A Phase II Study of a Primary Dose of Investigational RSV Maternal Vaccine, Given Alone or With Boostrix, With a 2nd Dose Investigational RSV Maternal Vaccine
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Sponsor: GlaxoSmithKline

 
 
 
 
 
 
Protocol 
209141 
Phase II randomized, observer-blind, placebo-controlled, multi-country study in healthy non-pregnant 
women 18-45 years of age to evaluate the safety, reactogenicity and immunogenicity of a 1st intramuscular 
dose of GSK Biologicals’ investigational RSV maternal vaccine (GSK388550A) when given alone and 
given in co-administration with a single intramuscular dose of Boostrix (US formulation SB776423 or ex-
US formulation SB263855) and to evaluate the safety, reactogenicity and immunogenicity of a 2nd dose of 
the RSV maternal vaccine. 
EudraCT number: 2019-002258-22 
Date of Document: 14 APRIL 2021 
 

CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
1 
 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA 
Rue de l’Institut 89, 
1330 Rixensart, Belgium 
Primary Study vaccine(s) 
and number(s) 
GlaxoSmithKline (GSK) Biological Respiratory 
Syncytial Virus (RSV) RSVPreF3 candidate vaccine 
(GSK3888550A) 
Other Study 
vaccine(s)/product(s) 
GSK Biologicals’ combined reduced-antigen-content 
diphtheria, tetanus and acellular pertussis (dTpa) 
vaccine (Boostrix [US formulation SB776423]) 
GSK Biologicals’ combined reduced-antigen-content 
diphtheria, tetanus and acellular pertussis (dTpa) 
vaccine (Boostrix [ex-US formulation SB263855]) 
Placebo (150 mM Sodium chloride [NaCl]) 
eTrack study number and 
abbreviated title 
209141 (RSV MAT-011) 
Investigational New Drug 
(IND) number 
18434 
EudraCT number 
2019-002258-22 
Date of protocol 
Final Version 3: 23 August 2019 
Date of protocol 
amendment 
Amendment 1 Final: 21 October 2019 
Amendment 2 Final: 23 January 2020 
Amendment 3 Final: 3 April 2020 
Amendment 4 Final: 28 August 2020 
Amendment 5 Final: 2 November 2020 
Amendment 6 Final: 9 April 2021 
Title 
Phase II randomized, observer-blind, placebo-
controlled, multi-country study in healthy non-pregnant 
women 18-45 years of age to evaluate the safety, 
reactogenicity and immunogenicity of a 1st 
intramuscular dose of GSK Biologicals’ investigational 
RSV maternal vaccine (GSK388550A) when given 
alone and given in co-administration with a single 
intramuscular dose of Boostrix (US formulation 
SB776423 or ex-US formulation SB263855) and to 
evaluate the safety, reactogenicity and immunogenicity 
of a 2nd dose of the RSV maternal vaccine. 
Short title 
A Phase II study of a primary dose of investigational 
RSV maternal vaccine, given alone or with Boostrix, 
with a 2nd dose investigational RSV maternal vaccine. 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
3 
Protocol Amendment 6 Sponsor Signatory Approval 
eTrack study number and 
Abbreviated Title 
209141(RSV MAT-011) 
IND number 
18434 
EudraCT number 
2019-002258-22 
Date of protocol amendment 
Amendment 6 Final: 9 April 2021 
Short Title 
A Phase II study of a primary dose of investigational 
RSV maternal vaccine, given alone or with Boostrix, 
with a 2nd dose of investigational RSV maternal 
vaccine. 
Sponsor signatory 
Joon Hyung Kim, Clinical Epidemiology Project 
Lead 
 
 
Signature 
 
 
 
Date 
 
 
 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
4 
Protocol Amendment 6 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline (GSK) Biologicals SA. 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.  
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study vaccine(s) 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 subject and/or the subject’s legally acceptable representative. 
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).  
• 
To co-operate with a representative of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine(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. 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
5 
Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
course of the study and for 1 year following completion of the study.  
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and other documents 
required by regulatory agencies for this study. 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
6 
eTrack study number and 
Abbreviated Title 
209141(RSV MAT-011) 
IND number  
18434 
EudraCT number 
2019-002258-22 
Date of protocol amendment 
Amendment 6 Final: 9 April 2021 
Short Title 
A Phase II study of a primary dose of investigational 
RSV maternal vaccine, given alone or with Boostrix, 
with a 2nd dose investigational RSV maternal vaccine. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
7 
SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA 
Rue de l’institut 89, 
1330 Rixensart, Belgium 
2. Sponsor Medical Expert for the Study 
Refer to the local study contact information document. 
3. Sponsor Study Monitor 
Refer to the local study contact information document. 
4. Sponsor Study Contact for Reporting of a Serious Adverse Event 
GSK Central Back-up Study Contact for Reporting SAEs: refer to protocol Section 
12.5.8.3  
Study Contact for Reporting SAEs: refer to the local study contact information 
document. 
5. GSK Central Safety Physician On-Call Contact information for Emergency 
Unblinding 
GSK Central Safety Physician and Back-up Phone contact: refer to protocol Section 
8.5.5.1. 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
8 
PROTOCOL AMENDMENT/ADMINISTRATIVE CHANGE 
SUMMARY OF CHANGES TABLE 
Table 1 
Document history 
Document 
Date 
Amendment 6 
9-APR-2021 
Amendment 5 
2-NOV-2020 
Amendment 4 
28-AUG-2020 
Amendment 3 
3-APR-2020 
Amendment 2 
23-JAN-2020 
Amendment 1 
21-OCT-2019 
Original Protocol 
23-AUG-2019 
Amendment 6: 9 April 2021 
Overall Rationale for Amendment 6:  
This study has been amended to include a clarification in the Exclusion criteria section to 
align with Protocol section 7.5.2 and reflect the flexibility of reducing the interval 
between administration of a coronavirus disease 2019 (COVID-19) vaccine and the RSV 
maternal vaccine. Also, several administrative changes in personnel and minor edits to 
the protocol are included. 
Table 2 
List of main changes in the protocol and their rationale 
Section # and Name 
Description of Change 
Brief Rationale 
Contributing Authors 
New SDL as added 
New personnel replaced 
previous personnel  
6.4.2 Prior/Concomitant therapy for extension 
Note added describing flexibility of 
reducing vaccination window in 
case COVID-19 mass vaccination    
To allow flexibility to allowed 
vaccination window in case 
of emergency mass 
vaccination on COVID-19 
pandemic 
8.3.2 Medical and vaccination history 
Medical history and concomitant 
medications will both be reported 
To align with rest of protocol  
8.5.5.1 Contact information for reporting of 
serious adverse events (SAEs), pregnancies 
and study holding rules 
New GSK Clinical Safety & 
Pharmacovigilance email address  
The email address recently 
changed and is updated here 
8.5.4 Reporting of serious adverse events, 
pregnancies, and other events 
Changed Pregnancy Reporting 
from 2 weeks to 24 hrs 
To align the protocol with the 
SOP for pregnancy reporting 
all new amendments should 
make this edit per the new 
templates 
12.5.8.4 Completion and transmission of 
pregnancy reports to GSK 
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CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
9 
TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 7 
PROTOCOL AMENDMENT/ADMINISTRATIVE CHANGE SUMMARY OF 
CHANGES TABLE ................................................................................................... 8 
1. 
SYNOPSIS ............................................................................................................. 16 
2. 
SCHEDULE OF ACTIVITIES (SOA) ....................................................................... 20 
3. 
INTRODUCTION .................................................................................................... 24 
3.1. 
Study rationale ............................................................................................ 24 
3.2. 
Background ................................................................................................ 25 
3.3. 
Benefit/Risk assessment ............................................................................. 25 
3.3.1. 
Risk assessment .......................................................................... 25 
3.3.2. 
Benefit assessment ..................................................................... 26 
3.3.3. 
Overall Benefit: Risk conclusion ................................................... 26 
4. 
OBJECTIVE(S) AND ENDPOINT(S) ...................................................................... 27 
5. 
STUDY DESIGN .................................................................................................... 29 
5.1. 
Scientific rationale for study design ............................................................. 29 
5.2. 
Overall design ............................................................................................. 30 
5.3. 
Number of subjects ..................................................................................... 35 
5.4. 
Subject and study completion ..................................................................... 35 
6. 
STUDY POPULATION ........................................................................................... 35 
6.1. 
Inclusion criteria for enrolment (primary study) ........................................... 35 
6.2. 
Exclusion criteria for enrolment (primary study) .......................................... 36 
6.2.1. 
Medical conditions ....................................................................... 36 
6.2.2. 
Prior/Concomitant therapy ........................................................... 37 
6.2.3. 
Prior/Concurrent clinical study experience ................................... 37 
6.2.4. 
Other exclusions .......................................................................... 38 
6.3. 
Inclusion criteria for study extension ........................................................... 38 
6.4. 
Exclusion criteria for extension ................................................................... 38 
6.4.1. 
Medical conditions for extension .................................................. 39 
6.4.2. 
Prior/Concomitant therapy for extension (Amended 09-
APR-2021) ................................................................................... 39 
6.4.3. 
Prior/Concurrent clinical study experience for extension .............. 40 
6.4.4. 
Other exclusions for extension ..................................................... 40 
6.5. 
Criteria for temporary delay for enrolment and vaccination ......................... 40 
6.6. 
Screen and baseline failures ....................................................................... 40 
6.7. 
Screen failures to the extension .................................................................. 41 
7. 
TREATMENTS ....................................................................................................... 41 
7.1. 
Treatments administered ............................................................................ 41 
7.2. 
Method of treatment assignment ................................................................. 44 
7.2.1. 
Subject identification .................................................................... 44 
7.2.1.1. 
Randomisation of supplies .......................................... 44 
7.2.1.2. 
Treatment allocation to the subject ............................. 44 
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209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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7.2.1.2.1. 
Study group and treatment 
number allocation ................................... 44 
7.3. 
Blinding and unblinding ............................................................................... 45 
7.3.1. 
Emergency unblinding ................................................................. 45 
7.4. 
Handling, storage and replacement of study vaccine(s)/product(s) ............. 47 
7.4.1. 
Storage and handling of study vaccine(s) .................................... 47 
7.4.2. 
Replacement of unusable vaccine(s) doses ................................. 47 
7.5. 
Concomitant medication(s)/product(s) and concomitant vaccinations ......... 48 
7.5.1. 
Recording of concomitant medications/products and 
concomitant vaccinations ............................................................. 48 
7.5.2. 
Concomitant medications/products/vaccines that may lead 
to the elimination of a subject from per-protocol analyses ............ 48 
7.6. 
Intercurrent medical conditions that may lead to elimination of a 
subject from per-protocol analyses ............................................................. 49 
7.7. 
Contraindications to subsequent vaccine(s) administration ......................... 49 
7.8. 
Warnings and precautions .......................................................................... 49 
7.9. 
Treatment after completion of the study ...................................................... 50 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 50 
8.1. 
Study Procedures During Special Circumstances ....................................... 50 
8.2. 
General study aspects ................................................................................ 52 
8.3. 
Pre-vaccination procedures ........................................................................ 52 
8.3.1. 
Collection of demographic data .................................................... 52 
8.3.2. 
Medical and vaccination history (Amended 09 APR 2021) ........... 52 
8.3.3. 
Physical examination ................................................................... 52 
8.3.4. 
Pregnancy test ............................................................................. 53 
8.3.5. 
Pre-vaccination body temperature ............................................... 53 
8.3.6. 
Pre-vaccination Vital Signs .......................................................... 53 
8.4. 
Immunogenicity assessments ..................................................................... 53 
8.4.1. 
Use of specified study materials .................................................. 54 
8.4.2. 
Biological samples ....................................................................... 54 
8.4.3. 
Laboratory assays ....................................................................... 55 
8.4.4. 
Biological samples evaluation ...................................................... 60 
8.4.4.1. 
Immunological read-outs ............................................ 60 
8.4.5. 
Immunological correlates of protection ......................................... 61 
8.4.5.1. 
RSV ............................................................................ 61 
8.4.5.2. 
Boostrix ...................................................................... 61 
8.5. 
Safety Assessments ................................................................................... 61 
8.5.1. 
Safety definitions ......................................................................... 61 
8.5.2. 
Time period and frequency for collecting AE and serious 
adverse event (SAE) information ................................................. 62 
8.5.3. 
Method of detecting AEs and SAEs ............................................. 64 
8.5.4. 
Reporting of serious adverse events, pregnancies, and 
other -events (Amended 09-APR-2021 ........................................ 64 
8.5.5. 
Post-study adverse events and serious adverse events ............... 64 
8.5.5.1. 
Contact information for reporting of serious 
adverse events (SAEs), pregnancies and study 
holding rules (Amended 09 APR 2021)....................... 65 
8.5.6. 
Follow-up of AEs and SAEs ......................................................... 65 
8.5.7. 
Treatment of adverse events ....................................................... 65 
8.5.8. 
Clinical safety laboratory assessments ........................................ 66 
8.5.9. 
Subject card ................................................................................. 66 
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209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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8.6. 
Holding rules and safety monitoring ............................................................ 66 
8.7. 
Genetic Research (Pharmacogenetics) ...................................................... 67 
8.8. 
Biomarkers and pharmacogenomics ........................................................... 67 
8.9. 
Economic assessment ................................................................................ 68 
8.9.1. 
Regulatory reporting requirements for SAEs ................................ 68 
9. 
DISCONTINUATION CRITERIA ............................................................................. 68 
9.1. 
Discontinuation from the study .................................................................... 68 
9.2. 
Discontinuation of study vaccine(s) ............................................................. 69 
9.3. 
Lost to follow-up.......................................................................................... 70 
10. STATISTICAL CONSIDERATIONS ........................................................................ 70 
10.1. 
Sample size determination .......................................................................... 70 
10.1.1. 
Hypotheses related to primary and secondary objectives ............ 70 
10.1.2. 
Sample size calculation ............................................................... 70 
10.2. 
Populations for analyses ............................................................................. 72 
10.3. 
Statistical analyses ..................................................................................... 73 
10.3.1. 
Subjects disposition ..................................................................... 73 
10.3.2. 
Demography and baseline characteristics analyses ..................... 73 
10.3.3. 
Immunogenicity analyses ............................................................. 73 
10.3.4. 
Safety analyses ........................................................................... 75 
10.4. 
Sequence of analyses................................................................................. 77 
11. REFERENCES ....................................................................................................... 78 
12. APPENDICES ........................................................................................................ 79 
12.1. 
Appendix 1: Abbreviations, glossary of terms and trademarks .................... 79 
12.1.1. 
List of abbreviations ..................................................................... 79 
12.1.2. 
Glossary of terms ......................................................................... 81 
12.1.3. 
Trademarks ................................................................................. 85 
12.2. 
Appendix 2: Clinical and safety laboratory tests .......................................... 86 
12.3. 
Appendix 3: Clinical laboratories ................................................................. 87 
12.4. 
Appendix 4: Study governance considerations ........................................... 88 
12.4.1. 
Regulatory and ethical considerations ......................................... 88 
12.4.2. 
Financial disclosure ..................................................................... 88 
12.4.3. 
Informed consent process ............................................................ 89 
12.4.4. 
Data protection ............................................................................ 89 
12.4.5. 
Committees structure ................................................................... 89 
12.4.6. 
Publication policy ......................................................................... 90 
12.4.7. 
Dissemination of clinical study data ............................................. 90 
12.4.8. 
Data quality assurance ................................................................ 91 
12.4.9. 
Source documents ....................................................................... 91 
12.4.10. Study and site closure.................................................................. 92 
12.5. 
Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting ............................................ 93 
12.5.1. 
Definition of AE ............................................................................ 93 
12.5.1.1. AE Definition............................................................... 93 
12.5.1.2. Events Meeting the AE Definition ............................... 93 
12.5.1.3. Events NOT Meeting the AE Definition ....................... 94 
12.5.2. 
Definition of SAE .......................................................................... 94 
12.5.3. 
Solicited adverse events .............................................................. 95 
12.5.4. 
Unsolicited adverse events .......................................................... 95 
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Protocol Amendment 6 Final 
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12 
12.5.5. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as adverse events or serious 
adverse events ............................................................................ 96 
12.5.6. 
Events or outcomes not qualifying as adverse events or 
serious adverse events ................................................................ 96 
12.5.6.1. Pregnancy .................................................................. 96 
12.5.7. 
Detecting and recording adverse events, serious adverse 
events and pregnancies ............................................................... 97 
12.5.7.1. Time period for detecting and recording 
adverse events, serious adverse events and 
pregnancies ................................................................ 97 
12.5.7.2. Evaluation of adverse events and serious 
adverse events ........................................................... 98 
12.5.7.2.1. Active questioning to detect 
adverse events and serious 
adverse events ....................................... 98 
12.5.7.2.2. Assessment of adverse events ............... 99 
12.5.7.2.3. Medically attended visits ....................... 101 
12.5.8. 
Reporting of serious adverse events, pregnancies, and 
other events ............................................................................... 102 
12.5.8.1. Prompt reporting of serious adverse events, 
pregnancies, and other events to GSK ..................... 102 
12.5.8.2. SAEs requiring expedited reporting to GSK .............. 102 
12.5.8.3. Back-up system in case the electronic 
reporting system does not work ................................ 102 
12.5.8.4. Completion and transmission of pregnancy 
reports to GSK (Amended 09-APR-2021) ................. 102 
12.5.9. 
Updating of SAE, pregnancy, information after removal of 
write access to the subject’s eCRF ............................................ 103 
12.5.10. Follow-up of adverse events, serious adverse events, and 
pregnancies ............................................................................... 103 
12.5.10.1. Follow-up during the study ........................................ 103 
12.5.10.2. Follow-up after the subject is discharged from 
the study ................................................................... 103 
12.5.10.3. Follow-up of pregnancies.......................................... 104 
12.6. 
Appendix 6: Contraceptive guidance and collection of pregnancy 
information ................................................................................................ 105 
12.6.1. 
Definitions .................................................................................. 105 
12.6.1.1. Woman of Childbearing Potential (WOCBP) ............. 105 
12.6.1.1.1. Women in the following categories 
are not considered WOCBP .................. 105 
12.6.2. 
Contraception guidance ............................................................. 105 
12.6.3. 
Collection of pregnancy information ........................................... 106 
12.6.3.1. Female Subjects who become pregnant ................... 106 
12.7. 
Appendix 7: Genetics ................................................................................ 107 
12.8. 
Appendix 8: Country-specific requirements ............................................... 107 
12.9. 
Appendix 9: Protocol Amendment/Administrative change History ............. 108 
 
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209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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13 
LIST OF TABLES 
PAGE 
Table 1 
Document history ..................................................................................... 8 
Table 2 
List of main changes in the protocol and their rationale ............................ 8 
Table 3 
Schedule of Activities ............................................................................. 20 
Table 4 
Intervals between study visits ................................................................. 24 
Table 5 
Study objectives and endpoints .............................................................. 27 
Table 6 
Study groups, treatment and epochs foreseen in the study .................... 34 
Table 7 
Treatments administered (Part 1) ........................................................... 41 
Table 8 
Treatments administered (Part 2) ........................................................... 43 
Table 9 
Contact information for emergency unblinding ....................................... 46 
Table 10 
Intervals between study visits under Special Circumstances .................. 51 
Table 11 
Biological samples ................................................................................. 55 
Table 12 
Humoral Immunity (Antibody determination) ........................................... 56 
Table 13 
Immunological read-outs ........................................................................ 60 
Table 14 
Reporting periods for collecting safety information ................................. 63 
Table 15 
Timeframes for submitting serious adverse event, pregnancy and 
other events reports to GSK ................................................................... 64 
Table 16 
Contact information for reporting of serious adverse events 
(SAEs), pregnancies and study holding rules ......................................... 65 
Table 17 
Study holding rules ................................................................................. 66 
Table 18 
Exact 95% confidence interval (CI) on the probability of a subject 
with AEs events following vaccination of 50 subjects per group, 
(100 subjects per group in US and ex-US combined) and 400 
subjects with RSVPreF3 groups combined ............................................. 71 
Table 19 
Precision and power in terms of RSV-A neutralizing antibody 
titers with a sample size of 100 subjects per group and 50 
subjects per group .................................................................................. 72 
Table 20 
Protocol-Required Safety Laboratory Assessments ............................... 86 
Table 21 
GSK laboratories, ................................................................................... 87 
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Table 22 
Outsourced laboratories ......................................................................... 87 
Table 23 
Solicited local adverse events ................................................................ 95 
Table 24 
Solicited general adverse events ............................................................ 95 
Table 25 
Intensity scales for solicited symptoms in adults and children of 6 
years of age or more .............................................................................. 99 
Table 26 
Highly Effective Contraceptive Methods ............................................... 106 
 
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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview ........................................................................... 30 
 
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1. 
SYNOPSIS 
Indication:  
Active immunization of pregnant women during the third trimester of pregnancy to 
prevent respiratory syncytial virus (RSV) - associated lower respiratory tract illness 
(LRTI) in infants by placental transfer of maternal antibodies. 
Rationale: 
GSK is developing an investigational RSV maternal vaccine (RSVPreF3) against RSV 
disease in infants through maternal immunization. In the RSV maternal program to date, 
a Phase 1/2 study (study RSV MAT-001; NCT 03674177) is ongoing in healthy non-
pregnant women 18-45 years of age (YOA) to determine the safety and immunogenicity 
of 3 dose levels of RSVPreF3 (30, 60 and 120µg) vaccine compared to placebo. 
Preliminary safety and immunogenicity information is available in the investigator 
brochure. 
In many countries, the use of acellular pertussis vaccination is recommended for women 
during pregnancy to protect young infants against pertussis before they can benefit from 
the infant vaccination series [Mazzilli, 2018]. Boostrix, a vaccine against diphtheria, 
tetanus and acellular pertussis is administered in the third trimester of pregnancy in many 
countries. Since RSVPreF3 is intended for administration in the third trimester of 
pregnancy, it will be important to evaluate any potential interference of co-administration 
with Boostrix.  
This study (RSV MAT-011), in healthy non-pregnant women, will be the first to evaluate 
co-administration of 2 dose levels of RSVPreF3 with Boostrix (dTpa). Selection of the 60 
and 120µg RSVPreF3 doses was based on preliminary results of the ongoing (RSV MAT 
001) Phase 1 / 2 study. 
Two formulations of dTpa vaccine, each containing either 300 micrograms or 500 
micrograms of aluminum are licensed in the US and outside the US (ex-US), 
respectively. As such, the Boostrix (US formulation) (dTpa_300) will be administered to 
subjects in centers located in the US, while the Boostrix (ex-US formulation) (dTpa_500) 
will be administered to subjects in centers ex-US [Christy, 1995]. In previous studies 
both, Boostrix formulations have had a similar immunogenicity and safety profiles. 
Therefore, any potential differences in immune response to Boostrix in this study may be 
the result of population differences or immune response in the setting of RSVPreF3 co-
administration [Theeten, 2005; Melville-Smith, 1983]. 
This will be a Phase II study to evaluate safety and reactogenicity of co-administration of 
RSVPreF3 and dTpa_300 or dTpa_500 in non-pregnant women 18-45 YOA. 
Additionally, this study will evaluate whether co-administration of dTpa affects the 
magnitude of the immune response to RSVPreF3 and whether RSVPreF3 affects the 
magnitude of the immune response to dTpa.  
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For those who provide consent, the durability of the response to RSVPreF3 will be 
measured from 12 to 18 months following initial vaccination. In addition, a second 
immunization with the RSV Maternal (120µg) vaccine will be administered from 12 
months to 18 months after the first vaccination to evaluate the immunogenicity and safety 
profile of RSVPreF3 vaccine second dose.  
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary (US + ex-US data to be pooled) 
Safety 
• 
To evaluate the safety and reactogenicity of 2 dose 
levels (60 and 120 µg) of RSVPreF3 when given 
alone or co-administered with dTpa from 
Vaccination up to Day 31.  
Safety 
• 
Occurrence of any Adverse Events (AEs) from 
Vaccination to Day 31:  
− 
Occurrence of each solicited local AEs at the 
site of injection in both limbs from Vaccination 
to Day 8; 
− 
Occurrence of solicited general AEs from 
Vaccination to Day 8; 
− 
Occurrence of any unsolicited AEs from 
Vaccination to Day 31;  
− 
Occurrence of Serious Adverse Events (SAEs) 
from Vaccination to Day 31.  
• 
To evaluate the safety of a 2nd dose of RSVPreF3 
given from 12 up to18 months post 1st Dose up to 
Day 31 days post 2nd dose vaccination 
• 
Occurrence of any AEs from 2nd dose to Day 31 
post-2nd dose vaccination, for all subjects:  
• 
Occurrence of each solicited local AE at the site of 
injection in both deltoids from 2nd dose vaccination 
to Day 8 post-2nd dose vaccination 
• 
Occurrence of solicited general AEs from 2nd dose 
vaccination to Day 8 post 2nd dose vaccination 
• 
Occurrence of any unsolicited AEs from 2nd dose to 
Day 31 post- 2nd dose vaccination 
• 
Occurrence of Serious Adverse Events (SAEs) from 
2nd dose vaccination to Day 31 post 2nd dose 
vaccination. 
Immunogenicity 
• 
To evaluate the humoral immune response to 2 
dose levels (60 and 120 µg) of RSVPreF3 when 
given alone and co-administered with dTpa, at 
Screening, Day 8 and Day 31 post 1st dose 
vaccination 
Immunogenicity 
• 
RSV A neutralizing antibody titers at Screening, 
Day 8 and Day 31 in all groups  
• 
RSV IgG antibody concentrations at Screening, Day 
8 and Day 31. 
Secondary (US and ex-US data to be considered pooled, then separately) 
Safety 
• 
To evaluate the safety and reactogenicity of 2 dose 
levels (60 and 120 µg) of RSVPreF3 when given 
alone or co-administered with dTpa from 1st dose 
vaccination up to Day 31 by formulation.  
Safety 
• 
Occurrence of any AEs from Vaccination to Day 31, 
for all subjects:  
− 
Occurrence of each solicited local AE at the 
site of injection in both limbs from Vaccination 
to Day 8 
− 
Occurrence of solicited general AEs from 
Vaccination to Day 8 
− 
Occurrence of any unsolicited AEs from 
Vaccination to Day 31  
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Objectives 
Endpoints 
• 
Occurrence of Serious Adverse Events (SAEs) from 
Vaccination to Day 31.  
• 
To evaluate the safety of 2 dose levels (60 and 
120 µg) of RSVPreF3 when given alone and co-
administered with dTpa compared to dTpa-Placebo 
groups from 1st dose vaccination up to Day 181. 
• 
Occurrence of SAEs from Vaccination up to Day 
181. 
• 
To evaluate the safety of 2 dose levels (60 and 
120 µg) of RSVPreF3 when given alone and co-
administered from Vaccination up to Day 181 by 
formulation. 
• 
Occurrence of SAEs from Vaccination up to Day 
181.  
• 
To evaluate the safety of RSVPreF3 (pooled for all 
groups receiving RSVPreF3) for the 1st dose 
vaccination. 
• 
Occurrence of SAEs from Vaccination up to Day 
181. 
• 
To evaluate the safety of 2nd dose of RSVPreF3 
given from 12 to up to 18 months post 1st dose 
vaccination up to Day 181 post 2nd dose vaccination. 
• 
Occurrence of SAEs from 2nd dose vaccination up to 
Day 181 post-2nd dose vaccination. 
Immunogenicity 
• 
To evaluate the humoral immune response and 
persistence to 2 dose levels (60 and 120 µg) of 
RSVPreF3 when given alone and co-administered 
with dTpa at Screening, Day 8, and Day 31 post 1st 
dose vaccination, and at 12 to 18 months by 
formulation. 
Immunogenicity 
• 
RSV A neutralizing antibody titers at Screening, Day 
8, Day 31, and a single timepoint between 12 to 18 
months post 1st vaccination. 
• 
RSV IgG antibody concentrations at Screening, Day 
8, Day 31, and a single timepoint between 12 to 18 
months post 1st vaccination. 
• 
To evaluate the humoral immune response to the 
pertussis component of the dTpa vaccine when 
given alone and co-administered with 2 dose levels 
(60 and 120 µg) of RSVPreF3 at Screening and Day 
31 post 1st dose vaccination by formulation.  
• 
Antibody concentrations against pertussis toxoid 
(anti-PT), filamentous hemagglutinin (anti-FHA), and 
pertactin (anti-PRN) concentrations at Screening 
and Day 31. 
• 
To evaluate the humoral immune response to the 
diphtheria (D) component of dTpa vaccine when 
given alone and co-administered with 2 dose levels 
(60 and 120 µg) of RSVPreF3 at Screening and Day 
31 post 1st dose vaccination by formulation. 
• 
Anti-D concentrations at Screening and Day 31. 
• 
To evaluate the humoral immune response to the 
tetanus (T) component of dTpa vaccine when given 
alone and co-administered with 2 dose levels (60 
and 120 µg) of RSVPreF3 at Screening and Day 31 
post 1st dose vaccination by formulation. 
• 
Anti-T concentrations at Screening and Day 31. 
• 
To evaluate the humoral immune response of a 2nd 
dose vaccination of RSVPreF3 (120 µg), following a 
first dose vaccination of either 60 µg or 120 µg.  
• 
RSV A neutralizing antibody titers concentrations 31 
days post 2nd dose vaccination. 
• 
RSV IgG antibody concentrations 31 days post 2nd 
dose vaccination. 
Tertiary 
If necessary, additional testing to further characterize the response to the RSV maternal investigational vaccine will 
be performed.  
 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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Note: study groups labeled X = ex-US; study groups labeled U = US. V = visit, C = phone contact 
= Vaccination; N = number of subjects; V = Visit; D = Day; AE = adverse event; UP = Urine pregnancy test;  
CHS = Chemical/Hematological Screening, FU = follow-up 
BSH = blood sample (5 mL) for humoral immune responses (RSV-A neutralization and RSV IgG antibody concentrations at Screening, Visit 2, [Day 8] Visit 3, [Day 31], Visit 4, [up to 
D7 prior to 2nd vaccination], and Visit 6 [D31 post 2nd vaccination] 
dTpa ELISAs at Screening and Visit 3 [Day 31])  
* All subject groups will be given RSV 120mcg and subjects will be followed in an open labeled study 
** Hematological and biochemical laboratory testing at Visit 4 (D -7 up to and including 2nd dose vaccination) at the investigator’s discretion  
***There will be no follow-up between C1 and V4. New medical history and relevant new safety events during this period will be recorded at visit 4 for subjects who agree to the study 
extension and sign the informed consent addendum. 
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CONFIDENTIAL 
209141 (RSV MAT-011) 
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2. 
SCHEDULE OF ACTIVITIES (SOA) 
Table 3 
Schedule of Activities  
Epoch 
Epoch 001 
Epoch 002  
(Vaccination 1) 
Epoch 
003  
(Follow-
up 1) 
 
Epoch 004  
(Vaccination 2) 
Epoch 005 
(Follow-up 2) 
Type of contact 
Screening Visit 
1 
Visit 2 Visit 3 Phone 
Contact 1 
 
Visit 4 
Visit 5 
Phone 
Contact 2 
Visit 6 
Phone 
Contact 3 
Time points 
Day -7 to 
Day 1 
Day 
1 
Day 8 Day 
31 
Day 181  
Day 181 to -7 
before 2nd 
vaccination 
Day -7 to Day 
of 2nd 
vaccination 
 
From 12 up to 18 
months post 1st 
vaccination 
Day 8 post 2nd 
vaccination 
 
Day 31 post 
2nd 
vaccination 
Day 181 post 
2nd 
vaccination 
 
Sampling time points 
Pre-Vacc 1 Vacc 
1 
Post-
Vacc 
1 
Post-
Vacc 
1 
Post-
Vacc 1 
Pre-Vacc 2 
Pre-Vacc 2 
Vacc 2 
Post-Vacc 2 
Post-Vacc 2 
Post-Vacc 2 
Informed consent  
● 
 
 
 
 
 
● 
 
 
 
 
Assign subject number  
● 
 
 
 
 
 
 
 
 
 
 
Check inclusion/exclusion 
criteria  
● 
O 
 
 
 
 
● 
 
 
 
 
Check contraindications to 
subsequent vaccine(s) 
administration  
 
 
 
 
 
 
O 
O 
 
 
 
Phone contact 
 
 
 
 
● 
 
 
 
● 
 
● 
Collect demographic data  
●1 
 
 
 
 
 
 
 
 
 
 
Medical history  
O 
● 
 
 
 
 
●  
 
 
 
 
Physical examination 2  
● 
● 
● 
O 
 
 
● 
 
 
O 
 
Urine pregnancy test 3  
● 
● 
 
 
 
 
 
● 
 
 
 
Pre-vaccination body 
temperature and heart rate 
 
● 
 
 
 
 
 
 
 
 
 
Pre-vaccination vital sign 
readings4 
 
 
 
 
 
 
 
● 
 
 
 
Distribution of subject card 
 
O 
 
 
 
 
 
O 
 
 
 
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Epoch 
Epoch 001 
Epoch 002  
(Vaccination 1) 
Epoch 
003  
(Follow-
up 1) 
 
Epoch 004  
(Vaccination 2) 
Epoch 005 
(Follow-up 2) 
Type of contact 
Screening Visit 
1 
Visit 2 Visit 3 Phone 
Contact 1 
 
Visit 4 
Visit 5 
Phone 
Contact 2 
Visit 6 
Phone 
Contact 3 
Time points 
Day -7 to 
Day 1 
Day 
1 
Day 8 Day 
31 
Day 181  
Day 181 to -7 
before 2nd 
vaccination 
Day -7 to Day 
of 2nd 
vaccination 
 
From 12 up to 18 
months post 1st 
vaccination 
Day 8 post 2nd 
vaccination 
 
Day 31 post 
2nd 
vaccination 
Day 181 post 
2nd 
vaccination 
 
Sampling time points 
Pre-Vacc 1 Vacc 
1 
Post-
Vacc 
1 
Post-
Vacc 
1 
Post-
Vacc 1 
Pre-Vacc 2 
Pre-Vacc 2 
Vacc 2 
Post-Vacc 2 
Post-Vacc 2 
Post-Vacc 2 
Hematological and biochemical 
laboratory testing (~5.5 mL) 
O 
 
 
 
 
 
O9 
 
 
 
 
Blood sampling for humoral 
immune response (~5 mL) 5 
● 
 
● 
● 
 
 
● 
 
 
● 
 
Study group and treatment 
number allocation (SBIR)  
 
O 
 
 
 
 
 
 
 
 
 
Treatment number allocation 
(SBIR) 
 
 
 
 
 
 
 
O 
 
 
 
Vaccine administration  
 
● 
 
 
 
 
 
● 
 
 
 
Recording of administered 
treatment number  
 
● 
 
 
 
 
 
● 
 
 
 
60 minutes post vaccination 
observation period  
 
O 
 
 
 
 
 
O 
 
 
 
Training on use of diary cards  
 
O 
O 
 
 
 
 
O 
 
 
 
Distribution of diary cards6  
 
O 
O 
 
 
 
 
O 
 
 
 
Collection of diary cards  
 
 
O 
O 
 
 
 
 
 
O 
 
Diary card transcription by 
investigator or designate 
 
 
● 
● 
 
 
 
 
 
● 
 
Recording of solicited adverse 
events  
 
● 
● 
 
 
 
 
● 
● 
 
 
Recording of unsolicited adverse 
events  
 
● 
● 
● 
 
 
 
● 
● 
● 
 
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Epoch 
Epoch 001 
Epoch 002  
(Vaccination 1) 
Epoch 
003  
(Follow-
up 1) 
 
Epoch 004  
(Vaccination 2) 
Epoch 005 
(Follow-up 2) 
Type of contact 
Screening Visit 
1 
Visit 2 Visit 3 Phone 
Contact 1 
 
Visit 4 
Visit 5 
Phone 
Contact 2 
Visit 6 
Phone 
Contact 3 
Time points 
Day -7 to 
Day 1 
Day 
1 
Day 8 Day 
31 
Day 181  
Day 181 to -7 
before 2nd 
vaccination 
Day -7 to Day 
of 2nd 
vaccination 
 
From 12 up to 18 
months post 1st 
vaccination 
Day 8 post 2nd 
vaccination 
 
Day 31 post 
2nd 
vaccination 
Day 181 post 
2nd 
vaccination 
 
Sampling time points 
Pre-Vacc 1 Vacc 
1 
Post-
Vacc 
1 
Post-
Vacc 
1 
Post-
Vacc 1 
Pre-Vacc 2 
Pre-Vacc 2 
Vacc 2 
Post-Vacc 2 
Post-Vacc 2 
Post-Vacc 2 
Recording of AE leading to 
withdrawal 
 
● 
● 
● 
● 
 
 
● 
● 
● 
● 
Recording of serious AE 7 
● 
● 
● 
● 
● 
 
● 
● 
● 
● 
● 
Recording of pregnancies  
 
● 
● 
● 
● 
 
● 
● 
● 
● 
● 
Recording of concomitant 
medications/vaccinations8 
 
● 
● 
● 
● 
 
● 
● 
● 
● 
● 
Record any intercurrent medical 
conditions  
 
 
● 
● 
● 
 
● 
● 
● 
● 
● 
Screening conclusion  
● 
 
 
 
 
 
 
 
 
 
 
Investigator sign-off on eCRF 
before analysis 
● 
 
 
● 
● 
 
 
 
 
● 
● 
COVID-19 eCRFs log page 
 
 
 
 
 
 
● 
● 
● 
● 
● 
Study conclusion primary study 
 
 
 
 
● 
 
 
 
 
 
 
Study conclusion extension  
 
 
 
 
 
 
 
 
 
 
● 
Vacc: vaccination 
● 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 subject not of childbearing potential, the specific reason should be 
documented in the eCRF) (see Section 12.6.1.1.1 for more detail). 
2 Physical examination including resting vital signs (blood pressure, heart rate and respiratory rate, temperature) measured after at least 10 minutes of rest.  
Screening: Physical exam, vital signs (blood pressure, heart rate and respiratory rate, temperature), and weight, height and BMI will be recorded in the eCRF.  
Visit 1: History directed physical exam will be performed and the vital signs will be recorded in the eCRF 
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Visit 2 Physical examination will be performed only if deemed necessary by the investigator.  If performed, only vital signs (blood pressure, heart rate and respiratory rate) will be 
required recorded in the eCRF 
Visit 3: Physical examination will be performed only if deemed necessary by the investigator.   
Visit 4: Perform history directed physical exam will be performed and vital signs (blood pressure, heart rate and respiratory rate, temperature) will be recorded in the eCRF. Weight, 
height and BMI should also be recorded in the eCRF.  
Visit 6: Physical examination will be performed only if deemed necessary by the investigator.   
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. 
4Pre-vaccination vital signs: At Visit 5, the pre-vaccination vital signs (blood pressure, heart rate and respiratory rate, temperature) will be recorded in the eCRF 
5 Sub-groups, Method, cut-off, and laboratory locations will be defined in Section 8.4.3. 
6 Primary Vaccination: The diary card will be distributed at the day of vaccination and will be used for recording solicited and unsolicited AEs, and concomitant medications/products on 
the day of vaccination and for 6 subsequent days and for recording unsolicited AEs and concomitant medications/products and vaccinations from Day 8 to Day 31.  
Second Vaccination: The diary card will be distributed at the day of vaccination and will be used for recording solicited and unsolicited AEs, and concomitant medications/products on 
the day of vaccination and for 6 subsequent days and for recording unsolicited AEs and concomitant medications/products and vaccinations from Day 8 to Day 31. 
7. For Screening and Visit 1 (prior to study vaccine administration), only those SAEs that are considered related to study participation need to be recorded.  
8 Recording of Concomitant medications/vaccinations/products will be described in Section 7.5 
9 Hematological and biochemical laboratory testing at Visit 4 (D -7 up to and including 2nd dose vaccination) at the investigator’s discretion 
 
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Whenever possible, the investigator should arrange study visits within the intervals 
described in Table 4. 
Table 4 
Intervals between study visits  
Interval 
Optimal timing  
Allowed interval 
Screening Visit→ Visit 1  
≤7 days  
-7 - 1 days* 
Visit 1 → Visit 2  
8 days  
7 - 10 days  
Visit 1 → Visit 3  
31 days 
30 - 45 days  
Visit 1 → Phone Contact 1 
181 days 
165 - 195 days  
Visit 4 →Visit 5 
≤7 days 
-7 to 1 days* 
Visit 1 → Visit 5 
365 days 
365 - 548 days** 
Visit 5 → Phone Contact 2 
8 days  
7 - 10 days  
Visit 5 → Visit 6 
31 days 
30 - 45 days  
Visit 5 → Phone Contact 3 
181 days 
165 - 195 days  
*From 7 days prior to vaccination up to and including the day of vaccination. 
** For a 6-month period ≥12 to <18 months post 1st vaccination 
3. 
INTRODUCTION 
3.1. 
Study rationale 
GSK is developing an investigational RSV maternal vaccine (RSVPreF3) against RSV 
disease in infants through maternal immunization. In the RSV maternal program to date, 
a Phase 1/2 study (study RSV MAT-001; NCT 03674177) is ongoing in healthy non-
pregnant women 18-45 years of age (YOA) to determine the safety and immunogenicity 
of 3 dose levels of RSVPreF3 (30, 60 and 120 µg) compared to placebo. Preliminary 
safety information is available in the investigator brochure. 
In many countries, the use of acellular pertussis vaccination is recommended for women 
during pregnancy to protect young infants against pertussis before they can benefit from 
the infant vaccination series [Mazzilli, 2018]. Boostrix, a vaccine against diphtheria, 
tetanus and acellular pertussis is administered in the third trimester of pregnancy in many 
countries. Since RSVPreF3 is intended for administration in the third trimester of 
pregnancy, it will be important to evaluate any potential interference of co-administration 
with Boostrix.  
This study (RSV MAT-011), in healthy non-pregnant women, will be the first to evaluate 
co-administration of RSVPreF3 with Boostrix (dTpa). Selection of the 60 and 120g 
RSVPreF3 doses was based on preliminary results of the ongoing (RSV MAT 001) Phase 
1/2 study.  
Two formulations of dTpa vaccine, one containing 300 micrograms and the other 
containing 500 micrograms of aluminum are licensed in the US and outside the US (ex-
US), respectively. As such, the Boostrix (US formulation) (dTpa_300) will be 
administered to subjects in centers located in the US, while the Boostrix (ex-US 
formulation) (dTpa_500) will be administered to subjects in centers ex-US. In previous 
studies both, Boostrix formulations have had a similar immunogenicity and safety 
profiles. Therefore, any potential differences in immune response to Boostrix in this study 
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may be the result of population differences or immune response in the setting of 
RSVPreF3 co-administration [Theeten, 2005]. 
This will be a Phase II study to evaluate safety and reactogenicity of co-administration of 
RSVPreF3 and dTpa_300 or dTpa_500 in non-pregnant women 18-45 YOA. 
Additionally, this study will evaluate whether co-administration of dTpa affects the 
magnitude of the immune response to RSVPreF3 and whether RSVPreF3 affects the 
magnitude of the immune response to dTpa. 
Finally, a second dose vaccination of RSVPreF3 (120 µg) will be administered to the 
consenting subjects from 12 to 18 months following initial vaccination to evaluate the 
immunogenicity and safety profile of RSVPreF3. This extension of the study will recruit 
the same non-pregnant women as a proxy for women who may require additional dosing 
in successive pregnancies.  
3.2. 
Background 
Please refer to the current Investigator Brochure for information regarding the pre-
clinical and clinical studies of the RSV maternal (RSVPreF3) vaccine and background 
information pertaining to maternal immunization and RSV infection. 
3.3. 
Benefit/Risk assessment 
Please refer to the current Investigator Brochure for the summary of potential risks and 
benefits of the RSV maternal (RSVPreF3) vaccine. 
Please refer to the local Prescribing Information for information regarding the summary 
of potential risks and benefits of Boostrix. 
3.3.1. 
Risk assessment 
The investigational RSV maternal (RSVPreF3) vaccine is in an early stage of clinical 
development. This is the first time that the RSV maternal (RSVPreF3) and Boostrix 
vaccines will be co-administered. 
Based on the following data, there are currently no known important risks associated with 
the investigational RSV maternal (RSVPreF3) vaccine or its co-administration with 
Boostrix that preclude further development: 
• 
Extensive prior experience with Boostrix administered alone. 
• 
Results of non-clinical studies of the RSV maternal (RSVPreF3) vaccine given alone 
and co-administered with Boostrix. 
• 
Available safety data from an ongoing Phase I/II study of the RSV maternal 
(RSVPreF3) vaccine administered alone. 
All 500 enrolled subjects will remain under observation at the vaccination center for at 
least 60 minutes after vaccination. 
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3.3.2. 
Benefit assessment 
Subjects may or may not benefit from receiving the investigational RSV maternal vaccine 
and / or Boostrix. The efficacy of the RSV maternal vaccine has not yet been evaluated. 
Subjects who receive Boostrix may have the benefit of being protected against diphtheria, 
tetanus and pertussis diseases [Mazzilli, 2018]. However, the effects of administering 
Boostrix together with the RSV maternal vaccine are unknown.  
At the time of screening, the investigator will review the potential participant dTpa 
vaccination history. All women who are not up-to-date with dTpa vaccine based on local 
recommendations will be informed of their options: 
1. to participate in the trial and potentially be randomized to receive a dose of Boostrix 
or  
2. to opt out of the study. 
Of these women, those who chose to participate and did not receive Boostrix as part of 
the trial, will counselled on their options to receive the vaccine at the time of unblinding.  
3.3.3. 
Overall Benefit: Risk conclusion 
The balance of anticipated benefits and apparent risks associated with the RSV maternal 
(RSVPreF3) vaccine, with Boostrix, and with co-administration of the RSV maternal 
(RSVPreF3) vaccine and Boostrix continues to be acceptable following the ongoing 
systematic review of safety data. 
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209141 (RSV MAT-011) 
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27 
4. 
OBJECTIVE(S) AND ENDPOINT(S) 
Table 5 
Study objectives and endpoints  
Objectives 
Endpoints 
Primary (US + ex-US data to be pooled) 
Safety 
• 
To evaluate the safety and reactogenicity of 2 dose 
levels (60 and 120 µg) of RSVPreF3 when given 
alone or co-administered with dTpa from 
Vaccination up to Day 31.  
Safety 
• 
Occurrence of any Adverse Events (AEs) from 
Vaccination to Day 31:  
− 
Occurrence of each solicited local AEs at the 
site of injection in both limbs from Vaccination 
to Day 8; 
− 
Occurrence of solicited general AEs from 
Vaccination to Day 8; 
− 
Occurrence of any unsolicited AEs from 
Vaccination to Day 31;  
− 
Occurrence of Serious Adverse Events (SAEs) 
from Vaccination to Day 31.  
• 
To evaluate the safety of a 2nd dose of RSVPreF3 
given from 12 up to18 months post 1st Dose up to 
Day 31 days post 2nd dose vaccination 
• 
Occurrence of any AEs from 2nd dose to Day 31 
post-2nd dose vaccination, for all subjects:  
• 
Occurrence of each solicited local AE at the site of 
injection in both deltoids from 2nd dose vaccination 
to Day 8 post-2nd dose vaccination 
• 
Occurrence of solicited general AEs from 2nd dose 
vaccination to Day 8 post 2nd dose vaccination 
• 
Occurrence of any unsolicited AEs from 2nd dose to 
Day 31 post- 2nd dose vaccination 
• 
Occurrence of Serious Adverse Events (SAEs) from 
2nd dose vaccination to Day 31 post 2nd dose 
vaccination. 
Immunogenicity 
• 
To evaluate the humoral immune response to 2 
dose levels (60 and 120 µg) of RSVPreF3 when 
given alone and co-administered with dTpa, at 
Screening, Day 8 and Day 31 post 1st dose 
vaccination 
Immunogenicity 
• 
RSV A neutralizing antibody titers at Screening, 
Day 8 and Day 31 in all groups  
• 
RSV IgG antibody concentrations at Screening, Day 
8 and Day 31. 
Secondary (US and ex-US data to be considered pooled, then separately) 
Safety 
• 
To evaluate the safety and reactogenicity of 2 dose 
levels (60 and 120 µg) of RSVPreF3 when given 
alone or co-administered with dTpa from 1st dose 
vaccination up to Day 31 by formulation.  
Safety 
• 
Occurrence of any AEs from Vaccination to Day 31, 
for all subjects:  
− 
Occurrence of each solicited local AE at the 
site of injection in both limbs from Vaccination 
to Day 8 
− 
Occurrence of solicited general AEs from 
Vaccination to Day 8 
− 
Occurrence of any unsolicited AEs from 
Vaccination to Day 31  
− 
Occurrence of Serious Adverse Events (SAEs) 
from Vaccination to Day 31.  
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209141 (RSV MAT-011) 
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Objectives 
Endpoints 
• 
To evaluate the safety of 2 dose levels (60 and 
120 µg) of RSVPreF3 when given alone and co-
administered with dTpa compared to dTpa-Placebo 
groups from 1st dose vaccination up to Day 181. 
• 
Occurrence of SAEs from Vaccination up to Day 
181. 
• 
To evaluate the safety of 2 dose levels (60 and 
120 µg) of RSVPreF3 when given alone and co-
administered from Vaccination up to Day 181 by 
formulation. 
• 
Occurrence of SAEs from Vaccination up to Day 
181.  
• 
To evaluate the safety of RSVPreF3 (pooled for all 
groups receiving RSVPreF3) for the 1st dose 
vaccination. 
• 
Occurrence of SAEs from Vaccination up to Day 
181. 
• 
To evaluate the safety of 2nd dose of RSVPreF3 
given from 12 to up to 18 months post 1st dose 
vaccination up to Day 181 post 2nd dose vaccination. 
• 
Occurrence of SAEs from 2nd dose vaccination up to 
Day 181 post-2nd dose vaccination. 
Immunogenicity 
• 
To evaluate the humoral immune response and 
persistence to 2 dose levels (60 and 120 µg) of 
RSVPreF3 when given alone and co-administered 
with dTpa at Screening, Day 8, and Day 31 post 1st 
dose vaccination, and at 12 to 18 months by 
formulation. 
Immunogenicity 
• 
RSV A neutralizing antibody titers at Screening, Day 
8, Day 31, and a single timepoint between 12 to 18 
months post 1st vaccination. 
• 
RSV IgG antibody concentrations at Screening, Day 
8, Day 31, and a single timepoint between 12 to 18 
months post 1st vaccination. 
• 
To evaluate the humoral immune response to the 
pertussis component of the dTpa vaccine when 
given alone and co-administered with 2 dose levels 
(60 and 120 µg) of RSVPreF3 at Screening and Day 
31 post 1st dose vaccination by formulation.  
• 
Antibody concentrations against pertussis toxoid 
(anti-PT), filamentous hemagglutinin (anti-FHA), and 
pertactin (anti-PRN) concentrations at Screening 
and Day 31. 
• 
To evaluate the humoral immune response to the 
diphtheria (D) component of dTpa vaccine when 
given alone and co-administered with 2 dose levels 
(60 and 120 µg) of RSVPreF3 at Screening and Day 
31 post 1st dose vaccination by formulation. 
• 
Anti-D concentrations at Screening and Day 31. 
• 
To evaluate the humoral immune response to the 
tetanus (T) component of dTpa vaccine when given 
alone and co-administered with 2 dose levels (60 
and 120 µg) of RSVPreF3 at Screening and Day 31 
post 1st dose vaccination by formulation. 
• 
Anti-T concentrations at Screening and Day 31. 
• 
To evaluate the humoral immune response of a 2nd 
dose vaccination of RSVPreF3 (120 µg), following a 
first dose vaccination of either 60 µg or 120 µg.  
• 
RSV A neutralizing antibody titers concentrations 31 
days post 2nd dose vaccination. 
• 
RSV IgG antibody concentrations 31 days post 2nd 
dose vaccination. 
Tertiary 
If necessary, additional testing to further characterize the response to the RSV maternal investigational vaccine will 
be performed.  
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5. 
STUDY DESIGN 
5.1. 
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 LRTI through maternal immunisation. This study will 
evaluate the safety and immunogenicity of the RSVPreF3 vaccine when it is co-
administered with Boostrix in healthy non-pregnant women aged 18 to 45 years old. Two 
dose levels of RSVPreF3 will be evaluated in order to optimally select the dose level for 
further development. Two formulations of Boostrix, one containing 300 
micrograms (dTpa_300) and the other containing 500 micrograms (dTpa_500) of 
aluminum are licensed in the US and outside the US (ex-US), respectively. The 
difference between the two formulations being the level of aluminium adjuvant. Both 
formulations will be studied. 
Approximately 500 women will be randomised to 5 equal study groups corresponding to 
the two dose levels of RSVPreF3 given with and without co-administration of Boostrix 
and a comparator group receiving Boostrix plus a placebo. To facilitate decision making 
in the clinical development plan the primary analysis will take place at day 31. The 
primary objectives compare the safety and the immune response to RSVPreF3, 31 days 
after vaccination in the five pooled study groups. The sample size of 100 subjects per 
group in the combined formulations is planned to provide reasonable confidence to 
evaluate the AE rate and quantify immunogenicity interference. If an AE is not observed 
in a given treatment group, then this sample size provides at least 95% confidence to rule 
out an AE rate greater than 3.6% and there will be at least 90% power to claim non- 
inferiority with a margin of 1.5 between RSVPreF3 alone and RSVPreF3 in co-
administration with Boostrix. 
By enrolling approximately half the subjects in the US and half outside the US, as 
secondary objectives the effect of co-administration of RSVPreF3 data will be collected 
on both commercial Boostrix formulations. While secondary analyses will be described 
by formulation, differences between the US and ex-US formulations could be explained 
by ethnic and environmental differences. Specified secondary endpoints will be described 
pooled across all subjects or by formulation. 
Finally, a second dose vaccination of RSVPreF3 will be administered to consenting 
subjects from 12 months to 18 months following 1st vaccination to evaluate the 
immunogenicity and safety profile of RSVPreF3. The intention of this study extension is 
to assess the durability of the immune response after the first dose vaccination, and to 
assess the safety and immunogenicity following a second dose vaccination of the 
RSVPreF3 maternal vaccine. This extension of the study will recruit the same non-
pregnant women as a proxy for women who may require additional dosing in successive 
pregnancies.  
 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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CHS = Chemical/Hematological Screening, FU = follow-up 
BSH = blood sample (5 mL) for humoral immune responses (RSV-A neutralization and RSV IgG antibody concentrations at Screening, Visit 2, [Day 8] Visit 3, [Day 31], Visit 4, [up to 
D7 prior to 2nd vaccination], and Visit 6 [D31 post 2nd vaccination] 
dTpa ELISAs at Screening and Visit 3 [Day 31])  
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CONFIDENTIAL 
209141 (RSV MAT-011) 
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31 
*All subject groups will be given RSV 120mcg and subjects will be followed in an unblinded open label manner 
** Hematological and biochemical laboratory testing at Visit 4 (D -7 up to and including 2nd dose vaccination) at the investigator’s discretion  
*** There will be no follow-up between C1 and V4. New medical history and relevant new safety events during this period will be recorded at visit 4 for subjects who agree to the study 
extension and sign the informed consent addendum. 
 
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The study will be conducted with 2 formulations of dTpa, dTpa_300 (in the US) and 
dTpa_500 (ex-US). 
Approximately 500 eligible subjects (250 in the US and 250 ex-US) will be enrolled. Of 
these, approximately 250 subjects will be randomized to 5 US study groups in a 1:1:1:1:1 
ratio using SBIR, and the remaining approximately 250 will be randomized to 5 ex-US 
study groups in a 1:1:1:1:1 ratio using SBIR. The randomization algorithm will use a 
minimization procedure by treating study formulation (US and ex-US) as a stratification 
factor, and age at the time of vaccination (18-32 or 33-45 years of age) and center as 
minimization factors. 
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. Therefore, adherence to the study design requirements, 
including those specified in the schedule of activities (Section 2), are essential and 
required for study conduct. 
• 
Type of study: self-contained 
• 
Experimental design:  
− 
Primary Vaccination: multi-centric study, multi-country Phase II, observer-
blind, randomized, with 5 parallel groups in each formulation (US, ex-US).  
Study Extension: multi-centric study, multi-country Phase II, open unblinded, with all 5 
parallel groups in each formulation (US, ex-US) receiving the experimental RSV 
maternal (120µg) vaccine. 
• 
Duration of the study: The primary study will be approximately 6 months for each 
enrolled subject and from 18 up to 24 months for subjects that agree to participate in 
the study extension. 
− 
Primary Vaccination 
• 
Epoch 001: Screening 
• 
Epoch 002: Primary vaccination starting at Visit 1 (Day 1) and ending just 
before the Visit 3 (Day 31)  
• 
Epoch 003: Follow-up after Visit 3 (Day 31) to Phone Contact 1 on (Day 
181)  
− 
End of Primary Study: Subjects must sign the ICF addendum to join the study 
extension. 
− 
Study Extension: 6-month period starting at the beginning of 12th month up to 
the beginning of 18th month after Visit 1 (≥12 to <18 months) 
• 
Epoch 004: 2nd dose vaccination starting from Visit 4 (up -7 days prior to 
vaccination) to Visit 6 (Day 31 post 2nd dose vaccination) 
• 
Epoch 005: 2nd dose vaccination Study Follow-up 2 starting after Visit 6 
(Day 31 post 2nd dose vaccination) and ending at Phone Contact 3 (Day 
181 post 2nd vaccination). 
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• 
Primary completion Date (PCD): Visit 3 (Day 31) or last visit of Primary Epoch  
Refer to glossary of terms for the definition of PCD. 
• 
End of Study (EoS): Last testing results released of samples collected at Visit 6, to 
occur no later than 8 months after last subject last visit (LSLV), which occurs with 
phone contact 3 on Day 181 post 2nd vaccination. 
Refer to glossary of terms for the definition of EoS. 
 
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• 
Study groups: 
Table 6 
Study groups, treatment and epochs foreseen in the study 
Study Groups 
Number of 
subjects 
Age 
(Min-
Max) 
Treatment 
name 1 
Treatment 
name 2 
Epochs 
(Blinding) 
 
 
Epoch 001 
(Screening) 
Epoch 002 
(observer-
blind) 
Epoch 003 
(single-
blind) 
Epoch 
004 (open 
study) 
Epoch 00 
5 
 
(open 
study) 
XRSV120_dTpa 
50 
18 – 45 
years 
RSV MAT 120  
Boostrix-ex-US 
(dTpa_500) 
RSV MAT 120  
x 
x 
x 
x 
x 
Xplacebo_RSV120 
50 
18 – 45 
years 
RSV MAT 120 
Placebo 
RSV MAT 120  
x 
x 
x 
x 
x 
XRSV60_dTpa 
50 
18 – 45 
years 
RSV MAT 60 
Boostrix-ex-US 
(dTpa_500) 
RSV MAT 120  
x 
x 
x 
x 
x 
Xplacebo_RSV60 
50 
18 – 45 
years 
RSV MAT 60 
Placebo  
RSV MAT 120  
x 
x 
x 
x 
x 
Xplacebo_dTpa 
50 
18 – 45 
years 
Boostrix-ex-US 
(dTpa_500) 
Placebo 
RSV MAT 120  
x 
x 
x 
x 
x 
URSV120_dTpa 
50 
18 – 45 
years 
RSV MAT 120 
Boostrix-US 
(dTpa_300) 
RSV MAT 120  
x 
x 
x 
x 
x 
Uplacebo_RSV120 
50 
18 – 45 
years  
RSV MAT 120 
Placebo 
RSV MAT 120  
x 
x 
x 
x 
x 
URSV60_dTpa 
50 
18 – 45 
years  
RSV MAT 60 
Boostrix-US 
RSV MAT 120  
x 
x 
x 
x 
x 
Uplacebo_RSV60  
50 
18 – 45 
years 
RSV MAT 60 
Placebo 
RSV MAT 120  
x 
x 
x 
x 
x 
Uplacebo_dTpa 
50 
18 – 45 
years 
Boostrix-US 
(dTpa_300) 
Placebo 
RSV MAT 120  
x 
x 
x 
x 
x 
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• 
Control: (active comparator). 
• 
Treatment allocation: (randomised stratified).  
• 
Blinding: As described in Table 6. 
• 
Data collection: standardised Electronic Case Report Form (eCRF). Solicited 
symptoms will be collected using a subject paper Diary (pDiary). 
• 
Safety monitoring 
If the investigator becomes aware of a holding rule being met, he/she will suspend 
vaccination and will inform GSK immediately. 
Refer to section 8.6 for detailed description of holding rules and safety monitoring. 
5.3. 
Number of subjects 
Approximately 500 subjects will be randomised such that approximately 475 (based on 
5% drop out rate) evaluable subjects complete the study. 
Withdrawals will not be replaced. 
5.4. 
Subject and study completion 
A subject is considered to have completed the study if she is available for the concluding 
phone contact 3 (Day 181 post second vaccination) as described in the protocol.  
For those subjects that do not agree to participate in the study extension, the concluding 
contact will be the Day 181 phone contact as described in previous version of protocol 
(RSV MAT-011 (209141) Protocol Amendment 3 (03-APR-2020). 
Global completion of the study is required in order to provide sufficient subjects as 
defined in Section 10.1 Sample Size Determination. 
6. 
STUDY POPULATION 
6.1. 
Inclusion criteria for enrolment (primary study) 
Deviations from inclusion criteria are not allowed because they can potentially jeopardise 
the scientific integrity, regulatory acceptability of the study or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
All subjects must satisfy ALL the following criteria at study entry: 
• 
Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary card, return for follow-up 
visits).  
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• 
Written or witnessed/thumb printed informed consent obtained from the subject prior 
to performance of any study specific procedure.  
• 
Healthy female subjects; as established by medical history and clinical examination, 
aged 18 to 45 years at the time of the first vaccination; 
• 
Female subjects of childbearing potential may be enrolled in the study, if the subject: 
− 
has practiced adequate contraception for 30 days prior to primary vaccination, 
and 
− 
has a negative pregnancy test on the day of primary vaccination, and 
− 
has agreed to continue adequate contraception for 90 days after completion of 
the vaccination.  
− 
No local condition precluding injection in both left and right deltoid muscles. 
6.2. 
Exclusion criteria for enrolment (primary study) 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 
The following criteria should be checked at the time of study entry. If ANY exclusion 
criterion applies, the subject must not be included in the study. 
6.2.1. 
Medical conditions 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccines; 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required); 
• 
Hypersensitivity to latex; 
• 
Major congenital defects, as assessed by the investigator; 
• 
Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal 
functional abnormality, as determined by medical history, physical examination or 
laboratory screening tests;  
• 
Significant or uncontrolled psychiatric illness; 
• 
Recurrent history or un-controlled neurological disorders or seizures; 
• 
Documented HIV-positive subject; 
• 
History of or current autoimmune disease; 
• 
Body mass index (BMI) > 40 kg/m2; 
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• 
Any clinically significant hematological parameter (hemoglobin level, white blood 
cell, lymphocyte, neutrophil, eosinophil, platelet red blood cell count and erythrocyte 
mean corpuscular volume) and/or biochemical (alanine aminotransferase [ALT], 
aspartate aminotransferase [AST], creatinine, blood urea nitrogen) laboratory 
abnormality.  
− 
The investigator should use his/her clinical judgement to decide which 
abnormalities are clinically significant. 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the subject due to participation in the study. 
6.2.2. 
Prior/Concomitant therapy 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study vaccines during the period starting 30 days before the 
first dose of study vaccines (Day -29 to Day 1), or planned use during the study 
period; 
• 
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 first dose of study vaccines 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 vaccine dose(s). For corticosteroids, this will mean 
prednisone 5 mg/day, or equivalent. Inhaled and topical steroids are allowed; 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol within the period starting 30 days before and ending 30 days after study 
primary vaccination, with the exception of any licensed influenza vaccine which may 
be administered ≥ 15 days before or after study vaccination; 
• 
Administration of a vaccine containing diphtheria, tetanus or pertussis antigens or 
diphtheria and tetanus toxoids within the previous 5 years (by participant report); 
• 
Previous experimental vaccination against RSV; 
6.2.3. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the subject has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or medical device); 
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6.2.4. 
Other exclusions 
• 
Pregnant or lactating female; 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions; 
• 
History of alcoholism, drug abuse and/or use disorder within the past two years (as 
defined in DSM-5 Diagnostic Criteria) [Camargo, 1984; Christy, 1995; Hasin, 2013]; 
• 
Any study personnel or their immediate dependents, family, or household members. 
6.3. 
Inclusion criteria for study extension 
Deviations from inclusion criteria are not allowed because they can potentially jeopardise 
the scientific integrity, regulatory acceptability of the study or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential. 
• 
Completed in primary study and received 1st dose vaccination of a study vaccine 
(RSVPreF3 or Boostrix). 
• 
Written or witnessed/thumb printed informed consent obtained from the subject prior 
to performance of any study specific procedure to the study extension. 
Are eligible if they meet the following criteria below 
All subjects must satisfy ALL the following criteria: 
• 
Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary card, return for follow-up 
visits).  
• 
Female subjects remain healthy; as established by medical history and clinical 
examination, aged 18 to 45 years at the time of the first vaccination; 
• 
Female subjects of childbearing potential are eligible for the extension, if the subject: 
− 
has practiced adequate contraception for 30 days prior to 2nd vaccination 
− 
has a negative pregnancy test with results available on the day of 2nd vaccination 
− 
has agreed to continue adequate contraception for 90 days after completion of 
the 2nd vaccination. 
6.4. 
Exclusion criteria for extension 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 
The following criteria should be checked at the time of entry to the extension. If ANY 
exclusion criterion applies, the subject must not be included in the extension. 
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6.4.1. 
Medical conditions for extension 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccines; 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required); 
• 
Hypersensitivity to latex; 
• 
Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal 
functional abnormality, as determined by medical history, physical examination or 
laboratory screening tests;  
• 
Significant or uncontrolled psychiatric illness; 
• 
Recurrent history or un-controlled neurological disorders or seizures; 
• 
Documented HIV-positive subject; 
• 
History of or current autoimmune disease; 
• 
Body mass index (BMI) > 40 kg/m2; 
• 
Participants who experienced any SAE judged to be possibly or probably related to 
first dose vaccination of RSVPreF3, including hypersensitivity reactions. 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the subject due to participation in the study. 
6.4.2. 
Prior/Concomitant therapy for extension (Amended 09-APR-2021) 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study vaccines during the period starting 30 days before the 
second dose of study vaccine (Day -29 to Day 1), or planned use during the 6 month 
study extension period; 
• 
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 first dose of study vaccines 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 vaccine dose(s). For corticosteroids, this will mean 
prednisone 5 mg/day, or equivalent. Inhaled and topical steroids are allowed; 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol within the period starting 30 days before and ending 30 days after study 2nd 
dose vaccination*, with the exception of any licensed influenza vaccine which may 
be administered ≥15 days before or after study vaccination. 
*Note: In case an emergency mass vaccination for an unforeseen public health 
threat (e.g.: a pandemic) is organised by the public health authorities, outside the 
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routine immunisation program, the time period described above can be reduced if 
necessary for that vaccine provided it is licensed and used according to its Summary 
of Product Characteristics (SmPC) or Prescribing Information and according to the 
local governmental recommendations. 
6.4.3. 
Prior/Concurrent clinical study experience for extension 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the subject has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or medical device); 
6.4.4. 
Other exclusions for extension 
• 
Pregnant or lactating female at the time of Visit 4; 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions; 
• 
History of alcoholism, drug abuse and/or use disorder within the past two years (as 
defined in DSM-5 Diagnostic Criteria) [Camargo, 1984; Christy, 1995; Hasin, 2013]; 
• 
Any study personnel or their immediate dependents, family, or household members. 
6.5. 
Criteria for temporary delay for enrolment and vaccination  
Vaccination may be postponed within the allowed time interval until transient 
circumstances cited below have been resolved: 
• 
Haematological/biochemical values out of normal range at screening, if expected to 
be temporary. Subjects must be re-screened at a later date within the allowed time 
interval. 
• 
Acute disease and/or fever at the time of enrollment; 
− 
Fever is defined as body temperature ≥ 38○C/100.4○F. The preferred location for 
measuring temperature in this study will be the oral cavity. 
− 
For subjects with acute disease and/or fever at the time of enrollment, Visit 1 for 
primary vaccination and Visit 5, the 2nd vaccination will be rescheduled within 
the allowed window for the visit. 
− 
Screening hematological/biochemical do not need to be repeated if obtained 
within 30 days of each vaccination. 
Subjects with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be enrolled at the discretion of the investigator. 
6.6. 
Screen and baseline failures 
“Screening failures” are subjects who withdraw or are withdrawn from the study after 
giving informed consent, but before study eligibility (presence of all inclusion and 
absence of all exclusion criteria) is confirmed. 
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Discovery during screening of any condition that violates the requirements for study 
eligibility should be considered a screening failure. Discovery during Visit 1 of any 
condition that violates the requirements for study eligibility should also be considered a 
screening failure. 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. 
The development of such conditions (after Visit 1) does not constitute screening failure 
and should be captured on the eCRF, as applicable. 
6.7. 
Screen failures to the extension 
“Screening failures” for the extension are subjects who withdraw or are withdrawn from 
the extension after giving informed consent to the extension, but before extension 
eligibility (presence of all inclusion and absence of all exclusion criteria) is confirmed. 
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. 
7. 
TREATMENTS 
Study treatment is defined as a set of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a subject. 
7.1. 
Treatments administered 
Table 7 
Treatments administered (Part 1) 
 
RSV MAT 120 
RSV MAT 60 
Boostrix-ex-
US 
(dTpa_500) 
Boostrix-US 
(dTpa_300) 
 
Placebo  
Vaccines 
/Products 
RSVPreF3 high 
dose 
RSVPreF3 mid 
dose 
dTpa 
dTpa 
NaCl 
NaCl 
NaCl 
Presentation 
Powder for 
suspension for 
injection (vial) 
(174mcg/vial)  
Powder for 
suspension for 
injection (vial) 
(87mcg/vial) 
Suspension for 
injection 
(syringe) 
Suspension for 
injection 
(syringe) 
Solution for 
injection; vial) 
Solution for solution 
for injection; (vial) 
Solution for 
solution for 
injection; (vial) 
Formulation 
RSVPreF3(120 
µg)/Trehalose(12.73 
mg).  
NaCl solution (4.5 
mg/0.5 mL, ~150 
mM) 
RSVPreF3(60 
µg)/Trehalose(6.42 
mg).  
NaCl solution (4.5 
mg/0.5 mL, ~150 
mM) 
Diphtheria 
toxoid (≥ 2 IU) 
adsorbed on 
aluminium 
hydroxide and 
aluminium 
phosphate; 
Tetanus toxoid 
(≥ 20 IU) 
Diphtheria 
toxoid (≥ 2 IU) 
adsorbed on 
aluminium 
hydroxide; 
Tetanus toxoid 
(≥ 20 IU) 
adsorbed on 
aluminium 
NaCl solution 
(4.5 mg/0.5 
mL, ~150 
mM) 
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RSV MAT 120 
RSV MAT 60 
Boostrix-ex-
US 
(dTpa_500) 
Boostrix-US 
(dTpa_300) 
 
Placebo  
adsorbed on 
aluminium 
hydroxide and 
aluminium 
phosphate; 
Pertussis 
toxoid (8 µg) 
adsorbed on 
aluminium 
hydroxide and 
aluminium 
phosphate; 
Filamentous 
haemagglutinin 
(8 µg) 
adsorbed on 
aluminium 
hydroxide and 
aluminium 
phosphate; 
Pertactin (69 
kDa outer 
membrane 
protein) (2.5 
µg) adsorbed 
on aluminium 
hydroxide and 
aluminium 
phosphate; 
Aluminium 
hydroxide (0.3 
mg Al³+); 
Aluminium 
phosphate (0.2 
mg Al³+); 
Sodium 
chloride; Water 
for injections 
q.s. 0.5 mL 
hydroxide; 
Pertussis 
toxoid (8 µg) 
adsorbed on 
aluminium 
hydroxide; 
Filamentous 
haemagglutinin 
(8 µg) 
adsorbed on 
aluminium 
hydroxide; 
Pertactin (69 
kDa outer 
membrane 
protein) (2.5 
µg) adsorbed 
on aluminium 
hydroxide; 
Aluminium 
hydroxide (0.3 
mg Al³+); 
Sodium 
chloride (4.4 
mg); Water for 
injections q.s. 
0.5 mL 
Route of 
Administration  Intramuscular use 
Intramuscular use 
Intramuscular 
use 
Intramuscular 
use 
Intramuscular 
use 
Administration site 
Location 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Laterality 
Refer to Table 8. 
No of doses 
2 
1 
1 
1 
1 
Dose volume 
0.5 ml 
0.5 ml 
0.5 ml 
0.5 ml 
0.5 ml  
Packaging and 
Labelling 
Refer to the SPM  
Refer to the SPM  
Refer to the 
SPM  
Refer to the 
SPM  
Refer to the 
SPM  
Manufacturer 
RSVPreF3: GSK 
Biologicals 
NaCl: GSK 
Biologicals 
RSVPreF3: GSK 
Biologicals 
NaCl: GSK 
Biologicals  
GSK 
Biologicals 
GSK 
Biologicals 
GSK 
Biologicals 
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The vaccinations will be administered in each arm as follows: 
Table 8 
Treatments administered (Part 2) 
Primary Vaccination 
Group 
Formulation N 
 
Laterality 
 
Laterality 
XRSV120_dTpa 
ex-US 
50 
RSVPreF3=120µg  
Left Arm 
dTpa 500 
Right Arm 
Xplacebo_RSV120 
50 
RSVPreF3=120µg 
Left Arm 
Placebo 
Right Arm 
XRSV60_dTpa 
50 
RSVPreF3=60µg 
Left Arm 
dTpa 500 
Right Arm 
Xplacebo_RSV60 
50 
RSVPreF3=60µg  
Left Arm 
Placebo 
Right Arm 
Xplacebo_dTpa 
50 
Placebo 
Left Arm 
dTpa 500 
Right Arm 
URSV120_dTpa 
US 
50 
RSVPreF3=120µg 
Left Arm 
dTpa 300 
Right Arm 
Uplacebo_RSV120 
50 
RSVPreF3=120µg  
Left Arm 
Placebo  
Right Arm 
URSV60_dTpa 
50 
RSVPreF3=60µg  
Left Arm 
dTpa 300 
Right Arm 
Uplacebo_RSV60 
50 
RSVPreF3=60µg  
Left Arm 
Placebo 
Right Arm 
Uplacebo_dTpa 
50 
Placebo 
Left Arm 
dTpa 300 
Right Arm 
2nd Vaccination 
Groups in primary 
vaccination 
Formulation 
in primary 
vaccination 
N 
Groups in 2nd 
vaccination 
Laterality 
XRSV120_dTpa 
ex-US 
50 
RSVPreF3=120µg  
Non-Dominant  
Xplacebo_RSV120 
50 
RSVPreF3=120µg  
Non-Dominant  
XRSV60_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
Xplacebo_RSV60 
50 
RSVPreF3=120µg  
Non-Dominant  
Xplacebo_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
URSV120_dTpa 
US 
50 
RSVPreF3=120µg  
Non-Dominant  
Uplacebo_RSV120 
50 
RSVPreF3=120µg  
Non-Dominant  
URSV60_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
Uplacebo_RSV60 
50 
RSVPreF3=120µg  
Non-Dominant  
Uplacebo_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
Note: study groups labeled X = ex-US; study groups labeled U = US. 
Refer to the Study Procedures Manual (SPM) for detailed instructions on study vaccine 
reconstitution. 
After completing all prerequisite procedures prior to vaccination (refer to Section 7.7 
regarding the contraindications to subsequent vaccination), the assigned study vaccines 
(Table 9) will be administered as shown in Table 7and Table 8. 
If the investigator or delegate determines that the subject’s health on the day of 
administration temporarily precludes vaccine(s) administration, the visit will be 
rescheduled within the allowed interval for this visit (refer to Table 4). 
The subjects will be observed closely for at least 60 minutes following the administration 
of the vaccine(s), with appropriate medical treatment readily available in case of 
anaphylaxis and syncope. 
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7.2. 
Method of treatment assignment 
7.2.1. 
Subject identification 
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study, according to the range of subject identification 
numbers allocated to each study centre. The subject identification number will be the 
same in the study extension. No new subjects will be recruited. 
7.2.1.1. 
Randomisation of supplies 
The randomisation of supplies within blocks will be performed at GSK, using MATerial 
Excellence (MatEx), a program developed for use in Statistical Analysis System (SAS) 
(Cary, NC, USA) by GSK. Entire blocks will be shipped to the study centres/warehouse. 
7.2.1.2. 
Treatment allocation to the subject 
The treatment numbers will be allocated by component (2 treatment numbers will be 
allocated for each subject – one for each vaccine/product administered).  
For the second vaccination, 1 treatment number will be allocated for each subject. 
7.2.1.2.1. Study group and treatment number allocation 
The target will be to enrol approximately 500 eligible subjects (250 in the US and 250 ex-
US). Of these, 250 subjects will be randomized to 5 study groups in a 1:1:1:1:1 ratio 
using SBIR in the US, and the other approximately 250 will also be randomized to 5 
study groups in a 1:1:1:1:1 ratio using SBIR ex-US. 
Allocation of the subject to a study group at the investigator site will be performed using 
a randomisation system on internet (SBIR). The randomisation algorithm will use a 
minimisation procedure by treating study formulation (US and ex-US) as a stratification 
factor, and age at the time of vaccination (18-32 or 33-45 years of age) and center as 
minimization factors. 
When SBIR is not available, please refer to the SBIR user guide or the Study Procedures 
Manual (SPM) for specific instructions. 
After obtaining the signed or witnessed/thumb printed and dated ICF from the subject 
and having checked the eligibility of the subject, the study staff in charge of the vaccine 
administration will access SBIR. Upon providing the formulation (US or ex-US), age, 
centre and the subject identification number, the randomisation system will determine the 
study group and will provide the treatment number to be used for each dose. 
The number of each administered treatment must be recorded in the eCRF on the Vaccine 
Administration screen. 
Note that as soon as the target number of approximately 250 subjects in the US or 250 
subjects ex-US has been reached, the enrolment will be frozen for this formulation. 
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Since the second dose vaccination is open study, the treatment number will be allocated 
for each subject sequentially at each centre. 
7.3. 
Blinding and unblinding 
Data will be collected in an observer-blind manner during the primary study. By 
observer-blind, it is meant that during the course of the study, the vaccine(s) recipient and 
those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity) 
will all be unaware of which vaccines were administered. To do so, vaccine preparation 
and administration will be done by authorised medical personnel who will not participate 
in any of the study clinical evaluation assays. 
Investigators will remain blinded to each subject’s assigned study treatment until 
completion of the primary vaccination day 181 database freeze for analysis. In order to 
maintain this blind, a nurse or pharmacist who will not participate in any other study 
related activity will be responsible for the reconstitution and dispensation of all study 
treatment. 
After the Day 181 phone contact (C1) for a given subject, the investigator will be 
informed of the subject’s treatment assignment and will communicate this to the 
subject. The study extension will then be conducted as an open label study. 
Unblinded monitors and in the event of a Quality Assurance audit, the auditor(s) will be 
allowed access to un-blinded study treatment records at the site(s) to verify that 
randomisation/dispensing has been done accurately. Please refer to the SPM for details 
on blinding of the vaccine.  
7.3.1. 
Emergency unblinding 
Unblinding of a subject’s individual treatment code should occur only in the case of a 
medical emergency when knowledge of the treatment is essential for the clinical 
management or welfare of the subject. 
The emergency unblinding process consists of the automated Internet-based system 
(SBIR) that allows the investigator to have unrestricted, immediate and direct access to 
the subject’s individual study treatment. 
As back up process, the investigator has the option of contacting a GSK Helpdesk (refer 
to Table 9) if he/she needs support to perform the unblinding (i.e. he/she cannot access 
the automated Internet-based system). 
Non-investigator physician (e.g. physician from emergency room) or subject/care 
giver/family member can also request emergency unblinding either via the investigator 
(preferred option) or via the GSK Helpdesk (back up process). Contact details of 
investigator and GSK Helpdesk are reported in the patient/subject card. 
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Table 9 
Contact information for emergency unblinding 
GSK Helpdesk 
24/24 hour and 7/7 day availability 
The Helpdesk is available by phone, fax and email 
Phone: +32.2.656.68.04 
For Canada, US and Puerto Rico  
Toll-free number: 877.870.0019 
Fax: +32.2.401.25.75 
email: rix.ugrdehelpdesk@gsk.com 
GSK policy (which incorporates ICH E2A guidance, EU Clinical Trial Directive and US 
Federal Regulations) is to unblind the report of any SAE which is unexpected and 
attributable/suspected to be attributable to the study vaccine(s), prior to regulatory 
reporting. Vaccines Clinical Safety and Pharmacovigilance (VCSP) is responsible for 
unblinding the treatment assignment in accordance with the specified timeframes for 
expedited reporting of SAEs (refer to Section 12.5.8). 
A subject should continue in the study if that subject’s treatment assignment is unblinded. 
GSK Vaccines Clinical Safety and Pharmacovigilance (VCSP) staff may unblind the 
treatment assignment for any subject in case of Suspected Unexpected Serious Adverse 
Reaction (SUSAR) as well as in case of fatal or life-threatening cases. If the SAE 
requires that an expedited regulatory report be sent to 1 or more regulatory agencies, a 
copy of the report, identifying the subject’s treatment assignment, may be sent to 
investigators in accordance with local regulations and/or GSK policy. 
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7.4. 
Handling, storage and replacement of study 
vaccine(s)/product(s) 
7.4.1. 
Storage and handling of study vaccine(s) 
The study vaccine(s) must be stored at the respective label storage temperature conditions 
in a safe and locked place. Access to the storage space should be limited to authorised 
study personnel. The storage conditions will be assessed during pre-study activities under 
the responsibility of the sponsor study contact. The storage temperature should be 
continuously monitored with calibrated (if not validated) temperature monitoring 
device(s) and recorded. Refer to the Module on Clinical Trial Supplies in the SPM for 
more details on storage of the study vaccine(s). 
A temperature excursion is any temperature that is not in range of the label storage 
temperature conditions. Temperatures outside the range of label storage temperature 
conditions must be reported and/or documented. Temperature excursion impacting study 
vaccine(s) must be reported and/or documented. 
In the frame of the reporting, the lack/absence of temperature monitoring documentation 
from a device meeting GSK requirements has to be considered as a temperature 
excursion. 
Study vaccine(s) that are impacted by a temperature excursion may not be used and must 
be quarantined at label storage conditions until usage approval has been obtained 
from/via the local study contact (e.g. Site Monitor). 
Refer to the Module on Clinical Trial Supplies in the SPM for details and instructions on 
the temperature excursion reporting and usage decision process, packaging and 
accountability of the study vaccine(s). 
7.4.2. 
Replacement of unusable vaccine(s) doses 
In addition to the vaccine doses provided for the planned number of subjects (including 
over-randomisation when applicable), at least 10% additional vaccine doses will be 
supplied to replace those that are unusable.  
The investigator will use SBIR to obtain the replacement product number. The 
replacement numbers will be allocated by component. The system will ensure, in a 
blinded manner, that the replacement product matches the formulation the subject was 
assigned to by randomisation. 
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7.5. 
Concomitant medication(s)/product(s) and concomitant 
vaccinations 
7.5.1. 
Recording of concomitant medications/products and 
concomitant vaccinations 
At each study visit/contact, the investigator or delegate should question the subject about 
any medications/products taken and vaccinations received by the subject. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF. 
• 
All concomitant medications/products, except vitamins and dietary supplements, 
administered during the period of 31 days post primary vaccination and 2nd 
vaccination. 
• 
Any concomitant vaccination administered in the period starting 30 days before the 
dose of study vaccine(s) and ending at the last study visit/contact (Day -30 to Day 
181 post 2nd vaccination). 
• 
Prophylactic medication (i.e. medication administered in the absence of ANY 
symptom and in anticipation of a reaction to the vaccination). 
An anti-pyretic is considered to be prophylactic when it is given in the absence of fever 
and any other symptom, to prevent fever from occurring fever is defined as temperature. 
38.0°C/100.4°F regardless the location of measurement. The preferred location for 
measuring temperature in this study will be the oral cavity. 
• 
Any concomitant medications/products/vaccines leading to the withdrawal or non-
eligibility of the subject from the study. 
• 
Any concomitant medications/products/vaccines relevant to an SAE to be reported as 
per protocol or administered at any time during the study period for the treatment of 
an SAE. In addition, concomitant medications relevant to SAEs need to be recorded 
on the expedited Adverse Event report. 
• 
Any antipyretic administered in the period starting 6 hours before vaccination and 
ending 12 hours after vaccination needs to be recorded on the specific page of the 
eCRF. 
• 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7.5.2. 
Concomitant medications/products/vaccines that may lead to the 
elimination of a subject from per-protocol analyses 
The use of the following concomitant medications/products/vaccines will not require 
withdrawal of the subject from the study but may determine a subject’s evaluability in the 
per-protocol analysis. See Section 10.2 for populations to be analysed. 
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Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine(s) used during the study period.  
• 
Immunosuppressants or other immune-modifying drugs administered chronically 
(i.e. more than 14 days in total) during the study period. For corticosteroids, this will 
mean prednisone 5 mg/day (for adult subjects) or 0.5 mg/kg/day (for paediatric 
subjects), or equivalent. Inhaled and topical steroids are allowed. 
• 
Long-acting immune-modifying drugs administered at any time during the study 
period (e.g. infliximab). 
• 
A vaccine not foreseen by the study protocol administered during the period starting 
30 days before the dose and ending 30 days after each dose of vaccine(s). 
Note: In case an emergency mass vaccination for an unforeseen public health threat 
(e.g.: a pandemic) is organised by the public health authorities, outside the routine 
immunisation program, the time period described above can be reduced if necessary 
for that vaccine provided it is licensed and used according to its Summary of Product 
Characteristics (SmPC) or Prescribing Information and according to the local 
governmental recommendations and provided a written approval of the Sponsor is 
obtained. 
• 
Immunoglobulins and/or any blood products administered during the study period. 
• 
Drug and/or alcohol abuse. 
7.6. 
Intercurrent medical conditions that may lead to elimination 
of a subject from per-protocol analyses 
At each study visit subsequent to the vaccination visit, it must be verified if the subject 
has experienced or is experiencing any intercurrent medical condition that may lead to 
elimination from per protocol analysis. If it is the case, the condition(s) must be recorded 
in the eCRF. 
For example, subjects may be eliminated from the per-protocol set for immunogenicity if, 
during the study, they incur a condition that has the capability of altering their immune 
response (i.e. varicella) or are confirmed to have an alteration of their initial immune 
status. 
7.7. 
Contraindications to subsequent vaccine(s) administration 
N/A  
7.8. 
Warnings and precautions 
Warnings and precautions to vaccination must be checked at the beginning of each 
vaccination visit.  
Refer to the local approved product Prescribing Information for Boostrix. 
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7.9. 
Treatment after completion of the study 
The investigator is encouraged to share the immunological assay results for Boostrix non-
responders with the study subjects. 
For the subjects identified as non-responders, it remains the responsibility of the 
investigator in charge of the subject’s clinical management to determine the medical care 
needed as per local/regional practices (such as re-vaccination of the subject(s)). 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are described in the SoA (Section 2). 
Protocol waivers or exemptions are not allowed unless necessary for the management of 
immediate safety concerns. 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the subject(s) should discontinue study 
treatment. 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable. The lab results will be considered valid for a period 
of 30 days from the date of initial screening. 
Procedures conducted as part of the subject’s routine clinical management (e.g. blood 
count) and obtained before signing of ICF may be utilised for screening or baseline 
purposes provided the procedure met the protocol-specified criteria and was performed 
within the time frame defined in the SoA. 
8.1. 
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: 
• 
Reconsent of subjects for the study extension may be placed on hold. Decisions on 
re-starting will be made in a manner consistent with guidance from public health and 
other competent authorities.  
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• 
Informed consent must take place in a face to face contact with the investigator but 
informing the potential subject ahead of giving written consent may be done 
remotely for example by mailing the informed consent or telephone or 
videotelephony conversation. 
• 
Certain procedures may be performed at an alternate location. This includes, signing 
of informed consent, physical examination and vaccine dosing. If vaccinating in an 
alternate location, it must be assured that trained staff and equipment are available to 
manage an acute vaccine reaction. Biological samples may be collected at a different 
location* other than the study site or at participant’s home. Biological samples should 
not be collected if they cannot be processed in a timely manner or appropriately 
stored until the intended use. 
• 
Safety follow-up may be made by a telephone call, other means of virtual contact or 
home visit, if appropriate. 
• 
 “Medically attended visits” include instances where, due to the special 
circumstances, the subject cannot seek medical advice for symptoms/an illness by 
visiting a medical facility or arranging for a home visit, and seeks this advice instead 
via telephone, SMS, email, videotelephony or telemedicine, or other means.  
• 
The paper Diary card provided to the subject may be transmitted from and to the site 
by electronic means and or conventional mail. 
• 
If despite best efforts it is not possible to collect the biological samples within the 
interval predefined in the protocol (see Table 4), then the interval may be extended 
up to a maximum length described in Table 10, however efforts should be made to 
adhere as closely as possible to the optimal timing.  
• 
If despite best efforts it is not possible to administer the dose of study vaccine as 
defined in the protocol (see Table 4), a maximum dose interval described in Table 10 
may be used, however efforts should be made to adhere as closely as possible to the 
optimal timing. 
Table 10 
Intervals between study visits under Special Circumstances 
Interval 
Optimal timing  
Allowed interval 
Adapted interval 
under special 
circumstances 
Screening Visit →Visit 1  
≤7 days  
-7- 1 days  
-30 to 1 days 
Visit 1 → Visit 2  
8 days  
7- 10 days  
7- 10 days 
Visit 1 →Visit 3  
31 days 
30- 45 days  
30 – 60 days 
Visit 1 → Phone Contact 1 
181 days 
165- 195 days  
165 – 195 days 
Visit 4 → Visit 5 
 
-7 to 1 days 
-30 – 1 days* 
Visit 1 → Visit 5 
365 days 
365-548 days** 
 
Visit 5 to Phone Contact 2 
8 days  
7- 10 days  
7- 10 days  
Visit 5 →Visit 6 
31 days 
30- 45 days  
30 – 90 days 
Visit 5 →Phone Contact 3 
181 days 
165- 195 days  
165 – 195 days 
*From 30 days prior to vaccination up to and including the day of vaccination. 
** For a 6-month period ≥12 to <18 months post 1st vaccination 
Impact on the per protocol set for immunogenicity will be determined on a case by case 
basis.  
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• 
Any impact of above-mentioned measures on the study results will be described in 
the clinical study report. 
 * 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 subjects by investigator and staff at a site other than the designated study 
site.  
8.2. 
General study aspects 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SPM. The SPM provides the investigator and the site 
personnel with administrative and detailed technical information that does not impact the 
safety of the subjects. 
8.3. 
Pre-vaccination procedures 
8.3.1. 
Collection of demographic data 
Record demographic data such as date of birth, sex, race and ethnicity in the subject’s 
eCRF. 
8.3.2. 
Medical and vaccination history (Amended 09 APR 2021) 
Obtain the subject’s medical and vaccination history by interview and/or review of the 
subject’s medical records and record any pre-existing conditions or signs and/or 
symptoms present in a subject prior to the study vaccination in the eCRF. Significant 
medical conditions and vaccinations that occurred during the C1-V4 will be reviewed 
during the screening for the second vaccination and reported as medical history and 
concomitant medications, respectively.  
8.3.3. 
Physical examination  
• 
Perform a full physical examination of the subject at screening visit, including 
assessment of axillary or 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 history directed physical exam plus vital signs at Visit 1 [Day 1]  
• 
Perform a history directed physical exam plus vital signs at Visit 4 [D-7 2nd 
vaccination to 2nd vaccination]. Note that laboratory assessments of haematology and 
biochemistry may be made on the investigator’s discretion. 
• 
Physical examinations at each study visit subsequent to the vaccination visit, will be 
performed only if the subject indicates during questioning that there might be some 
underlying pathology(ies) or if deemed necessary by the Investigator or delegate.  
• 
Any vital signs measured at Visit 2 [Day 8] and Visit 5 [2nd Vaccination] should be 
recorded in the eCRF. 
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• 
Collected information needs to be recorded in the eCRF. 
• 
If the investigator determines that the subject’s health on the day of vaccination 
temporarily precludes vaccination, the visit will be rescheduled within the acceptable 
range. 
• 
Treatment of any abnormality observed during this examination has to be performed 
according to local medical practice outside this study or by referral to an appropriate 
health care provider. 
8.3.4. 
Pregnancy test 
Female subjects of childbearing potential are to have a urine pregnancy test prior to any 
study vaccine administration. The study vaccine(s) 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. 
The results of the applicable test will be recorded in the eCRF. The study vaccine may 
only be administered if the pregnancy test is negative. 
Note: Pregnancy test must be performed even if the subject is menstruating at the time of 
the study visit. 
8.3.5. 
Pre-vaccination body temperature 
The body temperature (oral preferred) of each subject needs to be measured prior to any 
study vaccine(s) administration. If the subject has fever [temperature 38.0°C/100.4°F 
regardless of the location of measurement on the day of vaccination, the vaccination visit 
will be rescheduled within the allowed interval for this visit (see Section 6.5). 
8.3.6. 
Pre-vaccination Vital Signs  
Pre-vaccination vital signs: At Visit 5, the pre-vaccination vital signs (blood pressure, 
heart rate and respiratory rate, temperature) will be recorded in the eCRF. 
8.4. 
Immunogenicity assessments 
Please refer to the SPM for details on biospecimen management (handling, storage and 
shipment). 
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the subject and study (without any link to the treatment 
attributed to the subject) to each sample. 
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Collected samples will be used for protocol mandated research and purposes related to 
the improvement, development and quality assurance of the laboratory tests described in 
this protocol. This may include the management of the quality of these tests, the 
maintenance or improvement of these tests, the development of new test methods, as well 
as making sure that new tests are comparable to previous methods and work reliably. 
It is also possible that future findings may make it desirable to use the samples acquired 
in this study for future research, not described in this protocol. Therefore, all subjects in 
countries where this is allowed will be asked to give a specific consent to allow GSK or a 
contracted partner to use the samples for future research. Future research will be subject 
to the laws and regulations in the respective countries and will only be performed once an 
independent Ethics Committee or Review Board has approved this research. 
Information on further investigations and their rationale can be obtained from GSK. 
Any sample testing will be done in line with the consent of the individual subject. 
Refer also to the Investigator Agreement, where it is noted that the investigator cannot 
perform any other biological assays except those described in the protocol or its 
amendment(s). 
If additional testing is performed, the marker priority ranking given in Section 8.4.4 may 
be changed. 
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed 
and agreed with GSK. 
8.4.1. 
Use of specified study materials 
When materials are provided by GSK, it is MANDATORY that all clinical samples 
(including serum samples) be collected and stored exclusively using those materials in 
the appropriate manner. The use of other materials could result in the exclusion of the 
subject from the per-protocol analysis (See Section 10.2 for the definition of populations 
for analyses). The investigator must ensure that his/her personnel and the laboratory(ies) 
under his/her supervision comply with this requirement. However, when GSK does not 
provide material for collecting and storing clinical samples, appropriate materials from 
the investigator’s site must be used. Refer to the Module on Clinical Trial Supplies in the 
SPM. 
8.4.2. 
Biological samples 
Biological samples to evaluate immunogenicity and safety will be collected as specified 
in Section 2, Schedule of Activities (SoA). Table 11 summarizes biological samples and 
minimum total blood volumes to be collected from study subjects. 
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Refer to the Module on Biospecimen Management in the SPM for detailed instructions 
for the collection, handling and processing of the samples. 
Table 11 
Biological samples  
Sample type 
Collected to Evaluate 
Minimum 
Quantity 
per subject 
Unit 
Time point 
Additional Information 
Whole blood for 
hematology, 
biochemistry and 
immune response 
10.5 
ml 
screening visit 
Hematology, chemistry: 5.5 mL. 
Immune response: 5 mL (~ 2 mL 
serum). 
Whole blood for 
immune response  
5  
ml 
Visit 2 (Day 8) 
Immune response : 5 mL (~ 2 mL 
serum). 
Whole blood for 
immune response  
5 
ml 
Visit 3 (Day 31) 
Immune response : 5 mL (~ 2 mL 
serum). 
Whole blood for 
hematology, 
biochemistry* 
Whole blood for 
immune response 
10.5 or 5 
ml 
Visit 4 (up Day -7 prior 
to 2nd vaccination) 
Hematology, chemistry: 5.5 mL. 
Immune response: 5 mL (~ 2 mL 
serum). 
Whole blood for 
immune response  
5 
ml 
Visit 6 (Day 31 post 2nd 
vaccination) 
Immune response : 5 mL (~ 2 mL 
serum). 
 
36 or 30.5 
ml 
Minimum Total, not including repeat or unscheduled 
samples 
Urine for Pregnancy 
- 
- 
screening visit 
Visit 1 (Day 1) and Visit 
5 (2nd Vaccination) 
 
*Hematological and biochemical laboratory testing at Visit 4 (D -7 up to and including 2nd dose vaccination) at the 
investigator’s discretion 
8.4.3. 
Laboratory assays 
Protocol-required hematology/biochemistry assays are listed in Section 12.2. Assays 
performed by GSK are listed below. 
Please refer to Section 12.3 for the address of the clinical laboratories used for sample 
analysis. 
 
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Table 12 
Humoral Immunity (Antibody determination)  
Sampling 
time points 
System 
Component 
Method 
Kit/ 
Manufacturer 
Unit 
Cut-off 
Groups 
Number of 
subjects 
Laboratory*** 
Screening 
Serum 
Respiratory Syncytial Virus A Ab 
neutralizing 
NEU 
In house 
ED60 and/or 
IU 
(international 
unit) 
18 for ED60 
56 for IU 
All 
500 
GSK 
Serum 
Respiratory Syncytial Virus 
PreF3 Ab.IgG concentration 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Serum 
Bordetella pertussis.Filamentous 
Hemaglutinin Ab.IgG 
ELI 
In house 
IU/mL 
2.046 
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Serum 
Bordetella pertussis.Pertactin 
Ab.IgG 
ELI 
In house 
IU/mL 
2.187 
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Serum 
Bordetella pertussis.Pertussis 
Toxin Ab.IgG 
ELI  
In house 
IU/mL 
2.693 
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Serum 
Corynebacterium 
diphtheriae.Diphtheria Toxoid 
Ab.IgG 
ELI 
In house 
IU/mL 
0.030  
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Serum 
Clostridium tetani.Tetanus 
Toxoid Ab.IgG 
ELI 
In house 
IU/mL 
0.037 
XRSV120_dTpa, 
XRSV60_dTpa, 
300 
GSK 
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Sampling 
time points 
System 
Component 
Method 
Kit/ 
Manufacturer 
Unit 
Cut-off 
Groups 
Number of 
subjects 
Laboratory*** 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
Day 8 
Serum 
Respiratory Syncytial Virus A Ab 
neutralizing 
NEU 
In house 
ED60 and/or 
IU 
(international 
unit) 
18 for ED60 
56 for IU 
All 
500 
GSK 
Serum 
Respiratory Syncytial Virus 
PreF3 Ab.IgG concentration 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Day 31 
Serum 
Respiratory Syncytial Virus A Ab 
neutralizing 
NEU 
In house 
ED60 and/or 
IU 
(international 
unit) 
18 for ED60 
56 for IU 
All 
500 
GSK 
Serum 
Respiratory Syncytial Virus 
PreF3 Ab.IgG concentration 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Serum 
Bordetella pertussis.Filamentous 
Hemaglutinin Ab.IgG 
ELI 
In house 
IU/mL 
2.046 
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Serum 
Bordetella pertussis.Pertactin 
Ab.IgG 
ELI 
In house 
IU/mL 
2.187 
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Serum 
Bordetella pertussis.Pertussis 
Toxin Ab.IgG 
ELI  
In house 
IU/mL 
2.693 
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
300 
GSK 
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Sampling 
time points 
System 
Component 
Method 
Kit/ 
Manufacturer 
Unit 
Cut-off 
Groups 
Number of 
subjects 
Laboratory*** 
URSV60_dTpa, 
Uplacebo_dTpa 
Serum 
Corynebacterium 
diphtheriae.Diphtheria Toxoid 
Ab.IgG 
ELI 
In house 
IU/mL 
0.030  
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Serum 
Clostridium tetani.Tetanus 
Toxoid Ab.IgG 
ELI 
In house 
IU/mL 
0.037 
XRSV120_dTpa, 
XRSV60_dTpa, 
Xplacebo_dTpa, 
URSV120_dTpa, 
URSV60_dTpa, 
Uplacebo_dTpa 
300 
GSK 
Day -7 up to 
2nd 
vaccination 
Serum 
Respiratory Syncytial Virus A Ab 
neutralizing 
NEU 
In house 
ED60 and/or 
IU 
(international 
unit) 
18 for ED60 
56 for IU 
All 
500 
GSK 
Serum 
Respiratory Syncytial Virus 
PreF3 Ab.IgG concentration 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
D31 post 2nd 
vaccination 
Serum 
Respiratory Syncytial Virus A Ab 
neutralizing 
NEU 
In house 
ED60 and/or 
IU 
(international 
unit) 
18 for ED60 
56 for IU 
All 
500 
GSK 
Serum 
Respiratory Syncytial Virus 
PreF3 Ab.IgG concentration 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Ab = antibody; ELI = Enzyme-linked immunosorbent assay (ELISA); ELU=ELISA unit; IgG = immunoglobulin G; RSV = respiratory syncytial virus; ED60 = serum dilution inducing 60% 
inhibition in plaque forming units; IU/ml = International units/milliliter, IU= International units; TBD = to be determined 
Assay cut-off and unit might be subject to change before starting of testing (e.g. in case of requalification, revalidation or standardisation). In this case, this will be documented in the 
clinical report. 
***GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium; Marburg, Germany. 
 
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Other assays may be performed with the aim to explore tertiary objectives of the study. 
The research may include, but is not limited to: 
Additional testing on the vaccine and/or on the disease under study may be performed 
within the framework of the study if deemed necessary for accurate interpretation of the 
data or should such assay(s) become available at GSK. These assays may not be 
represented in the objectives/endpoints of the study protocol. 
The 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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8.4.4. 
Biological samples evaluation 
8.4.4.1. 
Immunological read-outs 
Table 13 
Immunological read-outs 
Blood sampling timepoint 
Subset name 
Approximate 
No. subjects 
Component 
Components 
priority rank  
Type of contact 
and timepoint* 
Sampling 
timepoint 
Screening visit 
Pre-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
Boostrix* 
recipients  
300 
Bordetella 
pertussis.Filamentous 
Hemaglutinin Ab.IgG  
3 
Boostrix 
recipients 
300 
Bordetella 
pertussis.Pertactin Ab.IgG  
3 
Boostrix 
recipients 
300 
Bordetella 
pertussis.Pertussis Toxin 
Ab.IgG  
3 
Boostrix 
recipients 
300 
Corynebacterium 
diphtheriae.Diphtheria 
Toxoid Ab.IgG  
4 
Boostrix 
recipients 
300 
Clostridium tetani.Tetanus 
Toxoid Ab.IgG  
5 
Visit 2 (Day 8) 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
Visit 3 (Day 31) 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
Boostrix 
recipients 
300 
Bordetella 
pertussis.Filamentous 
Hemaglutinin Ab.IgG  
3 
Boostrix 
recipients 
300 
Bordetella 
pertussis.Pertactin Ab.IgG  
3 
Boostrix 
recipients 
300 
Bordetella 
pertussis.Pertussis Toxin 
Ab.IgG  
3 
Boostrix 
recipients 
300 
Corynebacterium 
diphtheriae.Diphtheria 
Toxoid Ab.IgG  
4 
Boostrix 
recipients 
300 
Clostridium tetani.Tetanus 
Toxoid Ab.IgG  
5 
Day -7 up to 2nd 
vaccination 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
D31 post 2nd 
vaccination 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
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*Boostrix recipients = subjects in the following study groups: -XRSV120_dTpa, XRSV60_dTpa, Xplacebo_dTpa, 
URSV120_dTpa, URSV60_dTpa, Uplacebo_dTpa. 
In case of insufficient blood sample volume to perform assays for all antibodies, the 
samples will be analysed according to priority ranking provided in Table 13. 
8.4.5. 
Immunological correlates of protection 
8.4.5.1. 
RSV 
No generally accepted immunological correlate of protection has been established so far 
for the antigen used in the RSV maternal (RSVPreF3) vaccine. 
8.4.5.2. 
Boostrix 
The following cut-offs are accepted as immunological correlates of protection: 
• 
Specific antibodies against diphtheria toxoid (anti-diphtheria) and tetanus toxoid 
(anti-tetanus) will be measured by Enzyme-linked immunosorbent assay (ELISA). 
Subjects with antibody concentrations of at least 0.1 International Units per ml 
(IU/ml) by ELISA are deemed to be protected [Camargo, 1984; Melville-Smith, 
1983]. In this study, the booster response will be defined by the percentage of 
subjects with concentration ≥ 1.0 IU/mL. 
• 
No serological correlate of protection against pertussis has been established [Vidor, 
2008]. Antibodies against the pertussis components pertussis toxoid (PT), 
filamentous haemagglutinin (FHA) and pertactin (PRN) will be measured by ELISA. 
The current seropositivity cut-off is 2.693 IU/ml for anti-PT, 2.046 IU/ml for anti-
FHA and 2.187 IU/ml for anti-PRN (see Table 12). Subjects with antibody 
concentration below the cut-off will be considered seronegative. 
The immunological assay results will be communicated to the investigator within 12 
months after the last study visit has been completed. 
Refer to section 7.9 for details regarding treatment for non-responders. 
8.5. 
Safety Assessments 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and any 
designees remain responsible for following up AEs that are serious, considered related to 
the study treatment or the study, or that caused the subject to discontinue the study.  
8.5.1. 
Safety definitions 
Please refer to Section 12.5 for safety definitions. 
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8.5.2. 
Time period and frequency for collecting AE and serious adverse 
event (SAE) information 
An overview of the protocol-required reporting periods for AEs, SAEs, and pregnancies 
is given in Table 14 . Refer to the Section 12.5.7.1 for details on the time period for 
recording safety information. 
 
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Table 14 
Reporting periods for collecting safety information 
Event 
Pre- 
V1* 
 V1 
V2 
V3 
C1  
C1 to 
V4** 
V4 
V5* 
 
C2 
 
V6 
C3 
D1 D7 D8 D30 D31 
D181 
 
D -7 up to 
2nd 
vaccination 
2nd vaccination 
From 12 up to 18 
months post 1st 
vaccination 
D7 post 
second 2nd 
vaccination 
D8 post 
second 2nd 
vaccination 
D30 post 
second 2nd 
vaccination 
D31 post 
2nd 
vaccination  
181 Days 
post 2nd 
vaccination 
Solicited local and 
general AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to 
withdrawal from the 
study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies*** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained. Pre-V: pre-vaccination; V: vaccination; Post-V: post-vaccination; D: Day, M: Month 
** There will be no follow-up between C1 and V4. New medical history and relevant new safety events during this period will be recorded at visit 4 for subjects who agree to the study 
extension and sign the informed consent addendum. In addition, SAE related to vaccination are reported during the period C1-V4 will be reported to the Investigator at the time of 
awareness. 
***Pregnancies that occurred during the C1-V4 period will be reported as medical history  
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All SAEs will be recorded and reported via Expedited AE Reporting Form to the sponsor 
or designee immediately and under no circumstance should this exceed 24 hours after the 
investigator became aware of it, as indicated in Section 12.5. The investigator will submit 
any updated SAE data to the sponsor within 24 hours of it being available. 
8.5.3. 
Method of detecting AEs and SAEs 
The method of recording, evaluating, and assessing intensity, causality and outcome of 
AEs and SAEs and the procedures for completing and transmitting SAE reports are 
provided in Section 12.5.7. 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the subjects is the preferred method to inquire about 
AE occurrence. 
8.5.4. 
Reporting of serious adverse events, pregnancies, and other -
events (Amended 09-APR-2021  
Table 15 
Timeframes for submitting serious adverse event, 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 
2 weeks* 
Paper pregnancy notification 
report/electronic pregnancy 
report 
24 hours* 
electronic pregnancy report  
* Timeframe allowed after receipt or awareness of the information. 
‡ 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. 
8.5.5. 
Post-study adverse events and serious adverse events 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 14. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the investigator learns of any SAE at 
any time after a subject has been discharged from the study, and he/she considers the 
event reasonably related to the investigational vaccine/product, the investigator will 
promptly notify the Study Contact for Reporting SAEs. 
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8.5.5.1. 
Contact information for reporting of serious adverse events (SAEs), 
pregnancies and study holding rules (Amended 09 APR 2021) 
Table 16 
Contact information for reporting of serious adverse events (SAEs), 
pregnancies and study holding rules  
Study contact for questions regarding SAEs, pregnancies and study holding rules 
Refer to the local study contact information document 
Study Contact for Reporting of study holding rules  
As soon as the investigator is aware that a holding rule is met, he/she must immediately 
inform the local contact.  
Back-up Study Contact for Reporting SAEs, pregnancies and study holding rules 
24/24 hour and 7/7-day availability: 
GSK Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: PV.ICSRManagement@gsk.com 
US sites only: 
Fax: 1-610-787-7053 
Canadian sites only: 
Fax: 1-866-903-4718 
8.5.6. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts. All SAEs, will be followed until the event is 
resolved, stabilised, otherwise explained, or the subject is lost to follow-up. Further 
information on follow-up procedures is given in Section 12.5.10. 
8.5.7. 
Treatment of adverse events 
Treatment of any AE is at the sole discretion of the investigator and according to current 
good medical practice. Any medication administered for the treatment of a SAE should 
be recorded in Expedited Adverse Event Report of the subject’s eCRF (refer to Section 
7.5). 
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8.5.8. 
Clinical safety laboratory assessments 
Refer to Section 12.2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency. 
• 
The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
eCRF. The laboratory reports must be filed with the source documents. Clinically 
significant abnormal laboratory findings are those which are associated with an 
underlying disease, unless judged by the investigator to be more severe than 
expected for the subject’s condition. All laboratory tests with values considered 
clinically significant abnormal during participation in the study or within 30 days 
after the last dose of study treatment should be repeated until the values return to 
normal or baseline or are no longer considered significantly abnormal by the 
investigator or medical monitor. Refer to the Section 12.5.5 for clinical laboratory 
abnormal assessments qualified as AEs or SAEs. 
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
All protocol-required laboratory safety assessments, as defined in Section 12.2, must be 
conducted in accordance with the laboratory manual and the SoA. 
8.5.9. 
Subject card 
Study subjects must be provided with the address and telephone number of the main 
contact for information about the clinical study. 
The investigator (or designate) must therefore provide a “subject card” to each subject. In 
an emergency situation, this card serves to inform the responsible attending physician 
that the subject is in a clinical study and that relevant information may be obtained by 
contacting the investigator. 
Subjects must be instructed to keep subject cards in their possession at all times during 
the study duration. 
8.6. 
Holding rules and safety monitoring 
The safety holding rules are defined in Table 17. Holding rules 1a-b will be assessed by 
the investigator on a continuous basis. Meeting any of these holding rules will trigger a 
hold of vaccination irrespective of number of subjects enrolled. 
Table 17 
Study holding rules 
Holding 
Rule 
Event 
Number of Subjects 
1a 
Death or any life-threatening SAE occurring within 30 days from 
vaccination 
≥1 
1b 
Any SAE that can be reasonably attributed to the vaccination 
≥1 
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The investigator is not permitted to start the administration of the next dose until receipt 
of the favourable outcome of the safety evaluation, documented and provided in writing, 
authorising the investigator to proceed. While vaccinations are on hold, the investigator 
should not consent subjects into the study. 
Moreover, if the investigator becomes aware of a holding rule being met, he/she will 
suspend vaccination and will inform GSK immediately (e.g. meeting of holding rules 1a-
b). 
The below flow of communication has to be followed: 
• 
The concerned site staff has to put vaccination and enrolment on hold. 
• 
The concerned site staff must immediately inform their local contact defined in the 
Table 16. 
• 
The local contact will escalate the information immediately to the central study team 
(ie SDL and CRDL). 
• 
The central study team will ensure SBIR is blocked and all vaccinating centres are 
informed. 
• 
GSK Safety Review Team (SRT) will further evaluate the case and escalate to GSK 
VSMB for making the decision to stop or to restart the vaccination. All site staff will 
be informed about that final decision by their local GSK contact. 
If the Central Team becomes aware of a holding rule being met, the below flow of 
communication must be followed: 
• 
CRDL inform the local Study team (Table 16) 
• 
The LML/delegate of each country confirm the reception of the holding rule to the 
CRDL and inform all the investigators. 
• 
The concerned site staff has to put vaccination and enrolment on hold. 
• 
The central study team will ensure SBIR is blocked and all vaccinating centres are 
informed. 
• 
GSK Safety Review Team (SRT) will further evaluate the case and escalate to GSK 
VSMB for making the decision to stop or to restart the vaccination. All site staff will 
be informed about that final decision by their local GSK contact. 
8.7. 
Genetic Research (Pharmacogenetics) 
Genetics are not evaluated in this study. 
8.8. 
Biomarkers and pharmacogenomics 
Not applicable. 
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8.9. 
Economic assessment 
Not applicable. 
8.9.1. 
Regulatory reporting requirements for SAEs 
Prompt notification of an SAE by the investigator to the sponsor is essential for meeting 
legal obligations and ethical responsibilities for the safety of subjects and the safety of a 
study treatment under clinical investigation. 
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (e.g. summary or listing of SAE) from the sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 
9. 
DISCONTINUATION CRITERIA 
9.1. 
Discontinuation from the study  
Subjects will complete the study at day 181 with a phone contact. For the subjects that 
enroll in the study extension, the conclusion of the study will be on Day 181 following 
the second immunization as described in the protocol.  
From an analysis perspective, a ‘withdrawal’ from the study refers to any subject was not 
available for the concluding contact foreseen in the protocol. 
All data and samples collected until the date of withdrawal/last contact of the subject will 
be used for the analysis. 
A subject is considered a ‘withdrawal’ from the study when no study procedure has 
occurred, no follow-up has been performed and no further information has been collected 
for this subject from the date of withdrawal/last contact. 
Investigators will make 3 attempts followed by a certified letter to contact those subjects 
who do not return for scheduled visits or follow-up. 
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Primary reason for study withdrawal will be documented in the eCRF. The investigator 
will document whether the decision to withdraw a subject from the study was made by 
the subject himself/herself, or by the investigator, as well as which of the following 
possible reasons was responsible for withdrawal: 
• 
Adverse events requiring expedited reporting 
• 
Unsolicited non-serious adverse event 
• 
Solicited adverse event 
• 
Protocol deviation  
• 
Withdrawal by subject, not due to an adverse event* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
*In case a subject is withdrawn from the study because she has withdrawn consent, the 
investigator will document the reason for withdrawal of consent, if specified by the 
subject in the eCRF. 
Subjects who are withdrawn from the study because of SAEs/AEs must be clearly 
distinguished from subjects who are withdrawn for other reasons. Investigators will 
follow subjects who are withdrawn from the study as result of a SAE/AE until resolution 
of the event (see Section 12.5.10). 
9.2. 
Discontinuation of study vaccine(s)  
‘Discontinuation’ of study intervention refers to any participant who has not received all 
planned doses of study intervention. A participant who discontinued study intervention 
may continue other study procedures (e.g. safety or immunogenicity), planned in the 
study protocol at the discretion of the investigator.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• 
Adverse event requiring expedited reporting to GSK 
• 
Unsolicited non-serious adverse event  
• 
Solicited adverse event 
• 
Not willing to be vaccinated 
• 
Other (specify). 
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9.3. 
Lost to follow-up 
A subject will be considered lost to follow-up if she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or should 
continue in the study. 
• 
Before a subject is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• 
Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
Sample size determination 
10.1.1. 
Hypotheses related to primary and secondary objectives 
No hypothesis driven sample size calculation was conducted due to the descriptive nature 
of the study. 
10.1.2. 
Sample size calculation 
The sample size of 50 subjects per group and 100 subjects per group in the combined 
formulations at the first vaccination were planned to provide reasonable confidence to 
evaluate the AE rate and quantify immunogenicity interference. The table below 
illustrates the precision that can be obtained on the percentage of subjects with AEs 
following vaccination. If an AE is not observed in a given treatment group, a sample size 
of 50 subjects can provide at least 95% confidence to rule out an AE incidence greater 
than 7.1%, and a total of 100 subjects in the combined formulations can provide at least 
95% confidence to rule out an AE rate greater than 3.6%. A combined 400 subjects 
across the RSVPreF3 groups and formulations can provide at least 95% confidence to 
rule out an AE incidence rate greater than 0.9%. 
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Furthermore, a sample size of 50 subjects per group and 100 subjects per group in the 
combined formulations would provide a probability of 92% or 99% to observe at least 
one AE respectively, if the true AE rate is 5%. In addition, a sample size of 400 when 
combining the RSVPreF3 groups would provide a probability of 98% to observe at least 
one AE if the true AE rate is only 1%. 
Table 18 
Exact 95% confidence interval (CI) on the probability of a subject 
with AEs events following vaccination of 50 subjects per group, (100 
subjects per group in US and ex-US combined) and 400 subjects 
with RSVPreF3 groups combined 
Number of subjects per 
group 
Number (%) of subjects with 
an AE 
Exact 95% CI 
Lower Limit (%) 
Upper Limit (%) 
50 
0 (0%) 
0 
7.1 
50 
5 (10%) 
3.3 
21.8 
50 
10 (20%) 
10 
33.7 
50 
15 (30%) 
17.9 
44.6 
50 
20 (40%) 
26.4 
54.8 
50 
25 (50%) 
35.5 
64.5 
100 
0 (0%) 
0 
3.6 
100 
5 (5%) 
1.6 
11.3 
100 
10 (10%) 
4.9 
17.6 
100 
15 (15%) 
8.6 
23.5 
100 
20 (20%) 
12.7 
29.2 
100 
25 (25%) 
16.9 
34.7 
400 
0 (0%) 
0 
0.9 
400 
5 (1.25%) 
0.4 
2.9 
400 
10 (2.5%) 
1.2 
4.5 
400 
15 (3.75%) 
2.1 
6.1 
400 
20 (5%) 
3.1 
7.6 
400 
25 (6.25%) 
4.1 
9.1 
Exact 95% CI computed based on Clopper/Pearson formula 
In order to evaluate the humoral response to 2 dose levels (60 and 120 g) of RSVPreF3 
when given alone, and co-administered with dTpa, the difference between co-
administration with dTpa (RSVPreF3 dTpa) and RSVPreF3 alone (RSVPreF3 placebo) in 
terms of RSV-A neutralizing antibody (Nab) titers will be evaluated at Day 8 and Day 31 
post the first vaccination.  
Table 19 presents the precision estimation on the ratio of the Geometric Mean of RSV-A 
Nab titers (GMT) with their 90% CI between two study groups, and the power to claim 
non-inferiority, when the sample size is 100 subjects per group and 50 subjects per group, 
with a range of standard deviation (SD) of RSV-A Nab titers 0.3-0.5 on its log10 
transformation and non-inferiority margin of 1.5 between RSVPreF3 alone and 
RSVPreF3 dTpa. 
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If a SD of log10 transformed RSV-A Nab of 0.4 is assumed, when the sample size is 50 
subjects per group, the half width of the 90% CI on the log ratio of GMT between co-
administration with dTpa and RSVPreF3 alone is 0.133. With an observed GMT ratio of 
1, its 90% CI will be (0.74, 1.36). With subjects in US and ex-US combined, there will be 
at least 90% chance that the upper bound of one-sided 95% CI for the ratio of GMT of 
RSV-A Nab titer between RSVPreF3 alone and co-administration with dTpa is under 1.5-
fold. 
Table 19 
Precision and power in terms of RSV-A neutralizing antibody titers 
with a sample size of 100 subjects per group and 50 subjects per 
group 
Number of 
subjects per 
group 
Ratio of GMT 
between two 
groups 
SD* 
90% CI 
90% CI 
Power for non-
inferiority test (%) *** 
LL 
UL 
50 
0.9 
0.3 
0.71 
1.13 
97.9 
50 
0.9 
0.4 
0.66 
1.22 
86.6 
50 
0.9 
0.5 
0.61 
1.32 
71.2 
50 
1.0 
0.3 
0.79 
1.26 
89.8 
50 
1.0 
0.4 
0.74 
1.36 
70.5 
50 
1.0 
0.5 
0.68 
1.47 
54.1 
50 
1.1 
0.3 
0.87 
1.38 
72.0 
50 
1.1 
0.4 
0.81 
1.49 
51.0 
50 
1.1 
0.5 
0.75 
1.61 
37.9 
100 
0.9 
0.3 
0.77 
1.06 
100 
100 
0.9 
0.4 
0.73 
1.11 
98.8 
100 
0.9 
0.5 
0.69 
1.18 
93.1 
100 
1.0 
0.3 
0.85 
1.17 
99.4 
100 
1.0 
0.4 
0.81 
1.24 
92.7 
100 
1.0 
0.5 
0.76 
1.31 
79.8 
100 
1.1 
0.3 
0.94 
1.29 
93.5 
100 
1.1 
0.4 
0.89 
1.36 
76.6 
100 
1.1 
0.5 
0.84 
1.44 
60.0 
*Standard deviation of log10 of RSV-A Nab titer. The highest standard deviation observed 30 days after vaccination in a 
previous GSK RSV study was 0.4.  
**Precision estimation for log GMT ratio using PASS 12.0.2 (CI for two means), LL: Lower Limit, UL: Upper Limit 
***PASS: Non-Inferiority Tests for Two Means using Differences with one-sided alpha 5% and Non-Inferiority Margin 
0.176 on log 10 scale (corresponding to Non-Inferiority Margin 1.5 for GMT ratio). 
10.2. 
Populations for analyses 
For purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Enrolled 
Subjects who agreed to participate in a clinical study after completion of the 
informed consent process. And subject is not a screen failure.  
Exposed  
All subjects who received at least 1 dose of the study treatment. The allocation 
in a group is done in function of the administered treatment. 
Per Protocol  
All subjects who received at least 1 dose of the study treatment to which they 
are randomised and have post-vaccination data minus subjects with protocol 
deviations that lead to exclusion 
Solicited Safety  
All subjects who received at least 1 dose of the study treatment (Exposed Set) 
who have solicited safety data 
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10.3. 
Statistical analyses 
10.3.1. 
Subjects disposition 
The number of screened, enrolled, and vaccinated subjects included in each group or in 
total for a given age category or for all age categories will be described. These might be 
additionally broken down by country and/or by site. 
10.3.2. 
Demography and baseline characteristics analyses 
Demographic characteristics (age at first study vaccination in weeks, or months or years, 
gender, race and ethnicity [where applicable]), vaccination history, will be summarised 
by overall and vaccine groups using descriptive statistics: 
• 
Frequency tables will be generated for categorical variables such as centre. 
• 
Mean, standard deviation, median, minimum and maximum will be provided for 
continuous data such as age, height, weight and body mass index (BMI). 
10.3.3. 
Immunogenicity analyses 
The primary analysis will be based on the Per Protocol set for analysis of 
immunogenicity. If, in any study group and at any timepoint, the percentage of enrolled 
or vaccinated subjects with serological results excluded from the Per Protocol set for 
analysis of immunogenicity is 5% or more, a second analysis based on the Exposed Set 
will be performed to complement the Per Protocol analysis. 
Endpoint 
Statistical Analysis Methods 
Primary 
(US + ex-US data to be pooled for the first vaccination) 
For each group, at each time point that blood samples are collected for humoral immune 
response and for each assay (unless otherwise specified): 
• 
GMCs/GMTs and their 95% CI will be tabulated and represented graphically pooled. 
• 
Geometric mean of ratios of antibody titer/concentrations at each individual post-
vaccination time point over pre-vaccination (screening) will be tabulated with 95% CI 
pooled. 
• 
Antibody titer/concentration will be displayed using reverse cumulative curves pooled. 
• 
The kinetics of GMT/GMCs will be plotted as a function of time for subjects with results 
available at all time points pooled. 
• 
The GMT/GMCs ratio and their 90% CI between RSVPreF3 dTpa and RSVPreF3 alone in 
terms of RSV-A Nab titers and RSV IgG antibody concentrations may be calculated at 
Screening, and/or Day 8, and/or Day 31 pooled for all subjects. 
• 
A further exploratory between-groups analysis will be performed at Day 8 or Day 31 using 
an ANCOVA model by including study groups, study formulation (US and ex-US), age 
category, and level of antibodies at Screening as covariates. 
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Endpoint 
Statistical Analysis Methods 
Secondary 
(US and ex-US data to be considered pooled, then separately for the first vaccination) 
For each group, at each time point that blood samples are collected for humoral immune 
response and for each assay (unless otherwise specified): 
• 
GMCs/GMTs and their 95% CI will be tabulated and represented graphically by 
formulation (US and ex-US) Geometric mean of ratios of antibody titer/concentrations at 
each individual post-vaccination time point over pre-vaccination (screening) will be 
tabulated with 95% CI by formulation (US and ex-US). 
• 
Antibody titer/concentration will be displayed using reverse cumulative curves by 
formulation (US and ex-US). 
• 
The kinetics of GMT/GMCs will be plotted as a function of time for subjects with results 
available at all time points by formulation (US and ex-US). 
• 
Booster response rates for PT, FHA and PRN (with exact 95% CI) will be calculated by 
group for each formulation (US and ex-US). 
For the data collected for the second vaccination, the humoral immune response of RSV PreF3 
will be summarized based on 2 dose level (60 and 120 µg) from the first vaccination. 
• 
GMCs/GMTs and their 95% CI will be tabulated and represented graphically for prior and 
post 2nd dose vaccination 
• 
Geometric mean of ratios of antibody titer/concentrations at individual post- 2nd dose 
vaccination time point (visit 6) over prior 2nd dose vaccination time point (visit 4) will be 
tabulated with 95% CI 
• 
Antibody titer/concentration will be displayed using reverse cumulative curves on prior and 
post 2nd vaccination 
• 
The kinetics of GMT/GMCs will be plotted as a function of time for subjects with results 
available at all time points including the visits from the first vaccination. 
Booster responses to PT, FHA and PRN antigens are defined as: 
• 
For subjects with pre-vaccination antibody concentration below the assay cut-offs: post-
vaccination antibody concentration ≥ 4 times the assay cut-offs, 
• 
For subjects with pre-vaccination antibody concentration between the assay cut-offs and 
below 4 times the assay cut-offs: post-vaccination antibody concentration ≥ 4 times the 
pre-vaccination antibody concentration, and 
• 
For subjects with pre-vaccination antibody concentration ≥ 4 times the assay cut-offs: 
post-vaccination antibody concentration 2 times the pre-vaccination antibody 
concentration. 
− 
The percentage of subjects with anti-D antibody concentrations ≥1.0 IU/mL by 
ELISA and the percentage of subjects with anti-T antibody concentrations ≥1.0 
IU/mL by ELISA (with exact 95% CI) will be calculated by group for each formulation 
(US and ex-US). 
− 
The GMT/GMCs ratio and their 90% CI between RSVPreF3 dTpa and dTpa placebo 
in terms of anti-PT, anti-FHA, anti-PRN, anti-D, anti-T will be calculated at Screening 
and Day 31 pooled for all subjects and by formulation (US and ex-US). 
− 
A further exploratory between-groups analysis will be performed at Day 31 using an 
ANCOVA model by including study groups, study formulation (US and ex-US), age 
category, and level of antibodies at Screening as covariates. 
− 
For Boostrix booster response to antigens PT, FHA and PRN, the two-sided 
standardized asymptotic 95% CI for the group differences in the percentage of 
subjects with a booster response to each antigen in the RSVPreF3 dTpa vaccine 
group and (minus) the dTpa Placebo vaccine group on Day 31 post vaccination will 
be calculated for each formulation. 
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Endpoint 
Statistical Analysis Methods 
− 
For Boostrix seroprotection rate (percentage of subjects with antibody 
concentrations ≥ 0.1 IU/mL by ELISA) for antigens D and T, the two-sided 
standardized asymptotic 95% CI for the group differences in the percentage of 
subjects with antibody concentrations ≥0.1 IU/mL in the RSVPreF3 dTpa vaccine 
group and (minus) the dTpa Placebo vaccine group at Day 31 post vaccination will 
be calculated for each formulation. 
Tertiary 
Will be described in a Statistical Analysis Plan finalised before database unblinding/freezing. 
10.3.4. 
Safety analyses  
The primary safety analyses will be performed on the Exposed Set. The following safety 
analyses will be performed based on the Exposed Set. The following safety analysis will 
be performed on the pooled formulations, the US and ex-US separately. 
Endpoint 
Statistical Analysis Methods 
Primary 
(US + ex-US data to be pooled) 
For each group with 1st dose vaccination of RSVPreF3 (two dose levels) when given alone or 
co-ad with dTpa; the following points will be analysed for 1st and 2nd dose vaccination. 
The percentage of subjects with at least one local AE with at least one general AE and with any 
(“solicited or unsolicited”) AE during the 7-day or 30 -day follow up is for SAE visit post 1st and 
2nd vaccination period will be tabulated with exact 95% CI by study group. The same 
computations will be done for Grade 3 AEs, for any AEs considered related to vaccination, for 
Grade 3 AEs considered related to vaccination and for AEs resulting in medically attended visits. 
The percentage of subjects reporting each individual solicited local AE (any grade, Grade 3 and 
those resulting in a medically attended visit) and solicited general AE (any grade, Grade 3, any 
related, Grade 3 related and those resulting in a medically attended visit) during the 7-day 
follow-up period (i.e. on the day of vaccination and 6 subsequent days) will be tabulated based 
on maximum intensity for each group. 
For fever, the number and percentage of subjects reporting fever by half degree (°C) cumulative 
increments during the 7-day follow-up period will be tabulated for each group. Similar tabulations 
will be performed for any fever with a causal relationship to vaccination, Grade 3 or above 
(> 39.0°C/102.2°F) causally related fever, and fever resulting in a medically attended visit. In 
addition, the prevalence of any and Grade 3 fever will be presented graphically over time after 
each vaccination. 
The percentage of subjects with any unsolicited AEs during the 30-day follow-up period (i.e. on 
the day of vaccination and 29 subsequent days) with its exact 95% CI will be tabulated by group 
and by Medical Dictionary for Regulatory Activities (MedDRA) SOC and preferred term. Similar 
tabulation will be done for Grade 3 unsolicited AEs, for any causally related unsolicited AEs, for 
Grade 3 causally related unsolicited AEs and for unsolicited AEs resulting in a medically 
attended visit. The verbatim reports of unsolicited AEs will be reviewed by a physician and the 
signs and symptoms will be coded according to the MedDRA Dictionary for Adverse Reaction 
Terminology. 
The percentage of subjects with at least one report of SAE classified by the MedDRA Preferred 
Terms and reported during the 30-day follow-up period will be tabulated with exact 95% CI. 
SAEs will also be described in detail. 
The percentage of subjects using concomitant medication (any medication, any antipyretic and 
any antipyretic taken prophylactically, respectively) during the 7-day follow-up period and during 
the 30-day follow-up period will be summarized by each group and pooled.  
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Endpoint 
Statistical Analysis Methods 
Secondary 
(US and ex-US data to be considered pooled, then separately) 
For each group with 1st dose vaccination of RSVPreF3 (two dose level) when given alone or co-
ad with dTpa; the following points will be analysed for 1st and 2nd dose vaccination. 
The percentage of subjects with at least one local AE with at least one general AE and with any 
(“solicited or unsolicited”) AE during the 7-day or 30 -day follow-up as well any SAE up period to 
180 days post 1st and 2nd vaccination time points will be tabulated with exact 95% CI by study 
group. The same computations will be done for Grade 3 AEs, for any AEs considered related to 
vaccination, for Grade 3 AEs considered related to vaccination and for AEs resulting in medically 
attended visits. 
The percentage of subjects with at least one report of SAE classified by the MedDRA SOC and 
Preferred Terms and reported during the 30-day follow-up period will be tabulated with exact 
95% CI for each formulation (US and ex-US).  
The percentage of subjects reporting each individual solicited local AE (any grade, Grade 3 and 
those resulting in a medically attended visit) and solicited general AE (any grade, Grade 3, any 
related, Grade 3 related and those resulting in a medically attended visit) during the 7-day 
follow-up period (i.e. on the day of vaccination and 6 subsequent days) will be tabulated based 
on maximum intensity for each group for each formulation (US and ex-US). 
For fever, the number and percentage of subjects reporting fever by half degree (°C) cumulative 
increments during the 7-day follow-up period will be tabulated for each group for each 
formulation (US and ex-US). Similar tabulations will be performed for any fever with a causal 
relationship to vaccination, Grade 3 or above (> 39.0°C/102.2°F) causally related fever, and 
fever resulting in a medically attended visit. In addition, the prevalence of any and Grade 3 fever 
will be presented graphically over time after each vaccination. 
For each formulation (US and ex-US), the percentage of subjects with any unsolicited AEs 
during the 30-day follow-up period (i.e. on the day of vaccination and 29 subsequent days) with 
its exact 95% CI will be tabulated by group and by Medical Dictionary for Regulatory Activities 
(MedDRA) SOC and preferred term. Similar tabulation will be done for Grade 3 unsolicited AEs, 
for any causally related unsolicited AEs, for Grade 3 causally related unsolicited AEs and for 
unsolicited AEs resulting in a medically attended visit. The verbatim reports of unsolicited AEs 
will be reviewed by a physician and the signs and symptoms will be coded according to the 
MedDRA Dictionary for Adverse Reaction Terminology. 
Tertiary 
Will be described in a Statistical Analysis Plan finalised before database unblinding/freezing. 
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10.4. 
Sequence of analyses 
Analyses to evaluate objectives and endpoints will be performed in steps. 
• 
A first analysis will be performed on all data available and as clean as possible, 
when data for at least primary and secondary endpoints pertaining to safety and 
immunogenicity up to Day 31 are available. At this point, the statistician will be 
unblinded (i.e. individual subject treatment assignments will be available), but no 
individual listings will be provided to the study team. Given that summary safety 
results may unblind some specific subjects, the study will be considered as single-
blind from this point onwards, with subjects and investigators remaining blinded up 
to study end. The investigators will not be provided with the individual data listings 
or with the randomization listings until the end of study analysis.  
• 
The second analysis will evaluate safety data and will be performed when all 
subjects have completed visits up to (and including) C1 (Day 181) and the data are 
available. From this point the study is unblinded.  
• 
The third analysis will evaluate safety and immunogenicity data and will be 
performed when all subjects have completed visits up to (and including) Visit 6 
(Day 31 post 2nd dose vaccination) and the data are available. At this time, any 
available safety data will also be provided. 
• 
The final end-of-study will be performed when all data for at least primary and 
secondary endpoints up to study conclusion at Day 181 post 2nd dose vaccination 
(C3) are available. An integrated clinical study report containing all available data 
will be written and made available to the investigators  
The final study report will contain at least the final analyses of all primary and secondary 
endpoints. If the data for tertiary endpoints become available at a later stage, (an) 
additional analysis/ analyses will be performed. These analyses will be documented in 
annex(es) to the study report. 
If the data for tertiary endpoints become available at a later stage, (an) additional 
analysis/ analyses will 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. 
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11. 
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Disorders: Recommendations and Rationale. The American journal of psychiatry. 
2013;170(8):834-851. Doi:10.1176/appi.ajp.2013.12060782. 
Mazzilli S, Tavoschi L, Lopalco PL. Tdap vaccination during pregnancy to protect 
newborns from pertussis infection. Ann Ig. 2018 Jul-Aug;30(4):346-363. Doi: 
10.7416/ai.2018.2226. 
Melville-Smith ME, Seagroatt VA, Watkins JT. A comparison of enzyme-linked 
immunosorbent assay (ELISA) with the toxin neutralization test in mice as a method for 
the estimation of tetanus antitoxin in human sera. J Biol Stand. 1983 Apr;11(2):137-44. 
Theeten H, Van Damme P, Hoppenbrouwers K, et al. Effects of lowering the aluminium 
content of a dTpa vaccine on its immunogenicity and reactogenicity when given as a 
booster to adolescents. Vaccine 23(2005) 1515–1521. 
Vidor E, Plotkin SA. Immunogenicity of a two-component (PT & FHA) acellular 
pertussis vaccine in various combinations Hum Vaccin. 2008 Sep-Oct;4(5):328-40. 
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12. 
APPENDICES 
12.1. 
Appendix 1: Abbreviations, glossary of terms and 
trademarks 
12.1.1. 
List of abbreviations  
Ab 
Antibody 
AE 
Adverse Event 
AE(s) 
Adverse Event(s) 
Anti- 
Antibodies against 
BS H 
Blood Sample Humoral 
CDC 
Centers for Disease Control 
CI 
Confidence Interval 
CLS 
Clinical Laboratory Sciences 
CoP 
Correlate of Protection 
COVID 
Severe acute respiratory syndrome coronavirus 2 
D 
Diphtheria 
dTpa 
Diphtheria, Tetanus and acellular Pertussis 
eCRF 
electronic Case Report Form 
ELISA 
Enzyme-Linked Immunosorbent Assay 
EoS 
End of Study 
eTDF 
Electronic Temperature excursion Decision Form 
Ex-US 
Outside the US 
FDA 
Food and Drug Administration, United States of America 
FHA 
Filamentous Hemagglutinin 
FU 
Follow-up 
GCP 
Good Clinical Practice 
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GMC 
Geometric Mean Concentration 
GMT 
Geometric Mean Titer 
GSK 
GlaxoSmithKline 
GSK 
GlaxoSmithKline 
IAF 
Informed Assent Form 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin 
IM 
Intramuscular 
IMP 
Investigational Medicinal Product 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
iSRC 
Internal Safety Review Committee 
LAR 
Legally Acceptable Representative 
LSLV 
Last Subject Last Visit 
MACDP 
Metropolitan Atlanta Congenital Defects Program 
MedDRA 
Medical Dictionary for Regulatory Activities 
Nab 
Neutralizing antibody 
PCD 
Primary Completion Date 
pIMD 
Potential Immune-Mediated Disease 
PP 
Per protocol 
PRN 
Pertactin 
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PRO 
Patient Related Outcomes 
PT 
Pertussis Toxoid 
RRA 
Recruitment/Randomisation Agreement 
RSV 
Respiratory Syncytial Virus 
RSVPreF3 
RSV maternal vaccine 
SAE 
Serious Adverse Event 
SAE 
Serious Adverse Event 
SBIR 
Source data Base for Internet Randomisation  
SD 
Standard Deviation 
SDV 
Source Document Verification 
SmPC 
Summary of Product Characteristics 
SPM 
Study Procedures Manual 
SRT 
Safety Review Team 
T 
Tetanus 
UP 
Urine Pregnancy Test 
VSMB 
Vaccine Safety Monitoring Board 
12.1.2. 
Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use 
of a medicinal product, whether or not considered related 
to the medicinal product. 
An adverse event (AE) can therefore be any unfavourable 
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. 
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Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the treatment 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 subject and the site and sponsor 
personnel involved in the clinical evaluation of the 
subjects are blinded while other study personnel may be 
aware of the treatment assignment (see Section 7.3 for 
details on observer-blinded studies).  
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. 
Child in care: 
A child who has been placed under the control or 
protection of an agency, organisation, institution or entity 
by the courts, the government or a government body, 
acting in accordance with powers conferred on them by 
law or regulation. The definition of a child in care can 
include a child cared for by foster parents or living in a 
care home or institution, provided that the arrangement 
falls within the definition above. The definition of a child 
in care does not include a child who is adopted or has an 
appointed legal guardian. 
Eligible: 
Qualified for enrolment 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: 
Subjects who agreed to participate in a clinical study after 
completion of the informed consent process. and subject 
is not a screen failure.  
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Epoch: 
Interval of time in the planned conduct of a study. An 
epoch is associated with a purpose (e.g. screening, 
randomisation, treatment, follow-up), which applies 
across all arms of a study. NOTE: Epoch is intended as a 
standardised term to replace: period, cycle, phase, stage.  
Essential documents: 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of the 
data produced. 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per-protocol analysis (see Section 10.2 for 
details on criteria for evaluability). 
Immunological correlate 
of protection: 
The defined immune response above which there is a high 
likelihood of protection in the absence of any host factors 
that might increase susceptibility to the infectious agent. 
Investigational vaccine: 
(Synonym of 
Investigational Medicinal 
Product) 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorisation 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.  
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: 
(The terms legal 
representative or legally 
authorised 
representative are used 
in some settings.) 
An individual or juridical or other body authorised under 
applicable law to consent, on behalf of a prospective 
subject, to the subject's participation in the clinical trial. 
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Primary completion 
date: 
The date that the final subject 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 subjects, 
scope of the investigation, study design, or scientific 
integrity of the study. 
Randomisation: 
Process of random attribution of treatment to subjects in 
order to reduce bias of selection. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Site Monitor: 
An individual assigned by the sponsor who is responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Solicited adverse event: 
AEs to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively 
solicited from the subject or an observer during a 
specified post-vaccination follow-up period. 
Source data: 
All information in original records and certified copies of 
original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data are 
contained in source documents (original records or 
certified copies). 
Source documents: 
Original documents, data, and records (e.g. hospital 
records, clinical and office charts, laboratory notes, 
memoranda, subjects' 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, subject files, and records kept at the pharmacy, at 
the laboratories and at medico-technical departments 
involved in the clinical trial). 
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Study vaccine/product: 
Any investigational vaccine/product being tested and/or 
any authorised use of a vaccine/product/placebo as a 
reference or administered concomitantly, in a clinical trial 
that evaluates the use of an investigational 
vaccine/product. 
Sub-cohort: 
A group of subjects for whom specific study procedures 
are planned as compared to other subjects or a group of 
subjects who share a common characteristic (e.g. ages, 
vaccination schedule…) at the time of enrolment. 
Subject: 
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the clinical study, either as a recipient of 
the vaccine(s) or as a control. 
Subject number: 
A unique number identifying a subject, assigned to each 
subject consenting to participate in the study. 
Treatment: 
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 subject. 
Treatment number: 
A number identifying a treatment to a subject, according 
to treatment allocation. 
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. 
12.1.3. 
Trademarks 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Generic description 
Boostrix  
 
Combined diphtheria, tetanus and acellular 
pertussis vaccine (adsorbed) 
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12.2. 
Appendix 2: Clinical and safety laboratory tests 
The tests detailed in Table 20 will be performed by the local laboratory. 
All clinical and safety laboratory tests will be performed by local laboratory(ies). All 
assessments of immune response (Section 8.4) will be performed centrally (by GSK or by 
a GSK-designated laboratory). 
Protocol-specific requirements for inclusion or exclusion of subjects 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 
Whole 
blood 
Haematology1 
Leukocytes (White Blood Cells) 
As per local 
practice 
Quantitative 
At 
investigator’s 
laboratory 
Lymphocytes 
Eosinophils 
Basophils 
Haemoglobin 
Platelets 
Neutrophils 
Serum 
Biochemistry 
Alanine Aminotransferase (ALT) 
As per local 
practice 
Quantitative 
Aspartate Aminotransferase 
(AST) 
Creatinine 
Blood Urea Nitrogen 
(BUN)/urea]* 
Urine1 
 
Pregnancy 
As per local 
practice; dipstick 
provided by GSK 
Biologicals  
Ordinal 
At 
investigator’s 
laboratory  
* Sites not able to directly test for BUN, will test for urea and then convert urea values into BUN using the applicable 
established conversion factor(s). 
1 In certain labs a complete blood counts will be required per local lab practice (more than just those listed in table) 
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12.3. 
Appendix 3: Clinical laboratories 
Table 21 
GSK laboratories, 
Laboratory 
Address 
GSK Biological’s Clinical Laboratory Sciences, 
Rixensart  
Biospecimen Reception-B7/44 
Rue de l'Institut, 89-B-1330 Rixensart-Belgium  
GSK Biological’s Clinical Laboratory Sciences, 
Wavre-Nord Noir Epine 
Avenue Fleming, 20-B-1300 Wavre-Belgium 
GSK Vaccines GmbH 
Clinical Laboratory Sciences, Marburg, 
Germany 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
Table 22 
Outsourced laboratories  
Laboratory 
Address 
Nexelis Inc.  
525, Cartier Ouest Laval 
Quebec Canada H7V 3S8 
Nexelis Inc. 
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12.4. 
Appendix 4: Study governance considerations 
12.4.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organisations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, Informed Consent Form (ICF) or Informed 
Assent Form (IAF), 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 amendments to the protocol 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 subjects.  
• 
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. 
12.4.2. 
Financial disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interest prior 
initiation of the centre and at the end of the study. Investigators are responsible for 
providing an update of Financial Disclosure if their financial interest changes at any point 
during their participation in a study and for 1 year after completion of the study.  
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12.4.3. 
Informed consent process  
The investigator or his/her representative will explain the nature of the study to the 
subject or his/her legally authorised representative and answer all questions regarding the 
study.  
Subjects must be informed that their participation is voluntary.  
Freely given and written or witnessed/thumb printed informed consent must be obtained 
from each subject, as appropriate, prior to participation in the study.  
The content of informed consent form must meet the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study centre. 
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was 
obtained. The authorised person obtaining the informed consent must also sign the ICF. 
Subjects 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 subject. 
Subjects who are rescreened are required to sign a new ICF. 
12.4.4. 
Data protection 
Subject will be assigned a unique identifier by the sponsor. Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject’s 
names or any information which would make the subject identifiable will not be 
transferred.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  
The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorised personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
GSK will also ensure the protection of personal data of investigator and the site staff 
which will be collected within the frame and for the purpose of the study.  
12.4.5. 
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. 
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12.4.6. 
Publication policy 
GSK aims to publish the results of this study in searchable, peer reviewed scientific 
literature. GSK will target to submit within 18 months from LSLV for interventional 
studies and from the completion of the analysis for non-interventional studies and follows 
the guidance from the International Committee of Medical Journal Editors. 
12.4.7. 
Dissemination of clinical study data 
The key design elements of this protocol will be posted on the GSK Clinical Study 
Register and on publicly accessible registers including ClinicalTrials.gov. Where 
required, protocol summaries will also be posted on national or regional clinical trial 
registers or databases (e.g. EudraCT database) in compliance with the applicable 
regulations. 
GSK also assures that results will be submitted to ClinicalTrials.gov within the required 
time-frame, in compliance with the current regulations mentioned in the table below.  
At the time of study results posting, the full study protocol and statistical analysis plan 
will also be posted on ClinicalTrials.gov.  
In addition, for studies that are in scope of the EU Clinical Trial Directive, summaries of 
the results of GSK interventional studies (phase I-IV) in adult population will be posted 
within defined timelines on the publicly available EU Clinical Trial Register.  
If it is not possible to submit a summary of the results within the required timelines in the 
concerned EU member state, the summary of results shall be submitted as soon as it is 
available. In this case, the protocol shall specify when the results are going to be 
submitted, together with a justification.  
 
Clinicaltrial.gov 
EU 
Protocol summary 
Before enrolment of subjects 
As per CTA submission/Before 
enrolment of subjects 
Results summary 
Within 12 months of PCD (Primary 
and safety endpoint results)/Within 
12 months of LSLV* (for secondary 
endpoint results) 
Within 6 months (for paediatric 
population studies)/Within 12 months 
(for adult population studies) of EoS*. 
* As defined in the study protocol. 
Under the framework of the SHARE initiative, anonymised patient-level data from GSK 
sponsored interventional studies that evaluate products will be made available within 6 
months of this publication to independent researchers whose research proposals have 
been approved by an independent panel. Requests for access may be made through 
www.clinicalstudydatarequest.com. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, 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 subjects, as appropriate. 
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12.4.8. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents including source documents. The storage system used during the trial and for 
archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval.  
Essential documents for the trial may be added or reduced where justified (in advance of 
trial initiation) based on the importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, CRF), the copy should fulfil the 
requirements for certified copies.  
All subject data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g. laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF/eCRF.  
The investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial subjects that supports the 
information entered in the eCRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data.  
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorised site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data should be traceable, should not 
obscure the original entry, and should be explained if necessary (e.g. via an audit trail). 
Safety and rights of subjects must be protected and study be conducted in accordance 
with the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
Trial records and source documents, including signed ICF, pertaining to the conduct of 
this study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/equivalent summary unless local regulations or institutional 
policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor.  
12.4.9. 
Source documents 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Investigator should maintain a record of the location(s) of 
their source documents.  
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Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available. 
Definition of what constitutes source data and source documents can be found in the 
glossary of terms. 
12.4.10. 
Study and site closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK, provided there is sufficient notice given 
to account for patient’s safe exit from study participation. Study sites regular closure will 
be upon study completion. A study site is considered closed when all required 
data/documents and study supplies have been collected and a study-site closure visit has 
been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of subjects by the investigator 
• 
Discontinuation of further study treatment development 
The investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the Study Conclusion screen in the/eCRF. 
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12.5. 
Appendix 5: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting 
12.5.1. 
Definition of AE 
12.5.1.1. 
AE Definition 
An AE is any untoward medical occurrence in a clinical study subject, temporally 
associated with the use of a study treatment, whether or not considered related to the 
study treatment. 
NOTE: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment. 
12.5.1.2. 
Events Meeting the AE Definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study vaccine(s) administration even 
though they may have been present prior to the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
vaccine(s) or a concurrent medication (overdose per se should not be reported as an 
AE/SAE). 
• 
Signs, symptoms temporally associated with study vaccine(s) administration. 
• 
Significant failure of expected pharmacological or biological action.  
• 
Pre- or post-treatment events that occur as a result of protocol-mandated procedures 
(i.e. invasive procedures, modification of subject’s previous therapeutic regimen). 
• 
Medically attended visits related to adverse events (e.g. Hospital stays, physician 
visits and emergency room visits). 
AEs to be recorded as endpoints (solicited AEs) are described in Section 12.5.3. 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 fulfil the definition of an AE or SAE.  
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12.5.1.3. 
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 subject prior to the 
study vaccination. These events will be recorded in the medical history section of the 
eCRF. 
12.5.2. 
Definition of SAE 
A 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 subject 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 hospitalisation or prolongation of existing hospitalisation, 
Note: In general, hospitalisation signifies that the subject 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 hospitalisation are also considered AEs. If a complication prolongs 
hospitalisation or fulfils any other serious criteria, the event will also be considered 
serious. When in doubt as to whether ‘hospitalisation’ occurred, or was necessary, 
the AE should be considered serious. 
Hospitalisation for elective treatment of a pre-existing condition (known or 
diagnosed prior to informed consent signature) that did not worsen from baseline is 
NOT considered an AE. 
d. Results in disability/incapacity, OR 
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, diarrhoea, 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 subject. 
f. 
Medical or scientific judgement should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise 
the subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition. These should also be considered 
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serious. Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalisation. 
12.5.3. 
Solicited adverse events 
a. Solicited local (injection-site) adverse events 
The following local (injection-site) AEs will be solicited: 
Table 23 
Solicited local adverse events 
Pain at injection site 
Redness at injection site 
Swelling at injection site 
b. Solicited general adverse events 
The following general AEs will be solicited: 
Table 24 
Solicited general adverse events 
Fatigue 
Fever 
Gastrointestinal symptoms † 
Headache 
†Gastrointestinal symptoms include nausea, vomiting, diarrhoea and/or abdominal pain. 
Note: subjects will be instructed to measure and record the axillary or oral body 
temperature in the evening. Should additional temperature measurements be performed at 
other times of day, subjects will be instructed to record the highest temperature in the 
diary card. 
12.5.4. 
Unsolicited adverse events 
An unsolicited adverse event is an adverse event that was not solicited using a Subject 
Diary and that was spontaneously communicated by a subjects who has signed the 
informed consent. 
Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses 
requiring hospitalisation, or emergency room visit, or visit to/by a health care provider), 
or were of concern to the subjects. In case of such events, subjects will be instructed to 
contact the site as soon as possible to report the event(s). The detailed information about 
the reported unsolicited AEs will be collected by the qualified site personnel during the 
interview and will be documented in the subject’s records. 
Unsolicited AEs that are not medically attended nor perceived as a concern by subjects 
will be collected during interview with the subjects and by review of available medical 
records at the next visit. 
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12.5.5. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as adverse events or serious adverse events  
In absence of diagnosis, abnormal laboratory findings (e.g. clinical chemistry, 
haematology, urinalysis) or other abnormal assessment that are judged by the investigator 
to be clinically significant will be recorded as AE or SAE if they meet the definition of an 
AE or SAE (refer to Sections 12.5.1 and 12.5.2). 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. However, clinically significant abnormal laboratory findings or other abnormal 
assessments that are associated with the disease being studied, unless judged by the 
investigator as more severe than expected for the subject’s condition, or that are present 
or detected at the start of the study and do not worsen, will not be reported as AEs or 
SAEs. 
The investigator will exercise his or her medical and scientific judgement in deciding 
whether an abnormal laboratory finding or other abnormal assessment is clinically 
significant. 
12.5.6. 
Events or outcomes not qualifying as adverse events or serious 
adverse events 
12.5.6.1. 
Pregnancy 
Female subjects who become pregnant after the vaccination may continue the study at the 
discretion of the investigator. 
While pregnancy is not considered an AE or SAE, any adverse pregnancy outcome or 
complication or elective termination of a pregnancy for medical reasons will be recorded 
and reported as an AE or a SAE. 
Note: The pregnancy should always be recorded on an electronic pregnancy report. 
The following should always be considered as SAE and will be reported as described in 
Sections 12.5.8.1 and 12.5.8.4: 
• 
Spontaneous pregnancy loss, including: 
− 
spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation) 
− 
ectopic and molar pregnancy 
− 
stillbirth (intrauterine death of foetus after 22 weeks of gestation). 
Note: the 22 weeks’ cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure [EMA, 2006]. It is recognised that national 
regulations might be different. 
• 
Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life).  
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• 
Any congenital anomaly or birth defect identified in the offspring of a study subject 
(either during pregnancy, at birth or later) regardless of whether the foetus is 
delivered dead or alive. This includes anomalies identified by prenatal ultrasound, 
amniocentesis or examination of the products of conception after elective or 
spontaneous abortion. 
Furthermore, any SAE occurring as a result of a post-study pregnancy AND considered 
by the investigator to be reasonably related to the study vaccine(s) will be reported to 
GSK as described in Section 12.5.8. While the investigator is not obligated to actively 
seek this information from former subjects, he/she may learn of a pregnancy through 
spontaneous reporting. 
12.5.7. 
Detecting and recording adverse events, serious adverse events 
and pregnancies 
A Paper Diary (pDiary) hereafter referred to as Subject Diary will be used in this study to 
capture solicited or unsolicited adverse events. The subject should be trained on how and 
when to complete each field of the Subject Diary. 
The subjects will be instructed to contact the investigator immediately should the subject 
manifest any signs or symptoms they perceive as serious.  
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject 
Diary. This individual may not be the subject, but if a person other than the subject enters 
information into the Subject Diary, this person’s identity must be documented in the 
Subject Diary. Any individual that makes entries into the Subject Diary must receive 
training on completion of the Subject Diary at the time of the visit when Subject Diary is 
dispensed. This training must be documented in the subject’s source record. 
At the vaccination visit, the diary card will be provided to the subject. The subject/ will 
be instructed to measure and record the body temperature (oral preferred), and any 
solicited local/general AEs (i.e. on the day of vaccination and during the next 6 days) or 
any unsolicited AEs (i.e. on the day of vaccination and during the next 30 days occurring 
after the 1st and 2nd vaccination. The subject will be instructed to return the completed 
diary card to the investigator at the next study visit. 
12.5.7.1. 
Time period for detecting and recording adverse events, serious 
adverse events and pregnancies 
All AEs during 7 days following administration of each dose vaccination of study 
vaccine(s) (Day 1 to Day 7 post primary vaccination and Day 1 to Day 7 post 2nd 
vaccination ) must be recorded into the appropriate section of the eCRF, irrespective of 
intensity or whether or not they are considered vaccination-related. 
All AEs/SAEs leading to withdrawal from the study will be collected and recorded from 
the time of the receipt of study vaccine(s)/product(s). 
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SAEs that are related to the study vaccine(s) will be collected and recorded from the time 
of the receipt of study vaccine(s) until the subject is discharged from the study. 
In addition to the above-mentioned reporting requirements and in order to fulfil 
international reporting obligations, SAEs that are related to study participation (i.e. 
protocol-mandated procedures, invasive tests, a change from existing therapy) or are 
related to a concurrent GSK medication/vaccine will be collected and recorded from the 
time the subject consents to participate in the study until she/he is discharged from the 
study. 
The time period for collecting and recording pregnancies will begin at the receipt of study 
vaccine(s) and will end 181 days following administration of the dose of study 
vaccine(s). See section 12.5.8 for instructions on reporting of pregnancies. 
12.5.7.2. 
Evaluation of adverse events and serious adverse events 
12.5.7.2.1. Active questioning to detect adverse events and serious adverse 
events 
As a consistent method of collecting AEs, the subject should be asked a non-leading 
question such as: 
‘Have you felt different in any way since receiving the vaccine(s) or since the previous 
visit?’ 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) relative 
to the event. The investigator will then record all relevant information regarding an 
AE/SAE in the eCRF. The investigator is not allowed to send photocopies of the 
subject’s medical records to GSK instead of appropriately completing the eCRF. 
However, there may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers will be blinded on the copies of 
the medical records prior to submission to GSK. 
The investigator will attempt to establish a diagnosis pertaining to the event based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE and not the individual signs/symptoms. 
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Is there a reasonable possibility that the AE may have been caused by the study vaccine? 
YES 
: 
There is a reasonable possibility that the study vaccine(s) contributed to 
the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to the 
administration of the study vaccine(s). There are other, more likely 
causes and administration of the study vaccine(s) is not suspected to 
have contributed to the AE. 
If an event meets the criteria to be determined as ‘serious’ (see Section 12.5.2), additional 
examinations/tests will be performed by the investigator in order to determine ALL 
possible contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the vaccine(s)/product(s) (delete as applicable), if applicable. 
• 
Erroneous administration. 
• 
Other cause (specify). 
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). 
12.5.7.2.3. Medically attended visits 
For each solicited and unsolicited symptom the subject experiences, the subject will be 
asked if she received medical attention defined as hospitalisation, 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.  
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12.5.8. 
Reporting of serious adverse events, pregnancies, and other 
events 
12.5.8.1. 
Prompt reporting of serious adverse events, pregnancies, and other 
events to GSK 
SAEs that occur in the time period defined in Section 12.5.7 will be reported promptly to 
GSK within the timeframes described in Table 15, once the investigator determines that 
the event meets the protocol definition of a SAE. 
Pregnancies that occur in the time period defined in Section 12.5.7 will be reported 
promptly to GSK within the timeframes described in Table 15, once the investigator 
becomes aware of the pregnancy.  
12.5.8.2. 
SAEs requiring expedited reporting to GSK 
Once an investigator becomes aware that a SAE has occurred in a study subject, the 
investigator (or designate) must complete the information in the electronic Expedited 
Adverse Events Report WITHIN 24 HOURS. The report will always be completed as 
thoroughly as possible with all available details of the event. Even if the investigator does 
not have all information regarding a SAE, the report should still be completed within 24 
hours. Once additional relevant information is received, the report should be updated 
WITHIN 24 HOURS. 
The investigator will always provide an assessment of causality at the time of the initial 
report. The investigator will be required to confirm the review of the SAE causality by 
ticking the ‘reviewed’ box in the electronic Expedited Adverse Events Report within 72 
hours of submission of the SAE. 
12.5.8.3. 
Back-up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designate) must 
complete, then date and sign a paper Expedited Adverse Events Report and fax it to the 
Study Contact for Reporting SAEs (refer to the Sponsor Information) or to GSK Clinical 
Safety and Pharmacovigilance department within 24 hours.  
This back-up system should only be used if the electronic reporting system is not working 
and NOT if the system is slow. As soon as the electronic reporting system is working 
again, the investigator (or designate) must complete the electronic Expedited Adverse 
Events Report within 24 hours. The final valid information for regulatory reporting will 
be the information reported through the electronic SAE reporting system.  
12.5.8.4. 
Completion and transmission of pregnancy reports to GSK (Amended 
09-APR-2021) 
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 24 HOURS. 
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Note: Conventionally, the estimated gestational age (EGA) of a pregnancy is dated from 
the first day of the last menstrual period (LMP) of the cycle in which a woman conceives. 
If the LMP is uncertain or unknown, dating of EGA and the estimated date of delivery 
(EDD) should be estimated by ultrasound examination and recorded in the pregnancy 
report. 
12.5.9. 
Updating of SAE, pregnancy, information after removal of write 
access to the subject’s eCRF 
When additional SAE and pregnancy information is received after removal of the write 
access to the subject’s eCRF, new or updated information should be recorded on the 
appropriate paper report, with all changes signed and dated by the investigator. The 
updated report should be faxed to the Study Contact for Reporting SAEs (refer to the 
Sponsor Information) or to GSK Clinical Safety and Pharmacovigilance department 
within the designated reporting time frames specified in Table 15. 
12.5.10. 
Follow-up of adverse events, serious adverse events, and 
pregnancies 
12.5.10.1. Follow-up during the study 
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject and provide additional relevant information on the subject’s condition to GSK 
(within 24 hours for SAEs; refer to Table 15). 
All SAEs (serious or non-serious) documented at a previous visit/contact and designated 
as not recovered/not resolved or recovering/resolving will be reviewed at subsequent 
visits/contacts until the last visit of the subject. 
All AEs documented at a previous visit/contact and designated as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until 30 
days after the last vaccination. 
12.5.10.2. Follow-up after the subject is discharged from the study 
The investigator will follow subjects: 
• 
with SAEs, or subjects withdrawn from the study as a result of an AE, until the event 
has resolved, subsided, stabilised, disappeared, or until the event is otherwise 
explained, or the subject is lost to follow-up.  
If the investigator receives additional relevant information on a previously reported SAE, 
he/she will provide this information to GSK using a paper/electronic Expedited Adverse 
Events Report and/or pregnancy report as applicable. 
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GSK may request that the investigator performs or arranges the conduct of additional 
clinical examinations/tests and/or evaluations to elucidate as fully as possible the nature 
and/or causality of the AE or SAE. The investigator is obliged to assist. If a subject dies 
during participation in the study or during a recognised follow-up period, GSK will be 
provided with any available post-mortem findings, including histopathology. 
12.5.10.3. Follow-up of pregnancies 
Pregnant subjects 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 doesn’t 
need to be longer than 6 to 8 weeks after the estimated date of delivery. 
Regardless of the reporting period for SAEs for this study, if the pregnancy outcome is a 
SAE, it should always be reported as SAE 
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12.6. 
Appendix 6: Contraceptive guidance and collection of 
pregnancy information 
12.6.1. 
Definitions 
12.6.1.1. 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below) 
12.6.1.1.1. Women in the following categories are not considered WOCBP 
• 
Premenarchal 
Menarche is the onset of menses for the first time in a young female and is preceded 
by several changes associated with puberty including breast development and pubic 
hair growth. Menarche usually occurs within 1-2 years of breast development, 
thelarche. However, a young female can become pregnant before her first menses. 
Thus, a conservative definition of non-childbearing potential in a pre-menarcheal 
female is a young female who has not yet entered puberty as evidenced by lack of 
breast development (palpable glandular breast tissue). 
• 
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 subject’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 
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 1 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrolment. 
12.6.2. 
Contraception guidance 
• 
Female subjects of childbearing potential are eligible to participate if they agree to 
use an adequate contraception consistently and correctly according to the methods 
listed in GSK list of highly effective contraceptive methods provided in Table 26. 
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Table 26 
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 (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation  
• 
oral 
• 
intravaginal  
• 
transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulation  
• 
injectable  
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 
Vasectomised partner  
(A vasectomised 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 sterilisation prior to the female subject’s entry into the study, and this male is the sole partner for that 
subject, 
(The information on the male sterility can come from the site personnel’s review of the subject’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 subject.)  
NOTES:  
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for subjects in clinical studies.  
12.6.3. 
Collection of pregnancy information 
12.6.3.1. 
Female Subjects who become pregnant 
• 
Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 2 
weeks of learning of a subject's pregnancy.  
• 
Subject will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on subject and neonate, which will be 
forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
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• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.  
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such. 
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in 12.5.8. While the investigator is not obligated to actively seek this 
information in former study subjects, she may learn of an SAE through spontaneous 
reporting.  
Any female subject who becomes pregnant while participating will continue the study.  
12.7. 
Appendix 7: Genetics  
Not applicable 
12.8. 
Appendix 8: Country-specific requirements 
Not applicable. 
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12.9. 
Appendix 9: Protocol Amendment/Administrative change 
History 
The Protocol Amendment/Administrative change Summary of Changes Table for the 
current amendment/administrative change is located directly before the Table of Contents 
(TOC). 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 6 
9-APR-2021 
Amendment 5 
2-Nov-2020 
Amendment 4 
28-Aug-2020 
Amendment 3 
3-Apr-2020 
Amendment 2 
23-Jan-2020 
Amendment 1 
21-Oct-2019 
Original Protocol 
23-Aug-2019 
Overall Rationale for Amendment 1: The current holding rules do not include death or 
life-threatening SAEs considered related to vaccination that occur > 30 days post 
vaccination. In order to ensure inclusion of such events as triggers for study hold, the 
phrase “non-life-threatening” has been removed from holding rule 1b.  
Detailed description of Protocol Amendment 1 
Table 16 
Study holding rules  
Holding 
Rule 
Event 
Number of Subjects 
1a 
Death or any life-threatening SAE occurring within 30 days from 
vaccination 
≥1 
1b 
Any non-life-threatening SAE that can be reasonably attributed to 
the vaccination 
≥1 
Overall Rationale for Amendment 2  
This study has been amended to collect immunogenicity data to 12 months post dosing. 
Long term persistence data will be useful to inform the boosting schedule for women 
entering successive pregnancies. Unblinding after Day 181 will still occur and the 
extended study (epoch 4) will be open label. 
In addition, several discrepancies with the protocol with the study procedures manual 
were aligned. 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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To evaluate the safety of 2 dose levels (60 and 
120 μg) of RSVPreF3 when given alone and co-
administered with dTpa compared to dTpa-Placebo 
groups from Vaccination up to Day 181365. 
x
Occurrence of SAEs from Vaccination up to Day 181 
365. 
x
To evaluate the safety of 2 dose levels (60 and 
120 μg) of RSVPreF3 when given alone and co-
administered from Vaccination up to Day 181 365 by 
formulation. 
x
Occurrence of SAEs from Vaccination up to Day 
181365.  
x
To evaluate the safety of RSVPreF3 (pooled for all 
groups receiving RSVPreF3). 
x
Occurrence of SAEs from Vaccination up to Day 
181365. 
Immunogenicity 
x
To evaluate the humoral immune response to 2 
dose levels (60 and 120 μg) of RSVPreF3 when 
given alone and co-administered with dTpa at 
Screening, Day 8, and Day 31, Day 181, and Day 
365 post vaccination by formulation. 
Immunogenicity 
x
RSV A neutralizing antibody titers at Screening, Day 
8, and Day 31, Day 181, and Day 365 
x
RSV IgG antibody concentrations at Screening, Day 
8, and Day 31, Day 181, and Day 365 
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Note: study groups labeled X = ex-US; study groups labeled U = US. 
x
= Vaccination; N = number of subjects; CHS= Chemical/Hematological Screening Visit; D = Day; AE = 
adverse event; UP = Urine pregnancy test; FU = follow-up; BSH = blood sample (5 mL) for humoral immune responses 
(RSV-A neutralization and RSV IgG antibody concentrations at Screening, Visit 2 [Day 8],and Visit 3 [Day 31], Visit 4 
[Day 181], and Visit 5 [Day 365], and dTpa ELISAs at Screening and Visit 3 [Day 31]) 
For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 
as described in the protocol. Participants that do not sign the informed consent addendum will complete the 
study at day 181 with a phone contact. 
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Epoch 
Epoch 
001 
Epoch 002  
(Vaccination) 
Epoch 003  
(Follow-up)8 
Epoch 004  
(Extension Study)8 
Type of contact 
Screening Visit 1 Visit 2 Visit 3 Phone 
Contact 1 
Visit 4 
Visit 5 
Time points 
Day -7 to 
Day 1 
Day 1 Day 8 
Day 31 Day 181  
Day 181 
Day 365 
Sampling time points 
Pre-Vacc Vacc Post-
Vacc 
Post-
Vacc 
Post-Vacc 
Post Vacc 
Post Vacc 
Physical examination 2  
● 
● 
● 
O 
 
O 
O 
Informed consent for extension 
study 
 
 
 
 
 
● 
 
Phone contact 
 
 
 
 
● 
 
 
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209141 (RSV MAT-011) 
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Epoch 
Epoch 
001 
Epoch 002  
(Vaccination) 
Epoch 003  
(Follow-up)8 
Epoch 004  
(Extension Study)8 
Blood sampling for humoral 
immune response (~5 mL) 4 
● 
 
● 
● 
 
● 
● 
Recording of AE leading to 
withdrawal 
 
● 
● 
● 
● 
● 
●8 
Recording of serious AE 6 
● 
● 
● 
● 
● 
● 
●8 
Recording of pregnancies  
 
● 
● 
● 
● 
● 
●8 
Recording of concomitant 
medications/vaccinations 
 
● 
● 
● 
● 7 
● 
● 7, 8 
Record any intercurrent medical 
conditions  
 
 
● 
● 
● 
● 
●8 
Screening conclusion  
● 
 
 
 
 
 
 
Investigator sign-off on eCRF 
before analysis 
● 
 
 
 
●8 
 
●8 
Study conclusion 
 
 
 
 
 
 
●8 
2 Physical examination including resting vital signs (blood pressure, heart rate and respiratory rate, temperature) after 
at least 10 minutes of rest. Weight, height and BMI will only be collected at Screening. Physical examination at  
Visit 2, Visit 3, Visit 4 and Visit 5, will be performed only if deemed necessary by the investigator. For Visit 1 and 
Visit 2, (if performed), only vital signs will be collected in the eCRF. 
8 For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 
as described in the protocol. Participants that do not sign the informed consent addendum will complete the 
study at day 181 with a phone contact. 
Table 4 
Intervals between study visits 
Interval 
Optimal timing  
Allowed interval 
 Screening Visit →Visit 1  
≤7 days  
-7- 1 days  
Visit 1 →Visit 2  
8 days  
7- 10 days  
Visit 1 →Visit 3  
31 days 
30- 45 days  
Visit 1→Phone Contact  
181 days 
165- 195 days  
Phone Contact→ Visit 4 
 
0-30 days 
Visit 1 →Visit 5 
365 days 
335-395 days 
5.2 Overall design 
• 
Duration of the study: Approximately 6 months 1 year for each enrolled subject that 
signs the addendum for the extended study phase. For those that do not sign the 
addendum for the extended study phase the duration of the study will last 
approximately 6 months. 
− 
Epoch 001: Screening 
− 
Epoch 002: Primary (i.e., vaccination phase) starting at Visit 1 (Day 1) and 
ending just before the Visit 3 (Day 31)  
− 
Epoch 003: Follow-up Phone Ccontact Day 181)  
− 
Epoch 004: Follow Visit 4 (Day 181) to Visit 5 (Day 365) 
• 
Primary completion Date (PCD): Visit 3 (Day 31) or last visit of Primary Epoch  
Refer to glossary of terms for the definition of PCD. 
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• 
End of Study (EoS): Last testing results released of samples collected at Visit 5 3, to 
occur no later than 8 months after last subject last visit (LSLV), which occurs with 
Visit 5 Contact 1 on Day 365 181. 
Table 6 
Study groups, treatment and epochs foreseen in the study 
Study Groups 
Number 
of 
subjects 
Age 
(Min-
Max) 
Treatment 
name 
Epochs 
(Blinding) 
Epoch 001 
(Screening) 
Epoch 002 
(observer-
blind) 
Epoch 003 
(single-
blind) 
Epoch 
004 
(open 
study) 
XRSV120_dTpa 
50 
18 - 
45 
years 
RSV MAT 
120  
Boostrix-ex-
US 
(dTpa_500) 
x 
x 
x 
x 
XPlacebo_RSV120 
50 
18 - 
45 
years 
RSV MAT 
120 
Placebo 
x 
x 
x 
x 
XRSV60_dTpa 
50 
18 - 
45 
years 
RSV MAT 
60 
Boostrix-ex-
US 
(dTpa_500) 
x 
x 
x 
x 
XPlacebo_RSV60 
50 
18 - 
45 
years 
RSV MAT 
60 
Placebo  
x 
x 
x 
x 
XPlacebo_dTpa 
50 
18 - 
45 
years 
Boostrix-ex-
US 
(dTpa_500) 
Placebo 
x 
x 
x 
x 
URSV120_dTpa 
50 
18 – 
45 
years 
RSV MAT 
120 
Boostrix-US 
(dTpa_300) 
x 
x 
x 
x 
UPlacebo_RSV120 
50 
18 – 
45 
years  
RSV MAT 
120 
Placebo 
x 
x 
x 
x 
URSV60_dTpa 
50 
18 - 
45 
years  
RSV MAT 
60 
Boostrix-US 
x 
x 
x 
x 
UPlacebo_RSV60  
50 
18 - 
45 
years 
RSV MAT 
60 
Placebo 
x 
x 
x 
x 
UPlacebo_dTpa 
50 
18 – 
45 
years 
Boostrix-US 
(dTpa_300) 
Placebo 
x 
x 
x 
x 
5.4 Subject and study completion 
A subject is considered to have completed the study if he/she is available for the 
concluding contact visit (Visit 5, Day 181365) as described in the protocol. For those 
participants that do not sign the ICF amendment the EOS will be the Day 181 phone 
contact as described in previous version of protocol (RSV MAT-011 (209141) 
Protocol Amendment 1 (21-Oct-2019). 
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7.3 Blinding and unblinding 
After the Day 181 phone contact for a given subject, the investigator will be 
informed of the subject’s treatment assignment and will communicate this to the 
subject. For Visit 4 (Day 181) and Visit 5 (Day 365), the study will continue during 
the extended follow-up phase as an open study. 
7.5.1 Recording of concomitant medications/products and concomitant vaccinations 
• 
Any concomitant vaccination administered in the period starting 30 days before the 
dose of study vaccine(s) and ending at the last study visit/contact (Day -30 to Day 
181 365). 
8.0 Study assessments and procedures 
For subjects consenting to the extended follow-up phase, 2 additional evaluations 
will be performed at Day 181 (Visit 4) and Day 365 (Visit 5). The subject will be 
queried for the occurrence of SAE and associated concomitant medication, 
pregnancy, and vaccinations received. In addition, approximately 5 ml of blood will 
be collected for assessment of vaccine immunogenicity.  
8.2.3 Physical Examination 
Perform a physical examination of the subject, including assessment of axillary or 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 full physical examination of the subject at screening visit, including 
assessment of axillary or 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 history directed physical exam plus vital signs at Visit 1 [Day 1] 
Physical examinations at each study visit subsequent to the vaccination visit, will be 
performed only if the subject indicates during questioning that there might be some 
underlying pathology(ies) or if deemed necessary by the Investigator or delegate. Any 
vitals signs measured at Visit 2 (Day 8) should be recorded in the eCRF). 
8.3.Immunogenicity assessments 
Any sample testing will be done in line with the consent of the individual 
subject/subject’s parent(s)/LAR(s). 
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Table 10 
Biological samples 
Sample type 
Collected to Evaluate 
Minimum 
Quantity 
per subject 
Unit 
Time point 
Additional Information 
Whole blood for 
immune response* 
5 
ml 
Visit 4 (Day 181) 
Immune response: 5 mL (~ 2 mL 
serum). 
Whole blood for 
immune response*  
5 
ml 
Visit 5 (Day 365) 
Immune response: 5 mL (~ 2 mL 
serum). 
 
3020.5* 
ml 
Minimum Total, not including repeat or unscheduled 
samples 
*For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 
as described in the protocol and 30.5 mL of blood will be collected in total during the study. Participant’s 
that do not sign the informed consent addendum will complete the study at day 181 with a phone contact 
and 20.5 m of blood will be collected in total during the study. 
Table 11 
Humoral Immunity (Antibody determination) 
Sampli
ng time 
points 
Syste
m 
Component 
Metho
d 
Kit/ 
Manufactur
er 
Unit 
Cut-
off* 
Group
s 
Numbe
r of 
subjec
ts 
Laborato
ry 
Screeni
ng 
Serum 
Respiratory 
Syncytial 
Virus PreF3 
Ab.IgG 
concentratio
n 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Neomed 
Serum 
Respiratory 
Syncytial 
Virus PreF3 
Ab.IgG 
concentratio
n 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Neomed  
Day 31 
 
 
 
 
 
 
 
 
 
Serum 
Respiratory 
Syncytial 
Virus PreF3 
Ab.IgG 
concentratio
n 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Neomed  
Day 
181* 
Seru
m 
Respiratory 
Syncytial 
Virus A Ab 
neutralizing 
NEU 
In house 
ED60 
and/or IU 
(internatio
nal unit) 
18 
for 
ED6
0 
TBD 
for 
IU 
All 
500 
GSK 
Seru
m 
Respiratory 
Syncytial 
Virus PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
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Sampli
ng time 
points 
Syste
m 
Component 
Metho
d 
Kit/ 
Manufactur
er 
Unit 
Cut-
off* 
Group
s 
Numbe
r of 
subjec
ts 
Laborato
ry 
Day 
365* 
Seru
m 
Respiratory 
Syncytial 
Virus A Ab 
neutralizing 
NEU 
In house 
ED60 
and/or IU 
(internatio
nal unit) 
18 
for 
ED6
0 
TBD 
for 
IU 
All 
500 
GSK 
Seru
m 
Respiratory 
Syncytial 
Virus PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Ab = antibody; ELI = Enzyme-linked immunosorbent assay (ELISA); IgG = immunoglobulin G; RSV = respiratory 
syncytial virus; ED60 = serum dilution inducing 60% inhibition in plaque forming units; IU/ml = International 
units/milliliter, IU= International units; TBD = to be determined 
Assay cut-off and unit might be subject to change before starting of testing (e.g. in case of requalification, revalidation 
or standardisation). In this case, this will be documented in the clinical report. 
* For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 
as described in the protocol. Participant’s that do not sign the informed consent addendum will complete the 
study at day 181 with a phone contact. 
***GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium; Marburg, 
Germany. 
Table 12 
Immunological read-outs 
Blood sampling timepoint 
Subset name 
Approximate 
No. subjects 
Component 
Components 
priority rank  
Visit 4 (Day 
181)*** 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
Visit 5 (Day 
365)*** 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
*** For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 
365 as described in the protocol. Participant’s that do not sign the informed consent addendum will 
complete the study at day 181 with a phone contact. 
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Table 13 
Reporting periods for collecting safety information 
Event 
Pre- 
V1* 
 V1 
V2 
V3 
Phone contact 1 V4** 
V5 (Study 
Conclusion 
D1 D7 D8 D30 D31 
D181 
D181 
D365 
Solicited local and general 
AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* i.e. consent obtained. Pre-V: pre-vaccination; V: vaccination; Post-V: post-vaccination; D: Day, M: Month 
**For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 
365 as described in the protocol. Participant’s that do not sign the informed consent addendum will 
complete the study at day 181 with a phone contact. 
8.5 Holding rules and safety monitoring 
If the Central Team becomes aware of a holding rule being met, the below flow of 
communication must be followed: 
• CRDL to inform the local Study team (Table 15) 
• The LML/delegate of each country confirm the reception of the holding rule to 
the CRDL and inform all the investigators. 
• The concerned site staff has to put vaccination and enrolment on hold. 
• The central study team will ensure SBIR is blocked and all vaccinating centres 
are informed. 
• GSK Safety Review Team (SRT) will further evaluate the case and escalate to 
GSK VSMB for making the decision to stop or to restart the vaccination. All 
site staff will be informed about that final decision by their local GSK contact. 
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9.1 Discontinuation from the study 
For the participants that sign the informed consent addendum, the conclusion of the 
study will be on Day 365 as described in the protocol. Participants that do not sign 
the informed consent addendum will complete the study at day 181 with a phone 
contact. From an analysis perspective, a ‘withdrawal’ from the study refers to any 
subject was not available for the concluding contact foreseen in the protocol. 
10.1.2 Sample size calculation 
In order to evaluate the humoral response to 2 dose levels (60 and 120 g) of RSVPreF3 
when given alone, and co-administered with dTpa, the difference between co-
administration with dTpa (RSVPreF3 dTpa) and RSVPreF3 alone (RSVPreF3 placebo) in 
terms of RSV-A neutralizing antibody (Nab) titers will be evaluated at Day 8 and Day 31. 
Additional sampling at Day 181, and Day 365 will allow evaluation of the 
persistence of RSVPreF3 responses.  
10.2 Populations for analyses 
For purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Enrolled 
Subjects who agreed to participate in a clinical study after completion of 
the informed consent process. and subject is not a screen failure. Refer to 
the glossary of terms for the definition of ‘enrolled’ 
All subjects who completed the informed consent process and signed the 
informed consent form  
10.3.3 Immunogenicity analyses  
Endpoint 
Statistical Analysis Methods 
Primary 
The GMT/GMCs ratio and their 90% CI between RSVPreF3 dTpa and RSVPreF3 alone in terms 
of RSV-A Nab titers and RSV IgG antibody concentrations will may be calculated at Screening, 
and/or Day 8, and/or Day 31 pooled for all subjects. 
• 
A further exploratory between-groups analysis will be performed at Day 8 or Day 31 using 
an ANCOVA model by including study groups, study formulation (US and ex-US), age 
category, and level of antibodies at Screening as covariates. 
Secondary 
• 
The GMT/GMCs ratio and their 90% CI between RSVPreF3 dTpa and RSVPreF3 alone 
in terms of RSV-A Nab titers and RSV IgG antibody concentrations may be 
calculated at Day 181, and/or Day 365* pooled for all subjects. 
*For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 
as described in the protocol. Participant’s that do not sign the informed consent addendum, will complete 
the study at day 181 with a phone contact. 
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10.3.4 Safety analyses  
Primary 
(US + ex-US data to be pooled) 
The percentage of subjects with at least one local AE (solicited and unsolicited), with at least 
one general AE (solicited and unsolicited) and with any (“solicited or unsolicited”) AE during 
the 7-day or 30 follow up is for SAE post vaccination period will be tabulated with exact 95% 
CI by study group. The same computations will be done for Grade 3 AEs, for any AEs 
considered related to vaccination, for Grade 3 AEs considered related to vaccination and for 
AEs resulting in medically attended visits. 
Secondary 
The percentage of subjects with at least one local AE (solicited and unsolicited), with at 
least one general AE (solicited and unsolicited) and with any (“solicited or unsolicited”) 
AE during the 7-day or 30 -day as well any SAE up to 365 days post vaccination will be 
tabulated with exact 95% CI by study group. The same computations will be done for 
Grade 3 AEs, for any AEs considered related to vaccination, for Grade 3 AEs considered 
related to vaccination and for AEs resulting in medically attended visits*. 
The percentage of subjects with at least one report of SAE classified by the MedDRA Preferred 
Terms and reported during the 30-day follow-up period will be tabulated with exact 95% CI for 
each formulation (US and ex-US). The same analysis will be done covering the entire study 
period (from vaccination up to day 365) In addition, similar analyses covering the 30-day 
follow up period and the 365 day follow up period will be performed for pooled 
formulations and pooled all groups receiving RSVPreF3 SAEs.  
The percentage of subjects using concomitant medication (any medication, any antipyretic and 
any antipyretic taken prophylactically, respectively) from vaccination up to day 181* will be 
summarized by each group for each formulation (US and ex-US). 
*For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 
as described in the protocol. Participant’s that do not sign the informed consent addendum will complete 
the study at day 181 with a phone contact. 
10.4 Sequence of analyses 
The final end-of-study analysis will be performed when all data for at least primary and 
secondary endpoints up to study conclusion (D365) are available. 
After Day 181(Visit 4) the study participants will be unblinded and the study 
extension phase will continue as an open study until the final study visit (Visit 5). 
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Table 19 
Protocol-Required Safety Laboratory Assessments 
System 
Discipline 
Component 
Method 
Scale 
Laboratory 
Whole 
blood 
Haematology1 
Leukocytes (White Blood Cells) 
As per local 
practice 
Quantitative 
At 
investigator’s 
laboratory 
Lymphocytes 
Eosinophils 
Basophils 
Haemoglobin 
Platelets 
Neutrophils 
Serum 
Biochemistry 
Alanine Aminotransferase (ALT) 
As per local 
practice 
Quantitative 
Aspartate Aminotransferase 
(AST) 
Creatinine 
Blood Urea Nitrogen 
(BUN)/urea]* 
Urine1 
 
Pregnancy 
As per local 
practice; dipstick 
provided by GSK 
Biologicals  
Ordinal 
At 
investigator’s 
laboratory  
* Sites not able to directly test for BUN, will test for urea and then convert urea values into BUN using the applicable 
established conversion factor(s). Only BUN values will be entered into the eCRF. 
Serum pregnancy test (instead of urine test) may be performed if required by country, local or ethics committee 
regulations. 
1 In certain local labs a complete blood counts will be required per local laboratory 
practice (more than just those listed in table). 
Table 21 
Outsourced laboratories 
Laboratory 
Address 
Nexelis NÉOMED-LABS Inc.  
525, Cartier Ouest Laval 
Quebec Canada H7V 3S8 
Nexelis NÉOMED-LABS Inc. 
12.1.1. List of abbreviations  
VSMB 
Vaccine Safety Monitoring Board 
12.1.2 Glossary of terms  
Enrolled 
Subjects who agreed to participate in a clinical study 
after completion of the informed consent process. and 
subject is not a screen failure.  
12.5.7.1 Time period for detecting and recording adverse events, serious adverse 
events and pregnancies 
The time period for collecting and recording pregnancies will begin at the receipt of study 
vaccine(s) and will end 181 365 days following administration of the dose of study 
vaccine(s). 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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x
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x


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x
To evaluate the safety of 2 dose levels (60 and 
120 μg) of RSVPreF3 when given alone and co-
administered with dTpa compared to dTpa-Placebo 
groups from Vaccination up to Day 181365. 
x
Occurrence of SAEs from Vaccination up to Day 181 
365. 
x
To evaluate the safety of 2 dose levels (60 and 
120 μg) of RSVPreF3 when given alone and co-
administered from Vaccination up to Day 181 365 by 
formulation. 
x
Occurrence of SAEs from Vaccination up to Day 
181365.  
x
To evaluate the safety of RSVPreF3 (pooled for all 
groups receiving RSVPreF3). 
x
Occurrence of SAEs from Vaccination up to Day 
181365. 
Immunogenicity 
x
To evaluate the humoral immune response to 2 
dose levels (60 and 120 μg) of RSVPreF3 when 
given alone and co-administered with dTpa at 
Screening, Day 8, and Day 31, Day 181, and Day 
365 post vaccination by formulation. 
Immunogenicity 
x
RSV A neutralizing antibody titers at Screening, Day 
8, and Day 31, Day 181, and Day 365 
x
RSV IgG antibody concentrations at Screening, Day 
8, and Day 31, Day 181, and Day 365 
)LJXUH6WXG\'HVLJQRYHUYLHZ
Note: study groups labeled X = ex-US; study groups labeled U = US. 
x
= Vaccination; N = number of subjects; CHS= Chemical/Hematological Screening Visit; D = Day; AE = 
adverse event; UP = Urine pregnancy test; FU = follow-up; BSH = blood sample (5 mL) for humoral immune responses 
(RSV-A neutralization and RSV IgG antibody concentrations at Screening, Visit 2 [Day 8],and Visit 3 [Day 31], Visit 4 
[Day 181], and Visit 5 [Day 365], and dTpa ELISAs at Screening and Visit 3 [Day 31]) 
For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol. Participants that do not sign the informed consent addendum will complete the study at day 
181 with a phone contact. 
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CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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120 
Table 3 
Schedule of Activities 
Epoch 
Epoch 
001 
Epoch 002  
(Vaccination) 
Epoch 003  
(Follow-up)8 
Epoch 004  
(Extension Study)8 
Type of contact 
Screening Visit 1 Visit 2 Visit 3 Phone 
Contact 1 
Visit 4 
Visit 5 
Time points 
Day -7 to 
Day 1 
Day 1 Day 8 
Day 31 Day 181  
Day 181 
Day 365 
Sampling time points 
Pre-Vacc Vacc Post-
Vacc 
Post-
Vacc 
Post-Vacc 
Post Vacc 
Post Vacc 
Physical examination 2  
● 
● 
● 
O 
 
O 
O 
Informed consent for extension 
study 
 
 
 
 
 
● 
 
Phone contact 
 
 
 
 
● 
 
 
Blood sampling for humoral 
immune response (~5 mL) 4 
● 
 
● 
● 
 
● 
● 
Recording of AE leading to 
withdrawal 
 
● 
● 
● 
● 
● 
●8 
Recording of serious AE 6 
● 
● 
● 
● 
● 
● 
●8 
Recording of pregnancies  
 
● 
● 
● 
● 
● 
●8 
Recording of concomitant 
medications/vaccinations7 
 
● 
● 
● 
● 7 
● 
● 7, 8 
Record any intercurrent medical 
conditions  
 
 
● 
● 
● 
● 
●8 
Screening conclusion  
● 
 
 
 
 
 
 
Investigator sign-off on eCRF 
before analysis 
● 
 
 
 
●8 
 
●8 
Study conclusion 
 
 
 
 
● 
 
●8 
2 Physical examination including resting vital signs (blood pressure, heart rate and respiratory rate, temperature) after 
at least 10 minutes of rest. Weight, height and BMI will only be collected at Screening. Physical examination at  
Visit 2, and Visit 3, Visit 4 and Visit 5, will be performed only if deemed necessary by the investigator. For Visit 1 and 
Visit 2, (if performed), only vital signs will be collected in the eCRF. 
8 For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol. Participants that do not sign the informed consent addendum will complete the study at day 
181 with a phone contact. 
Table 4 
Intervals between study visits 
Interval 
Optimal timing  
Allowed interval 
Screening Visit →Visit 1  
≤7 days  
-7- 1 days  
Visit 1→Visit 2  
8 days  
7- 10 days  
Visit 1→Visit 3  
31 days 
30- 45 days  
Visit 1→Phone Contact  
181 days 
165- 195 days  
Phone Contact→Visit 4 
 
0-30 days 
Visit 1 →Visit 5 
365 days 
335-396 days 
5.2 Overall design 
• 
Duration of the study: Approximately 6 months 1 year for each enrolled subject that 
signs the addendum for the extended study phase. For those that do not sign the 
addendum for the extended study phase the duration of the study will last 
approximately 6 months. 
• 
Epoch 001: Screening 
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209141 (RSV MAT-011) 
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121 
• 
Epoch 002: Primary (i.e., vaccination phase) starting at Visit 1 (Day 1) and 
ending just before the Visit 3 (Day 31)  
• 
Epoch 003: Follow-up Phone Contact (Day 181)  
• 
Epoch 004: Follow Visit 4 (Day 181) to Visit 5 (Day 365) 
• 
Primary completion Date (PCD): Visit 3 (Day 31) or last visit of Primary Epoch  
Refer to glossary of terms for the definition of PCD. 
• 
End of Study (EoS): Last testing results released of samples collected at Visit 5 3, to 
occur no later than 8 months after last subject last visit (LSLV), which occurs with 
Visit 5 Contact 1 on Day 365 181. 
Table 6 
Study groups, treatment and epochs foreseen in the study 
Study Groups 
Number 
of 
subjects 
Age 
(Min-
Max) 
Treatment 
name 
Epochs 
(Blinding) 
Epoch 001 
(Screening) 
Epoch 002 
(observer-
blind) 
Epoch 003 
(single-
blind) 
Epoch 004 
(open 
study) 
XRSV120_dTpa 
50 
18 - 
45 
years 
RSV MAT 
120  
Boostrix-ex-
US 
(dTpa_500) 
x 
x 
x 
x 
XPlacebo_RSV120 
50 
18 - 
45 
years 
RSV MAT 
120 
Placebo 
x 
x 
x 
x 
XRSV60_dTpa 
50 
18 - 
45 
years 
RSV MAT 
60 
Boostrix-ex-
US 
(dTpa_500) 
x 
x 
x 
x 
XPlacebo_RSV60 
50 
18 - 
45 
years 
RSV MAT 
60 
Placebo  
x 
x 
x 
x 
XPlacebo_dTpa 
50 
18 - 
45 
years 
Boostrix-ex-
US 
(dTpa_500) 
Placebo 
x 
x 
x 
x 
URSV120_dTpa 
50 
18 – 
45 
years 
RSV MAT 
120 
Boostrix-US 
(dTpa_300) 
x 
x 
x 
x 
UPlacebo_RSV120 
50 
18 – 
45 
years  
RSV MAT 
120 
Placebo 
x 
x 
x 
x 
URSV60_dTpa 
50 
18 - 
45 
years  
RSV MAT 
60 
Boostrix-US 
x 
x 
x 
x 
UPlacebo_RSV60  
50 
18 - 
45 
years 
RSV MAT 
60 
Placebo 
x 
x 
x 
x 
UPlacebo_dTpa 
50 
18 – 
45 
years 
Boostrix-US 
(dTpa_300) 
Placebo 
x 
x 
x 
x 
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122 
5.4 Subject and study completion 
A subject is considered to have completed the study if he/she is available for the 
concluding contact visit (Visit 5, Day 181365) as described in the protocol. For those 
participants that do not sign the ICF amendment the EOS will be the Day 181 phone 
contact as described in previous version of protocol (RSV MAT-011 (209141) Protocol 
Amendment 1 (21-Oct-2019). 
7.3 Blinding and unblinding 
After the Day 181 phone contact for a given subject, the investigator will be informed of 
the subject’s treatment assignment and will communicate this to the subject. For Visit 4 
(Day 181) and Visit 5 (Day 365), the study will continue during the extended follow-up 
phase as an open study. 
7.5.1 Recording of concomitant medications/products and concomitant vaccinations 
• 
Any concomitant vaccination administered in the period starting 30 days before the 
dose of study vaccine(s) and ending at the last study visit/contact (Day -30 to Day 
181 365). 
8.0 Study assessments and procedures 
For subjects consenting to the extended follow-up phase, 2 additional evaluations will be 
performed at Day 181 (Visit 4) and Day 365 (Visit 5). The subject will be queried for the 
occurrence of SAE and associated concomitant medication, pregnancy, and vaccinations 
received. In addition, approximately 5 ml of blood will be collected for assessment of 
vaccine immunogenicity.  
Table 10 
Biological samples 
Sample type 
Collected to Evaluate 
Minimum 
Quantity 
per subject 
Unit 
Time point 
Additional Information 
Whole blood for 
immune response* 
5 
ml 
Visit 4 (Day 181) 
Immune response: 5 mL (~ 2 mL 
serum). 
Whole blood for 
immune response*  
5 
ml 
Visit 5 (Day 365) 
Immune response: 5 mL (~ 2 mL 
serum). 
 
3020.5* 
ml 
Minimum Total, not including repeat or unscheduled samples 
*For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol and 30.5 mL of blood will be collected in total during the study. Participant’s that do not sign 
the informed consent addendum will complete the study at day 181 with a phone contact and 20.5 m of blood will be 
collected in total during the study. 
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209141 (RSV MAT-011) 
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Table 11 
Humoral Immunity (Antibody determination) 
Samplin
g time 
points 
Syste
m 
Componen
t 
Metho
d 
Kit/ 
Manufactur
er 
Unit 
Cut-
off* 
Group
s 
Numbe
r of 
subject
s 
Laborato
ry 
Screeni
ng 
Serum 
Respiratory 
Syncytial 
Virus 
PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
 
Serum 
Respiratory 
Syncytial 
Virus 
PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
 
Day 31 
 
 
 
 
 
 
 
 
 
Serum 
Respiratory 
Syncytial 
Virus 
PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
 
Day 
181* 
Serum 
Respiratory 
Syncytial 
Virus A Ab 
neutralizing 
NEU 
In house 
ED60 
and/or IU 
(internation
al unit) 
18 
for 
ED6
0 
TBD 
for 
IU 
All 
500 
GSK 
Serum 
Respiratory 
Syncytial 
Virus 
PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
Day 
365* 
Serum 
Respiratory 
Syncytial 
Virus A Ab 
neutralizing 
NEU 
In house 
ED60 
and/or IU 
(internation
al unit) 
18 
for 
ED6
0 
TBD 
for 
IU 
All 
500 
GSK 
Serum 
Respiratory 
Syncytial 
Virus 
PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
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CONFIDENTIAL 
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124 
Ab = antibody; ELI = Enzyme-linked immunosorbent assay (ELISA); IgG = immunoglobulin G; RSV = respiratory 
syncytial virus; ED60 = serum dilution inducing 60% inhibition in plaque forming units; IU/ml = International 
units/milliliter, IU= International units; TBD = to be determined 
Assay cut-off and unit might be subject to change before starting of testing (e.g. in case of requalification, revalidation 
or standardisation). In this case, this will be documented in the clinical report. 
* For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol. Participant’s that do not sign the informed consent addendum will complete the study at 
day 181 with a phone contact. 
***GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium; Marburg, 
Germany. 
Table 12 
Immunological read-outs  
Blood sampling timepoint 
Subset name 
Approximate 
No. subjects 
Component 
Components 
priority rank  
Visit 4 (Day 
181)*** 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
Visit 5 (Day 
365)*** 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
*** For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol. Participant’s that do not sign the informed consent addendum will complete the study at 
day 181 with a phone contact. 
Table 13 
Reporting periods for collecting safety information 
Event 
Pre- 
V1* 
 V1 
V2 
V3 
Phone contact 1 V4** 
V5 (Study 
Conclusion 
D1 D7 D8 D30 D31 
D181 
D181 
D365 
Solicited local and general 
AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading to withdrawal from 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to study 
participation  
or concurrent GSK 
medication/vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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125 
* i.e. consent obtained. Pre-V: pre-vaccination; V: vaccination; Post-V: post-vaccination; D: Day, M: Month 
**For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol. Participant’s that do not sign the informed consent addendum will complete the study at 
day 181 with a phone contact. 
9.1 Discontinuation from the study 
For the participants that sign the informed consent addendum, the conclusion of the study 
will be on Day 365 as described in the protocol. Participants that do not sign the informed 
consent addendum will complete the study at day 181 with a phone contact. From an 
analysis perspective, a ‘withdrawal’ from the study refers to any subject was not available 
for the concluding contact foreseen in the protocol. 
10.1.2 Sample size calculation 
In order to evaluate the humoral response to 2 dose levels (60 and 120 g) of RSVPreF3 
when given alone, and co-administered with dTpa, the difference between co-
administration with dTpa (RSVPreF3 dTpa) and RSVPreF3 alone (RSVPreF3 placebo) in 
terms of RSV-A neutralizing antibody (Nab) titers will be evaluated at Day 8 and Day 31. 
Additional sampling at Day 181, and Day 365 will allow evaluation of the persistence of 
RSVPreF3 responses.  
10.3.3 Immunogenicity analyses  
Endpoint 
Statistical Analysis Methods 
Secondary 
• 
The GMT/GMCs ratio and their 90% CI between RSVPreF3 dTpa and RSVPreF3 alone in 
terms of RSV-A Nab titers and RSV IgG antibody concentrations may be calculated at Day 
181, and/or Day 365* pooled for all subjects. 
*For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol. Participant’s that do not sign the informed consent addendum, will complete the study at 
day 181 with a phone contact. 
10.3.4 Safety analyses  
Secondary 
The percentage of subjects with at least one local AE (solicited and unsolicited), with at least 
one general AE (solicited and unsolicited) and with any (“solicited or unsolicited”) AE during the 
7-day or 30 -day as well any SAE up to 180 365 days post vaccination will be tabulated with 
exact 95% CI by study group. The same computations will be done for Grade 3 AEs, for any 
AEs considered related to vaccination, for Grade 3 AEs considered related to vaccination and 
for AEs resulting in medically attended visits*. 
*For the participants that sign the informed consent addendum, the conclusion of the study will be on Day 365 as 
described in the protocol. Participant’s that do not sign the informed consent addendum will complete the study at 
day 181 with a phone contact. 
10.4 Sequence of analyses 
The final end-of-study analysis will be performed when all data for at least primary and 
secondary endpoints up to study conclusion (D181365) are available. 
After Day 181(Visit 4) the study participants will be unblinded and the study extension 
phase will continue as an open study until the final study visit (Visit 5). 
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209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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126 
12.5.7.1 Time period for detecting and recording adverse events, serious adverse 
events and pregnancies 
The time period for collecting and recording pregnancies will begin at the receipt of study 
vaccine(s) and will end 181 365 days following administration of the dose of study 
vaccine(s). 
Overall Rationale for Amendment 4  
This study has been amended to collect immunogenicity data to 12 months post dosing. 
Long term persistence data will be useful to inform the boosting schedule for women 
entering successive pregnancies. Unblinding after Day 181 will still occur and the 
extended study (epoch 4) will be open label. 
In addition, several discrepancies with the protocol with the study procedures manual 
were aligned. 
Detailed description of Protocol Amendment 4 
This study has been amended to administer a second dose of the 120 µg RSVPreF3 
Maternal investigational vaccine to all consenting subjects within a 6-month period from 
the beginning of 12 months to the beginning of 18 months following initial immunization 
(≥12 to <18 months). This extension part of the study will use non-pregnant women as a 
proxy for women who may require additional dosing in successive pregnancies. 
Specifically, this extension will provide information on:  
1. Long term immunogenicity of a 1st dose of 60 µg or 120 µg RSVPreF3 vaccine 
2. Safety and immunogenicity of 2nd dose of 120 µg RSVPreF3 vaccine 
In addition, this protocol amendment outlines measures that may be applicable during 
special circumstances (e.g., COVID-19 pandemic). The purpose of the amendment is to 
protect the subject’s welfare, and as far as possible ensure the potential benefit to the 
subject and promote data integrity.  
Title 
Phase II randomized, observer-blind, placebo-controlled, multi-country study in healthy 
non-pregnant women 18-45 years of age to evaluate the safety, reactogenicity and 
immunogenicity of a 1stsingle intramuscular dose of GSK Biologicals’ investigational 
RSV maternal vaccine (GSK388550A) when given alone and given in co-administration 
with a single intramuscular dose of Boostrix (US formulation SB776423 or ex-US 
formulation SB263855) and to evaluate the safety, reactogenicity and 
immunogenicity of a 2nd dose of the RSV maternal vaccine.  
A Phase II study of a primary 2 dose levels of an investigational RSV maternal vaccine, 
given alone or with Boostrix, with a 2nd dose investigational RSV maternal vaccine to 
healthy non-pregnant women. 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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WKHLPPXQRJHQLFLW\DQGVDIHW\SURILOHRI5693UH)YDFFLQHVHFRQGGRVH
2EMHFWLYH
x
To evaluate the safety of a 2nd dose of RSVPreF3 
given from 12 up to18 months post 1st Dose up 
to Day 31 days post 2nd dose vaccination 
x
Occurrence of any AEs from 2nd dose to Day 31 
post-2nd dose vaccination, for all subjects:  
x
Occurrence of each solicited local AE at the site 
of injection in both deltoids from 2nd dose 
vaccination to Day 8 post-2nd dose vaccination 
x
Occurrence of solicited general AEs from 2nd 
dose vaccination to Day 8 post 2nd dose 
vaccination 
x
Occurrence of any unsolicited AEs from 2nd dose 
to Day 31 post- 2nd dose vaccination 
x
Occurrence of Serious Adverse Events (SAEs) 
from 2nd dose vaccination to Day 31 post 2nd 
dose vaccination. 
x
To evaluate the safety of 2nd dose of RSVPreF3 
given from 12 to up to 18 months post 1st dose 
vaccination up to Day 181 post 2nd dose 
vaccination. 
x
Occurrence of SAEs from 2nd dose vaccination 
up to Day 181 post-2nd dose vaccination. 
Immunogenicity 
x
To evaluate the humoral immune response and 
persistence to 2 dose levels (60 and 120 μg) of 
RSVPreF3 when given alone and co-administered 
with dTpa at Screening, Day 8, and Day 31 post 1st 
dose31post vaccination, and at 12 to 18 months 
by formulation. 
Immunogenicity 
x
RSV A neutralizing antibody titers at Screening, Day 
8, and Day 31, a single timepoint between 12 to 
18 months post 1st vaccination. 
x
RSV IgG antibody concentrations at Screening, Day 
8 and Day 31, a single timepoint between 12 to 18 
months post 1st vaccination. 
x
To evaluate the humoral immune response of a 
2nd dose vaccination of RSVPreF3 (120 μg), 
following a first dose vaccination of either 60 μg 
or 120 μg.  
x
RSV A neutralizing antibody titers 
concentrations 31 days post 2nd dose 
vaccination. 
x
RSV IgG antibody concentrations 31 days post 
2nd dose vaccination. 
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CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
9 April 2021 
128 
Overall Design 
 
 
BSH = blood sample (5 mL) for humoral immune responses (RSV-A neutralization and RSV IgG antibody 
concentrations at Screening, Visit 2, [Day 8] and Visit 3, [Day 31], Visit 4, [up to D7 prior to 2nd vaccination], and 
Visit 6 [D31 post 2nd vaccination] 
And dTpa ELISAs at Screening and Visit 3 [Day 31])  
* All subject groups will be given RSV 120mcg and subjects will be followed in an open labeled study 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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** Hematological and biochemical laboratory testing at Visit 4 (D -7 up to and including 2nd dose vaccination) at 
the investigator’s discretion  
***There will be no follow-up between C1 and V4. New medical history and relevant new safety events during 
this period will be recorded at visit 4 for subjects who agree to the study extension and sign the informed 
consent addendum. 
2. Schedule of Activities 
Epoch 
 
Epoch 004  
(Vaccination 2) 
Epoch 005 
(Follow-up 
2) 
Type of contact 
 
Visit 4 
Visit 5 
Phone 
Contact 2 
Visit 6 
Phone 
Contact 3 
Time points 
Day 181 to -7 
before 2nd 
vaccination 
Day -7 to 
Day of 2nd 
vaccination 
 
From 12 up to 
18 months 
post 1st 
vaccination 
Day 8 post 
2nd 
vaccination 
 
Day 31 post 
2nd 
vaccination 
Day 181 
post 2nd 
vaccination 
 
Sampling time points 
Pre-Vacc 2 
Pre-Vacc 2 
Vacc 2 
Post-Vacc 2 Post-Vacc 2 Post-Vacc 2 
Informed consent  
 
● 
 
 
 
 
Check inclusion/exclusion 
criteria  
 
● 
 
 
 
 
Check contraindications to 
subsequent vaccine(s) 
administration  
 
O 
O 
 
 
 
Phone contact 
 
 
 
● 
 
● 
Medical history  
 
●  
 
 
 
 
Physical examination 2  
 
● 
 
 
O 
 
Urine pregnancy test 3  
 
 
● 
 
 
 
Pre-vaccination body 
temperature and heart rate 
 
 
● 
 
 
 
Distribution of subject card 
 
 
O 
 
 
 
Hematological and 
biochemical laboratory 
testing (~5.5 mL) 
 
O8 
 
 
 
 
Blood sampling for humoral 
immune response (~5 mL) 4 
 
● 
 
 
● 
 
Treatment number allocation 
(SBIR) 
 
 
O 
 
 
 
Vaccine administration  
 
 
● 
 
 
 
Recording of administered 
treatment number  
 
 
● 
 
 
 
60 minutes post vaccination 
observation period  
 
 
O 
 
 
 
Training on use of diary 
cards  
 
 
O 
 
 
 
Distribution of diary cards5  
 
 
O 
 
 
 
Collection of diary cards  
 
 
 
 
O 
 
Diary card transcription by 
investigator or designate 
 
 
 
 
● 
 
Recording of solicited 
adverse events  
 
 
● 
● 
 
 
Recording of unsolicited 
adverse events  
 
 
● 
● 
● 
 
Recording of AE leading to 
withdrawal 
 
 
● 
● 
● 
● 
Recording of serious AE 6 
 
● 
● 
● 
● 
● 
Recording of pregnancies  
 
● 
● 
● 
● 
● 
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Epoch 
 
Epoch 004  
(Vaccination 2) 
Epoch 005 
(Follow-up 
2) 
Type of contact 
 
Visit 4 
Visit 5 
Phone 
Contact 2 
Visit 6 
Phone 
Contact 3 
Time points 
Day 181 to -7 
before 2nd 
vaccination 
Day -7 to 
Day of 2nd 
vaccination 
 
From 12 up to 
18 months 
post 1st 
vaccination 
Day 8 post 
2nd 
vaccination 
 
Day 31 post 
2nd 
vaccination 
Day 181 
post 2nd 
vaccination 
 
Sampling time points 
Pre-Vacc 2 
Pre-Vacc 2 
Vacc 2 
Post-Vacc 2 Post-Vacc 2 Post-Vacc 2 
Recording of concomitant 
medications/vaccinations7 
 
● 
● 
● 
● 
● 
Record any intercurrent 
medical conditions  
 
● 
● 
● 
● 
● 
Investigator sign-off on 
eCRF before analysis 
 
 
 
 
● 
● 
COVID-19 eCRFs log page 
 
● 
● 
● 
● 
● 
Study conclusion 
extension  
 
 
 
 
 
● 
2 Physical examination including resting vital signs (blood pressure, heart rate and respiratory rate, temperature) after 
at least 10 minutes of rest. Weight, height and BMI will only be collected at Screening and V4. Physical examination 
at Visit 2,and Visit 3, and Visit 4 will be performed only if deemed necessary by the investigator. For Visit 1 and Visit 
2 (if performed), only vital signs will be collected in the eCRF.  
Table 4 
Intervals between study visits  
Interval 
Optimal timing  
Allowed interval 
Screening Visit →Visit 1  
≤7 days  
-7- 1 days * 
Visit 1→Visit 2  
8 days  
7- 10 days  
Visit 1→Visit 3  
31 days 
30- 45 days  
Visit 1→Phone Contact 1 
181 days 
165- 195 days  
Visit 4→Visit 5 
≤7 days 
-7 to 1 days* 
Visit 1→Visit 5 
365 days 
365 - 548 days** 
Visit 5→Phone Contact 2 
8 days  
7 - 10 days  
Visit 5→Visit 6 
31 days 
30 - 45 days  
Visit 5→Phone Contact 3 
181 days 
165 - 195 days  
*From 7 days prior to vaccination up to and including the day of vaccination. 
** For a 6-month period ≥12 to <18 months post 1st vaccination 
3.1 Study Rationale 
Finally, a second dose vaccination of RSVPreF3 (120 µg) will be administered to the 
consenting subjects from 12 months to 18 months following initial vaccination to 
evaluate the immunogenicity and safety profile of RSVPreF3. This extension of the 
study will recruit the same non-pregnant women as a proxy for women who may 
require additional dosing in successive pregnancies.  
4 Objectives  
(See 1. Synopsis for Objectives and Outcome Table) 
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5.1 Scientific rationale for study design 
Finally, a second dose vaccination of RSVPreF3 will be administered to consenting 
subjects from 12 months to 18 months following 1st vaccination to evaluate the 
immunogenicity and safety profile of RSVPreF3. The intention of this study 
extension is to assess the durability of the immune response after the first dose 
vaccination, and to assess the safety and immunogenicity following a second dose 
vaccination of the RSVPreF3 maternal vaccine. This extension of the study will 
recruit the same non-pregnant women as a proxy for women who may require 
additional dosing in successive pregnancies.  
5.2 
Study Design 
(See 1. Synopsis for Design Figure) 
− 
Primary Vaccination 
− 
Epoch 001: Screening 
− 
Epoch 002: Primary (i.e., vaccination phase) starting at Visit 1 (Day 1) and 
ending just before the Visit 3 (Day 31)  
− 
Epoch 003: Follow-up after Visit 3 (Day 31) to Phone Contact 1contact on 
(Day 181)  
− 
End of Primary Study: Subjects must sign the ICF addendum to join the 
study extension. 
− 
Study Extension: 6-month period starting at the beginning of 12 months up 
to the beginning of 18th month after Visit 1 (≥12 to <18 months) 
• 
Epoch 004: 2nd dose vaccination starting from Visit 4 (up -7 days prior 
to vaccination) to Visit 6 (Day 31 post 2nd dose vaccination) 
• 
Epoch 005: 2nd dose vaccination Study Follow-up 2 starting after Visit 6 
(Day 31 post 2nd dose vaccination) and ending at Phone Contact 3 (Day 
181 post 2nd vaccination). 
• 
End of Study (EoS): Last testing results released of samples collected at Visit 63, to 
occur no later than 8 months after last subject last visit (LSLV), which occurs with 
phone contact 31 on Day 181 post 2nd vaccination. 
Table 6 Study groups, treatment and epochs foreseen in the study 
Study Groups 
Numbe
r of 
subject
s 
Age 
(Min
-
Max
) 
Treatmen
t name 1 
Treatme
nt name 
2 
Epochs 
(Blinding) 
 
 
Epoch 
001 
(Screenin
g) 
Epoch 
002 
(observe
r-blind) 
Epoch 
003 
(singl
e-
blind) 
Epoc
h 004 
(open 
study
) 
Epoc
h 00 
5 
 
(open 
study
) 
XRSV120_dTpa 
50 
18 – 
45 
RSV MAT 
120  
RSV 
MAT 120  x 
x 
x 
x 
x 
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Study Groups 
Numbe
r of 
subject
s 
Age 
(Min
-
Max
) 
Treatmen
t name 1 
Treatme
nt name 
2 
Epochs 
(Blinding) 
 
 
Epoch 
001 
(Screenin
g) 
Epoch 
002 
(observe
r-blind) 
Epoch 
003 
(singl
e-
blind) 
Epoc
h 004 
(open 
study
) 
Epoc
h 00 
5 
 
(open 
study
) 
year
s 
Boostrix-
ex-US 
(dTpa_50
0) 
Xplacebo_RSV1
20 
50 
18 – 
45 
year
s 
RSV MAT 
120 
Placebo 
RSV 
MAT 120  x 
x 
x 
x 
x 
XRSV60_dTpa 
50 
18 – 
45 
year
s 
RSV MAT 
60 
Boostrix-
ex-US 
(dTpa_50
0) 
RSV 
MAT 120  
x 
x 
x 
x 
x 
Xplacebo_RSV6
0 
50 
18 – 
45 
year
s 
RSV MAT 
60 
Placebo  
RSV 
MAT 120  x 
x 
x 
x 
x 
Xplacebo_dTpa 
50 
18 – 
45 
year
s 
Boostrix-
ex-US 
(dTpa_50
0) 
Placebo 
RSV 
MAT 120  
x 
x 
x 
x 
x 
URSV120_dTpa 
50 
18 – 
45 
year
s 
RSV MAT 
120 
Boostrix-
US 
(dTpa_30
0) 
RSV 
MAT 120  
x 
x 
x 
x 
x 
Uplacebo_RSV1
20 
50 
18 – 
45 
year
s  
RSV MAT 
120 
Placebo 
RSV 
MAT 120  x 
x 
x 
x 
x 
URSV60_dTpa 
50 
18 – 
45 
year
s  
RSV MAT 
60 
Boostrix-
US 
RSV 
MAT 120  x 
x 
x 
x 
x 
Uplacebo_RSV6
0  
50 
18 – 
45 
year
s 
RSV MAT 
60 
Placebo 
RSV 
MAT 120  x 
x 
x 
x 
x 
Uplacebo_dTpa 
50 
18 – 
45 
year
s 
Boostrix-
US 
(dTpa_30
0) 
Placebo 
RSV 
MAT 120  
x 
x 
x 
x 
x 
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5.4 
Subject and study completion 
A subject is considered to have completed the study if she is available for the concluding 
phone contact 3 (Day 181 post second vaccination) as described in the protocol.  
For those subjects that do not agree to participate in the study extension, the 
concluding contact will be the Day 181 phone contact as described in previous 
version of protocol (RSV MAT-011 (209141) Protocol Amendment 3 (03-APR-2020). 
6.3 Inclusion criteria for study extension 
Deviations from inclusion criteria are not allowed because they can potentially 
jeopardise the scientific integrity, regulatory acceptability of the study or subject 
safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
• 
Completed in primary study and received 1st dose vaccination of a study vaccine 
(RSVPreF3 or Boostrix). 
• 
Written or witnessed/thumb printed informed consent obtained from the 
subject prior to performance of any study specific procedure to the study 
extension. 
Are eligible if they meet the following criteria below 
All subjects must satisfy ALL the following criteria: 
• 
Subjects who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of the diary card, return for 
follow-up visits).  
• 
Female subjects remain healthy; as established by medical history and clinical 
examination, aged 18 to 45 years at the time of the first vaccination; 
• 
Female subjects of childbearing potential are eligible for the extension, if the 
subject: 
− 
has practiced adequate contraception for 30 days prior to 2nd vaccination 
− 
has a negative pregnancy test with results available on the day of 2nd 
vaccination 
− 
has agreed to continue adequate contraception for 90 days after completion 
of the 2nd vaccination. 
6.4 Exclusion criteria for extension 
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardize the scientific integrity, regulatory acceptability of the study or subject 
safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
The following criteria should be checked at the time of entry to the extension. If 
ANY exclusion criterion applies, the subject must not be included in the extension. 
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6.4.1 Medical conditions for extension 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the vaccines; 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing 
required); 
• 
Hypersensitivity to latex; 
• 
Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or 
renal functional abnormality, as determined by medical history, physical 
examination or laboratory screening tests;  
• 
Significant or uncontrolled psychiatric illness; 
• 
Recurrent history or un-controlled neurological disorders or seizures; 
• 
Documented HIV-positive subject; 
• 
History of or current autoimmune disease; 
• 
Body mass index (BMI) > 40 kg/m2; 
• 
Participants who experienced any SAE judged to be possibly or probably 
related to first dose vaccination of RSVPreF3, including hypersensitivity 
reactions. 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the subject due to participation in the study. 
6.4.2 Prior/Concomitant therapy for extension 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study vaccines during the period starting 30 days before 
the second dose of study vaccine (Day -29 to Day 1), or planned use during the 6 
month study extension period; 
• 
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 first dose of study 
vaccines 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 vaccine 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 
study 2nd dose vaccination, with the exception of any licensed influenza vaccine 
which may be administered ≥ 15 days before or after study vaccination. 
6.4.3 Prior/Concurrent clinical study experience for extension 
• 
Concurrently participating in another clinical study, at any time during the 
study period, in which the subject has been or will be exposed to an 
investigational or a non-investigational vaccine/product (drug or medical 
device); 
6.4.4 .Other exclusions for extension 
• 
Pregnant or lactating female at the time of Visit 4; 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions; 
• 
History of alcoholism, drug abuse and/or use disorder within the past two years 
(as defined in DSM-5 Diagnostic Criteria) [Camargo, 1984; Christy, 1995; 
Hasin, 2013]; 
• 
Any study personnel or their immediate dependents, family or household 
members 
6.7 Screen failures for the extension 
“Screening failures” for the extension are subjects who withdraw or are withdrawn 
from the extension after giving informed consent to the extension, but before 
extension eligibility (presence of all inclusion and absence of all exclusion criteria) is 
confirmed. 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. 
7.1 Treatments administered 
 
RSV MAT 120 
RSV MAT 60 
Boostrix-ex-US 
(dTpa_500) 
Boostrix-US 
(dTpa_300) 
 
Placebo  
 
NaCl 
NaCl 
 
 
 
Presentatio
n 
Powder for 
suspension for 
injection (vial) 
Freeze-dried 
Antigen 
(174mcg/vial)  
Powder for 
suspension for 
injection (vial) 
Freeze-dried 
Antigen 
(87mcg/vial) 
Suspension for 
injection 
prefilled syringe) 
Suspension 
for injection 
prefilled 
syringe) 
Solution for 
injection; 
vial)Clear 
liquid in 
monodose 
ampule or vial  
Solution for 
solution for 
injection; 
(vial)Clear liquid in 
monodose ampule 
or vial 
Solution for 
solution for 
injection; 
(vial)Clear liquid in 
monodose ampule 
or vial 
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RSV MAT 120 
RSV MAT 60 
Boostrix-ex-US 
(dTpa_500) 
Boostrix-US 
(dTpa_300) 
 
Placebo  
 
NaCl 
NaCl 
 
 
 
Formulation 
RSVPreF3(120 
µg)/Trehalose(12.7
3 mg).  
NaCl solution (4.5 
mg/0.5 mL, ~150 
mM) 
NaCl=150mM 
RSVPreF3(60 
µg)/Trehalose(6.4
2 mg).  
NaCl solution (4.5 
mg/0.5 mL, ~150 
mM) 
NaCl=150mM 
Diphtheria 
toxoid (≥ 2 IU) 
adsorbed on 
aluminium 
hydroxide and 
aluminium 
phosphate; 
Tetanus toxoid 
(≥ 20 IU) 
adsorbed on 
aluminium 
hydroxide and 
aluminium 
phosphate; 
Pertussis toxoid 
(8 µg) adsorbed 
on aluminium 
hydroxide and 
aluminium 
phosphate; 
Filamentous 
haemagglutinin 
(8 µg) adsorbed 
on aluminium 
hydroxide and 
aluminium 
phosphate; 
Pertactin (69 
kDa outer 
membrane 
protein) (2.5 µg) 
adsorbed on 
aluminium 
hydroxide and 
aluminium 
phosphate; 
Aluminium 
hydroxide (0.3 
mg Al³+); 
Aluminium 
phosphate (0.2 
mg Al³+); 
Sodium 
chloride; Water 
for injections 
q.s. 0.5 mL  
 DT>=2IU; 
TT>=20IU; 
PT=8µg; 
FHA=8µg; 
PRN=2.5µg; 
Aluminium=500µ
g Al3+ 
Diphtheria 
toxoid (≥ 2 IU) 
adsorbed on 
aluminium 
hydroxide; 
Tetanus 
toxoid (≥ 20 
IU) adsorbed 
on aluminium 
hydroxide; 
Pertussis 
toxoid (8 µg) 
adsorbed on 
aluminium 
hydroxide; 
Filamentous 
haemagglutini
n (8 µg) 
adsorbed on 
aluminium 
hydroxide; 
Pertactin (69 
kDa outer 
membrane 
protein) (2.5 
µg) adsorbed 
on aluminium 
hydroxide; 
Aluminium 
hydroxide (0.3 
mg Al³+); 
Sodium 
chloride (4.4 
mg); Water for 
injections q.s. 
0.5 
mLDT>=2IU; 
TT>=20IU; 
PT>=8µg; 
FHA=8µg; 
PRN=2.5µg; 
Al(OH)3=300µg 
Al3+ 
NaCl 
solution (4.5 
mg/0.5 mL, 
~150 mM) 
NaCl=150mM 
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RSV MAT 120 
RSV MAT 60 
Boostrix-ex-US 
(dTpa_500) 
Boostrix-US 
(dTpa_300) 
 
Placebo  
 
NaCl 
NaCl 
 
 
 
Route of 
Administratio
n  
Intramuscular 
useIM 
Intramuscular 
useIM 
Intramuscular 
useIM 
Intramuscular 
useIM 
Intramuscula
r useIM 
No of doses 
21 
1 
1 
1 
1 
Manufacturer 
RSVPreF3: GSK 
Biologicals 
NaCl: GSK 
Biologicals 
RSVPreF3: GSK 
Biologicals 
NaCl: GSK 
Biologicals 
GSK Biologicals 
GSK 
Biologicals 
GSK 
Biologicals 
Table 8 Treatments administered (Part 2) 
Primary Vaccination 
2nd Vaccination 
Groups in primary 
vaccination 
Formulation 
in primary 
vaccination 
N 
Groups in 2nd 
vaccination 
Laterality 
XRSV120_dTpa 
ex-US 
50 
RSVPreF3=120µg  
Non-Dominant  
Xplacebo_RSV120 
50 
RSVPreF3=120µg  
Non-Dominant  
XRSV60_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
Xplacebo_RSV60 
50 
RSVPreF3=120µg  
Non-Dominant  
Xplacebo_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
URSV120_dTpa 
US 
50 
RSVPreF3=120µg  
Non-Dominant  
Uplacebo_RSV120 
50 
RSVPreF3=120µg  
Non-Dominant  
URSV60_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
Uplacebo_RSV60 
50 
RSVPreF3=120µg  
Non-Dominant  
Uplacebo_dTpa 
50 
RSVPreF3=120µg  
Non-Dominant  
7.2.1 Subject identification 
The subject identification number will be the same in the study extension. No new 
subjects will be recruited. 
7.2.1.2 Treatment allocation by subject 
For the second vaccination, 1 treatment number will be allocated for each subject. 
7.2.1.2.1 Study group and treatment number allocation 
Since the second dose vaccination is open study, the treatment number will be 
allocated for each subject sequentially at each centre. 
7.3 Blinding and unblinding 
Data will be collected in an observer-blind manner during the primary study.  
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Investigators will remain blinded to each subject’s assigned study treatment until 
completion throughout the course of the primary vaccination day 181 database freeze 
for analysis. study.  
After the Day 181 phone contact (C1) for a given subject, the investigator will be 
informed of the subject’s treatment assignment and will communicate this to the 
subject. The study extension will then be conducted as an open label study. 
Unblinded monitors and in the event of a Quality Assurance audit, the auditor(s) will be 
allowed access to un-blinded study treatment records at the site(s) to verify that 
randomisation/dispensing has been done accurately. Please refer to the SPM for details 
on blinding of the vaccine.  administration. 
8.1 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: 
• 
Reconsent of subjects for the study extension may be placed on hold. Decisions 
on re-starting will be made in a manner consistent with guidance from public 
health and other competent authorities.  
• 
Informed consent must take place in a face to face contact with the investigator 
but informing the potential subject ahead of giving written consent may be done 
remotely for example by mailing the informed consent or telephone or 
videotelephony conversation. 
• 
Certain procedures may be performed at an alternate location. his includes, 
signing of informed consent, physical examination and vaccine dosing. If 
vaccinating in an alternate location, it must be assured that trained staff and 
equipment are available to manage an acute vaccine reaction. Biological 
samples may be collected at a different location* other than the study site or at 
participant’s home. Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until the intended use. 
• 
Safety follow-up may be made by a telephone call, other means of virtual 
contact or home visit, if appropriate. 
• 
 “Medically attended visits” include instances where, due to the special 
circumstances, the subject cannot seek medical advice for symptoms/an illness 
by visiting a medical facility or arranging for a home visit, and seeks this advice 
instead via telephone, SMS, email, videotelephony or telemedicine, or other 
means.  
• 
The paper Diary card provided to the subject may be transmitted from and to 
the site by electronic means and or conventional mail. 
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• 
If despite best efforts it is not possible to collect the biological samples within 
the interval predefined in the protocol (see Table 4), then the interval may be 
extended up to a maximum length described in Table 10, however efforts should 
be made to adhere as closely as possible to the optimal timing.  
• 
If despite best efforts it is not possible to administer the dose of study vaccine as 
defined in the protocol (see Table 4), a maximum dose interval described in 
Table 10 may be used, however efforts should be made to adhere as closely as 
possible to the optimal timing. 
Table 10 Intervals between study visits under Special Circumstances 
Interval 
Optimal timing  
Allowed interval 
Adapted interval 
under special 
circumstances 
Screening Visit →Visit 1  
≤7 days  
-7- 1 days  
-30 to 1 days 
Visit 1 →Visit 2  
8 days  
7- 10 days  
7- 10 days 
Visit1 →Visit 3  
31 days 
30- 45 days  
30 – 60 days 
Visit 1→Phone Contact 1 
181 days 
165- 195 days  
165 – 195 days 
Visit 4→Visit 5 
 
-7 to 1 days 
-30 – 1 days* 
Visit 1→Visit 5 
365 days 
365-548 days** 
 
Visit 5 to Phone Contact 2 
8 days  
7- 10 days  
7- 10 days  
Visit 5→Visit 6 
31 days 
30- 45 days  
30 – 90 days 
Visit 5→Phone Contact 3 
181 days 
165- 195 days  
165 – 195 days 
*From 30 days prior to vaccination up to and including the day of vaccination. 
** For a 6-month period ≥12 to <18 months post 1st vaccination 
Impact on the per protocol set for immunogenicity will be determined on a case by 
case basis.  
• 
Any impact of above-mentioned measures on the study results will be described 
in the clinical study report. 
 * 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 subjects by investigator and staff 
at a site other than the designated study site.  
8.3.2 Medical and vaccination history 
Significant medical conditions and vaccinations that occurred during the C1-V4 will 
be reviewed during the screening for the second vaccination and reported as 
medical history. 
8.3.3 Physical Exam 
• 
Perform a history directed physical exam plus vital signs at Visit 4 [D-7 2nd 
vaccination to 2nd vaccination]. Note that laboratory assessments of 
haematology and biochemistry may be made on the investigator’s discretion. 
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8.4.2 Biological samples 
Whole blood for 
hematology, 
biochemistry* 
Whole blood for 
immune response 
10.5 or 5 
ml 
Visit 4 (up Day -7 prior 
to 2nd vaccination) 
Hematology, chemistry: 5.5 mL. 
Immune response: 5 mL (~ 2 mL 
serum). 
Whole blood for 
immune response  
5 
ml 
Visit 6 (Day 31 post 
2nd vaccination) 
Immune response : 5 mL (~ 2 mL 
serum). 
 
36 or 3020.5 
ml 
Minimum Total, not including repeat or unscheduled samples 
Urine for Pregnancy 
- 
- 
screening visit 
Visit 1 (day 1) and Visit 
5 (2nd Vaccination) 
 
*Hematological and biochemical laboratory testing at Visit 4 (D -7 up to and including 2nd dose vaccination) at 
the investigator’s discretion 
8.4.3 Laboratory Assays 
Table 12 
Humoral Immunity (Antibody determination) 
Sampling 
time 
points 
Syste
m 
Component 
Metho
d 
Kit/ 
Manufactur
er 
Unit 
Cut-
off 
Group
s 
Numb
er of 
subjec
ts 
Laboratory
*** 
Day -7 up 
to 2nd 
vaccinati
on 
 
Seru
m 
Respiratory 
Syncytial 
Virus A Ab 
neutralizing 
NEU 
In house 
ED60 
and/or IU 
(internatio
nal unit) 
18 
for 
ED6
0 56 
for 
IU 
All 
500 
GSK 
Seru
m 
Respiratory 
Syncytial 
Virus PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
 
D31 post 
2nd 
vaccinati
on 
 
Seru
m 
Respiratory 
Syncytial 
Virus A Ab 
neutralizing 
NEU 
In house 
ED60 
and/or IU 
(internatio
nal unit) 
18 
for 
ED6
0 56 
for 
IU 
All 
500 
GSK 
Seru
m 
Respiratory 
Syncytial 
Virus PreF3 
Ab.IgG 
concentrati
on 
ELI 
In house 
ELU/mL 
25 
All 
500 
Nexelis 
 
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Table 13 
Immunological read-outs  
Blood sampling timepoint 
Subset name 
Approximate 
No. subjects 
Component 
Components 
priority rank  
Type of contact 
and timepoint* 
Sampling 
timepoint 
Day -7 up to 2nd 
vaccination 
 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
D31 post 2nd 
vaccination 
 
Post-Vacc 
All 
500 
RSV-A neutralizing 
antibody 
1 
 
All 
500 
RSVPreF3 IgG antibody 
concentration 
2 
* The results of this testing might potentially impact the subject medical care 
Boostrix recipients = subjects in the following study groups: -XRSV120_dTpa, XRSV60_dTpa, Xplacebo_dTpa, 
URSV120_dTpa, URSV60_dTpa, Uplacebo_dTpa. 
8.5.2 Time period and frequency for collecting AE and serious adverse event (SAE) 
information 
Table 14  
Reporting periods for collecting safety information  
Event 
Phone 
Contac
t C1  
C1 
to 
V4** 
V4 
V5* 
 
C2 
 
V6 
C3 
D181 
 
D -7 up 
to 2nd 
vaccinat
ion 
2nd 
vaccinat
ion 
From 12 
up to 18 
months 
post 1st 
vaccinat
ion 
D7 post 
second 
2nd 
vaccinat
ion 
D8 post 
second 
2nd 
vaccinat
ion 
D30 
post 
second 
2nd 
vaccinat
ion 
D31 
post 2nd 
vaccinat
ion  
181 
Days 
post 2nd 
vaccinat
ion 
Solicited 
local and 
general AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unsolicited 
AEs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AEs leading 
to withdrawal 
from the 
study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAEs related to 
study 
participation  
or concurrent 
GSK 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Event 
Phone 
Contac
t C1  
C1 
to 
V4** 
V4 
V5* 
 
C2 
 
V6 
C3 
D181 
 
D -7 up 
to 2nd 
vaccinat
ion 
2nd 
vaccinat
ion 
From 12 
up to 18 
months 
post 1st 
vaccinat
ion 
D7 post 
second 
2nd 
vaccinat
ion 
D8 post 
second 
2nd 
vaccinat
ion 
D30 
post 
second 
2nd 
vaccinat
ion 
D31 
post 2nd 
vaccinat
ion  
181 
Days 
post 2nd 
vaccinat
ion 
medication/vacc
ine 
Pregnancies*
** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
** There will be no follow-up between C1 and V4. New medical history and relevant new safety events during 
this period will be recorded at visit 4 for subjects who agree to the study extension and sign the informed 
consent addendum. In addition, SAE related to vaccination are reported during the period C1-V4 will be 
reported to the Investigator at the time of awareness. 
***Pregnancies that occurred during the C1-V4 period will be reported as medical history  
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 13. Investigators are not obligated to actively seek AEs 
or SAEs in former study subjects. However, if the investigator learns of any SAE, 
including a death, at any time after a subject has been discharged from the study, and 
he/she considers the event to be reasonably related to the study vaccine(s), the 
investigator will promptly notify the Study Contact for Reporting SAEs. 
8.5.5 Post-study adverse events and serious adverse events 
A post-study AE/SAE is defined as any event that occurs outside of the AE/SAE 
reporting period defined in Table 14. Investigators are not obligated to actively seek 
AEs or SAEs in former study participants. However, if the investigator learns of any 
SAE at any time after a subject has been discharged from the study, and he/she 
considers the event reasonably related to the investigational vaccine/product, the 
investigator will promptly notify the Study Contact for Reporting SAEs. 
9.1 Discontinuation from the study 
Subjects will complete the study at day 181 with a phone contact. For the subjects 
that enroll in the study extension, the conclusion of the study will be on Day 181 
following the second immunization as described in the protocol.  
Investigators will make 3 attempts followed by a certified letteran attempt to contact 
those subjects who do not return for scheduled visits or follow-up. 
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9.2 Discontinuation of study vaccine(s) 
‘Discontinuation’ of study intervention refers to any participant who has not 
received all planned doses of study intervention. A participant who discontinued 
study intervention may continue other study procedures (e.g. safety or 
immunogenicity), planned in the study protocol at the discretion of the investigator.  
The primary reason for premature discontinuation of the study intervention will be 
documented on the eCRF as follows: 
• 
Adverse event requiring expedited reporting to GSK 
• 
Unsolicited non-serious adverse event  
• 
Solicited adverse event 
• 
Not willing to be vaccinated 
• 
Other (specify). 
• 
Not applicable. 
10.2 Population for analysis 
Analysis Set 
Description 
Enrolled 
Subjects who agreed to participate in a clinical study after completion of the 
informed consent process. And subject is not a screen failure.  
Full Analysis  
All subjects who received at least 1 dose of the study treatment and have post-
vaccination immunogenicity data  
Per Protocol  
All subjects who received at least 1 dose of the study treatment to which they 
are randomised and have post-vaccination data (Full Analysis Set) minus 
subjects with protocol deviations that lead to exclusion 
Unsolicited Safety  
All subjects who received at least 1 dose of the study treatment (Exposed Set) 
that report unsolicited AEs/report not having unsolicited AEs 
10.3.3. Immunogenicity analysis 
The primary analysis will be based on the Per Protocol set for analysis of 
immunogenicity. If, in any study group and at any timepoint, the percentage of enrolled 
or vaccinated subjects with serological results excluded from the Per Protocol set for 
analysis of immunogenicity is 5% or more, a second analysis based on the Exposed Full 
Analysis Set will be performed to complement the Per Protocol analysis. 
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10.3.4 Safety Analysis 
Endpoint 
Statistical Analysis Methods 
Primary 
(US + ex-US data to be pooled) 
For each group with 1st dose vaccination of RSVPreF3 (two dose levels) when given alone 
or co-ad with dTpa; the following points will be analysed for 1st and 2nd dose vaccination. 
The percentage of subjects with at least one local AE (solicited and unsolicited), with at least 
one general AE (solicited and unsolicited and with any (“solicited or unsolicited”) AE during the 
7-day or 30 -day as well 180 day follow up is for SAE visit post 1st and 2nd vaccination period will 
be tabulated with exact 95% CI by study group. The same computations will be done for Grade 
3 AEs, for any AEs considered related to vaccination, for Grade 3 AEs considered related to 
vaccination and for AEs resulting in medically attended visits. 
The percentage of subjects with any unsolicited AEs during the 30-day follow-up period (i.e. on 
the day of vaccination and 29 subsequent days) with its exact 95% CI will be tabulated by group 
and by Medical Dictionary for Regulatory Activities (MedDRA) SOC and preferred term. Similar 
tabulation will be done for Grade 3 unsolicited AEs, for any causally related unsolicited AEs, for 
Grade 3 causally related unsolicited AEs and for unsolicited AEs resulting in a medically 
attended visit. The verbatim reports of unsolicited AEs will be reviewed by a physician and the 
signs and symptoms will be coded according to the MedDRA Dictionary for Adverse Reaction 
Terminology.  
Endpoint 
Statistical Analysis Methods 
Primary 
(US + ex-US data to be pooled for the first vaccination) 
Secondary 
(US and ex-US data to be considered pooled, then separately for the first vaccination) 
For the data collected for the second vaccination, the humoral immune response of RSV 
PreF3 will be summarized based on 2 dose level (60 and 120 µg) from the first 
vaccination. 
• 
GMCs/GMTs and their 95% CI will be tabulated and represented graphically for prior 
and post 2nd dose vaccination 
• 
Geometric mean of ratios of antibody titer/concentrations at individual post- 2nd 
dose vaccination time point (visit 6) over prior 2nd dose vaccination time point (visit 
4) will be tabulated with 95% CI 
• 
Antibody titer/concentration will be displayed using reverse cumulative curves on 
prior and post 2nd vaccination 
• 
The kinetics of GMT/GMCs will be plotted as a function of time for subjects with 
results available at all time points including the visits from the first vaccination. 
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209141 (RSV MAT-011) 
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Endpoint 
Statistical Analysis Methods 
Secondary 
(US and ex-US data to be considered pooled, then separately) 
For each group with 1st dose vaccination of RSVPreF3 (two dose level) when given alone 
or co-ad with dTpa; the following points will be analysed for 1st and 2nd dose vaccination. 
The percentage of subjects with at least one local AE (solicited and unsolicited), with at least 
one general AE (solicited and unsolicited) and with any (“solicited or unsolicited”) AE during the 
7-day or 30 -day follow-up as well any SAE up period to 180 days post 1st and 2nd vaccination 
time points will be tabulated with exact 95% CI by study group. The same computations will be 
done for Grade 3 AEs, for any AEs considered related to vaccination, for Grade 3 AEs 
considered related to vaccination and for AEs resulting in medically attended visits. 
The percentage of subjects with at least one report of SAE classified by the MedDRA SOC and 
Preferred Terms and reported during the 30-day follow-up period will be tabulated with exact 
95% CI for each formulation (US and ex-US).  
For each formulation (US and ex-US), the percentage of subjects with any unsolicited AEs 
during the 30-day follow-up period (i.e. on the day of vaccination and 29 subsequent days) with 
its exact 95% CI will be tabulated by group and by Medical Dictionary for Regulatory Activities 
(MedDRA) SOC and preferred term. Similar tabulation will be done for Grade 3 unsolicited AEs, 
for any causally related unsolicited AEs, for Grade 3 causally related unsolicited AEs and for 
unsolicited AEs resulting in a medically attended visit. The verbatim reports of unsolicited AEs 
will be reviewed by a physician and the signs and symptoms will be coded according to the 
MedDRA Dictionary for Adverse Reaction Terminology. 
10.4 Sequence of analysis 
• 
The second analysis will evaluate safety data and will be performed when all 
subjects have completed visits up to (and including) C1 (Day 181) and the data 
are available. From this point the study is unblinded.  
• 
The third analysis will evaluate safety and immunogenicity data and will be 
performed when all subjects have completed visits up to (and including) Visit 6 
(Day 31 post 2nd dose vaccination) and the data are available. At this time, any 
available safety data will also be provided. 
• 
The final end-of-study analysis will be performed when all data for at least primary 
and secondary endpoints up to study conclusion at Day 181 post 2nd dose 
vaccination (C3) are available. (D181) are available. Any available tertiary 
endpoints will also be analyzed in this step. Individual listings will only be provided 
at this stage. An integrated clinical study report containing all available data will be 
written and made available to the investigators 
12.5.7.1 Time period for detecting and recording adverse events, serious adverse 
events and pregnancies 
All AEs during 7 days following administration of each the dose vaccination of study 
vaccine(s) (Day 1 to Day 7 post primary vaccination and Day 1 to Day 7 post 2nd 
vaccination ) must be recorded into the appropriate section of the eCRF, irrespective of 
intensity or whether or not they are considered vaccination-related. 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

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Type of contact 
Screening Visit 
1 
Visit 
2 
Visit 
3 
Phone 
Contact 1 
 Visit 
4 
Visit 
5 
Phone 
Contact 2 
Visit 
6 
Phone 
Contact 3 
Pre-vaccination body 
temperature and heart rate 
 
● 
 
 
 
 
 
● 
 
 
 
Pre-vaccination vital sign 
readings4 
 
 
 
 
 
 
 
● 
 
 
 
2 Physical examination including resting vital signs (blood pressure, heart rate and respiratory rate, temperature) 
measured after at least 10 minutes of rest.  
Screening: Physical exam, vital signs (blood pressure, heart rate and respiratory rate, temperature), and 
weight, height and BMI will be recorded in the eCRF.  
Visit 1: History directed physical exam will be performed and the vital signs will be recorded in the eCRF 
Visit 2 Physical examination will be performed only if deemed necessary by the investigator.  If performed, 
only vital signs (blood pressure, heart rate and respiratory rate) will be required recorded in the eCRF 
Visit 3: Physical examination will be performed only if deemed necessary by the investigator.   
Visit 4: Perform history directed physical exam will be performed and vital signs (blood pressure, heart rate 
and respiratory rate, temperature) will be recorded in the eCRF. Weight, height and BMI should also be 
recorded in the eCRF.  
Visit 6: Physical examination will be performed only if deemed necessary by the investigator.   
Weight, height and BMI will only be collected at Screening and V4. Physical examination at Visit 2, Visit 3, and Visit 4 
will be performed only if deemed necessary by the investigator. For Visit 1 and Visit 2 (if performed), only vital signs 
will be collected in the eCRF. 
4Pre-vaccination vital signs: At Visit 5, the pre-vaccination vital signs (blood pressure, heart rate and 
respiratory rate, temperature) will be recorded in the eCRF 
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CONFIDENTIAL 
209141 (RSV MAT-011) 
Protocol Amendment 6 Final 
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148 
8.5.4 Reporting of serious adverse events, pregnancies, and other events 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on a 
Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
Pregnancies 
2 weeks* 
Paper pregnancy notification 
report/electronic pregnancy 
report 
2 weeks 24 
hours* 
electronic pregnancy report  
 
8.5.5.1 Contact information for reporting of serious adverse events (SAEs), pregnancies 
and study holding rules 
24/24 hour and 7/7-day availability: 
GSK Clinical Safety & Pharmacovigilance 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: Rix.CT-safety-vac@gsk.com PV.ICSRManagement@gsk.com 
12.5.8.4 Completion and transmission of pregnancy reports to GSK  
Once the investigator becomes aware that a subject is pregnant, the investigator (or 
designate) must complete the required information onto the electronic pregnancy report 
WITHIN 2 WEEKS 24 HOURS. 
8.3.2 Medical and vaccination history  
Significant medical conditions and vaccinations that occurred during the C1-V4 will be 
reviewed during the screening for the second vaccination and reported as medical history 
and concomitant medications, respectively.  
 
 
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0

Signature Page for  209141 TMF-11921449 v1.0
Signature Page for TMF-11921449 v1.0
Reason for signing: Approved
Name: Joon Hyung Kim
Role: Approver
Date of signature: 14-Apr-2021 19:05:50 GMT+0000
209141 | Protocol Amendment 6 14 Apr 2021 | TMF-11921449 | 1.0