) * 
Immune response: 10 mL (~ 4 mL 
serum). 
 
20  
ml 
Minimum Total, not including repeat or unscheduled samples 
Urine for Pregnancy 
- 
- 
Visit 1 (Day 1) 
 
*The blood sample at Visit 2 for immune must be taken before administering the Flu D-QIV vaccine as a standard of 
care. 
8.1.2. 
Laboratory assays  
All laboratory testing will be performed at GSK laboratory or in a laboratory designated 
by GSK. 
Table 9 
Laboratory assays 
Sampling 
time points 
System 
Component 
Method 
Unit 
Groups 
Laboratory 
Visit 1 
Serum 
Respiratory Syncytial Virus A Ab 
neutralizing 
NEU 
IU* and/or 
ED60   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
Serum 
Respiratory Syncytial Virus B Ab 
neutralizing 
NEU 
IU and/or 
ED60   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
Serum 
Respiratory Syncytial Virus PreF3 
Ab.IgG concentration 
ELI 
ELU/ml 
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
Nexelis 
Serum 
Flu D-QIV ** 
• 
A/Victoria/2570/2019 
(H1N1) Ab 
• 
A/Tasmania/503/2020 
(H3N2) Ab 
• 
B/Washington/02/2019 Ab 
• 
B/Phuket/3073/2013 Ab 
HI 
assay 
1/Dil 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
Flu+P 
GSK 
designated 
lab 

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Sampling 
time points 
System 
Component 
Method 
Unit 
Groups 
Laboratory 
Day 31 
Serum 
Respiratory Syncytial Virus A Ab 
neutralizing 
NEU 
IU and/or 
ED60*   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
Serum 
Respiratory Syncytial Virus B Ab 
neutralizing 
NEU 
IU and/or 
ED60   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
Serum 
Respiratory Syncytial Virus PreF3 
Ab.IgG concentration 
ELI 
ELU/mL 
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
Nexelis 
Serum 
Flu D-QIV** 
• 
A/Victoria/2570/2019 
(H1N1) Ab 
• 
A/Tasmania/503/2020 
(H3N2) Ab 
• 
B/Washington/02/2019 Ab 
• 
B/Phuket/3073/2013 Ab 
HI 
assay 
1/Dil 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
Flu+P 
GSK 
designated 
lab 
*IU=international units     ED60= serum dilution inducing 60% inhibition in plaque forming units (ED60) 
** Flu D-QIV strains will depend on the World Health Organisation recommendation for the 2021/2022 season 
Please refer to the Section 10.2 for a brief description of the assays performed in the 
study. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 
GSK clinical laboratories have established a Quality System supported by procedures. 
The activities of GSK clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. 

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8.1.3. 
Immunological read-outs 
All participants will have Visit 1 (Day 1) and Visit 2 (Day 31) blood samples tested. 
Table 10 
Immunological read-outs 
Blood sampling timepoint 
Approximate No. 
participants 
Component* 
Type of 
contact and 
timepoint 
Sampling 
timepoint 
V1 (Day 1) 
pre-
vaccination 
1101 
Respiratory Syncytial Virus A Ab neutralizing 
1101 
Respiratory Syncytial Virus B Ab neutralizing 
1101 
Respiratory Syncytial Virus PreF3 Ab.IgG concentration 
881 
Flu D-QIV * 
V2 (Day 31) 
post 
vaccination 
1101 
Respiratory Syncytial Virus A Ab neutralizing 
1101 
Respiratory Syncytial Virus B Ab neutralizing 
1101 
Respiratory Syncytial Virus PreF3 Ab.IgG concentration 
881 
Flu D-QIV * 
V = Visit; IgG: immunoglobulin G; Ab =Antibody 
*Testing for COVID-19 in any suspected infected participant should be performed as the standard of care. 
8.1.4. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen(s) used in the RSVPreF3 vaccine. 
Although there is no accepted correlate of immunity against influenza, the protective role 
of antibodies against HA and, to a lesser extent, neuraminidase, is well established and 
has been demonstrated both in experimentally infected animals and humans [Brydak, 
2000]. 
For this reason, the induction of HA-specific antibodies was used as marker of potential 
vaccine efficacy and the serum HI assay was used to demonstrate this humoral response. 
HI antibody titers of 1:40 or greater have been associated with protection from influenza 
illness in at least 50% of participants in challenge studies [Hannoun, 2004] as well as to 
correlate with vaccine effectiveness [Beyer, 1989]. 
8.2. 
Safety Assessments 
The investigator and his/her designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and designees 
are responsible for following up AEs that are serious, considered related to the study 
intervention or the study, or that caused the participant’s withdrawal from the study. 
The safety analyses will be performed on the Exposed set or Solicited Safety set. Safety 
endpoints including solicited AEs, unsolicited AEs, SAEs, AEs leading to study 
termination will be descriptively summarized by group and overall. Numbers and 
percentage with 95% CI of participants reporting above AEs will be reported. 

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8.2.1. 
Pre-vaccination procedures 
Obtain the participant’s medical/vaccination history by interviewing her and/or reviewing 
her medical records. Record any pre-existing participant conditions, signs and/or 
symptoms present prior to the study vaccination in the eCRF. 
8.2.1.1. 
Informed consent agreement 
Before performing any study procedure, the signed informed consent of the participant 
needs to be obtained. Refer to Section 10.1.3 for the requirements on how to obtain 
informed consent. 
8.2.1.2. 
Collection of demographic data 
Demographic data such as age, year of birth, gender, height, weight, race, and ethnicity 
will be recorded in the participant’s eCRF. 
8.2.1.3. 
Medical/vaccination history 
Obtain the participant’s medical/vaccination history by interviewing the participant 
and/or review of the participant’s medical records. Record any pre-existing conditions, 
signs and/or symptoms present prior to study intervention in the eCRF. All prior therapy 
including hematological products (e.g. plasma transfusion, blood transfusion etc.), 
medications, and vaccines received by the participant in the last 30 days prior to study 
start should be collected and recorded with exception of seasonal flu vaccine. Seasonal 
flu vaccine history must be collected and recorded for the last 6 months. 
8.2.1.4. 
Physical examination 
• 
Perform a full physical examination of the participant at the Visit 1 [Day 1], 
including assessment of oral body temperature and resting vital signs: 
systolic/diastolic blood pressure, heart rate and respiratory rate after at least 10 
minutes of rest. 
• 
A history directed physical exam and vital signs at Visit 2 [Day 31] may be 
performed.  
8.2.1.5. 
Pregnancy test 
Participants of childbearing potential must perform a urine pregnancy test before the 
administration of any dose of study intervention. Pregnancy testing must be done even if 
the participant is menstruating at the time of the study visit. The study intervention may 
only be administered if the pregnancy test is negative. 
A serum pregnancy test instead of a urine pregnancy test should be performed if required 
by country, local or ethics committee regulations. 

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Refer to the Section 10.4.3.1 for the information on study continuation for participants 
who become pregnant during the study. 
8.2.1.6. 
Warnings and precautions to vaccination 
Warnings and precautions to administration of study intervention must be checked at 
each visit with planned administration of study intervention. 
8.2.2. 
Study holding rules and safety monitoring 
Not applicable 
8.3. 
AEs, SAEs and other safety reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE, and other 
safety information 
An overview of the protocol required reporting periods for AEs, SAEs, and pregnancies 
is given in Table 11. 
Table 11 
Reporting periods for collecting safety information 
Event 
V1 
 
TC1 
 
V2 
TC2 
D1 
D7 
D8 
D30 
D31 
D181 
Administration site and systemic 
solicited events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs/SAEs leading to withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs* 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
V: visit; TC: telephone contact; D: Day 
*SAEs related to study participation or concurrent GSK medication/vaccine will be monitored from the time of screening 
to the time of the immunization. Both will be conducted on the same visit 
The investigator or designee will record and immediately report all SAEs to the sponsor 
or designee via the Expedited AE Reporting Form. Reporting should, under no 
circumstances, occur later than 24 hours after the investigator becomes aware of an SAE, 
as indicated in Section 10.3.10. The investigator will submit any updated SAE data to the 
sponsor within 24 hours of it being available. 

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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 11. Investigators are not obligated to actively seek AEs 
or SAEs from former study participants. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, and 
he/she considers the event to be reasonably related to the study intervention, the 
investigator will promptly notify the study contact for reporting SAEs mentioned in the 
Table 13. 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and other 
events 
Detection and recording of AE/SAE/pregnancies are detailed in Section 10.3.8. 
Assessment of AE/SAE intensity, causality and outcome are described in Section 10.3.9. 
Open-ended and non-leading verbal questioning of participants is the preferred method of 
acquiring information related to an AE/SAE/pregnancy. 
8.3.2.1. 
Clinically significant abnormal laboratory findings 
The investigator must review the laboratory report, document that he/she did so, and 
record any clinically relevant changes occurring during the study in the AE section of the 
eCRF. Clinically significant abnormal laboratory findings are those which are not 
associated with an underlying disease, unless judged by the investigator to be more 
severe than expected for the participant's condition. 
• 
All clinically significant abnormal laboratory test values reported during the study or 
within 30 days after the last dose of study intervention should be repeated until the 
values return to normal/baseline, or until they are no longer considered significantly 
abnormal by the investigator or LML. Refer to the Section 10.3.6 for more 
information on clinically abnormal laboratory assessments that qualify as an AE or 
SAE. 
• 
If such values do not return to normal/baseline after an interval judged reasonable by 
the investigator, the etiology of the abnormal value should be identified, and the 
sponsor notified. 
8.3.3. 
Regulatory reporting requirements for SAEs, pregnancies and 
other events 
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/pregnancy, it must be reported to GSK using the required 
documentation and within the timeframes mentioned in Table 12. This is essential for 
meeting GSK legal obligations and ethical responsibilities for participant safety and the 
safety of a study intervention under clinical investigation. 
For SAEs the investigator must always provide an assessment of causality at the time of 
the initial report, as defined in the Section 10.3.9.2. 

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Local regulatory requirements and sponsor policy for preparation of an investigator 
safety report of Suspected Unexpected Serious Adverse Reactions (SUSAR) must be 
followed. These reports will be forwarded to investigators as necessary. 
The sponsor has the legal responsibility to notify local authorities and other regulatory 
agencies about the safety of an investigational study intervention. The sponsor will 
comply with country-specific regulatory requirements related to safety reporting to the 
regulatory authority, IRB/IEC, and investigators. 
Please refer to the Section 10.3.10 for further details regarding the reporting of 
SAEs/pregnancies. 
Table 12 
Timeframes for submitting SAE, pregnancy and other events reports to 
GSK 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours* ‡ 
electronic Expedited 
Adverse Events Report 
24 hours* 
electronic Expedited Adverse 
Events Report 
Pregnancies  
24 hours * 
electronic pregnancy report 
24 hours * 
electronic pregnancy report 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
‡ The investigator will be required to confirm review of the SAE causality by ticking the ‘reviewed’ box in the electronic 
Expedited Adverse Events Report within 72 hours of submission of the SAE 
8.3.3.1. 
Contact information for reporting SAEs, AESIs, pregnancies and study 
holding rules  
Table 13 
Contact information for reporting SAEs and pregnancies  
Study contact for questions regarding SAEs, pregnancies  
Refer to the local study contact information document 
Back up study contact for reporting SAEs, pregnancies 
Available 24/24 hours and 7/7 days: 
GSK Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: ogm28723@gsk.com 
US sites only: 
Fax: 1 610 787 7053 
Canadian sites only: 
Fax: 1 866 903 4718 
8.3.4. 
Treatment of adverse events 
Any medication administered for the treatment of an SAE should be recorded in the 
Expedited Adverse Event Report of the participant’s eCRF screen (refer to the Section 
10.3.10.1).  

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8.3.5. 
COVID-19 Infection 
COVID-19 cases identified during the study (as per standard of care) will be captured and 
reported using standard AE or SAE criteria, as outlined in Section 10.3. 
COVID-19 cases should be reported in the eCRF according to the WHO Case Definition, 
[WHO, 2020] using one of the following terms: 
• 
Suspected COVID-19 infection 
• 
Probable COVID-19 infection 
• 
Confirmed COVID-19 infection 
8.3.6. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in his/her/their possession for the duration of the study. 
In an emergency, this card serves to inform the responsible attending physician/LAR/care 
giver/family member that the participant is in a clinical study and that relevant 
information may be obtained by contacting the investigator or his/her back up. 
8.3.7. 
Medical device deficiencies 
The study intervention is a combination product constituted of a device and biologic 
product (e.g. pre-filled syringes). Refer to the Section 10.6.1 for the definition of 
combination product and medical device deficiency. 
8.3.7.1. 
Detection, follow-up and prompt reporting of medical device deficiency 
The investigator is responsible for the detection, documentation and prompt reporting of 
any medical device deficiency occurring during the study to GSK. This applies to any 
medical device provided for the conduct of the study. 
Device deficiencies will be reported to GSK within 24 hours after the investigator 
determines that the event meets the protocol definition of a device deficiency. Refer to 
Section 10.6.1 for definitions and details on recording and reporting of these events. 
The investigator will ensure that follow-up includes any additional investigations to 
elucidate the nature and/or related of the device deficiency to the incident. Follow-up 
applies to all participants, including those who discontinue study intervention or the 
study. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator and reported to GSK within 24 hours. 

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8.3.7.2. 
Regulatory reporting of medical device deficiency when used as 
combination product 
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study to GSK. GSK has a legal responsibility to notify 
appropriate regulatory authorities and other entities about safety information linked to 
medical devices being used in clinical studies. Refer to section 10.6 for details of 
reporting. 
The investigator, or responsible person according to local requirements (e.g. the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/IEC. 
8.4. 
Pharmacokinetics 
Not applicable. 
8.5. 
Genetics 
Not applicable. 
8.6. 
Biomarkers 
Not applicable. 
8.7. 
Immunogenicity 
Immunogenicity analysis will be performed on the Per Protocol set. If, in any study group 
and at any timepoint, the percentage of vaccinated participants with immunogenicity 
results excluded from the Per Protocol set for analysis of immunogenicity is 5% or more, 
a second analysis based on the Full Analysis Set will be performed to complement the 
Per Protocol analysis. 
Refer to Section 8.1. for more details 
8.8. 
Health outcomes 
Not applicable. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
The statistical hypothesis for each confirmatory objective is detailed below. 
9.2. 
Sample size determination 
Approximately 1541 participants will be randomized to achieve appropriately 1400 
evaluable participants. 
Assessments of both immunogenicity and safety data were considered when determining 
sample size for this study. 
Participants who withdraw from the study will not be replaced. 
The sections below describe the assumptions, adjustment and methodology used for the 
sample size calculation. 
9.2.1. 
Primary objective for Lot-to-Lot consistency  
The primary objective of lot-to-lot consistency will be evaluated on the RSVPreF3 
immunogenicity as measured by RSVPreF3 IgG ELISA concentration at Day 31. 
The lot-to-lot consistency will be demonstrated only if two-sided 95% confidence 
intervals for the 3 pair-wise geometric mean ratios of RSVPreF3 IgG ELISA 
concentration at Day 31 (30 days post vaccination) falls within 0.67 and 1.5. 
With the assumptions of a SD of log10 transformed RSVPreF3 IgG ELISA concentration 
of 0.35, true GMC ratio of 1 between 2 lots, type I error of 0.025, and 10% of non-
evaluable rate, 220 enrolled participants per lot provides at least 99% global power to 
conclude lot-to-lot consistency (see details in Table 14 below). 
Table 14 
Power to demonstrate Lot-to-Lot consistency on immune responses 
of RSVPreF3 IgG ELISA concentration at Day 31 post vaccination 
Endpoint 
Clinically acceptable 
bounds for 
consistency 
Group 
description 
Number of 
evaluable 
participants in 
each lot 
Reference 
SD ** 
Power  
*RSVPreF3 IgG GMC 
ratio 
(0.67, 1.5] 
Lot 1/2 
200 
0.35 
99.8% 
*RSVPreF3 IgG GMC 
ratio 
(0.67, 1.5] 
Lot 1/3 
200 
0.35 
99.8% 
*RSVPreF3 IgG GMC 
ratio 
(0.67, 1.5] 
Lot 2/3 
200 
0.35 
99.8% 
Global power 
 
 
 
 
99.3% 
* Pass 2019, Two-Sample T-test for equivalence allowing unequal variance, alpha=2.5%; 
**References used for the sample size calculation: Study RSV MAT 011 (209141)  

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9.2.2. 
Primary objective: To demonstrate Non-inferiority of immune 
response of Flu D-QIV vaccine when co-administered with 
RSVPreF3 vaccine or administered alone at Day 31 post dose 
vaccination (Amended 26 May 2022) 
Possible interference of RSVPreF3 on influenza immune responses will be evaluated by 
using Flu D-QIV HI antibody titers against the 3 influenza strains from RSVPreF3 + Flu 
(pooled of RSV1+Flu, RSV2+Flu, RSV3+Flu) and Flu+P group at Day 31. In the 
description of the subsequent analysis, the RSVPreF3+ Flu D-QIV vaccine group are 
RSV1+Flu, RSV2+Flu, RSV3+Flu groups pooled. 
The hypothesis is that co-administration of RSVPreF3+ Flu D-QIV vaccine is non-
inferior to Flu D-QIV vaccine with respect to GMT ratio for immune response of 
influenza antigen in non-pregnant women at Day 31 post vaccination. 
The criteria to evaluate non-inferiority for A/Tasmania/503/2020 (H3N2) IVR-221, 
B/Washington/02/2019, and B/Phuket/3073/2013 is that the lower limits of the 95% CI 
on the GMT ratio (RSV PreF3 + Flu D-QIV divided by Flu D-QIV) is greater than 0.67 
at Day 31 post vaccination. 
Table 15 presents the power on the ratio of the GMT of Flu D-QIV 3 strains. The power 
is at least 95% when the sample size is 400 participants per group with standard deviation 
(SD) of 0.6 on its log10 transformation and non-inferiority margin of 0.67 between 
RSVPreF3 co-administrated with Flu D-QIV group and Flu D-QIV vaccine administered 
alone group. 
Table 15 
Power to demonstrate non-inferiority of immune response between 
Flu D-QIV vaccine co-administered with RSVPreF3 or administered 
alone in term of GMT for Flu D-QIV strains at Day 31 post 1st 
vaccination with assumed GMT ratio 1 (Amended 26 May 2022) 
Endpoint 
NI criteria 
Number of 
evaluable 
participants in 
each group 
Reference* 
Power  
B/Washington/02/2019 
GMT ratio 
LL of 95% CI for GMC ratio >0.67 
400 
0.60 
98.56% 
A/Tasmania/503/2020 
(H3N2)** IVR-221 GMT 
ratio 
LL of 95% CI for GMT ratio >0.67 
400 
0.60 
98.56% 
B/Phuket/3073/2013 
GMT ratio 
LL of 95% CI for GMT ratio >0.67 
400 
0.60 
98.56% 
Global power 
 
 
 
95.68% 
By Pass 2019, Non-Inferiority Tests for Two Means using Differences, one-sided alpha=2.5%; 
*References used for the sample size calculation: Study Flu D-QIV -008 E1_01 Table 34. 
**A/Tasmania/503/2020 (H3N2) IVR-221 (an A/Cambodia/e0826360/2020 (H3N2)-like virus). 

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9.2.3. 
Secondary objectives  
To control the global type I error, a hierarchical procedure will be used for confirmatory 
objectives assessment.  
For instance, the secondary objective to demonstrate the non-inferiority of RSV A 
neutralizing antibodies using GMT ratios can only be assessed if the primary objective 
assessing the non-inferiority of GMT ratio for Flu D-QIV strains is met. As per the 
hierarchical procedure, secondary objective assessing the non-inferiority based on SCR 
difference of Flu D-QIV will only be assessed if the non-inferiority of RSV A 
neutralizing antibodies using GMT ratios is met. 
9.2.3.1. 
To demonstrate the non-inferiority of immune response between 
RSVPreF3 co-administered with Flu D-QIV and RSVPreF3 alone in term 
of RSV A Neutralizing antibody titers at Day 31 post administration 
Hypothesis under consideration is that immune response when the co-administration of 
RSVPreF3 vaccine + Flu D-QIV vaccine is non-inferior to that when RSV PreF3 vaccine 
(pooled RSV1, RSV2 and RSV3 group) is administered alone with respect to GMT ratio 
for RSV A neutralizing antibody titer in non-pregnant women at Day 31 post vaccination. 
This hypothesis test is conducted only if the primary objective of non-inferiority of 
immune response between Flu D-QIV vaccine when co-administered with RSVPreF3 and 
Flu D-QIV vaccine administered alone is met. 
The criteria to evaluate non-inferiority for RSV A Nab is that the lower limits of the 95% 
CI on the GMT ratio (RSVPreF3+Flu D-QIV vaccine divided by RSV PreF3 vaccine 
(pooled RSV1, RSV2 and RSV3 group) is greater than the pre-defined clinical limit of 
0.67 at Day 31 post vaccination. 
If a SD of log10 transformed RSV A Nab of 0.4 is assumed, with an assumption of GMT 
ratio of 1.0, there will be at least 99% chance that the lower bound of 95% CI for the ratio 
of GMT of RSV A Nab titer between RSVPreF3 co-administration with Flu D-QIV and 
administered alone is above 0.67 (Table 16). 
Table 16 
Power to demonstrate non-inferiority of immune response of 
RSVPreF3 vaccine when co-administered with Flu D-QIV vaccine or 
administered alone at Day 31 post vaccination 
Endpoint 
NI criteria 
N1:N2 
(evaluable) 
Reference* 
Power  
RSV A GMT ratio 
LL of 95% CI for GMT ratio >0.67 
400:600 
0.40 
99.99% 
By Pass 2019 Non-Inferiority Tests for Two Means using Differences, one-sided alpha=2.5%; 
*References used for the sample size calculation: Study RSV MAT 011 (209141) 
N1: Number of evaluable participants in the co-administration of RSVPreF3 vaccine + Flu D-QIV vaccine. 
N2: Number of evaluable participants in the RSVPreF3 vaccine alone group with 3 lots pooled. 

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9.2.3.2. 
To demonstrate the non-inferiority of immune response between 
RSVPreF3 co-administered with Flu D-QIV and Flu D-QIV alone in term 
of SCR at Day 31 post 1st dose administration (Amended 26 May 2022) 
Potential interference of RSVPreF3 on influenza immune responses will be evaluated by 
comparing the Day 31 seroconversion rate of Flu D-QIV HI antibody titers against the 3 
influenza strains between RSVPreF3+ Flu D-QIV vaccine group and Flu D-QIV+P 
group. 
The criteria to evaluate non-inferiority with respect to the SCR difference for Flu D-QIV 
antibody titers against 3 influenza strains is that the upper limits of the 95% CI on the 
SCR difference (Flu D-QIV vaccine minus RSVPreF3+Flu D-QIV vaccine) is less than 
the pre-defined clinical limit of 10% at Day 31 post vaccination. 
With the assumptions of SCR for the reference group as indicated in Table 17, 
significance level 0.025, non-inferiority margin 10%, 400 evaluable participants (10% 
non-evaluable rate) provides at least 80% power to conclude non-inferiority for each 
strain (Table 17). 
Table 17 
Powers to demonstrate non-inferiority in terms of HI antibody SCR 
for Flu D-QIV strains between Flu D-QIV vaccine co-administered 
with RSVPreF3 vaccine and administered alone at Day 31 post 
vaccination (Amended 26 May 2022) 
Endpoint 
NI criteria 
Anticipated SCR*  
Number of participants 
per group (evaluable) 
Power 
B/Washington/02/2019 SCR 
10% 
65% 
400 
84.39% 
A/Tasmania/503/2020 
(H3N2)** IVR-221 SCR 
10% 
65% 
400 
84.39% 
B/Phuket/3073/2013 SCR 
10% 
65% 
400 
84.39% 
By Pass 2019, Non-Inferiority Tests for the difference between two proportions, alpha=2.5% 
*SCR used in the reference group for power calculation is from Study Tdap-0.3-008, Suppl. Table 36. 
**A/Tasmania/503/2020 (H3N2) IVR-221 (an A/Cambodia/e0826360/2020 (H3N2)-like virus). 
9.2.4. 
Safety consideration 
The sample size of 660 participants when pooled 3 lots and 440 participants per group in 
the co-administration group at the first vaccination were planned to provide reasonable 
confidence to evaluate the AE rate. The table below illustrates the precision that can be 
obtained on the percentage of participants with AEs following vaccination. If an AE is 
not observed in a given treatment group, a sample size of 660 participants for pooled 
RSV lots can provide at least 95% confidence to rule out an AE incidence greater than 
0.56%. Considering the sample size of 440 vaccinated in co-administration groups, it can 
provide at least 95% confidence to rule out an AE incidence rate greater than 0.83%. 
In addition, a sample size of 440 in co-administration group would provide a probability 
of 98.8% to observe at least one AE if true AE rate is 1%. 

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Table 18 
Exact 95% confidence interval (CI) on the percentage of participants 
with AEs following vaccination from 660 participants with 3 lots 
pooled, and 440 participants from RSVPreF3 co-administration 
group 
Number of participants per 
group 
Number (%) of participants 
with an AE 
Exact 95% CI 
Lower Limit (%) 
Upper Limit (%) 
660 
0 (0%) 
0 
0.56 
660 
33 (5%) 
3.47 
6.95 
660 
66 (10%) 
7.82 
12.55 
660 
99 (15%) 
12.36 
17.96 
440 
0 (0%) 
0 
0.83 
440 
22 (5%) 
3.16 
7.47 
440 
44 (10%) 
7.36 
13.19 
440 
66 (15%) 
11.79 
18.68 
9.3. 
Analysis sets 
Table 19 
Analysis sets 
Analysis Set 
Description 
Enrolled  
Participants who agreed to participate in a clinical study after completion of the informed 
consent process  
Exposed  
All Participants who received at least 1 dose of the study treatment. The allocation in a 
group is done as a function of the administered treatment 
Full Analysis  
All Participants who received at least 1 dose of the study intervention and have post-
vaccination immunogenicity data  
Per Protocol  
All Participants who received at least 1 dose of the study treatment to which they are 
randomized and have post-vaccination data minus participants with protocol deviations that 
lead to exclusion 
Solicited Safety  
All Participants who received at least 1 dose of the study intervention (Exposed Set) who 
have solicited safety data 
9.3.1. 
Criteria for elimination from analysis 
If the participant meets one of the criteria mentioned below or ones listed in the Section 
7.1.1 she may be eliminated from per protocol analysis. 
If the participant has a protocol deviation deemed as major, he/she may be eliminated 
from the per protocol analysis sets. 
Major protocol deviations leading to exclusion will be defined in the Statistical Analysis 
Plan (SAP) and will be finalized prior to the first analysis defined in Section 9.4.3. 
Key major deviations include, but are not limited to, the following: 
• 
Participants enrolled who did not meet entry criteria including age at enrollment 
• 
Participants incorrectly vaccinated 
• 
Participants who did not receive study vaccinations as planned in protocol 
• 
Participants who did not have blood draws as planned in protocol 
• 
Participants with a blood draw outside of allowed time window 

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These key major deviations will be assessed based on the data collected in the eCRFs 
A complete list of criteria for elimination from per protocol analysis will be detailed in 
the Statistical Analysis Plan (SAP). 
9.4. 
Statistical analyses(Amended 26 May 2022) 
9.4.1. 
Primary endpoints/estimands analysis  
Primary Safety Endpoints  
Statistical Analysis Methods 
The number and percentage of 
participants in each group reporting 
• 
Each solicited administration 
site AE collected during the 7 
days follow-up period (Day 1 
to Day 7). 
• 
Each solicited systemic events 
in the 7 days follow-up period.  
The number and percentage with exact 95% CI of participants reporting 
each solicited administration site event (any grade, each grade,) and 
solicited systemic event (any, each grade) during the 7-day follow-up 
period after dosing will be tabulated by maximum intensity per participant for 
each study group. 
For fever during the 7-day follow-up period after vaccination, the number 
and percentage of participants reporting any fever (i.e., temperature ≥38 
°C) and fever by half degree (°C) cumulative increments, any Grade 3 
fevers, will be reported. 
The number and percentage of 
participants in each group reporting 
• 
Unsolicited AEs collected 
during the 30 days follow-up 
period (Day 1 to Day 30) 
• 
SAEs in the 30 days follow-up 
period (Day 1 to Day 30). 
• 
SAEs in the 180 days follow-
up period (Day 1 to Day 181) 
The number and percentage of participants reporting unsolicited AEs 
within 30 days after dosing with exact 95% CIs will be tabulated by group 
and by Medical Dictionary for Regulatory Activities (MedDRA) preferred 
term. 
Similar tabulations will be done for Grade 3 unsolicited AEs, for any causally 
related unsolicited AEs, and for Grade 3 related unsolicited AEs. 
The number and percentage of participants reporting at least one SAE 
within 30 days after dosing with exact 95% CIs will be tabulated by group 
and by MedDRA terms. 
The number and percentage of participants reporting at least one SAE 
up to study end with exact 95% CIs will be tabulated by group and by 
MedDRA terms. 
By-subject listings of SAEs and AEs leading to study withdrawal will be 
prepared. 
Primary Immunological 
Endpoints  
Statistical Analysis Methods 
RSVPreF3 IgG ELISA concentration 
at Day 31 (30 days post 
administration) 
Measured by ratio of GMC between 
lots in terms of RSVPreF3 IgG 
ELISA titers at Day 31 (30 days post 
administration) 
Flu D-QIV antibody titers against 3 
influenza strains at Day 31 (30 days 
post administration) 
Measured by ratio of 
Haemagglutinin inhibition (HI) GMT 
between group of Flu D-QIV vaccine 
co-administered with RSVPreF3 
vaccine and Flu D-QIV vaccine 
Primary confirmatory analyses: 
Lot-to-lot consistency among 3 lots of RSV vaccine for RSVPreF3 IgG 
ELISA concentration at Day 31: 
The 2-sided 95% CI for GMC ratio (each pair of comparison is between 2 
out of 3 lots) for RSVPreF3 IgG ELISA concentration at Day 31 will be 
computed based on the fact that the difference in the mean of log10 
transformed RSVPreF3 IgG ELISA concentration on Day 31 between 2 lots 
follows t-distribution. 
Lot-to-lot consistency will be demonstrated if all 3 two-sided 95% CIs for 
GMC ratio fall within 0.67 and 1.5. 
Non-inferiority of Flu D-QIV co-administered with RSVPreF3 vaccine 
compared to Flu D-QIV group with respect to 3 Flu D-QIV strains at Day 31: 
The 2-sided 95% CIs for A/Tasmania/503/2020 (H3N2) IVR-221 GMT ratio, 
B/Washington/02/2019 GMT ratio and B/Phuket/3073/2013 GMT ratio 

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Primary Safety Endpoints  
Statistical Analysis Methods 
alone group against 3 strains at Day 
31 (30 days post administration)  
(RSVPreF3 co-administered with Flu D-QIV group versus Flu D-QIV group) 
will be computed based on the fact that the difference in the mean of log10 
transformed titers on Day 31 between 2 groups follows a t-distribution. 
No interference on quadrivalent seasonal influenza vaccine (Flu D-QIV) 
from RSVPreF3 vaccine is demonstrated if lower bounds of all three 2-
sided 95% CIs are above 0.67. 
9.4.2. 
Secondary endpoints/estimands analysis 
Secondary Immunological 
Endpoints/Estimands  
Statistical Analysis Methods 
RSV A neutralizing antibody titers at Day 31 
(30 days post administration) 
Measured by ratio of GMT between group of 
RSVPreF3 vaccine co-administered with Flu 
D-QIV and RSVPreF3 vaccine alone (pooled 
lot 1,2,3) group in term of RSV A neutralizing 
antibody titers at Day 31 (30 days 
administration) 
Seroconversion rate to Flu D-QIVHI antibody 
titers against the 3 influenza strains at Day 31 
Measured by the difference of proportion of 
participants achieving seroconversion for HI 
antibody at Day 31 in the group of Flu D-QIV 
vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine 
alone 
Secondary confirmatory immunogenicity analyses: 
Non-inferiority of RSVPreF3 vaccine co-administered with Flu D-
QIV vaccine compared to RSV alone group in terms of RSV A 
neutralizing antibody titers at Day 31 
The 2-sided 95% CI for GMT ratio (RSV co-administered with Flu 
D-QIV group versus RSV group) will be computed based on the 
fact that the difference in the mean of log10 transformed RSV A 
neutralizing antibody titers at Day 31 between 2 groups follows a 
t-distribution. 
No interference on RSVPreF3 vaccine from quadrivalent seasonal 
influenza vaccine (Flu D-QIV) is demonstrated if lower bound of 
the 2-sided 95% CI of GMT ratio is above 0.67.Non-inferiority of 
Flu D-QIV co-administered with RSVPreF3 vaccine compared to 
Flu D-QIV vaccine alone with respect to each of the 3 Flu D-QIV 
strains at Day 31 in terms of Seroconversion rate (SCR) 
The 2-sided 95% CI for the difference of SCR (Flu D-QIV group 
minus RSV co-administered with Flu D-QIV group) will be 
calculated for each strain. Non-inferiority is demonstrated if the 
upper bound of 95% CI is less than or equal to the pre-defined 
clinical limit of 10% at Day 31 post vaccination. 
RSV A, RSV B neutralizing antibody titers and 
RSVPreF3 IgG concentration at Day 1 and 
Day 31 
GMT of RSV A and RSV B neutralizing 
antibody, GMC of RSVPreF3 IgG at Day 1 
and Day 31, in the group of RSVPreF3 
vaccine co-administered with Flu D-QIV and 
the group of RSVPreF3 vaccine alone. 
Flu D-QIV HI antibody titers against the 3 
influenza strains at Day 1 and Day 31 
HI GMT in the 3 influenza strains at Day 1 and 
Day 31 in the group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and the 
group of Flu D-QIV vaccine alone 
Seroprotection rate to Flu D-QIV HI antibody 
titers against the 3 influenza strains at Day 1 
and Day 31 
Descriptive immunogenicity analyses: 
For each assay, descriptive immunogenicity analysis may include 
but not limited to the following: 
• 
GMT/GMCs will be tabulated with 95% CI at each timepoint 
and represented graphically by group. 
• 
Geometric mean of ratios of antibody titers/concentrations at 
Day 31 over pre-vaccination will be tabulated with 95% CI 
by group. 
• 
Number and percentage of participants achieving 
seroconversion for HI antibody at Day 31 will be tabulated 
with its 95% CI in the group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and the group of Flu 
D-QIV vaccine alone. 
• 
Number and percentage of participants achieving HI 
antibody titer ≥ 1:40 at Day 1 and Day 31 will be tabulated 
with its 95% CI in the group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and the group of Flu 
D-QIV vaccine alone. 

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Secondary Immunological 
Endpoints/Estimands  
Statistical Analysis Methods 
Measured by the proportion of participants 
achieving an HI antibody titer ≥1:40 at Day 1 
and Day 31 in the group of Flu D-QIV vaccine 
co-administered with RSVPreF3 vaccine and 
the group of Flu D-QIV vaccine alone 
Seroconversion rate to Flu D-QIV HI antibody 
titers against the 3 influenza strains at Day 31 
Measured by the proportion of participants 
achieving seroconversion for HI antibody at 
Day 31 in the group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and the 
group of Flu D-QIV vaccine alone 
RSV A, RSV B neutralizing antibody titers and 
RSVPreF3 IgG antibody concentrations at 
pre-vaccination and Day 31 from each lot 
Geometric mean titer/concentration 
(GMT/GMC) in term of RSV A, RSV B 
neutralizing antibody and RSVPreF3 IgG 
antibody at Day 1 (pre-vaccination) and Day 
31 in each of 3 lots of the investigational 
PreF3 vaccine. 
Other descriptive analyses of immunogenicity if needed will be 
detailed in the SAP’ 
Exploratory immunogenicity between group analyses: 
Exploratory comparisons between study groups will also be 
explored through statistical modeling for the applicable primary 
and secondary immunogenicity endpoints. 
The GMT/GMC ratio of involved study groups and the two-sided 
95% CI will be computed by fitting an ANCOVA model on the 
logarithm10 transformation of the titers/concentrations, including 
the study group as fixed effect, age category at the time of 
vaccination (18-32 vs. 33-49) and pre-vaccination 
titers/concentrations as covariates, covariates in the model may 
be further adjusted when performing the analysis if appropriate 
and needed. 
9.4.3. 
Tertiary endpoints/estimands analysis 
The same statistical methods that are used to analyze the 3 strains in the primary and 
secondary endpoints will be used to analyze the A/Victoria/2570/2019 (H1N1) IVR-215 
strain. 
9.5. 
Conduct of analyses  
9.5.1. 
Sequence of analyses (Amended 26 May 2022) 
No interim analyses are planned. 
The final analysis will be performed when all data for at least primary and secondary 
endpoints up to study conclusion are available. A clinical study report (CSR) 
containing all available data will be written and made available to the investigators at 
that time. 
If the data for tertiary endpoints become available at a later stage, (an) additional 
analysis/ analyses may be performed. These data will be documented in annex(es) to the 
study report and will be made available to the investigators at that time. 
9.5.2. 
Statistical consideration for analysis (Amended 26 May 2022) 
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, ICF or Informed Assent Form, 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/EC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators must provide the sponsor with full and accurate 
financial disclosure, as requested, to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators must provide their financial interest information before initiation of the 
study center and again at the end of the study. Investigators are responsible for providing 

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a financial disclosure update if their financial interests change at any point during study 
participation and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
The investigator or his/her representative must fully explain the nature of the study to the 
participant and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. 
Freely given and written/witnessed/thumb printed informed consent must be obtained 
from each participant as appropriate, prior to participation in the study. 
The content of the informed consent form must meet the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written, or witnessed/thumb printed 
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 transferred to the sponsor will contain only the identifier. Name and any other 
information which would identify the participant will not be transferred. 
The participants must be informed that: 
• 
Her personal study-related data will be used by the sponsor in accordance with local 
data protection law. 
• 
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 ensure protection of the personal data of the investigator and site staff 
which is collected within the framework of and for the purpose of the study, in 
accordance with the Data Privacy Notice that will be sent to the site staff. 
The participants must be notified about their rights regarding the use of their personal 
data in accordance with the data privacy section of the ICF. 

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10.1.5. 
Committees structure 
Safety oversight will be provided by a safety review team (SRT) composed of GSK RSV 
team members.  
10.1.6. 
Dissemination of clinical study data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocols summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines. 
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical trial registers. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the investigator 
with the full summary of the study results. The investigator is encouraged to share the 
summary results with the study participants, as appropriate. 
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis. 
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 document storage system used during the 
trial and for archiving (irrespective of the type of media used) should provide for 
document identification, version history, search, and retrieval. 
Essential trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, CRF), the copy should fulfill the 
requirements for certified copies. 
All participant data related 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. 

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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 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 for such review and inspection. 
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 
in the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g. via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 
Quality tolerance limits (QTLs) will be pre-defined in the Study Management Plan to 
identify systematic issues that can impact participant safety and/or the reliability of study 
results. These pre-defined parameters will be monitored during the study. Important 
deviations from the QTLs and remedial actions taken will be summarized in the CSR. 
Trial records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the investigator for 25 years from issuance of the final 
CSR/equivalent summary unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of 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 to establish the existence of the participant and 
substantiate the integrity of collected data. The investigator should maintain a record of 
the location(s) of their source documents. 
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any 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. 
Definitions of what constitutes source data and 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 its sole discretion, provided there is sufficient notice given to 
account for all participants safe exit from study. 
Regular closure of study sites will occur upon study completion. A study site is 
considered closed when all required data/documents and study supplies have been 
collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice 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 the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the Last Subject Last Visit (LSLV) for 
interventional studies and follows the guidance from the International Committee of 
Medical Journal Editors (ICMJE). 

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10.2. 
Appendix 2: Clinical laboratory tests (Amended 26 May 
2022) 
10.2.1. 
Protocol required safety laboratory assessments  
Assay descriptions could be subject to change, due to assay re-development and/or 
qualification. 
RSV-A and RSV-B neutralization assays  
The RSV-A and RSV-B neutralization assays are functional assays that measure 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 with serial 
dilutions of the test serum. Then, the serum-virus mixture is transferred onto a Vero cells 
culture and incubated for two days to allow infection of Vero cells. Thereafter, RSV-
infected cells are detected by the visualization of the number of plaques.  
RSVPreF3 IgG ELISA  
The ELISA assay is based on an indirect ELISA allowing the detection and the 
quantification of specific IgG antibodies directed against RSVPreF3 in human serum 
samples and related to reference standard. 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). 
FLU Hemagglutination-inhibition (HI) assay 
Hemagglutination inhibition (HI) antibody titres are determined using the method 
derived from the WHO Manual on Animal Influenza Diagnosis and Surveillance, 
WHO/CDS/CSR/NCS/2002.5.  
Measurements are conducted on thawed frozen serum samples with a standardized and 
comprehensively validated micro-method. Briefly, serum samples are treated with 
receptor destroying enzyme (RDE) overnight, diluted to 1:10, and serial diluted 2- fold 
in triplicate from 1:10 to 1:10240. After addition of an equal volume of standardized 
virus (4 HA / 25 μL), neutralization is performed for 1 hour at room temperature, 
followed by addition of the RBCs. After 30 minutes, plates are tilted and the titer is the 
reciprocal of the last dilution that fully inhibits hemagglutination as compared to a RBC 
control well. Each sera sample will be tested in triplicate within the same assay. The 
three titer results will be reported as will the geometric mean titer (GMT) for the 
triplicate. 
The tests detailed in Table 20 will be performed by the local laboratory. 

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All clinical and safety laboratory tests will be performed by local laboratory(ies). All 
assessments of immune response will be performed centrally (by GSK or by a GSK 
designated laboratory). 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 6 of the protocol. 
The investigator is not allowed to do extra testing on samples outside of what has been 
agreed upon by the ethics committees. 
Table 20 
Protocol required safety laboratory assessments 
System 
Discipline 
Component 
Method 
Scale 
Laboratory 
Urine1 
 
Pregnancy 
As per local practice; dipstick 
provided by GSK Biologicals  
Ordinal 
At investigator’s 
laboratory  
The tests detailed in Table 20 will be performed by the local laboratory. 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of 
AE 
10.3.1. 
Definition of an AE 
An AE is any untoward medical occurrence (an unfavorable/unintended sign - including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical 
study participant that is temporally associated with the study intervention. The AE may or 
may not be considered related to the study intervention. 
10.3.1.1. 
Events Meeting the AE Definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 

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• 
Signs, symptoms that require medical attention (e.g. hospital stays, physician visits 
and emergency room visits). 
• 
Significant failure of an expected pharmacologic or biological action. 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated 
procedures (i.e. invasive procedures, modification of participant’s previous 
therapeutic regimen). 
• 
Clinically significant abnormal laboratory findings or other abnormal assessments 
that are present at baseline and significantly worsen following the start of the study 
will also be reported as AEs or SAEs. 
• 
AEs to be recorded as solicited AEs are described in the Section 10.3.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
• 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfill the definition of an AE or SAE. 
10.3.1.2. 
Events NOT Meeting the AE Definition 
• 
Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
• 
Pre-existing conditions or signs and/or symptoms present in a participant before 
the study intervention. These events will be recorded in the medical history section 
of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• 
Disease-related events (DRE), typically associated with the disease under study. 
These events will be recorded in the participant’s eCRF and will be monitored by 
the SRT on a routine basis. However, if 1 or both of the following conditions 
apply, then the event should be reported promptly to GSK as an SAE (see Section 
10.3.8): 
− 
The event is, in the investigator’s opinion, of greater intensity, frequency, or 
duration than expected for the individual participant, or 
− 
The investigator considers that there is a reasonable possibility that the event 
was related to the administration of the study intervention 

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10.3.2. 
Definition of an SAE 
An SAE is any untoward medical occurrence that: 
a. 
Results in death. 
b. Is life-threatening 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, had it been more severe. 
c. 
Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the participant has been admitted at the 
hospital or emergency ward for observation and/or treatment that would not have been 
appropriate in the physician’s office or in an out-patient setting. Complications that 
occur during hospitalization are also considered AEs. The event will also be considered 
serious if a complication prolongs hospitalization or fulfills any other serious criteria. 
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. 
Abnormal pregnancy outcomes (e.g. spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy). 
g. Other situations 
Medical or scientific judgment must be exercised in deciding whether reporting is 
appropriate in other situations. Important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant 
or require medical or surgical intervention to prevent one of the other outcomes listed 
in the above definition should 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; and 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: 

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Table 21 
Solicited administration site events 
Pain  
Redness  
Swelling  
b. Solicited systemic events 
The following systemic events will be solicited: 
Table 22 
Solicited systemic events 
Fever 
Headache 
GI Symptoms (Nausea, Vomiting, Diarrhea, Abdominal pain) * 
Fatigue 
* Nausea, vomiting, diarrhea and abdominal pain are collected individually. 
Note: participants will be instructed to measure and record the axillary or oral 
temperature in the evening. If additional temperature measurements are taken at other 
times of the day, participants will be instructed to record the highest temperature in the e-
diary. 
10.3.4. 
Unsolicited adverse events 
An unsolicited adverse event is an adverse event that was not included in a list of 
solicited events using a Participant Diary. Unsolicited events must have been 
spontaneously communicated by a participant who has signed the informed consent. 
Unsolicited AEs include both serious and non-serious AEs.  
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or an 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/parental/LAR’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 or perceived as a concern by the 
participant will be collected during an interview with the participants and by review of 
available medical records at the next visit. 
10.3.5. 
Adverse events of special interest (AESIs) 
N/A 

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10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs 
In the absence of a diagnosis, abnormal laboratory findings assessments or other 
abnormal results the investigator considers clinically significant will be recorded as an 
AE or SAE, if they meet the definition of an AE or SAE (refer to the Sections 10.3.1 and 
10.3.2). 
The investigator must exercise his or her medical and scientific judgment in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs 
10.3.7.1. 
Pregnancy 
Female participants who become pregnant after administration of the study intervention 
may continue the study at the discretion of the investigator. 
While pregnancy itself is not considered an AE or SAE, any abnormal pregnancy 
outcome or complication or elective termination of a pregnancy for medical reasons will 
be recorded and reported as an SAE. Please refer to the Section 10.3.2 for definition of 
SAE. 
10.3.8. 
Recording and follow-up of AEs, SAEs, and pregnancies 
The participants will be instructed to contact the investigator immediately should they 
experience any signs or symptoms they perceive as serious. 
When an AE/SAE occurs, it is the investigator’s responsibility to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) related to 
the event. The investigator will then record all relevant information regarding an AE/SAE 
on the eCRF. The investigator may not send photocopies of the participant’s medical 
records to GSK instead of appropriately completing the eCRF. 
There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers will be blinded on 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 instead of individual signs/symptoms. 
An Electronic Diary (e-Diary), 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 the Participant Diary. 

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Anyone who measures administration site or systemic events and who will record the 
event in the Participant Diary should be trained on using the Diary. This training must be 
documented in the participant’s source record. 
Collect and verify completed e-diary during discussions with the participant on Visit 2 
(Day 31). 
• 
Any unreturned e-diary device 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. 
Refer to the SPM for more information regarding the use of e-Diary including the 
occurrence of unsolicited AEs. 
10.3.8.1. 
Time period for collecting and recording AEs, SAEs, and pregnancies 
All solicited events that occur during 7 days following administration of the dose of study 
intervention (Day 1 to Day 7) must be recorded into the e-Diary, irrespective of intensity. 
All other AEs occurring within this time frame should be recorded into the appropriate 
section of the eCRF, irrespective of their intensity or whether or not they are considered 
related to the study intervention. 
10.3.8.2. 
Follow-up of AEs, SAEs, pregnancies or any other events of interest 
After the initial AE/SAE/pregnancy or any other event of interest, the investigator is 
required to proactively follow each participant at subsequent visits/contacts. All SAEs 
will be followed until the event is resolved, stabilized, otherwise explained, or the 
participant is lost to follow-up. 
Other non-serious AEs must be followed until end of study or until the participant is lost 
to follow-up. 
10.3.8.2.1. Follow-up during the study 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.8.2.2. Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information to GSK on a 
previously reported SAE using a paper/electronic Expedited Adverse Events Report 
and/or pregnancy 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 SAE as fully as possible. 

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10.3.8.2.3. Follow-up of pregnancies 
Pregnant participants will be followed to determine the outcome of the pregnancy. At the 
end of the pregnancy, whether full-term or premature, information on the status of the 
mother and child will be forwarded to GSK using the electronic pregnancy report and the 
Expedited Adverse Events Report if applicable. Generally, the follow-up period does not 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, if the investigator becomes aware of any SAE occurring as a result of a post 
study pregnancy AND it is considered by the investigator to be reasonably related to the 
study intervention, he/she must report this information to GSK as described in the Section 
10.3.10. 
10.3.8.3. 
Updating of SAE and pregnancy information after removal of write 
access to the participant’s eCRF 
When additional SAE or pregnancy information is received after write access to the 
participant’s eCRF is removed, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study contact for reporting SAEs (refer to the 
Section 8.3.3.1 or to GSK VCSP department within the defined reporting time frames 
specified in the Table 12. 

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10.3.9.2. 
Assessment of causality 
The investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgment. Where several different 
interventions were administered, the investigator should specify, when possible, if the 
unsolicited AE/SAE could be causally related to a specific intervention. When a causal 
relationship to a specific study intervention cannot be determined, the investigator should 
indicate the unsolicited AE/SAE to be related to all interventions. 
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The investigator will also consult 
the Summary of Product Characteristics and/or Prescribing Information for marketed 
products to assist in making 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 intervention? 
YES 
: 
There is a reasonable possibility that the study intervention contributed 
to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study intervention. There are other, more likely 
causes and administration of the study intervention is not suspected to 
have contributed to the AE. 
If an event meets the criteria to be determined ‘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 study intervention, if applicable. 
• 
An error in study intervention administration. 
• 
Other cause (specify). 
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Expedited 
Adverse Events Report to GSK. 

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The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. The investigator may change his/her opinion of causality after receiving 
additional information and update the SAE information accordingly. 
10.3.9.3. 
Medically attended visits 
For each solicited and unsolicited symptom the participant experiences, the participant 
will be asked if she received medical attention defined as hospitalization, or an otherwise 
unscheduled visit to or from medical personnel for any reason, including emergency 
room visits. This information will be recorded in the eCRF. 
10.3.9.4. 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
10.3.10. 
Reporting of SAEs and pregnancies and other events 
10.3.10.1. Events requiring expedited reporting to GSK 
Once an investigator becomes aware that an SAE has occurred, the investigator (or 
designee) must complete information in the electronic Expedited Adverse Events Report 
WITHIN 24 HOURS, even if the investigator does not have complete information on the 
SAE. It must be completed as thoroughly as possible, with all available details of the 
event. 
The SAE report must be updated WITHIN 24 HOURS of the receipt of updated 
information on the SAE. The investigator will always provide an assessment of causality 
at the time of the initial report. 
Refer to the Table 12 for the details on timeframes for reporting of SAEs/pregnancies. 
The investigator will be required to confirm the review of SAE causality by ticking the 
‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 hours of 
submission of the SAE. 
Refer to the Section 10.3.10.2 for information on backup systems in case the electronic 
reporting system does not work. 

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10.3.10.2. Backup system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designee) must fax a 
completed, dated and signed paper Expedited Adverse Events Report to the study contact 
for reporting SAEs (refer to the Sponsor Information) or to GSK VCSP department 
within 24 hours of becoming aware of the SAE. 
Investigator (or designee) must complete the electronic Expedited Adverse Events Report 
within 24 hours after the electronic reporting system is working again. The information 
reported through the electronic SAE reporting system will be considered valid for 
regulatory reporting purposes. 
10.4. 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
10.4.1. 
Definitions 
10.4.1.1. 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
10.4.1.1.1. Women not considered as women of childbearing potential 
• 
Premenarchal 
Menarche is the first onset of menses in a young female. Menarche is normally 
preceded by several changes associated with puberty including breast development 
and pubic hair growth. 
Additional evaluation should be considered if a participant’s fertility status is unclear 
(e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention. 
• 
Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s: review of participant’s medical 
records, medical examination, or medical history interview. 
• 
Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in women not 

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using hormonal contraception or hormonal replacement therapy (HRT). However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 
• 
Females on HRT and whose menopausal status is in doubt will be required to use a 
non-hormonal, highly effective contraception method if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrollment. 
10.4.2. 
Contraception guidance  
• 
Female participants of childbearing potential are eligible to participate if they agree 
to use a highly effective contraceptive method consistently and correctly according 
to the methods listed in GSK’s list of highly effective contraceptive methods (Table 
24). 
Table 24 
Highly effective contraceptive methods 
Highly Effective Contraceptive Methods That Are User Dependent a 
Failure rate of <1% per year when used consistently and correctly  
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation 
• 
Oral 
• 
Intravaginal 
• 
Transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
injectable  
• 
oral 
Highly Effective Methods That Are User Independent  
• 
Implantable progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomized partner 
(A vasectomized partner is a highly effective contraception method provided that the partner is the 
sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used.)  
Male partner sterilization prior to the female participant’s entry into the study, and this male is the 
sole partner for that participant, 
(The information on the male sterility can come from the site personnel’s review of the participant’s 
medical records; medical examination and/or semen analysis, or medical history interview provided 
by her or her partner) 
Sexual abstinence 
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant.)  

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10.4.3. 
Collection of pregnancy information 
10.4.3.1. 
Female participants who become pregnant 
Refer to the Sections 8.3.1, 8.3.2, 10.3.8.1 and 10.3.8.3 for further information on 
detection, recording, reporting and follow-up of pregnancies. 
Any female participant who becomes pregnant during the study will be followed to 
determine the outcome of the pregnancy. 
10.5. 
Appendix 5: Genetics 
Not applicable. 
10.6. 
Appendix 6: Definition of medical device AE, adverse device 
effect (ADE), serious adverse device effect (SADE) and 
unanticipated SADE (USADE) 
10.6.1. 
Definition of medical device AE and adverse device effect (ADE) 
• 
Medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether considered related to a medical device or not. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a medical device. This definition includes events related to the medical device 
or comparator and events related to the procedures involved. 
• 
An adverse device effect (ADE) is an AE related to the use of a medical device. This 
definition includes any AE resulting from: 
− 
insufficient or inadequate instructions for use (i.e. user error), or 
− 
any malfunction of a medical device, or 
− 
intentional misuse of the medical device. 
10.6.2. 
Definition of medical device SAE, SADE and USADE 
A medical device SAE is any serious adverse event that: 
a. 
Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
− 
A life-threatening illness or injury. The term ‘life-threatening' in the definition 
of ‘serious' refers to an event in which the participant was at risk of death at 
the time of the event. It does not refer to an event, which hypothetically might 
have caused death, if it were more severe. 

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− 
A permanent impairment of a body structure or a body function. 
− 
Inpatient or prolonged hospitalization. Planned hospitalization for a pre-
existing condition, or a procedure required by the protocol, without serious 
deterioration in health, is not considered an SAE. 
− 
Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
c. 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
Serious Adverse Device Effect (SADE) definition 
• 
A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
• 
Any device deficiency that might have led to an SAE if appropriate action had not 
been taken or circumstances had been less fortunate. 
Unanticipated SADE (USADE) definition 
• 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a 
serious adverse device effect that by its nature, incidence, severity or outcome has 
not been identified in the current version of the IB. 
10.6.3. 
Recording and reporting of medical device AE, ADEs, SADEs and 
USADE 
• 
Any device deficiency must be reported to GSK within 24 hours after the 
investigator determines that the event meets the definition of a device deficiency. 
• 
Refer to paper ‘Medical device or combination product with device 
deficiency/incident report form’ for details on transmission of this information to the 
sponsor. 
• 
GSK will review all device deficiencies, determine and document in writing whether 
they could have led to an SAE. These device deficiencies will be reported to the 
regulatory authorities and IRBs/IECs as required by national regulations. 
• 
If required or in case of any issues refer to the general safety contacts for SAE/AE 
reporting in Section 8.3.3.1 
10.7. 
Appendix 7: Country-specific requirements 
This appendix includes all applicable requirements of specific local GSK requirements 
and identifies, item per item, the mandatory modifications or additional information to 
the study protocol. 

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10.7.1. 
South Korea 
As per Ministry of Food and Drug Safety the following Prior/Concomitant Therapy 
Exclusion Criteria will be applicable » 
• 
A participant who has participated in other clinical trial for healthy people within at 
least 6 months prior to enroll/study vaccination. 
• 
A female between, and including, 19 and 49 years of age at the time of signing of the 
informed consent. 
10.8. 
Appendix 8: Abbreviations and glossary of terms 
10.8.1. 
List of abbreviations 
AE: 
Adverse Event 
CLS: 
Clinical Laboratory Sciences 
COVID-19 
Corona Virus Disease 2019 
CSR 
Clinical Study Report 
DRE 
Disease-related event 
eCRF: 
electronic Case Report Form 
EoS: 
End of Study 
Flu D-QIV  
(Fluarix Quadrivalent, Fluarix Tetra, Fluarix Tetra, α-
RIX-Tetra and Influsplit Tetra) 
GCP: 
Good Clinical Practice 
GSK: 
GlaxoSmithKline 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
ICH: 
International Council on Harmonisation 
IDMC 
Independent Data Monitoring Committee (Amended 26 
May 2022) 
LML 
Local Medical Lead 
LSLV: 
Last Subject Last Visit 
MedDRA: 
Medical Dictionary for Regulatory Activities 

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QTL 
Quality Tolerance Limit 
RRA: 
Recruitment/Randomization Agreement 
SAE: 
Serious Adverse Event 
SBIR: 
Source data Base for Internet Randomization  
SmPC: 
Summary of Product Characteristics 
SPM: 
Study Procedures Manual 
WOCBP 
Woman of Childbearing Potential 
10.8.2. 
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 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 observer-blind study, the participant, the site and 
sponsor personnel involved in the clinical evaluation of 
the participants are blinded while other study personnel 
may be aware of the treatment assignment.  
In a single-blind study, the investigator and/or his staff 
are aware of the intervention assignment but the 
participant is not.  
Caregiver 
A ‘caregiver’ is someone who 
• 
lives in the close surroundings of a participant and 
has a continuous caring role or 

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• 
has substantial periods of contact with a participant 
and is engaged in his/her daily health care (e.g. a 
relative of the participant, a nurse who helps with 
daily activities in case of residence in a nursing 
home). 
In the context of a clinical study, a caregiver could 
include an individual appointed to oversee and support 
the participant's compliance with protocol-specified 
procedures. 
Certified copy: 
A copy (irrespective of the type of media used) of the 
original record that has been verified (i.e. by a dated 
signature or by generation through a validated process) 
to have the same information, including data that 
describe the context, content, and structure, as the 
original. 
Combination product 
Combination product comprises any combination of 
• 
drug 
• 
device 
• 
biological product 
Each drug, device and biological product included in a 
combination product is a constituent part.  
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
End of Study (EoS): 
(Synonym of End of Trial) 
For studies with collection of human biological samples 
and/or imaging data, the EoS is defined as Last subject 
last visit (Visit X) or Last testing results released of 
samples collected at Visit X* 
* In this case EoS must be achieved no later than 8 
months after LSLV.  
Enrolled participant 
‘Enrolled’ means a participant’s/parent’s/LAR’s 
agreement to participate in a clinical study following 
completion of the informed consent process. Potential 
participants who are screened for determining eligibility 
for the study, but do not participate in the study, are not 
considered enrolled, unless otherwise specified by the 
protocol. 
Refer to the Section 9.2.4 of the protocol for the 
definition of ‘enrolled set’ applicable to the study.  
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced 

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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. 
Immunological correlate of 
protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Intervention 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant 
Intervention number 
A number identifying an intervention to a participant, 
according to intervention allocation 
Investigational vaccine 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorization when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use. 
Synonym: Investigational Medicinal Product 
Investigator 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator. 
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
and functions 
Legally acceptable 
representative 
An individual, judicial or other body authorized under 
applicable law to consent on behalf of a prospective 
participant to the participant's participation in the 
clinical trial. 
The terms legal representative or legally authorized 
representative are used in some settings 
Participant 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject 
Participant number 
A unique identification number assigned to each 
participant who consents to participate in the study 

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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 administrative 
change 
A protocol administrative change addresses changes to 
only logistical or administrative aspects of the study  
Protocol amendment 
The International Council on Harmonisation (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK further details this to include a change to an 
approved protocol that affects the safety of participants, 
scope of the investigation, study design, or scientific 
integrity of the study 
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 
Solicited event 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified follow-up period following study 
intervention administration 
Source data 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical 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, laboratories and at medico-
technical departments involved in the clinical trial). 

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Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
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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10.9. 
Appendix 9: Protocol Amendment 
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 
21 April 2021 
Amendment 1 
24 May 2021 
Amendment 2 
17 November 2021 
Amendment 3 
26 May 2022 
Detailed description of the Protocol amendment 1: 
The protocol is being amended to align with the safety review team’s recommended and 
approved safety oversight approach for this study. The committee structure provided in 
the previous version was described in error and this amendment corrects this error. 
8.1.2 
Laboratory Assays 
Sampling 
time points 
System 
Component 
Method 
Unit 
Groups 
Laboratory 
Visit 1 
Serum 
Respiratory Syncytial Virus A 
Ab neutralizing 
NEU 
IU* and/or 
ED60   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
Serum 
Respiratory Syncytial Virus B 
Ab neutralizing 
NEU 
IU and/or 
ED60   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
Day 31 
Serum 
Respiratory Syncytial Virus A 
Ab neutralizing 
NEU 
IU and/or 
ED60   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
 
Serum 
Respiratory Syncytial Virus B 
Ab neutralizing 
NEU 
IU and/or 
ED60   
RSV1 
RSV2 
RSV3 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
GSK or GSK 
designated 
lab 
*IU=international units    ED60= serum dilution inducing 60% inhibition in plaque forming units (ED60) 

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8.3.3.1 
Contact information for reporting SAEs, AESIs, pregnancies and study 
holding rules 
Email address: ogm28723@gsk.comPV.ICSRManagement@gsk.com 
10.1.5 
Committees structure 
Safety oversight will be provided by a blinded safety review team (SRT) composed of 
GSK RSV team members. and by an unblinded, internal safety review committee 
composed of GSK personnel not affiliated with the RSV program 
Detailed description of the current Protocol amendment 2: 
Other study intervention(s) 
• 
Placebo (Saline solution [NaCl]) 
• 
Flu D-QIV vaccine [GSK2321138A] 
Title 
 
A Phase III, randomized, observer-blind, multi-
country study to evaluate the lot-to-lot 
consistency of GSK’s investigational RSV 
maternal vaccine and the immune response, 
safety and reactogenicity of RSV maternal 
vaccine when co-administered with GSK’s 
quadrivalent influenza D-QIV vaccine in healthy 
non-pregnant women 18-49 years of age. 
1.2 Schema 
The study is a This Phase III, observer-blind, randomized, multi-country study is 
observer-blinded to evaluate the lot-to-lot consistency of GSK RSVPreF3 vaccine, and 
single-blinded to evaluate the immune response, safety and reactogenicity when co-
administered with Flu D-QIV vaccine. A total of 1541 healthy non-pregnant women 18 to 
49 YOA will be enrolled in the study. 
All safety data will be reviewed by a blinded Safety Review Team (SRT) on an ongoing 
basis. 
1.3 Schedule of Activities 
Medical and vaccination history  
● 
 
O 
Physical examination and vital signs2,4 
● 
 
O  
Vital signs2,4 
● 
 
O 
2 Physical examination including (height and weight) BMI as well as resting vital signs (blood pressure, heart rate and 
respiratory rate, temperature) after at least 10 minutes of rest. 
At Day 1 (Visit 1) both physical exam and vital signs will be measured while. aAt Day 31 (Visit 2) only medical and 
vaccination history and vital signs will may be measured. 

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Table 2 
Intervals between study visits 
Interval 
Optimal timing  
Allowed interval (Study day) 
Visit 1*→ Phone Contact 1 
Day 8 days 
Day 7 – 10 days 
Visit 1→ Visit 2 
Day 31 days 
Day 31 -38 days 
Visit 1 → Phone Contact 2 
Day 181 days 
Day 165 - 195 days 
2.3 Benefit/Risk assessment 
Safety monitoring will be conducted throughout this study by a blinded Safety Review 
Team. 
4.1 Overall design 
The study is a This Phase III, randomized, multi-country study in healthy non-pregnant 
women 18-49 YOA is observer-blind to evaluate the lot-to-lot consistency of GSK 
RSVPreF3 vaccine and single-blind to evaluate the immune response, safety and 
reactogenicity of RSV maternal vaccine when co-administered with GSK quadrivalent 
influenza (Flu D-QIV) vaccine in healthy non-pregnant women 18-49 YOA. 
Blinding: This study will utilize an observer blinding design to evaluate the lot-to-lot 
consistency of GSK RSVPreF3 vaccine; and single-blinding design to evaluate the 
immune response, safety and reactogenicity of RSV maternal vaccine when co-
administered with GSK quadrivalent influenza that is described in Section 6.3.5 
5.2.2. Prior/Concomitant Therapy 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol within the period starting 30 days before* and ending 30 days after the 
vaccination dose*; 
* In case emergency mass vaccination for an unforeseen public health threat (e.g. a 
pandemic) is organised by public health authorities outside the routine immunisation 
programme, the time period described above can be reduced if, necessary for that 
vaccine, provided it is licensed and used according to its Product Information.  
(See Section 5.5 for more details on Criteria for Temporary Delaying Enrolment) 
5.4 Screen failures 
Screen failures are participants who consent to take part in this study but are determined 
ineligible and subsequently randomly not assigned to a study intervention. 
5.5 Criteria for temporarily delaying enrolment 
The standard time window for planned administration/administration of a vaccine not 
foreseen by the study protocol is 30 days before and after the day of vaccination with 
RSV vaccine. There may be an exception that can shorten the time window based on 
the local guidance, but it will not be less than 15 days before or after Visit 1.  

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6.1 Study intervention(s) administered  
Study intervention 
formulation: 
RSVPreF3(120 µg) 
Sodium Chloride 
(NaCl) (0.9%); Water 
for injections 
A/(H1N1) A/Victoria/2570/2019 
(H1N1), IVR-215 (15 µg HA); 
A/(H3N2) A/Tasmania/503/2020 
(H3N2), IVR-221 (15 µg HA);  
B/(Victoria Lineage) 
B/Phuket/3073/2013 (15 µg HA);  
B/(Yamagata Lineage) 
B/Washington/02/2019 (15 µg HA);  
Water for injections q.s. 0.5 mL 
Sodium Chloride 
(NaCl) (0.9%); 
Water for injections 
Volume to be 
administered**: 
whole content 
Full volume 0.5mL***  
whole content**** 
**Full volume (0.5mL) to be administered. 
*****A/Tasmania/503/2020 (H3N2) IVR-221 (an A/Cambodia/e0826360/2020 (H3N2)-like virus). 
6.3.5 Blinding and unblinding 
Data will be collected in an observer-blind manner to evaluate the lot-to-lot consistency 
of GSK RSVPreF3 vaccine and single-blind manner to evaluate the immune response, 
safety and reactogenicity of RSV maternal vaccine when co-administered with GSK 
quadrivalent influenza. 
− 
This study will utilize a single blind design as described below: 
− 
For the co-administration groups (Flu+RSV or Flu+P), the investigator and 
participant will both know that the participant is part of the co-administration 
study groups. However, they the participant will be blinded to the vaccine 
administration activities. Participant will be administered with either RSVPreF3 
or Flu D-QIV on the left arm. On the right arm, participant will be administered 
with either Flu D-QIV or the placebo. 
6.8 Concomitant therapy 
• 
Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination) up to the first 30 
days after vaccination. 

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8.1.2 Laboratory Assays 
Serum 
Flu D-QIV * 
• 
A/Victoria/2570/2019 (H1N1) Ab 
A/H1N1 vaccine strain 
Haemagglutinin Ab 
• 
A/Tasmania/503/2020 (H3N2) Ab 
A/H3N2 vaccine strain 
Haemagglutinin Ab 
• 
B/Washington/02/2019 Ab 
B/Yamagata vaccine strain 
(Hemagglutinin Ab) 
• 
B/Phuket/3073/2013 Ab 
B/Victoria vaccine strain 
(Hemagglutinin Ab) 
HI assay 
1/Dil 
RSV1+Flu 
RSV2+Flu 
RSV3+Flu 
Flu+P 
GSK 
designated 
lab 
8.2.1.4 Physical Exam 
• 
Perform a full physical examination of the participant at the first visit Visit 1 
[Day 1], including assessment of oral body temperature and resting vital signs: 
systolic/diastolic blood pressure, heart rate and respiratory rate after at least 10 
minutes of rest 
• 
Perform a A history directed physical exam and vital signs at Visit 12 [Day 31] may 
be performed  
• 
Measure only vital sign at Visit 2[Day 31] 
9.2.2 Primary objective: To demonstrate Non-inferiority of immune response of Flu 
D-QIV vaccine when co-administered with RSVPreF3 vaccine or administered 
alone at Day 31 post dose vaccination 
The criteria to evaluate non-inferiority for A/H1N1A/Victoria/2570/2019 (H1N1) IVR-
215, A/H3N2 A/Tasmania/503/2020 (H3N2) IVR-221, B/Victoria lineage 
B/Washington/02/2019, and B/Yamagata lineage B/Phuket/3073/2013 is that the lower 
limits of the 95% CI on the GMT ratio (RSV PreF3 + Flu D-QIV divided by Flu D-QIV) 
is greater than or equal to 0.67 at Day 31 post vaccination. 
Table 15: Power to demonstrate non-inferiority of immune response between Flu D-
QIV vaccine co-administered with RSVPreF3 or administered alone in term of 
GMT for Flu D-QIV strains at Day 31 post 1st vaccination with assumed GMT 
ratio 1 
Endpoint 
NI criteria 
Number of 
evaluable 
participants in 
each group 
Reference* 
Power  
A/H1N1 
A/Victoria/2570/2019 
(H1N1) IVR-215 GMT ratio 
LL of 95% CI for GMT ratio ≥>0.67 
400 
0.60 
98.56% 
B/Victoria lineage 
B/Washington/02/2019 
GMT ratio 
LL of 95% CI for GMC ratio ≥>0.67 
400 
0.60 
98.56% 

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Endpoint 
NI criteria 
Number of 
evaluable 
participants in 
each group 
Reference* 
Power  
A/H3N2 
A/Tasmania/503/2020 
(H3N2)** IVR-221 GMT 
ratio 
LL of 95% CI for GMT ratio≥ >0.67 
400 
0.60 
98.56% 
B/Yamagata lineage 
B/Phuket/3073/2013 GMT 
ratio 
LL of 95% CI for GMT ratio≥ >0.67 
400 
0.60 
98.56% 
Global power 
 
 
 
94.24% 
**A/Tasmania/503/2020 (H3N2) IVR-221 (an A/Cambodia/e0826360/2020 (H3N2)-like virus). 
9.2.3 Secondary objectives 
To control the global type I error, a hierarchical procedure will be used for 
confirmatory objectives assessment.  
For instance, the secondary objective to demonstrate the non-inferiority of RSV A 
neutralizing antibodies using GMT ratios can only be assessed if the primary objective 
assessing the non-inferiority of GMT ratio for Flu D-QIV strains is met. As per the 
hierarchical procedure, secondary objective assessing the non-inferiority based on SCR 
difference of Flu D-QIV will only be assessed if the non-inferiority of RSV A 
neutralizing antibodies using GMT ratios is met. 
In order to control the global type I error, the objectives will be assessed sequentially. 
The non-inferiority objective based on SCR difference of Flu D-QIV strains will only be 
assessed if the null hypothesis for the non-inferiority of GMT ratio for Flu D-QIV strains 
are rejected. 
The criteria to evaluate non-inferiority for RSV A Nab is that the lower limits of the 95% 
CI on the GMT ratio (RSVPreF3+Flu D-QIV vaccine divided by RSV PreF3 vaccine 
(pooled RSV1, RSV2 and RSV3 group)) is greater than or equal to the pre-defined 
clinical limit of 0.67 at Day 31 post vaccination. 
Table 16: Power to demonstrate non-inferiority of immune response of RSVPreF3 
vaccine when co-administered with Flu D-QIV vaccine or administered alone at Day 
31 post vaccination 
Endpoint 
NI criteria 
N1:N2 
(evaluable) 
Reference* 
Power  
RSV A GMT ratio 
LL of 95% CI for GMT ratio≥>0.67 
400:600 
0.40 
99.99% 
9.2.3.2 To demonstrate the non-inferiority of immune response between RSVPreF3 
co-administered with Flu D-QIV and Flu D-QIV alone in term of SCR at Day 31 
post 1st dose administration 
Table 17: Powers to demonstrate non-inferiority in terms of HI antibody SCR for 
Flu D-QIV strains between Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and administered alone at Day 31 post vaccination 

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Endpoint 
NI criteria 
Anticipated SCR*  
Number of participants 
per group (evaluable) 
Power 
A/Victoria/2570/2019 
(H1N1) IVR-215 A/H1N1 
SCR 
10% 
60% 
400 
82.49% 
B/Washington/02/2019 
B/Victoria lineage SCR  
10% 
65% 
400 
84.39% 
A/Tasmania/503/2020 
(H3N2)** IVR-221 A/H3N2 
SCR 
10% 
65% 
400 
84.39% 
B/Phuket/3073/2013 
B/Yamagata lineage SCR 
10% 
65% 
400 
84.39% 
**A/Tasmania/503/2020 (H3N2) IVR-221 (an A/Cambodia/e0826360/2020 (H3N2)-like virus). 
9.4.1 Primary endpoints/estimands analysis 
Primary Immunological 
Endpoints  
Statistical Analysis Methods 
RSVPreF3 IgG ELISA concentration 
at Day 31 (30 days post 
administration) 
Measured by ratio of GMC between 
lots in terms of RSVPreF3 IgG 
ELISA titers at Day 31 (30 days post 
administration) 
Flu D-QIV antibody titers against 4 
influenza strains at Day 31 (30 days 
post administration) 
Measured by ratio of 
Haemagglutinin inhibition (HI) GMT 
between group of Flu D-QIV vaccine 
co-administered with RSVPreF3 
vaccine and Flu D-QIV vaccine 
alone group against 4 strains at Day 
31 (30 days post administration)  
Primary confirmatory analyses: 
Lot-to-lot consistency among 3 lots of RSV vaccine for RSVPreF3 IgG 
ELISA concentration at Day 31: 
The 2-sided 95% CI for GMC ratio (each pair of comparison is between 2 
out of 3 lots) for RSVPreF3 IgG ELISA concentration at Day 31 will be 
computed based on the fact that the difference in the mean of log10 
transformed RSVPreF3 IgG ELISA concentration on Day 31 between 2 lots 
follows t-distribution. 
Lot-to-lot consistency will be demonstrated if all 3 two-sided 95% CIs for 
GMC ratio fall within 0.67 and 1.5. 
Non-inferiority of Flu D-QIV co-administered with RSVPreF3 vaccine 
compared to Flu D-QIV group with respect to 4 Flu D-QIV strains at Day 31: 
The 2-sided 95% CIs for A/Victoria/2570/2019 (H1N1) IVR-215 A/H1N1 
GMT ratio, A/Tasmania/503/2020 (H3N2) IVR-221 A/H3N2 GMT ratio, 
B/Washington/02/2019 B/Victoria lineage GMT ratio and 
B/Phuket/3073/2013 B/Yamagata lineage GMT ratio (RSVPreF3 co-
administered with Flu D-QIV group versus Flu D-QIV group) will be 
computed based on the fact that the difference in the mean of log10 
transformed titers on Day 31 between 2 groups follows a t-distribution. 
No interference on quadrivalent seasonal influenza vaccine (Flu D-QIV) 
from RSVPreF3 vaccine is demonstrated if lower bounds of all four 2-sided 
95% CIs are above 0.67. 
10.1.5 Committees Structure 
Safety oversight will be provided by a blinded safety review team (SRT) composed of 
GSK RSV team members.  
10.2.1 Protocol required safety laboratory assessments  
Assay descriptions could be subject to change, due to assay re-development and/or 
qualification. 

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RSV-A and RSV-B neutralization assays  
The RSV-A and RSV-B neutralization assays are functional assays that measure 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 with serial 
dilutions of the test serum. Then, the serum-virus mixture is transferred onto a Vero 
cells culture and incubated for two days to allow infection of Vero cells. Thereafter, 
RSV-infected cells are detected by the visualization of the number of plaques.  
RSVPreF3 IgG ELISA  
The ELISA assay is based on an indirect ELISA allowing the detection and the 
quantification of specific IgG antibodies directed against RSVPreF3 in human serum 
samples and related to reference standard. 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). 
10.4.2 Contraception Guidance 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
injectable  
• 
oral 
10.7.1, South Korea 
• 
A female between, and including, 19 and 49 years of age at the time of signing of 
the informed consent. 
10.8.2 Glossary of Terms 
Trademarks 
Trademarks of the GSK group of companies 
 
Generic description 
Flu-DQIV, Fluarix Quadrivalent, Fluarix Tetra, Fluarix 
Tetra, α-RIX-Tetra and Influsplit Tetra 
 
• 
A/H1/N1 vaccine strain (Hemagglutinin Ab) 
• 
A/H3N2 vaccine strain (Hemagglutinin Ab) 
• 
B/Yamagata vaccine strain (Hemagglutinin Ab) 
• 
B/Victoria vaccine strain (Hemagglutinin Ab) 
GSK’s quadrivalent seasonal influenza vaccine 
Blinding: 
In a single-blind study, the investigator and/or his staff 
are aware of the intervention assignment but the 
participant is not.  

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Detailed description of the current Protocol amendment 3: 
1.1. Synopsis 
In the RSV maternal program to date, a A Phase I/II, observer-blind study (RSV MAT-
001; NCT 03674177) in healthy non-pregnant women 18-45 YOA, to determine the 
safety and immunogenicity of 3 dose levels of the RSVPreF3 vaccine (30, 60, and 120 
µg) compared to placebo, has been completed. No safety concerns have been identified. 
Based on preliminary results of RSV MAT-001 study, the 60 and 120 µg dose levels 
were selected for further evaluation in the following 2 additional studies, which are 
ongoingcompleted: 
Based on the final results of RSV MAT-001, on the Day 31 results of RSV MAT-004 and 
RSV MAT-011 studies, the 120µg dose level has beenwas selected for evaluation in RSV 
MAT-010 study. In addition, the 120µg dose level is was currently also administered for 
in pregnant women participating in the Phase III study RSV MAT-009.  
2.1. Study rationale 
In the GSK RSV maternal program to date, aA Phase I/II study (study RSV MAT-001; 
NCT 03674177) in healthy non-pregnant women 18-45 YOA to determine the safety and 
immunogenicity of 3 dose levels of RSVPreF3 (30, 60 and 120µg) vaccine compared to 
placebo is now complete. The results from these studies this study demonstrated that the 
RSV maternal (RSVPreF3) vaccine is highly immunogenic and no safety concerns have 
been identified. Study results for safety and immunogenicity are now available in the 
Investigator Brochure. 
In another ongoing completed Phase II randomized, observer-blinded study (RSV MAT-
011) in non-pregnant women 18 to 45 YOA, two dose levels of the RSV maternal 
vaccine, 60 µg, and 120 µg, are being evaluated. The primary objectives are to evaluate 
the effects of Boostrix co-administration in terms of reactogenicity, safety and immune 
response to the RSV maternal vaccine at 1-month post study intervention (considering the 
US and outside the US data pooled). The effects of RSV maternal vaccine co-
administration on the safety and immune response to Boostrix were evaluated as 
secondary objectives. Additional secondary objectives included safety assessment up to 6 
months post-intervention, and evaluations of the safety and immune response considering 
the US and outside the US data both separately and pooled. Enrollment is complete and 
participant’s follow-up is ongoing to examine the persistence of antibody 12-18 months 
post-1st dose and safety of a 2nd dose of RSV PreF3 vaccine given from 12 up to 18 
months post 1st dose. Preliminary results are now available in the IB. Briefly, an 
acceptable safety profile was observed for both formulations and both dose levels of the 
investigational RSV maternal vaccine, and both dose levels elicited an immune response, 
no safety concern was observed in the study population of non-pregnant women. The 
safety and immunogenicity profile were also similar in another study (RSV MAT 004) 
examining RSV maternal vaccine in pregnant women. 

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This study (RSV MAT-010) will be the first to evaluate co-administration of 120 µg of 
the RSVPreF3 (RSV MAT) vaccine with Flu D-QIV in healthy non-pregnant women (see 
Figure 1). Selection of the RSVPreF3 antigen dose was based on preliminary results of 
the completed (RSV MAT-001) and ongoing completed studies (RSV MAT-001, RSV 
MAT-011 and RSV MAT-004) studies. 
2.3. Benefit/Risk assessment 
Following a recommendation from the Independent Data Monitoring Committee 
(IDMC), the Sponsor made the decision to pause the enrollment, randomization and 
vaccination of pregnant study participants in our active studies based on an 
observation of imbalance of the proportion of preterm births between the vaccine group 
and the placebo group in the RSV MAT-009 study in pregnant women. This pause was 
to allow for an evaluation of the available data in RSV MAT-009 to better understand 
the safety signal observed. Following a review of additional unblinded data from RSV 
MAT-009 trial in which a higher proportion of neonatal deaths reported in the 
treatment group compared to the placebo group was also observed, the Sponsor decided 
to STOP enrollment and vaccination in these studies.  
The safety signals are being investigated and, although at this time a cause has not 
been determined, as a precautionary measure GSK stopped active enrollment and 
further vaccination of participants in the RSV MAT studies enrolling both pregnant 
women on February 25, 2022. We also considered it not appropriate to enroll any 
additional participants in studies for the RSV maternal program and therefore also 
stopped active enrollment and further vaccination of participants in the RSV MAT 
studies enrolling non-pregnant women on March 1, 2022. The studies remain ongoing 
for safety follow-up. Participants already vaccinated will continue to be monitored until 
the end of the study. 
At this time, the safety observation has been observed only among pregnant trial 
participants. 

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Table 3. Study objectives, endpoints and estimands 
Objectives 
Endpoints/Estimands 
Primary 
Safety 
• 
To evaluate the safety and reactogenicity of 
RSVPreF3 when given alone (pooled lots) or co-
administered with Flu D-QIV up to Day 31study 
end. post administration. 
The number and percentage of participants in each group 
reporting 
• 
Each solicited administration site AE collected 
during the 7 days follow-up period (Day 1 to Day 7) 
• 
Each solicited systemic events in the 7 days follow-
up period 
• 
Unsolicited AEs collected during the 30 days follow-
up period (Day 1 to Day 30) 
• 
SAEs in the 30 days follow-up period (Day 1 to Day 
30) 
• 
SAEs in the 180 days follow-up period (Day 1 to 
Day 181)  
• 
To demonstrate non-inferiority of Flu D-QIV vaccine 
when co-administered with RSVPreF3 vaccine 
compared to Flu D-QIV given alone based on 
Geometric mean titer (GMT) of Flu D-QIV antibody 
titers against 4 3 influenza strains at Day 31 post 
administration 
Flu D-QIV antibody titers against 4 3 influenza strains at 
Day 31 (30 days post administration) 
Measured by ratio of Haemagglutinin inhibition (HI) GMT 
between group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and Flu D-QIV vaccine alone group 
against 4 3 strains at Day 31 (30 days post administration)  
Secondary 
Confirmatory Immunogenicity*** 
• 
To demonstrate the non-inferiority of Flu D-QIV 
vaccine co-administered with RSVPreF3 compared 
to given alone based on Seroconversion rate (SCR) 
of Flu D-QIV HI antibody titers against 4 3 influenza 
strains at Day 31 post study intervention 
• 
Seroconversion rate to Flu D-QIV* HI antibody titers 
against the 4 3 influenza strains at Day 31 
Measured by the difference of proportion of participants 
achieving seroconversion for HI antibody at Day 31 in the 
group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and the group of Flu D-QIV vaccine 
alone 
Descriptive Immunogenicity 
• 
To evaluate the humoral immune response to the 
Flu D-QIV vaccine when given alone and co-
administered with RSVPreF3 vaccine in terms of 
antibody titers against 3 influenza strains at Day 1 
and Day 31 
Flu D-QIV HI antibody titers against the 4 3 influenza 
strains at Day 1 and Day 31 
HI GMT in the 4 3 influenza strains at Day 1 and Day 31 in 
the group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and the group of Flu D-QIV vaccine 
alone 
• 
To evaluate seroprotection rate (SPR)* and 
Seroconversion rate (SCR)** of the Flu D-QIV 
vaccine when given alone and co-administered with 
RSVPreF3 vaccine 
Seroprotection rate to Flu D-QIV HI antibody titers against 
the 4 3 influenza strains at Day 1 and Day 31 
Measured by the proportion of participants achieving an HI 
antibody titer ≥1:40 at Day 1 and Day 31 in the group of 
Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine alone 
• 
Seroconversion rate to Flu D-QIV HI antibody titers 
against the 4 3 influenza strains† at Day 31 
Measured by the proportion of participants achieving 
seroconversion for HI antibody at Day 31 in the group of 

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Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine alone 
Tertiary Objective 
To demonstrate non-inferiority of Flu D-QIV vaccine 
when co-administered with RSVPreF3 vaccine 
compared to Flu D-QIV given alone based on 
Geometric mean titer (GMT) of Flu D-QIV antibody 
titers against the A/Victoria/2570/2019 (H1N1) 
influenza strain at Day 31 post administration 
Flu D-QIV* antibody titers against the 
A/Victoria/2570/2019 (H1N1) influenza strain at Day 31 
(30 days post administration) 
Measured by ratio of Haemagglutinin inhibition (HI) 
GMT between group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and Flu D-QIV 
vaccine alone group against the A/Victoria/2570/2019 
(H1N1) strain at Day 31 (30 days post administration)  
To demonstrate the non-inferiority of Flu D-QIV 
vaccine co-administered with RSVPreF3 compared to 
given alone based on Seroconversion rate (SCR) of 
Flu D-QIV HI antibody titers against the 
A/Victoria/2570/2019 (H1N1) influenza strain at Day 31 
post study intervention 
x
Seroconversion rate to Flu D-QIV* HI antibody 
titers against the A/Victoria/2570/2019 (H1N1) 
influenza strain at Day 31 
Measured by the difference of proportion of 
participants achieving seroconversion for HI antibody 
at Day 31 in the group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and the group of 
Flu D-QIV vaccine alone 
To evaluate the humoral immune response to the Flu 
D-QIV vaccine when given alone and co-administered 
with RSVPreF3 vaccine in terms of antibody titers 
against the A/Victoria/2570/2019 (H1N1) influenza 
strain at Day 1 and Day 31 
Flu D-QIVHI antibody titers against the 
A/Victoria/2570/2019 (H1N1) influenza strain at Day 1 
and Day 31 
HI GMT in the A/Victoria/2570/2019 (H1N1) influenza 
strain at Day 1 and Day 31 in the group of Flu D-QIV 
vaccine co-administered with RSVPreF3 vaccine and 
the group of Flu D-QIV vaccine alone 
To evaluate seroprotection rate (SPR)* and 
Seroconversion rate (SCR)** of the Flu D-QIV vaccine 
when given alone and co-administered with RSVPreF3 
vaccine 
Seroprotection rate to Flu D-QIV HI antibody titers 
against the A/Victoria/2570/2019 (H1N1) influenza 
strain at Day 1 and Day 31 
Measured by the proportion of participants achieving 
an HI antibody titer ≥1:40 at Day 1 and Day 31 in the 
group of Flu D-QIV vaccine co-administered with 
RSVPreF3 vaccine and the group of Flu D-QIV vaccine 
alone 
x
Seroconversion rate to Flu D-QIV HI antibody 
titers against the A/Victoria/2570/2019 (H1N1) 
influenza strain at Day 31 
Measured by the proportion of participants achieving 
seroconversion for HI antibody at Day 31 in the group 
of Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine alone 
*SPR is defined as the percentage of vaccines with a serum HI titer >1:40 that usually is accepted as indicating 
protection. 
** The SCR is defined as the proportion of participants with: 
A Day 1 (pre-vaccination) serum anti-HI titer <1:10 and a Day 31 (post-vaccination) serum anti-HI titer ≥1:40, or 
A Day 1 (pre-vaccination) serum anti-HI titer ≥ 1:10 and a fold increase (post/pre) ≥ 4 at Day 31 
*** Two confirmatory objectives will be tested sequentially. 
CCI

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6.3.5. Blinding and unblinding 
• 
This blinding strategy will apply from Visit 1 to Visit 2study end (Day 181) 
(Amended 26 May 2022).  after which the first analysis will be conducted and 
treatment-level unblinded summaries will be provided to GSK and regulatory 
agency for review. No individual treatment code will be shared with study 
participants, investigators, and the study team, except study statistician, until the end 
of the study. 
9.2.2. Primary objective: To demonstrate Non-inferiority of immune response of Flu 
D-QIV vaccine when co-administered with RSVPreF3 vaccine or administered 
alone at Day 31 post dose vaccination 
Possible interference of RSVPreF3 on influenza immune responses will be evaluated by 
using Flu D-QIV HI antibody titers against the 4 3 influenza strains from RSVPreF3 + 
Flu (pooled of RSV1+Flu, RSV2+Flu, RSV3+Flu) and Flu+P group at Day 31. In the 
description of the subsequent analysis, the RSVPreF3+ Flu D-QIV vaccine group are 
RSV1+Flu, RSV2+Flu, RSV3+Flu groups pooled. 
The criteria to evaluate non-inferiority for A/Victoria/2570/2019 (H1N1) IVR-215, 
A/Tasmania/503/2020 (H3N2) IVR-221, B/Washington/02/2019, and 
B/Phuket/3073/2013 is that the lower limits of the 95% CI on the GMT ratio (RSV PreF3 
+ Flu D-QIV divided by Flu D-QIV) is greater than 0.67 at Day 31 post vaccination. 
Table 15 presents the power on the ratio of the GMT of Flu D-QIV 4 3 strains. The 
power is at least 9495% when the sample size is 400 participants per group with standard 
deviation (SD) of 0.6 on its log10 transformation and non-inferiority margin of 0.67 
between RSVPreF3 co-administrated with Flu D-QIV group and Flu D-QIV vaccine 
administered alone group. 
Table 15 Power to demonstrate non-inferiority of immune response between Flu D-
QIV vaccine co-administered with RSVPreF3 or administered alone in term of 
GMT for Flu D-QIV strains at Day 31 post 1st vaccination with assumed GMT ratio 
1 
Endpoint 
NI criteria 
Number of 
evaluable 
participants in 
each group 
Reference* 
Power  
A/Victoria/2570/2019 
(H1N1) IVR-215 GMT ratio 
LL of 95% CI for GMT ratio >0.67 
400 
0.60 
98.56% 
B/Washington/02/2019 
GMT ratio 
LL of 95% CI for GMC ratio >0.67 
400 
0.60 
98.56% 
A/Tasmania/503/2020 
(H3N2)** IVR-221 GMT 
ratio 
LL of 95% CI for GMT ratio >0.67 
400 
0.60 
98.56% 
B/Phuket/3073/2013 
GMT ratio 
LL of 95% CI for GMT ratio >0.67 
400 
0.60 
98.56% 
Global power 
 
 
 
94.2495.68% 

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9.2.3.2. To demonstrate the non-inferiority of immune response between RSVPreF3 
co-administered with Flu D-QIV and Flu D-QIV alone in term of SCR at Day 31 
post 1st dose administration 
Potential interference of RSVPreF3 on influenza immune responses will be evaluated by 
comparing the Day 31 seroconversion rate of Flu D-QIV HI antibody titers against the 4 
3 influenza strains between RSVPreF3+ Flu D-QIV vaccine group and Flu D-QIV+P 
group. 
The criteria to evaluate non-inferiority with respect to the SCR difference for Flu D-QIV 
antibody titers against 4 3 influenza strains is that the upper limits of the 95% CI on the 
SCR difference (Flu D-QIV vaccine minus RSVPreF3+Flu D-QIV vaccine) is less than 
the pre-defined clinical limit of 10% at Day 31 post vaccination. 
Table 17. Powers to demonstrate non-inferiority in terms of HI antibody SCR for 
Flu D-QIV strains between Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and administered alone at Day 31 post vaccination 
Endpoint 
NI criteria 
Anticipated SCR*  
Number of participants 
per group (evaluable) 
Power 
A/Victoria/2570/2019 
(H1N1) IVR-215 SCR 
10% 
60% 
400 
82.49% 
B/Washington/02/2019 SCR 
10% 
65% 
400 
84.39% 
A/Tasmania/503/2020 
(H3N2)** IVR-221 SCR 
10% 
65% 
400 
84.39% 
B/Phuket/3073/2013 SCR 
10% 
65% 
400 
84.39% 

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9.4.1. Primary endpoints/estimands analysis  
Primary Safety Endpoints  
Statistical Analysis Methods 
The number and percentage of 
participants in each group reporting 
• 
Unsolicited AEs collected 
during the 30 days follow-up 
period (Day 1 to Day 30) 
• 
SAEs in the 30 days follow-up 
period (Day 1 to Day 30). 
• 
SAEs in the 180 days follow-
up period (Day 1 to Day 181) 
The number and percentage of participants reporting unsolicited AEs 
within 30 days after dosing with exact 95% CIs will be tabulated by group 
and by Medical Dictionary for Regulatory Activities (MedDRA) preferred 
term. 
Similar tabulations will be done for Grade 3 unsolicited AEs, for any causally 
related unsolicited AEs, and for Grade 3 related unsolicited AEs. 
The number and percentage of participants reporting at least one SAE 
within 30 days after dosing with exact 95% CIs will be tabulated by group 
and by MedDRA terms. 
The number and percentage of participants reporting at least one SAE 
up to study end with exact 95% CIs will be tabulated by group and by 
MedDRA terms. 
By-subject listings of SAEs and AEs leading to study withdrawal will be 
prepared (but will not be released until the final analysis has been 
completed). 
Primary Immunological 
Endpoints  
Statistical Analysis Methods 
RSVPreF3 IgG ELISA concentration 
at Day 31 (30 days post 
administration) 
Measured by ratio of GMC between 
lots in terms of RSVPreF3 IgG 
ELISA titers at Day 31 (30 days post 
administration) 
Flu D-QIV antibody titers against 4 3 
influenza strains at Day 31 (30 days 
post administration) 
Measured by ratio of 
Haemagglutinin inhibition (HI) GMT 
between group of Flu D-QIV vaccine 
co-administered with RSVPreF3 
vaccine and Flu D-QIV vaccine 
alone group against 4 3 strains at 
Day 31 (30 days post 
administration) 
Primary confirmatory analyses: 
Lot-to-lot consistency among 3 lots of RSV vaccine for RSVPreF3 IgG 
ELISA concentration at Day 31: 
The 2-sided 95% CI for GMC ratio (each pair of comparison is between 2 
out of 3 lots) for RSVPreF3 IgG ELISA concentration at Day 31 will be 
computed based on the fact that the difference in the mean of log10 
transformed RSVPreF3 IgG ELISA concentration on Day 31 between 2 lots 
follows t-distribution. 
Lot-to-lot consistency will be demonstrated if all 3 two-sided 95% CIs for 
GMC ratio fall within 0.67 and 1.5. 
Non-inferiority of Flu D-QIV co-administered with RSVPreF3 vaccine 
compared to Flu D-QIV group with respect to 4 3 Flu D-QIV strains at Day 
31: 
The 2-sided 95% CIs for A/Victoria/2570/2019 (H1N1) IVR-215 GMT ratio, 
A/Tasmania/503/2020 (H3N2) IVR-221 GMT ratio, B/Washington/02/2019 
GMT ratio and B/Phuket/3073/2013 GMT ratio (RSVPreF3 co-administered 
with Flu D-QIV group versus Flu D-QIV group) will be computed based on 
the fact that the difference in the mean of log10 transformed titers on Day 
31 between 2 groups follows a t-distribution. 
No interference on quadrivalent seasonal influenza vaccine (Flu D-QIV) 
from RSVPreF3 vaccine is demonstrated if lower bounds of all four three 2-
sided 95% CIs are above 0.67. 

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9.4.2. Secondary endpoints/estimands analysis  
Secondary Safety Endpoints/Estimands  
Statistical Analysis Methods 
The number and percentage of participants 
reporting SAEs from first vaccination up to 
study end. [Day 1 to Day 180] 
The number and percentage of participants reporting at least one 
SAE from vaccination up to study end with exact 95% CIs will be 
tabulated by group and by MedDRA terms 
By participant listings of SAEs and(S)AEs leading to study 
withdrawal will be prepared but will not be released until the final 
analysis has been completed 
Secondary Immunological 
Endpoints/Estimands  
Statistical Analysis Methods 
RSV A neutralizing antibody titers at Day 31 
(30 days post administration) 
Measured by ratio of GMT between group of 
RSVPreF3 vaccine co-administered with Flu 
D-QIV and RSVPreF3 vaccine alone (pooled 
lot 1,2,3) group in term of RSV A neutralizing 
antibody titers at Day 31 (30 days 
administration) 
Seroconversion rate to Flu D-QIVHI antibody 
titers against the 43 influenza strains at Day 
31 
Measured by the difference of proportion of 
participants achieving seroconversion for HI 
antibody at Day 31 in the group of Flu D-QIV 
vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine 
alone 
Secondary confirmatory immunogenicity analyses: 
Non-inferiority of RSVPreF3 vaccine co-administered with Flu D-
QIV vaccine compared to RSV alone group in terms of RSV A 
neutralizing antibody titers at Day 31 
The 2-sided 95% CI for GMT ratio (RSV co-administered with Flu 
D-QIV group versus RSV group) will be computed based on the 
fact that the difference in the mean of log10 transformed RSV A 
neutralizing antibody titers at Day 31 between 2 groups follows a 
t-distribution. 
No interference on RSVPreF3 vaccine from quadrivalent seasonal 
influenza vaccine (Flu D-QIV) is demonstrated if lower bound of 
the 2-sided 95% CI of GMT ratio is above 0.67.Non-inferiority of 
Flu D-QIV co-administered with RSVPreF3 vaccine compared to 
Flu D-QIV vaccine alone with respect to each of the  43 Flu D-QIV 
strains at Day 31 in terms of Seroconversion rate (SCR) 
The 2-sided 95% CI for the difference of SCR (Flu D-QIV group 
minus RSV co-administered with Flu D-QIV group) will be 
calculated for each strain. Non-inferiority is demonstrated if the 
upper bound of 95% CI is less than or equal to the pre-defined 
clinical limit of 10% at Day 31 post vaccination. 

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RSV A, RSV B neutralizing antibody titers and 
RSVPreF3 IgG concentration at Day 1 and 
Day 31 
GMT of RSV A and RSV B neutralizing 
antibody, GMC of RSVPreF3 IgG at Day 1 
and Day 31, in the group of RSVPreF3 
vaccine co-administered with Flu D-QIV and 
the group of RSVPreF3 vaccine alone. 
Flu D-QIV HI antibody titers against the 43 
influenza strains at Day 1 and Day 31 
HI GMT in the  43 influenza strains at Day 1 
and Day 31 in the group of Flu D-QIV vaccine 
co-administered with RSVPreF3 vaccine and 
the group of Flu D-QIV vaccine alone 
Seroprotection rate to Flu D-QIV HI antibody 
titers against the  43 influenza strains at Day 1 
and Day 31 
Seroconversion rate to Flu D-QIV HI antibody 
titers against the  43 influenza strains at Day 
31 
 
Descriptive immunogenicity analyses: 
For each assay, descriptive immunogenicity analysis may include 
but not limited to the following: 
• 
GMT/GMCs will be tabulated with 95% CI at each timepoint 
and represented graphically by group. 
• 
Geometric mean of ratios of antibody titers/concentrations at 
Day 31 over pre-vaccination will be tabulated with 95% CI 
by group. 
• 
Number and percentage of participants achieving 
seroconversion for HI antibody at Day 31 will be tabulated 
with its 95% CI in the group of Flu D-QIV vaccine co-
administered with RSVPreF3 vaccine and the group of Flu 
D-QIV vaccine alone. 
Number and percentage of participants achieving HI antibody titer 
≥ 1:40 at Day 1 and Day 31 will be tabulated with its 95% CI in the 
group of Flu D-QIV vaccine co-administered with RSVPreF3 
vaccine and the group of Flu D-QIV vaccine alone. 
9.4.3. Tertiary endpoints/estimands analysis  
The same statistical methods that are used to analyze the 3 strains in the primary and 
secondary endpoints will be used to analyze the A/Victoria/2570/2019 (H1N1) IVR-215 
strain. 
9.5.2. Statistical consideration for analysis 
The first analysis will be performed when final immunogenicity data is available, 
therefore, no statistical adjustment for multiple analyses is required.Not applicable. 
10.2.1. Protocol required safety laboratory assessments  
FLU Hemagglutination-inhibition (HI) assay 
Hemagglutination inhibition (HI) antibody titres are determined using the method 
derived from the WHO Manual on Animal Influenza Diagnosis and Surveillance, 
WHO/CDS/CSR/NCS/2002.5.  
Measurements are conducted on thawed frozen serum samples with a standardized and 
comprehensively validated micro-method. Briefly, serum samples are treated with 
receptor destroying enzyme (RDE) overnight, diluted to 1:10, and serial diluted 2- fold 
in triplicate from 1:10 to 1:10240. After addition of an equal volume of standardized 
virus (4 HA / 25 μL), neutralization is performed for 1 hour at room temperature, 
followed by addition of the RBCs. After 30 minutes, plates are tilted and the titer is the 
reciprocal of the last dilution that fully inhibits hemagglutination as compared to a RBC 

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control well. Each sera sample will be tested in triplicate within the same assay. The 
three titer results will be reported as will the geometric mean titer (GMT) for the 
triplicate. 
10.8.1. List of abbreviations 
IDMC 
Independent Data Monitoring Committee 

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11. 
REFERENCES 
Beyer WEP, Palache AM., Baljet M et al. Antibody induction by influenza vaccines in 
elderly: a review of the literature. Vaccine. 1989; 7:385-394. 
Brydak L, Machala M. Humoral immune response to influenza vaccination in patients 
from high risk groups. Drugs. 2000; 60:35-53. 
Hannoun C, Megas F, and Piercy J. “ImmuFnogenicity and protective efficacy of 
influenza vaccination” Virus Res. 2004; 103:133-138. 
Haralambieva IH, Ovsyannikova IG, Pankratz VS, Kennedy RB, Jacobson RM, Poland 
GA. The genetic basis for interindividual immune response variation to measles vaccine: 
new understanding and new vaccine approaches. Expert Rev Vaccines. 2013; 12(1):57–
70. 
Hasin DS, O’Brien CP, Auriacombe M, et al. DSM-5 Criteria for Substance Use 
Disorders: Recommendations and Rationale. The American journal of psychiatry. 
2013;170(8):834-851. Doi:10.1176/appi.ajp.2013.12060782. 
Kollmann TR. Variation between Populations in the Innate Immune Response to Vaccine 
Adjuvants. Front Immunol. 2013; 4:81 
Pérez-Losada M, Posada D, Arenas M, et al. Ethnic differences in the adaptation rate of 
HIV gp120 from a vaccine trial. Retrovirology. 2009; 6:67. 
World Health Organization [WHO], Influenza (Seasonal) Fact sheet N°211, 2012; 
http://www.who.int/mediacentre/factsheets/fs211/en/. 
World Health Organization [WHO]. Global Surveillance for COVID-19 caused by 
human infection with COVID-19 virus: Interim Guidance. March 2020. Available at: 
https://apps.who.int/iris/rest/bitstreams/1272502/retrieve. Accessed 8 May 2020. 

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Trademarks  
The following trademarked products are referenced in the present protocol. 
Trademarks of the GSK group of companies 
 
Generic description 
Flu-DQIV, Fluarix Quadrivalent, Fluarix Tetra, Fluarix 
Tetra, α-RIX-Tetra and Influsplit Tetra 
 
GSK’s quadrivalent seasonal influenza vaccine 
 

Signature Page for  214709 TMF-14681251 v1.0
Signature Page for TMF-14681251 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 01-Jun-2022 12:51:50 GMT+0000
PPD