Clinical trial NCT04980391
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory Syncytial Virus Maternal vaccine Safety Reactogenicity Immune response High risk pregnant women Teenage girls
Sponsor: GlaxoSmithKline
Start date: 2021-08-03; Completion date: 2023-05-30
Enrollment: 384 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to evaluate the safety, reactogenicity and immune response of a single intramuscular dose of the respiratory syncytial virus (RSV) maternal vaccine compared to placebo, when administered in the second or third trimester of pregnancy in women, 15 to 49 years of age (YOA), with high risk pregnancies and in the infants born to the vaccinated mothers.

Following a recommendation from the Independent Data Monitoring Committee of NCT04605159 (RSV MAT 009), GSK made the decision to stop enrolment and vaccination in the study. Ongoing study participants at that time continued to be monitored as part of the study.

Detailed description:

Arms: arm 1: Maternal participants randomized to the RSV\_MAT Group received a single dose of the RSV MAT vaccine administered, between 24 and 36 weeks of gestation, at Day 1 in this study. arm 2: Maternal participants randomized to the Control Group received a single dose of Placebo administered, between 24 and 36 weeks of gestation, at Day 1 in this study. arm 3: This group consisted of infants born to mothers (from RSV\_MAT Group-Mother) who received a single dose of RSV MAT vaccine during pregnancy. arm 4: This group consisted of infants born to mothers (from Control Group-Mother) who received a single dose of placebo during pregnancy.
Interventions: intervention 1: RSV MAT intervention 2: Placebo
Intervention descriptions: intervention 1: Single dose of the RSV MAT vaccine reconstituted with NaCl solution, administered intramuscularly in the non-dominant arm, at Day 1. intervention 2: Single dose of placebo, administered intramuscularly in the non-dominant arm, at Day 1.

Protocol documents:
Prot_000.pdf: 
Protocol Amendment 1
Study ID:  214725
Official Title of Study: A Phase III, double-blind, randomized, placebo-controlled study 
to evaluate the safety, reactogenicity and immune response of a single intramuscular dose 
of unadjuvanted RSV Maternal vaccine, in high risk pregnant women aged 15 to 49 years 
and infants born to the vaccinated mothers. 
NCT ID: NCT04980391
Date of Document: 16 Mar 2022 


CONFIDENTIAL 
214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
15 March 2022 
1 
 
Clinical Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals SA (GSK) 
Primary study intervention 
and number 
GSK Respiratory Syncytial Virus (RSV) Maternal 
(RSVPreF3) Vaccine (GSK3888550A) 
Other study intervention 
Placebo (Lyophilized sucrose reconstituted with 
saline [NaCl] solution) 
eTrack study number and 
abbreviated title 
214725 (RSV MAT-012) 
EudraCT number 
2021-000994-96 
Date of protocol 
Final: 12 March 2021 
Date of protocol amendment 
Amendment 1 Final: 15 March 2022 
Title 
A Phase III, double-blind, randomized, placebo-
controlled study to evaluate the safety, 
reactogenicity and immune response of a single 
intramuscular dose of unadjuvanted RSV Maternal 
vaccine, in high risk pregnant women aged 15 to 49 
years and infants born to the vaccinated mothers. 
Brief title 
A study on the safety and immune response to an 
unadjuvanted RSV Maternal vaccine, in high risk 
pregnant women aged 15 to 49 years and infants 
born to the vaccinated mothers. 
Based on GlaxoSmithKline Biologicals SA Protocol WS v17.1 
©2021 GSK group of companies or its licensor. 


CONFIDENTIAL 
214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
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Protocol Amendment 1 Sponsor Signatory Approval 
eTrack study number and 
abbreviated title 
214725 (RSV MAT-012) 
EudraCT number 
2021-000994-96 
Date of protocol amendment 
Amendment 1 Final: 15 March 2022 
Title  
A Phase III, double-blind, randomized, placebo-
controlled study to evaluate the safety, 
reactogenicity and immune response of a single 
intramuscular dose of unadjuvanted RSV Maternal 
vaccine, in high risk pregnant women aged 15 to 49 
years and infants born to the vaccinated mothers. 
Sponsor signatory 
Joon Hyung Kim 
Clinical and Epidemiology Project Lead, RSV 
Maternal 
Signature 
 
 
 
Date 
 
 


CONFIDENTIAL 
214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
15 March 2022 
3 
Protocol Amendment 1 Investigator Agreement 
I agree: 
• 
To conduct the study in compliance with this protocol, any future protocol 
amendments or protocol administrative changes, with the terms of the clinical trial 
agreement and with any other study conduct procedures and/or study conduct 
documents provided by GlaxoSmithKline Biologicals SA (GSK). 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements. 
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study intervention and other study-related duties and functions as described 
in the protocol. 
• 
To supervise any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site. 
• 
To ensure that any individual or party to whom I have delegated trial-related duties 
and functions conducted at the trial site are qualified to perform those trial-related 
duties and functions. 
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality 
Assurance procedure manual. 
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the participant and/or the participant’s legally acceptable representative (LAR). 
• 
To perform no biological assays on the clinical samples other than those described in 
the protocol or its amendment(s). 
• 
To co-operate with representative(s) of GSK in the monitoring process of the study 
and in resolution of queries about the data. 
• 
To have control of all essential documents and records generated under my 
responsibility before, during, and after the trial. 
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational intervention(s), and more generally about his/her 
financial ties with the sponsor. GSK will use and disclose the information solely for 
the purpose of complying with regulatory requirements. 


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214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
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Hence, I: 
• 
Agree to supply GSK with any necessary information regarding ownership interest 
and financial ties (including those of my spouse and dependent children). 
• 
Agree to promptly update this information if any relevant changes occur during the 
study and for 1 year following completion of the study. 
• 
Agree that GSK may disclose any information about such ownership interests and 
financial ties to regulatory authorities. 
• 
Agree to provide GSK with an updated Curriculum Vitae and all other documents 
required by regulatory agencies for this study. 


CONFIDENTIAL 
214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
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eTrack study number and 
abbreviated title 
214725 (RSV MAT-012) 
EudraCT number 
2021-000994-96 
Date of protocol amendment 
Amendment 1 Final: 15 March 2022 
Title 
A Phase III, double-blind, randomized, placebo-
controlled study to evaluate the safety, 
reactogenicity and immune response of a single 
intramuscular dose of unadjuvanted RSV Maternal 
vaccine, in high risk pregnant women aged 15 to 49 
years and infants born to the vaccinated mothers. 
Investigator name 
 
 
 
Signature 
 
 
 
Date 
 
 
 
 


CONFIDENTIAL 
214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
15 March 2022 
6 
SPONSOR INFORMATION 
1. Sponsor 
GlaxoSmithKline Biologicals SA (GSK) 
2. Sponsor medical expert for the study 
Refer to the local study contact information document. 
3. Sponsor study monitor 
Refer to the local study contact information document. 
4. Sponsor study contact for reporting of a Serious Adverse Events (SAEs) 
GSK central back up study contact for reporting SAEs: refer to the protocol Section 
8.3.3.1. 
Study contact for reporting SAEs: refer to the local study contact information 
document. 
5. GSK Helpdesk for emergency unblinding  
Refer to the protocol Section 6.3.5.1. 


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214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Amendment 1 (15 March 2022): 
This amendment is considered substantial based on the criteria defined in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it significantly impacts the safety of participants, conduct of the trial and 
scientific value of the trial. 
Overall rationale for the current amendment:  
This protocol has been amended to reflect the following: 
• 
Following review of data collected so far from the RSV MAT-009 (212171) study, 
safety signals have been identified. An imbalance in the proportion of preterm births 
and neonatal deaths have been observed in infants born to vaccinated mothers who 
received RSV maternal vaccine versus those who received a placebo. The safety 
signals are being investigated and, although at this time a cause has not been 
determined, based on the above observations, the Sponsor has nevertheless decided 
to stop enrollment and vaccination for all actively enrolling RSV MAT studies. 
− 
There will be no additional participants included in the ongoing studies. All 
planned objectives will be assessed for the participants enrolled so far. 
− 
Safety monitoring will continue, with additional monitoring measures 
implemented, for both maternal and infant participants during the rest of the 
study period. 
− 
The ongoing studies were unblinded to ensure the safety monitoring of the 
participants. 
− 
Additional monitoring contact/s or visit/s for the maternal and infant participants 
has been included. 
− 
Respiratory tract illness surveillance for maternal participants will no longer be 
performed. 
− 
Placenta samples will be taken from all maternal participants at delivery visit, 
whenever feasible. These samples may be tested to support possible safety 
assessments, if necessary. 
− 
Blood samples for immunogenicity assessment at Visit 2-NB, Visit 3-NB and 
Visit 4-NB will no longer be collected from infant participants. 
• 
To remove the collection of hematocrit samples due to challenges (mostly due to the 
COVID-19 pandemic) faced in several countries preventing the samples from reaching 
the central lab in adequate time for testing. 
Also, this amendment includes clarifications, editorial changes to improve the 
consistency and typographical error corrections. 


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214725 (RSV MAT-012) 
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List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Section 1.1 Synopsis, Section 
1.2 Schema, Section 4.1 
Overall design, Section 4.3 
Justification for dose, Section 
5.5 Criteria for temporarily 
delaying study intervention 
administration, Section 6.1 
Study interventions 
administered, Section 6.3.2 
Randomization to study 
intervention, Section 6.4 Study 
intervention compliance, 
Section 8 Study assessments 
and procedures, Section 8.2.3.2 
Independent data monitoring 
committee (IDMC) evaluation 
Updated to revise the overall study 
design and impacted sections as 
no further enrollment and 
vaccination will be performed. 
Figure 1, Table 5 and Table 6 
have been updated to reflect the 
changes. 
To adapt the wording according to the new 
study requirements. 
Section 1.2 Schema, Section 
1.3 Schedule of activities (SoA), 
Section 4.1 Overall design, 
Section 4.2.5 Case definition, 
Section 4.2.5.1 Maternal, 
medically attended respiratory 
tract illness (MA-RTI), Section 
4.2.5.5 RSV infection, Section 8 
Study assessments and 
procedures, Section 8.1.1 
Biological samples, Section 
8.1.3 Immunological read-outs, 
Section 8.3.1 Time period and 
frequency for collecting AE, 
SAE and other safety 
information, Section 8.4.1.1 
Medically attended respiratory 
tract illnesses (MA-RTIs) in 
maternal participants, Section 
8.4.2.1 Maternal participants, 
Section 8.4.2.3 Maternal and 
infant participants, Section 
8.4.3.1 For a maternal MA-RTI, 
Section 8.4.4 Assessment visit 
procedures, Section 8.4.4.1 
Clinical evaluation, Section 
8.4.4.2 Nasal swab collection, 
Section 8.4.4.3 Missed 
assessment visit, Section 8.4.5 
RTI hospitalization during the 
surveillance interval 
Updated to remove Maternal RTI 
surveillance. 
Table 1, Table 6, Table 10, Table 
15, Table 17 and Figure 1 have 
been updated to reflect the 
changes. 
Updated to reduce the burden on the 
maternal participants. 
Section 1.2 Schema, Section 
1.3 Schedule of activities (SoA), 
Section 8.1.1 Biological 
samples,  
Update to remove blood sample 
collection at Visit 2-NB, Visit 3-NB 
and Visit 4-NB for the infant 
partcipants 
Updated to decrease the burden on the 
infant participants. 


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Section # and title 
Description of change 
Brief rationale 
Table 2, Table 12, Table 14, and 
Figure 2 have been updated to 
reflect the changes. 
Section 1.3 Schedule of 
activities 
Updated to have an allowed 
window of time to plan the delivery 
visit. 
Table 3 has been updated to 
reflect the changes. 
Updated to have an allowed window of 
time to plan the delivery visit. 
Section 1.3 Schedule of 
activities (SoA), Section 4.1 
Overall design, Section 
8.2.1.4.2 Monthly contacts, 
Section 10.2.1 
Updated to increase the number of 
safety contacts/visits to be made 
for maternal and infant participants 
and to collect placenta tissue 
samples from all participants. 
Table 1, Table 2, Table 3 and 
Figure 1 have been updated to 
reflect the changes. 
Updated to monitor better any safety event 
associated with the safety signal observed 
in RSV MAT-009 study and to further 
understand the cause of the event. 
Section 1.3 Schedule of 
activities, Section 4.1 Overall 
design, Section 8 Study 
assessments and procedures, 
Section 8.1.1 Biological 
samples, Section 8.1.2 
Laboratory assays, 
Section 8.1.3 Immunological 
read-outs, Section 10.2.2 
Descriptions of the assays to be 
performed in the study 
Updated to remove the collection 
of hematocrit samples. 
Table 1, Table 10, Table 13 and 
Figure 4 have been updated to 
reflect the changes. 
Previous Table 15 about 
hematocrit readout has been 
deleted to reflect the changes. 
Removed due to challenges (mostly due to 
the COVID-19 pandemic) faced in several 
countries preventing the samples from 
reaching the central lab in adequate time 
for testing. 
Samples collected until the current 
Protocol Amendment 1 is approved 
(unless IEC/IRB allows for immediate 
implementation of this measure to reduce 
participant’s burden, prior to full 
Amendment 1 being approved), will be still 
used for hematocrit analysis if required, as 
described in Section 10.2. 
Section 2.3 Benefit/Risk 
assessment 
Updated to provide details on the 
current status on expected 
benefits and risks from receiving 
the RSV MAT (RSVPreF3) 
vaccine 
Updated to reflect potential changes in the 
benefit-risk profile. 
Section 3 Objectives and 
Endpoints, Section 9.4.4.1 
Safety. 
Updated the objectives and 
endpoints plan and categorized 
the secondary safety objective as 
a primary one to assess safety of 
the infants. 
Updated to reflect the change to study’s 
safety assessment plan. 
Section 1.2 Schema, Section 
4.1 Overall design, Section 
6.3.5 – Blinding and unblinding, 
Section 6.3.5.1 Emergency 
unblinding, Section 8.2.3.1 
Safety evaluation by the Safety 
Review Team (SRT), Section 
8.2.3.2 Independent data 
monitoring committee (IDMC) 
evaluation, Section 9.4.3.1 
Safety, Section 9.4.4.1 Safety, 
Section 10.1.6 Dissemination of 
Updated to provide details on the 
blinding status of the study.  
Table 5 has been updated to 
reflect the changes and sections 
impacted by this change have 
been updated accordingly. 
Updated as the study team was unblinded 
while assessing the safety issue; and also 
to allow investigators to identify and inform 
the recipients of the potential risk 
observed with the RSV MAT vaccination. 


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Section # and title 
Description of change 
Brief rationale 
clinical study data, Section 
10.7.2 Glossary of terms 
Section 6.6 Continued access 
to study intervention after the 
end of the study 
Updated as there will be no 
access to RSV MAT vaccine after 
the study end. 
Updated because of the safety signal 
identified, leading to stopping of further 
enrollment and vaccination. 
Section 6.8.1 Maternal 
participants 
Included “antivirals” to the list of 
concomitant medications to be 
recorded (in addition to antibiotics, 
analgesics and anti-pyretics). 
Text added to record all infection-related 
medications taken within 7 days- prior to 
the study vaccination. 
Section 8.2.3 - Study holding 
rules and safety monitoring, 
Section 8.2.3.2 - Study holding 
rules, Section 10.1.5 - 
Commitees structure, Section 
10.7.1 - List of abbreviations 
Name of the GSK safety 
monitoring board changed from 
“Vaccine Monitoring Board 
(VSMB)” to “Global Safety Board”. 
Updated to include the new name of the 
GSK safety monitoring board. 
Section 8.3.3 Regulatory 
reporting requirements for SAE, 
subsequent pregnancies, and 
other events 
Timeframe for reporting 
subsequent pregnancy by the 
investigator/site staff after receipt 
or awareness, changed from 2 
weeks to 24 hours. 
Table 18 has been updated to 
reflect the changes. 
This change was made to correct 
inconsistencies between pregnancy 
reporting form and protocol template. 
Section 8.3.3.1 Contact 
information for reporting SAES, 
AESIs, subsequent 
pregnancies and other events 
Contact information updated for 
SAE reporting email address. 
Table 19 has been updated to 
reflect the changes. 
The email address is changed to align to 
the most recent GSK template related 
recommendation. 
Section 9.3 Analysis sets 
Definition of the enrolled set has 
been updated to exclude screen 
failures. 
Table 22 has been updated to 
reflect the changes. 
Updated to remove screen failures from 
the enrolled set. 
Section 9.5 Conduct of 
analyses, Section 9.5.1 
Sequence of analyses 
Updated to remove the 
intermediate analysis to evaluate 
all maternal and infant data 
collected up to Day 43 post-
delivery/birth visit. 
Updated to reflect the change to study’s 
statistical analysis plan from the decision 
to stop further enrollment and vaccination. 


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TABLE OF CONTENTS 
PAGE 
SPONSOR INFORMATION ............................................................................................ 6 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 7 
Overall rationale for the current amendment: ............................................................ 7 
List of main changes in the protocol and their rationale: ........................................... 8 
1. 
PROTOCOL SUMMARY ........................................................................................ 20 
1.1. 
Synopsis (Amended 15 March 2022) .......................................................... 20 
1.2. 
Schema (Amended 15 March 2022) ........................................................... 20 
1.3. 
Schedule of Activities (SoA) (Amended 15 March 2022) ............................. 22 
2. 
INTRODUCTION .................................................................................................... 36 
2.1. 
Study rationale ............................................................................................ 36 
2.2. 
Background ................................................................................................ 37 
2.3. 
Benefit/Risk assessment (Amended 15 March 2022) .................................. 38 
3. 
OBJECTIVES AND ENDPOINTS (AMENDED 15 MARCH 2022) .......................... 39 
4. 
STUDY DESIGN .................................................................................................... 42 
4.1. 
Overall design ............................................................................................. 42 
4.2. 
Scientific rationale for study design ............................................................. 48 
4.2.1. 
Study population .......................................................................... 48 
4.2.2. 
Use of placebo ............................................................................. 48 
4.2.3. 
Randomization ratio ..................................................................... 48 
4.2.4. 
Sub-cohorts for infant blood sampling .......................................... 48 
4.2.5. 
Case definition (Amended 15 March 2022) .................................. 48 
4.2.5.1. 
Maternal, medically attended respiratory tract 
illness (MA-RTI) (Amended 15 March 2022) ............... 49 
4.2.5.2. 
Respiratory tract illness (RTI) / Lower 
respiratory tract illness (LRTI) in infants ...................... 49 
4.2.5.3. 
RSV infection (Amended 15 March 2022) ................... 50 
4.3. 
Justification for dose (Amended 15 March 2022) ........................................ 50 
4.4. 
End of Study definition ................................................................................ 50 
5. 
STUDY POPULATION ........................................................................................... 51 
5.1. 
Inclusion criteria .......................................................................................... 51 
5.1.1. 
Maternal participants ................................................................... 51 
5.1.2. 
Infant participants ........................................................................ 53 
5.2. 
Exclusion criteria ......................................................................................... 53 
5.2.1. 
Maternal participants ................................................................... 53 
5.2.1.1. 
Medical conditions ...................................................... 53 
5.2.1.2. 
Prior/Concomitant therapy (Amended 15 March 
2022) .......................................................................... 54 
5.2.1.3. 
Prior/Concurrent clinical study experience .................. 55 
5.2.1.4. 
Other exclusions ......................................................... 55 
5.2.2. 
Infant participants ........................................................................ 56 
5.3. 
Lifestyle considerations ............................................................................... 56 
5.3.1. 
Demographic data ....................................................................... 56 
5.3.2. 
Lifestyle characteristics ................................................................ 56 


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5.3.2.1. 
Maternal participants .................................................. 56 
5.3.2.2. 
Infant participants ....................................................... 56 
5.4. 
Screen failures ............................................................................................ 56 
5.5. 
Criteria for temporarily delaying study intervention administration 
(Amended 15 March 2022) ......................................................................... 57 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY .................................. 57 
6.1. 
Study interventions administered (Amended 15 March 2022) ..................... 57 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 58 
6.3. 
Measures to minimize bias: randomization and blinding ............................. 58 
6.3.1. 
Participant identification ............................................................... 58 
6.3.2. 
Randomization to study intervention (Amended 15 March 
2022) ........................................................................................... 59 
6.3.3. 
Intervention allocation to the participant (Amended 15 
March 2022) ................................................................................ 59 
6.3.4. 
Allocation of participants to assay subsets ................................... 59 
6.3.5. 
Blinding and unblinding (Amended 15 March 2022) ..................... 60 
6.3.5.1. 
Emergency unblinding (Amended 15 March 
2022) .......................................................................... 60 
6.3.5.2. 
Unblinding prior to regulatory reporting of SAEs 
(Amended 15 March 2022) ......................................... 61 
6.4. 
Study intervention compliance (Amended 15 March 2022) ......................... 61 
6.5. 
Dose modification ....................................................................................... 62 
6.6. 
Continued access to study intervention after the end of the study 
(Amended 15 March 2022) ......................................................................... 62 
6.7. 
Treatment of overdose ................................................................................ 62 
6.8. 
Concomitant therapy ................................................................................... 62 
6.8.1. 
Maternal participants (Amended 15 March 2022) ......................... 62 
6.8.2. 
Infant participants ........................................................................ 63 
6.8.3. 
Maternal and Infant participants ................................................... 63 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 63 
7.1. 
Discontinuation of study intervention ........................................................... 63 
7.2. 
Participant discontinuation/withdrawal from the study ................................. 64 
7.3. 
Lost to follow-up.......................................................................................... 64 
8. 
STUDY ASSESSMENTS AND PROCEDURES (AMENDED 15 MARCH 
2022) ...................................................................................................................... 65 
Study procedures during special circumstances (Amended 15 March 2022) .......... 65 
8.1. 
Immunogenicity assessments ..................................................................... 67 
8.1.1. 
Biological samples (Amended 15 March 2022) ............................ 68 
8.1.2. 
Laboratory assays (Amended 15 March 2022) ............................ 70 
8.1.3. 
Immunological read-outs (Amended 15 March 2022) ................... 71 
8.1.4. 
Clinical safety laboratory assessments ........................................ 72 
8.1.5. 
Immunological correlates of protection ......................................... 72 
8.2. 
Safety assessments .................................................................................... 73 
8.2.1. 
Procedures for maternal participants ........................................... 73 
8.2.1.1. 
Collection of demographic data .................................. 73 
8.2.1.2. 
Collection of worsening of the pre-existing 
medical condition and/or obstetric complication .......... 73 
8.2.1.3. 
Medical/vaccination history ......................................... 73 


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8.2.1.4. 
Physical examination (General and obstetric 
examination) ............................................................... 74 
8.2.1.4.1. 
Pulse oximetry ........................................ 76 
8.2.1.4.2. 
Monthly contacts (Amended 15 
March 2022) ........................................... 76 
8.2.1.5. 
Warnings and precautions to administration of 
study intervention ....................................................... 76 
8.2.2. 
Procedures for infant participants ................................................ 76 
8.2.2.1. 
Physical examination at Visit 1-NB to Visit 5-
NB .............................................................................. 76 
8.2.3. 
Study holding rules and safety monitoring (Amended 15 
March 2022) ................................................................................ 77 
8.2.3.1. 
Safety evaluation by the Safety Review Team 
(SRT) (Amended 15 March 2022) ............................... 77 
8.2.3.2. 
Independent data monitoring committee 
(IDMC) evaluation (Amended 15 March 2022) ............ 77 
8.2.3.3. 
Study holding rules (Amended 15 March 2022) .......... 78 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and other 
safety reporting ........................................................................................... 80 
8.3.1. 
Time period and frequency for collecting AE, SAE and 
other safety information (Amended 15 March 2022) .................... 80 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and 
other events ................................................................................. 82 
8.3.2.1. 
Clinically significant abnormal laboratory 
findings ....................................................................... 82 
8.3.3. 
Regulatory reporting requirements for SAEs, subsequent 
pregnancies and other events (Amended 15 March 2022) ........... 83 
8.3.3.1. 
Contact information for reporting SAEs, AESIs, 
pregnancies and study holding rules (Amended 
15 March 2022) .......................................................... 84 
8.3.4. 
Additional reporting guidance for the study pregnancy ................. 84 
8.3.4.1. 
Labor and delivery ...................................................... 84 
8.3.4.2. 
Pregnancy outcomes .................................................. 84 
8.3.4.3. 
Reporting of congenital anomalies in relation to 
pregnancy outcomes and SAEs and/or AESIs ............ 85 
8.3.5. 
Treatment of adverse events (AEs).............................................. 86 
8.3.6. 
Participant card ............................................................................ 86 
8.4. 
Respiratory tract illnesses (RTIs) ................................................................ 86 
8.4.1. 
Definitions .................................................................................... 86 
8.4.1.1. 
Medically attended respiratory tract illnesses 
(MA-RTIs) in maternal participants (Amended 
15 March 2022) .......................................................... 86 
8.4.1.2. 
Respiratory tract illnesses (RTIs) in infant 
participants ................................................................. 86 
8.4.2. 
Surveillance ................................................................................. 87 
8.4.2.1. 
Maternal participants (Amended 15 March 
2022) .......................................................................... 87 
8.4.2.2. 
Infant participants ....................................................... 88 
8.4.2.2.1. 
RTI surveillance contacts ........................ 88 
8.4.2.2.2. 
RTI Diary cards ....................................... 88 
8.4.2.3. 
Maternal and infant participants (Amended 15 
March 2022) ............................................................... 89 


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8.4.3. 
When to conduct an assessment visit .......................................... 89 
8.4.3.1. 
For a maternal MA-RTI (Amended 15 March 
2022) .......................................................................... 89 
8.4.3.2. 
For an infant RTI (Amended 15 March 2022) .............. 91 
8.4.4. 
Assessment visit procedures (Amended 15 March 2022) ............ 93 
8.4.4.1. 
Clinical evaluation (Amended 15 March 2022) ............ 93 
8.4.4.2. 
Nasal swab collection (Amended 15 March 
2022) .......................................................................... 94 
8.4.4.3. 
Missed assessment visit (Amended 15 March 
2022) .......................................................................... 94 
8.4.5. 
RTI hospitalization during the surveillance interval 
(Amended 15 March 2022) .......................................................... 94 
8.4.6. 
Follow-up of infant respiratory tract illnesses (RTIs) ..................... 94 
8.4.7. 
Covid-19 Infection ........................................................................ 95 
8.5. 
Pharmacokinetics ....................................................................................... 95 
8.6. 
Genetics and/or Pharmacogenomics .......................................................... 95 
8.7. 
Biomarkers ................................................................................................. 95 
8.8. 
Immunogenicity........................................................................................... 95 
8.9. 
Health outcomes ......................................................................................... 95 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 95 
9.1. 
Statistical hypotheses ................................................................................. 95 
9.2. 
Sample size determination (Amended 15 March 2022) ............................... 95 
9.2.1. 
Safety .......................................................................................... 96 
9.2.2. 
Immunogenicity............................................................................ 97 
9.3. 
Analysis sets (Amended 15 March 2022) .................................................... 98 
9.3.1. 
Criteria for elimination from analysis ............................................ 98 
9.3.1.1. 
Intercurrent medical conditions and 
concomitant medications / products / vaccines 
that may lead to elimination of a participant 
(maternal/infant) from per protocol analyses 
(immunogenicity) ........................................................ 98 
9.3.1.1.1. 
Maternal participants .............................. 98 
9.3.1.1.2. 
Infant participants ................................... 98 
9.3.1.1.3. 
Maternal and Infant participants .............. 99 
9.3.1.2. 
Other situations that may lead to elimination of 
a participant (maternal / infant) from per 
protocol analyses (immunogenicity) ............................ 99 
9.4. 
Statistical analyses ..................................................................................... 99 
9.4.1. 
General considerations ................................................................ 99 
9.4.1.1. 
Safety ....................................................................... 100 
9.4.1.2. 
Immunogenicity ........................................................ 100 
9.4.2. 
Participant disposition ................................................................ 100 
9.4.3. 
Primary endpoints ...................................................................... 101 
9.4.3.1. 
Safety (Amended 15 March 2022) ............................ 101 
9.4.3.2. 
Immunogenicity ........................................................ 103 
9.4.4. 
Secondary endpoints ................................................................. 105 
9.4.4.1. 
Safety (Amended 15 March 2022) ............................ 105 
9.4.4.2. 
Immunogenicity ........................................................ 106 
9.4.5. 
Tertiary endpoints ...................................................................... 107 
9.4.6. 
Other analyses .......................................................................... 108 


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9.4.6.1. 
Demography and baseline characteristics 
analyses ................................................................... 108 
9.4.6.2. 
Other analyses for adolescent maternal 
participants ............................................................... 108 
9.4.6.2.1. 
Safety ................................................... 108 
9.4.6.2.2. 
Immunogenicity .................................... 109 
9.5. 
Conduct of analyses (Amended 15 March 2022) ...................................... 109 
9.5.1. 
Sequence of analyses (Amended 15 March 2022) ..................... 109 
9.5.2. 
Statistical consideration for interim analysis ............................... 109 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 110 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight considerations ........ 110 
10.1.1. 
Regulatory and ethical considerations ....................................... 110 
10.1.2. 
Financial disclosure ................................................................... 110 
10.1.3. 
Informed consent process .......................................................... 111 
10.1.4. 
Data protection .......................................................................... 111 
10.1.5. 
Committees structure (Amended 15 March 2022) ...................... 112 
10.1.6. 
Dissemination of clinical study data (Amended 15 March 
2022) ......................................................................................... 112 
10.1.7. 
Data quality assurance .............................................................. 113 
10.1.8. 
Source documents ..................................................................... 114 
10.1.9. 
Study and site start and closure ................................................. 114 
10.1.10. Publication policy ....................................................................... 115 
10.2. 
Appendix 2: Clinical laboratory tests ......................................................... 115 
10.2.1. 
Protocol-required safety laboratory assessments 
(Amended 15 March 2022) ........................................................ 115 
10.2.2. 
Descriptions of the assays to be performed in the study 
(Amended 15 March 2022) ........................................................ 116 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of AE ................ 117 
10.3.1. 
Definition of an adverse event (AE)............................................ 117 
10.3.1.1. Events meeting the AE definition .............................. 118 
10.3.1.2. Events NOT meeting the AE definition...................... 118 
10.3.2. 
Definition of an SAE ................................................................... 119 
10.3.3. 
Solicited events.......................................................................... 120 
10.3.4. 
Unsolicited adverse events (AEs) .............................................. 120 
10.3.5. 
Adverse events of special interest (AESIs) ................................ 121 
10.3.6. 
Clinical laboratory parameters and other abnormal 
assessments qualifying as AEs or SAEs .................................... 122 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs ................... 122 
10.3.7.1. Subsequent Pregnancy ............................................ 122 
10.3.8. 
Recording and follow-up of AEs, SAEs, AESIs and 
subsequent pregnancies ............................................................ 122 
10.3.8.1. Time period for collecting and recording AEs, 
SAEs, AESIs and subsequent pregnancies .............. 123 
10.3.8.2. Follow-up of AEs, SAEs, AESIs, subsequent 
pregnancies or any other events of interest .............. 123 
10.3.8.2.1. Follow-up during the study .................... 123 
10.3.8.2.2. Follow-up after the participant is 
discharged from the study .................... 124 


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10.3.8.2.3. Follow-up of subsequent 
pregnancies .......................................... 124 
10.3.8.3. Updating of SAE, AESI and subsequent 
pregnancy information after removal of write 
access to the participant’s eCRF .............................. 125 
10.3.9. 
Assessment of intensity and toxicity ........................................... 125 
10.3.9.1. Assessment of intensity ............................................ 125 
10.3.9.2. Assessment of causality ........................................... 126 
10.3.9.3. Medically attended visits ........................................... 127 
10.3.9.4. Assessment of outcomes.......................................... 127 
10.3.10. Reporting of SAEs, AESIs, subsequent pregnancies and 
other events ............................................................................... 128 
10.3.10.1. Events requiring expedited reporting to GSK ............ 128 
10.3.10.2. Back up system in case the electronic reporting 
system does not work ............................................... 128 
10.4. 
Appendix 4: Contraceptive guidance and collection of subsequent 
pregnancy information .............................................................................. 128 
10.5. 
Appendix 5: Genetics ................................................................................ 128 
10.6. 
Appendix 6: Country-specific requirements ............................................... 129 
10.7. 
Appendix 7: Abbreviations and glossary of terms ...................................... 129 
10.7.1. 
List of abbreviations (Amended 15 March 2022) ........................ 129 
10.7.2. 
Glossary of terms (Amended 15 March 2022) ............................ 132 
10.8. 
Appendix 8: Gestational Age Assessment ................................................ 137 
10.8.1. 
GAIA gestational age assessment form ..................................... 137 
10.8.2. 
Methods of gestational age assessment and estimation of 
due date .................................................................................... 138 
10.9. 
Appendix 9: Definitions of study AESIs and pregnancy outcomes ............ 139 
10.10. Appendix 10: Protocol Amendment history ............................................... 162 
11. REFERENCES ..................................................................................................... 193 
 


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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities (SoA) – Maternal participants (Amended 
15 March 2022) ...................................................................................... 24 
Table 2 
Schedule of activities (SoA) – Infant participants (Amended 15 
March 2022) ........................................................................................... 32 
Table 3 
Allowed windows for study visits (Amended 15 March 2022).................. 36 
Table 4 
Study objectives and endpoints (Amended 15 March 2022) ................... 39 
Table 5 
Study groups, intervention and blinding (Amended 15 March 
2022) ...................................................................................................... 47 
Table 6 
MA-RTI case definitions for data analysis in maternal participants 
(Amended 15 March 2022) ..................................................................... 49 
Table 7 
RTI/LRTI case definitions for data analysis in infants ............................. 49 
Table 8 
Study interventions administered (Amended 15 March 2022)................. 57 
Table 9 
Contact information for emergency unblinding ....................................... 61 
Table 10 
Biological samples - Maternal participants (Amended 15 March 
2022) ...................................................................................................... 68 
Table 11 
Biological samples - Cord blood ............................................................. 69 
Table 12 
Biological samples – Infant participants (Amended 15 March 
2022) ...................................................................................................... 69 
Table 13 
Laboratory assays (Amended 15 March 2022) ....................................... 70 
Table 14 
Immunological read-outs (Amended 15 March 2022) ............................. 71 
Table 15 
Molecular biology tests (Amended 15 March 2022) ................................ 72 
Table 16 
Holding rules assessed by the investigator ............................................. 78 
Table 17 
Timeframes for collecting and reporting of safety information 
(including RTI information) (Amended 15 March 2022) .......................... 80 
Table 18 
Timeframes for submitting SAE, subsequent pregnancy and 
other events reports to GSK (Amended 15 March 2022) ........................ 83 
Table 19 
Contact information for reporting SAEs, AESIs, subsequent 
pregnancies and study holding rules (Amended 15 March 2022) ........... 84 


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Table 20 
Exact 95% confidence interval (CI) on the percentage of 
participants with adverse events (AEs) following dosing in RSV-
MAT vaccine group ................................................................................ 96 
Table 21 
Precision estimation on fold increase and its 95% CI with 226 
participants in RSV-MAT vaccine group ................................................. 97 
Table 22 
Maternal Participants (Amended 15 March 2022) ................................... 98 
Table 23 
Infant participants ................................................................................... 98 
Table 24 
Protocol-Required Safety Laboratory Assessments ............................. 115 
Table 25 
Solicited administration site events....................................................... 120 
Table 26 
Solicited systemic events ..................................................................... 120 
Table 27 
Intensity scales for solicited events in adults ........................................ 125 
Table 28 
Fetal death / Stillbirth ........................................................................... 140 
Table 29 
Maternal Death .................................................................................... 143 
Table 30 
Hypertensive disorders of pregnancy (Gestational hypertension, 
Pre-eclampsia, Pre-eclampsia with severe features including 
eclampsia) ............................................................................................ 144 
Table 31 
Fetal growth restriction ......................................................................... 146 
Table 32 
Gestational diabetes mellitus (pregnancy induced 
hyperglycemia) ..................................................................................... 147 
Table 33 
Pathways to preterm birth .................................................................... 149 
Table 34 
Chorioamnionitis .................................................................................. 151 
Table 35 
Small for gestational age ...................................................................... 153 
Table 36 
Low Birth Weight (LBW) ....................................................................... 155 
Table 37 
Major Congenital anomalies ................................................................. 156 
Table 38 
Neonatal Death .................................................................................... 159 
Table 39 
Preterm Birth ........................................................................................ 161 
 


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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview – Maternal participants (Amended 15 
March 2022) ........................................................................................... 43 
Figure 2 
Study design overview – Infant participants (Amended 15 March 
2022) ...................................................................................................... 44 
Figure 3 
Risk assessment curve for the defined safety holding rules ................... 79 
Figure 4 
Decision Tree for site personnel – maternal surveillance and 
assessment ............................................................................................ 90 
Figure 5 
Decision Tree for site personnel - infant surveillance and 
assessment (Amended 15 March 2022) ................................................. 92 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis (Amended 15 March 2022) 
Rationale: 
The objective of the study is to evaluate the safety, reactogenicity, and immunogenicity * 
of the single intramuscular 120 µg dose of the study RSV maternal vaccine compared to 
placebo, in women with high risk pregnancies in the late second or third trimester of 
pregnancy and in the infants born to the vaccinated mothers. 
The study will enroll pregnant adult participants with prevalent obstetric complications 
and risk factors that increase the risk of adverse pregnancy and neonatal outcomes: 
gestational diabetes, gestational hypertension, pre-eclampsia, fetal growth restriction, 
history of preterm labor in the current pregnancy, Human Immunodeficiency Virus (HIV) 
infection or uncomplicated twin pregnancy.[ACOG, 2019; EPI-RSV-015, 2019; 
Kachikis, 2017]. This study will also enroll pregnant healthy adolescent participants, 
considered as a potential high risk group. 
Objectives and endpoints are presented in Table 4. 
* Based on all available safety information following vaccination with RSV MAT 
vaccine, there will be no further enrollment and vaccination of maternal participants. 
However, monitoring will continue for rest of the study. All planned objectives will be 
assessed for the participants enrolled so far.  
1.2. 
Schema (Amended 15 March 2022) 
The study is a Phase III, double-blind*, randomized, placebo-controlled, multi-center, 
multi-country study. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
Maternal participants 15 to 49 years of age (YOA) (inclusive, at the time of the study 
intervention administration) will be enrolled to receive either RSV maternal (RSV MAT) 
vaccine (120 µg of RSVPreF3) or the placebo control, between the 24 0/7 to 36 0/7 weeks 
of gestation (inclusive). 
Approximately 378 eligible maternal participants will be enrolled* and randomized (2:1) 
to receive either RSV MAT vaccine or the placebo control. At least eighteen (5%) of the 
enrolled and randomized maternal participants will be between 15 and 17 YOA, 
inclusive. At the same time, infant participants (as yet unborn) will be further randomized 
(1:1:1) into sub-cohorts for blood sample collection for the assessment of 
immunogenicity at one of 3 timepoints (Day 43, Day 121 or Day 181 post-birth). 
*Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants.  


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An automated internet-based system (SBIR) will be used to randomly allocate a study 
group and treatment number to each maternal participant and her infant participant (as yet 
unborn) to a blood sampling sub-cohort. Age at the time of study intervention 
administration (<18, ≥18 YOA) will be a stratification factor within the randomization 
algorithm, while: 
(a) gestational age at the time of study intervention administration (<28 0/7; ≥ 28 0/7 
weeks), 
(b) pre-existing HIV infection and obstetric complication status (HIV present and 
obstetric complication present, HIV present and obstetric complication absent, or HIV 
absent and obstetric complication present) for participants ≥18 YOA only, 
(c) center 
will be the minimization factors. Minimization factors will have equal weight in the 
algorithm. 
Study duration for maternal participants will be approximately 10 to 11 months 
(including screening visit, from informed consent/assent until 180 days post-delivery), 
and will be evaluated for safety, reactogenicity and immune responses. 
Blood samples for humoral immunogenicity will be collected from all maternal 
participants at Day 1 (pre-study intervention), Day 31 (only if the delivery occurs after 
Day 31 post-study intervention) and on delivery day. Cord blood samples to evaluate the 
transfer of RSV-specific antibodies from maternal participants to their infants will be 
collected from all maternal participants on delivery day. The primary immunogenicity 
analysis will be based on the per protocol set (PPS) for immunogenicity. A second 
analysis of immunogenicity based on the full analysis set (FAS) may be performed to 
complement the PPS analysis (Refer to Sections 9.3 and 9.4.1.2 for details). 
All maternal participants who receive the study intervention (exposed set [ES]) will be 
followed for safety and reactogenicity and evaluated for: solicited administration site and 
systemic adverse events (AEs) within 7 days of study intervention, unsolicited AEs 
within 30 days of study intervention, pregnancy outcomes and pregnancy-related adverse 
events of special interest (AESIs) within 42 days of delivery, serious adverse events 
(SAEs), medically attended respiratory tract illnesses (MA-RTIs)* and medically 
attended adverse events (MAEs) throughout the study period and up to the time of the 
last contact. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
Study duration for infant participants will be approximately 12 months (from birth until 
365 days post-birth) which is expected to cover at least 1 complete RSV season and will 
be evaluated for safety and immune responses. 
Blood samples for humoral immunogenicity will be collected from sub-cohorts of infant 
participants at Day 43, Day 121 and Day 181 post-birth*. The primary immunogenicity 
analysis will be based on the PPS for immunogenicity. A second analysis of 


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immunogenicity based on the FAS may be performed to complement the PPS analysis 
(Refer to Sections 9.3 and 9.4.1.2 for details). 
* Due to the change in the study requirements, there will no longer be collection of 
blood samples at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
All infant participants born to exposed maternal participants (ES) will be followed for 
safety and evaluated for: neonatal/infant related AESIs up to 42 days of birth, medically 
assessed, RSV-associated lower respiratory tract illnesses (RSV-LRTIs) up to 365 days 
post-birth which is expected to cover at least 1 complete RSV season, SAEs and MAEs 
throughout the study period and up to the time of the last visit. 
Section 4.1 provides an overview of the study design. 
Safety monitoring and safety data review will be performed by an internal Safety Review 
Team (SRT) and an external Independent Data Monitoring Committee (IDMC). 
1.3. 
Schedule of Activities (SoA) (Amended 15 March 2022) 
For maternal participants, Table 1 presents the Schedule of Activities (SoA). For infant 
participants, Table 2 presents the SoA. Table 3 describes the allowed windows for study 
visits for both maternal and infant participants. 
Whenever possible, the investigator should arrange study visits within the allowed visit 
window. Immunogenicity data from blood samples collected outside an allowed visit 
window may not be considered in the associated PPS for analysis. 
Please note: 
• 
Study visits, assessments and procedures do not replace local standards of care. 
If local standard of care recommends additional visits/medical evaluations (for 
maternal participants or their infants), participants should comply with these local 
recommendations. 
• 
Any AE / potential AE identified during a study visit or procedure should be treated 
according to local standards of care or by referral to an appropriate health care 
provider. 
• 
Maternal participant visits at screening / Visit 1 (Day 1) may take place at the study 
site or another medical facility. 
• 
When a maternal participant completes Visit 1 (study intervention), and again at 
Visit 3 (Delivery), site staff should, in so far as possible, ensure all site study 
obstetrician(s) and pediatrician(s) are informed. This will help to ensure that study 
pediatrician(s) and/or staff are aware of the maternal participant’s (approximate) date 
of delivery and potential enrollment of the neonate. 
• 
Maternal participant Visit 2 and 4, infant participant Visits 1-NB, 2-NB, 3-NB, 4-NB 
and 5-NB, and maternal and infant respiratory tract illness (RTI) assessment visits 
may take place at the investigator’s clinical facility, another medical facility, or via a 


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home visit by qualified site staff (or a designated third party), as appropriate per the 
judgment of the investigator (and as allowed by local law). 
• 
The visit location must have appropriate infrastructure and logistics to complete all 
study procedures if a visit is to be conducted at a different location other than the 
study site or at participant’s home. Blood samples including cord blood samples for 
immunogenicity collected outside of the study site must be centrifuged between 30 
minutes and at most, 24 hours after collection. 
• 
Contact may be via telephone, SMS, email, video-telephone/telemedicine or other 
means, depending on local best practice. If the study site is the participant’s primary 
healthcare facility, contact with study personnel may also be made in the context of a 
visit for routine or event-driven care. 
• 
Refer to Section 8 for information about special circumstances (e.g., the Covid 19 
pandemic) and their impact on study activities. 


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Table 1 
Schedule of Activities (SoA) – Maternal participants (Amended 15 March 2022) 
Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
Informed consent/assent 
● 
 
 
 
 
 
 
 
 
 
Section 10.1.3 
Due to the recent 
safety signal, there 
will be no further 
enrollment and 
vaccination of 
maternal 
participants. 
Check inclusion/exclusion 
criteria  
● 
O 
 
 
 
 
 
 
 
 
Sections 5.1.1 and 
5.1.2 
Assign maternal participant 
study number  
● 
 
 
 
 
 
 
 
 
 
Section 6.3.1 
Register maternal 
participant in SBIR 
O 
 
 
 
 
 
 
 
 
 
Assign infant participant 
study number  
 
O 
 
 
 
 
 
 
 
 
Record demographic data  
● 
 
 
 
 
 
 
 
 
 
Section 5.3 
Record lifestyle 
characteristics 
● 
● 
● 
● 
 
● 
● 
● 
 
 
Review & collect medical 
and vaccination history, 
O 
● 
 
 
 
 
 
 
 
 
Section 8.2.1.3 


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Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
including pre-existing 
medical conditions and/or 
obstetric complications 
Record outcome of fetal 
morphology ultrasound 
scan  
● 
 
 
 
 
 
 
 
 
 
Section 8.2.1.3 
Record the estimated fetal 
weight by ultrasound or 
record presence of fetal 
growth restriction if 
diagnosed using other 
ultrasound parameters 
● 
 
 
 
 
 
 
 
 
 
 
Record obstetric history 
from current pregnancy  
● 
O 
 
 
 
 
 
 
 
 
Section 8.2.1.3 
Record obstetric history 
from past pregnancies 
O 
● 
 
 
 
 
 
 
 
 
Section 8.2.1.3 
Record travel history to or 
living in Zika virus endemic 
countries/regions 
(During the current 
pregnancy only) 
● 
● 
● 
● 
 
● 
 
 
 
 
 
General and obstetric 
examination  
● 
● 
 
● 
 
● 
● 
 
O 
O 
Section 8.2.1.4 


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Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
Body temperature before 
study interventions 
administration 2 
 
● 
 
 
 
 
 
 
 
 
 
Review of safety lab data 
required for assessing 
eligibility criteria  
O 
 
 
 
 
 
 
 
 
 
Section 10.2.1 
OR 
Blood sample (hematology 
/ biochemistry, ~ 5.5 ml) if 
not performed as part of the 
routine care. 
Review of safety lab data 
required for assessing 
eligibility criteria 
O 
 
 
 
 
 
 
 
 
 
OR 
Urine sample (Dipstick) if 
not performed as part of the 
routine care 
Blood sample  
(immunogenicity ~ 10 ml) 
 
● 
 
● 
 
● 
 
 
 
 
Sections 8.1.1 and 
8.1.3 
Cord blood (~ 5 to 10 ml) 
 
 
 
 
 
● 
 
 
 
 
Sections 8.1.1 and 
8.1.3 


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Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
Nasal swab 7 
 
 
 
 
 
 
 
 
 
● 
Sections 8.1.1, 8.1.3, 
and 8.4.4 
Nasal swab samples 
will no longer be 
collected. 
Placental tissue sample 8 
 
 
 
 
 
● 
 
 
 
 
Section 10.2.1 
Samples will be 
collected at delivery 
from all participants, 
if feasible. 
Check contraindications, 
warnings and precautions 
to study interventions 
administration 
 
O 
 
 
 
 
 
 
 
 
Section 8.2.1.5 
Check criteria for temporary 
delay for study 
interventions administration 
 
O 
 
 
 
 
 
 
 
 
Section 7.1 
Allocate maternal study 
group, intervention number 
 
O 
 
 
 
 
 
 
 
 
Sections 6.3.2 and 
6.3.3 
Allocate infant sub-cohorts 
for immunogenicity 
assessment 3 
 
O 
 
 
 
 
 
 
 
 
 


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Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
Administer Intervention 
(study vaccine / placebo) 
 
● 
 
 
 
 
 
 
 
 
Sections 6.1 and 6.2 
Record administered 
intervention number 
 
● 
 
 
 
 
 
 
 
 
Observe for 30 minutes 
post-dose 
 
O 
 
 
 
 
 
 
 
 
Distribute maternal 
participant card 
O 
O 
 
 
 
 
 
 
 
 
Section 8.3.6 
Record Labor / delivery 
information  
 
 
 
 
 
● 
 
 
 
 
 
Record pregnancy / 
delivery outcomes (Day 1 
post-study intervention to 
Day 42 post-delivery)  
 
O 
O 
 
O 
● 
O 
 
 
 
Section 8.3.3. Must 
submit Expedited AE 
report for an adverse 
pregnancy outcome 
Train maternal 
participant/LAR on use of 
eDiary device 
 
O 
 
 
 
 
 
 
 
 
Section 10.3.8 
Distribute eDiary device to 
maternal participant / LAR.  
 
O 
 
 
 
 
 
 
 
 
Review eDiary entries 
 
O 
O 
O 
 
 
 
 
O 4 
O 4 
Section 8.3.1 
Return eDiary device 
 
 
 
O 
 
 
 
 
 
 
 


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Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
Concomitant medications / 
vaccinations. 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Sections 6.8.1 and 
6.8.3 
All solicited AEs (Day 1 
post-study intervention to 7 
days post-study 
intervention) 
 
O 
O 
 
 
 
 
 
O 
 
Sections 8.3.1, 10.3.4 
and 10.3.8 
All unsolicited AEs (Day 1 
post-study intervention to 
30 days post-study 
intervention)  
 
● 
● 
● 
 
 
 
 
● 
● 
Sections 8.3.1, 10.3.4 
and 10.3.8 
Record of worsening of pre-
existing medical conditions 
and/or obstetric 
complications (Day 1 post-
study intervention to 180 
days post-delivery) 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Section 8.2.1.2 
Pregnancy-related AESIs 
(Day 1 post-study 
intervention to 42 days 
post-delivery)  
 
● 
● 
● 
● 
● 
● 
 
● 
● 
Sections 8.3.1, 8.3.3, 
8.3.4 and 10.3.5. 
Must submit an 
Expedited AE report. 
Suspected, probable and 
confirmed cases of COVID-
19 infection (depending on 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Sections 8.4.7 


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Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
the epidemiological COVID-
19 situation) (Day 1 post-
study intervention to 180 
days post-delivery) 
MA-RTIs (Day 1 post-study 
intervention to 180 days 
post-delivery) 7 
 
O 5 
O 5 
O 5 
O 5 
O 5 
O 5 
O 5 
 
● 
Sections 8.3.1, 8.3.3, 
8.4 and 10.3.8 
MA-RTIs for the 
maternal 
participants will no 
longer be 
performed. 
SAEs, (S)AEs leading to 
study withdrawal, MAEs 
(Day 1 post-study 
intervention to 180 days 
post-delivery) 
 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Sections 7.2, 8.3.1 
and 10.3.8 
SAEs related to study 
participation (Screening to 
Day 1 pre-study 
intervention) 
● 
● 
 
 
 
 
 
 
 
 
Sections 8.3.1 and 
10.3.8 
Subsequent pregnancies 
 
 
 
 
 
 
● 
● 
● 
● 
Record interest in joining 
future extension study 
 
 
 
 
 
 
 
● 
 
 
Section 6.6 


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Visit / Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associated 
MA-RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoint 
D (-28) – D 1 
D1 
(24 0/7 - 36 0/7 
weeks of 
gestation) 
D8 
D31 
 
Delivery 
D43 
Post-
delivery 
D181 
Post-
delivery 
 
 
For monthly contacts: 
Section 8.4.2.1 
Additional contacts 
and/or visits can be 
made between Visit-
2 and the Delivery 
visit if deemed 
necessary. 
Screening conclusion  
● 
 
 
 
 
 
 
 
 
 
 
Study conclusion 
 
 
 
 
 
 
 
● 
 
 
Sections 4.4 and 
10.1.9 
V = visit; C = Contact; D = day; MA-RTI = medically attended respiratory tract illness; LAR = Legally acceptable representative 
● 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 Visit 2 (Day 31) may be replaced by Visit 3 (Delivery) in case of premature delivery. If the delivery date occurs prior to Day 31 post-study intervention, there will be no Visit 2 (Day 31). 
2 Fever is defined as temperature 38.0°C/100.4°F regardless of the location of measurement. The preferred location for measuring temperature in this study is the oral cavity. 
3 Recording will be done at Visit 1, upon maternal participant randomization but the eCRF entry will be done on the demography screen. 
4 For safety visit or RSV-associated MA-RTI visit, eDiary entries should be reviewed only if the visit occurs between Day 1 and Day 31. 
5 RSV-associated MA-RTI unscheduled visit should be planned if the maternal participant has any symptoms or signs as defined in Section 8.4.3.1. 
6 In addition to the monthly contacts between Visit-2 and the Delivery visit, additional not pre-specified contacts and/or visits can be made more often (at any desired 
frequency), as per investigator’s, maternal participant’s or LAR’s discretion. 
7 Due to the change in the study requirements, RTI surveillance/ assessment for the maternal participants will no longer be performed  
8 Placental tissue samples will be collected at delivery from all maternal participants, whenever feasible. These samples may be tested to support possible safety 
assessments, if necessary. Additional details are provided in the study procedures manual (SPM). 
Note: 
Contact may be via telephone, SMS, email, video-telephone/telemedicine or other means, depending on local best practice. If the study site is the participant’s primary healthcare 
facility, contact with study personnel may also be made in the context of a visit for routine or event-driven care. 
The timing of an event-driven site visit (e.g., to further evaluate a potential (S)AE or RSV-MA-RTIs) cannot be defined with precision in the protocol. Event-driven visits may occur 
throughout the study. 
In times of special circumstances, refer to Section 8 for study procedures. 


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Table 2 
Schedule of activities (SoA) – Infant participants (Amended 15 March 2022) 
Visit / Contact 
V1-NB 
Safety contact 
(recommended) 
5 
V2-NB 
C1-NB 
V3-NB 
V4-NB 
C2-NB 
V5-NB 
RTI Surveillance 
Notes 
 
Contacts 
(Section 
8.4.2.2.1) 
Visit 
Age of infant 
 
8 days 
6 
weeks 
3 
months 
4 
months 
6 
months 
9 
months 
12 
months 
 
 
Visit Day 
Birth 
D8  
Post-birth 
D43 
Post-
birth 
D91 
Post-
birth 
D121 
Post-
birth 
D181 
Post-
birth 
D271 
Post-
birth 
D366 
Post-
birth 
Birth to Day 366 
Post-birth 
Event-
Driven 
Check inclusion / 
exclusion criteria 
● 
 
 
 
 
 
 
 
 
 
Sections 5.1.2 and 
5.2.2 
Re-consent / Consent for 
infant participation if 
required by local 
regulations  
● 
 
 
 
 
 
 
 
 
 
 
Record infant participant 
study number  
● 
 
 
 
 
 
 
 
 
 
 
Record sub-cohort for 
immunogenicity 
assessment 
● 
 
 
 
 
 
 
 
 
 
Section 6.3.2 
Distribute infant’s 
participant card  
O 
 
 
 
 
 
 
 
 
 
Section 8.3.6 
Distribute infant RTI diary 
card 
O 
 
O 
 
O 
O 
 
O 
 
O 
Distribute at V1-
NB: Distribute 
additional RTI diary 
cards as needed. 
Review infant RTI diary 
card 
 
O 
O 
O 
O 
O 
O 
O 
O 
O 
 
Collect infant RTI diary 
card 
 
 
O 
 
O 
O 
 
O 
 
O 
Collect RTI diary 
cards that are fully 
filled out. 
Transcribe applicable 
infant RTI diary card data 
to eCRF 
 
O 
● 
● 
● 
● 
● 
● 
● 
● 
 


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Visit / Contact 
V1-NB 
Safety contact 
(recommended) 
5 
V2-NB 
C1-NB 
V3-NB 
V4-NB 
C2-NB 
V5-NB 
RTI Surveillance 
Notes 
 
Contacts 
(Section 
8.4.2.2.1) 
Visit 
Age of infant 
 
8 days 
6 
weeks 
3 
months 
4 
months 
6 
months 
9 
months 
12 
months 
 
 
Visit Day 
Birth 
D8  
Post-birth 
D43 
Post-
birth 
D91 
Post-
birth 
D121 
Post-
birth 
D181 
Post-
birth 
D271 
Post-
birth 
D366 
Post-
birth 
Birth to Day 366 
Post-birth 
Event-
Driven 
Demographic data 
● 
 
 
 
 
 
 
 
 
 
Section 5.3  
Lifestyle characteristics 1  
● 
O 
● 
● 
● 
● 
● 
● 
 
 
Apgar score (at 1, 5 and 
[if available/performed] 10 
minutes) 
● 
 
 
 
 
 
 
 
 
 
 
Weight, length, head 
circumference, physical 
examination  
● 
 
● 
 
● 
● 
 
● 
 
● 
Section 8.2.2.1 
Blood sample if no cord 
blood  
~2.5 ml 2 
● 
 
 
 
 
 
 
 
 
 
Table 12 
Blood sample 
(immunology, infants) 
~2.5 ml 3, 6  
 
 
● 
Sub-
cohort 1 
 
● 
Sub-
cohort 2 
● 
Sub-
cohort 3 
 
 
 
 
Table 12 
Samples will no 
longer be 
collected at Visit 
2-NB, Visit 3-NB 
and Visit 4-NB 
Concomitant vaccinations 
● 
O 
● 
● 
● 
● 
 
 
 
 
Sections 6.8.2 and 
6.8.3 
Concomitant medications  
● 
O 
● 
● 
● 
● 
● 
● 
● 
● 
Neonatal / Infant AESIs 
(Birth to 42 days post- 
birth) 
● 
 
● 
 
 
 
 
 
 
 
Section 8.3.1, 
8.3.3, 8.3.4, and 
10.3.5. Must submit 
an Expedited AE 
report. 
Suspected, probable and 
confirmed cases of 
COVID-19 infection 
● 
O 
● 
● 
● 
● 
● 
● 
● 
● 
Sections 8.4.7 


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Visit / Contact 
V1-NB 
Safety contact 
(recommended) 
5 
V2-NB 
C1-NB 
V3-NB 
V4-NB 
C2-NB 
V5-NB 
RTI Surveillance 
Notes 
 
Contacts 
(Section 
8.4.2.2.1) 
Visit 
Age of infant 
 
8 days 
6 
weeks 
3 
months 
4 
months 
6 
months 
9 
months 
12 
months 
 
 
Visit Day 
Birth 
D8  
Post-birth 
D43 
Post-
birth 
D91 
Post-
birth 
D121 
Post-
birth 
D181 
Post-
birth 
D271 
Post-
birth 
D366 
Post-
birth 
Birth to Day 366 
Post-birth 
Event-
Driven 
(depending on the 
epidemiological COVID-
19 situation) (Birth to 365 
days post-birth) 
LRTIs (including 
medically assessed, 
RSV-associated LRTIs) 
(Birth to 365 days post-
birth) 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
● 
Sections 8.3.1, 
8.3.3, 8.4 and 
10.3.8. 
Medically assessed, 
RSV-associated 
hospitalizations (Birth to 
365 days post-birth) 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
● 
Sections 8.3.1, 
8.3.3, 8.4 and 
10.3.8. 
SAEs, (S)AEs leading to 
study withdrawal, MAEs 
(Birth to 365 days post-
birth) 
● 
O 
● 
● 
● 
● 
● 
● 
● 
● 
Sections 7.2, 8.3.1 
and 10.3.8 
Symptom-directed 
physical examination 
(includes RTI signs, 
symptoms) 
 
 
 
 
 
 
 
 
 
● 
Section 8.4.4 
Nasal swab 
 
 
 
 
 
 
 
 
 
● 
Sections 8.1.1 and 
8.4.4.2 
Study conclusion 
 
 
 
 
 
 
 
● 
 
 
Sections 4.4 and 
10.1.9 
LAR = legally acceptable representative; V= visit; C = contact; D=day; NB = newborn. 
● indicates a study procedure that requires documentation in the individual eCRF. 
○ indicates a study procedure that does not require documentation in the individual eCRF. 


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1 Record at Visit 1-NB and if changes in lifestyle characteristics thereafter. 
2 Adjust volume if weight ≤ 2.5 Kg. If no cord blood was collected, an infant blood sample must be collected within 72 hours after birth. 
3 One sample at one of these visits, as per infant’s assigned sub-cohort. Adjust volume if weight ≤ 2.5 Kg. 
4 RTI unscheduled visit should be planned in case the infant participant has any symptoms or signs as defined in Section 8.4.3.2. 
5 An additional recommended safety contact may be performed ~7 days post-birth if deemed necessary by the investigator or by the parent/ LAR(s). 
6 Due to the change in the study requirements, there will no longer be collection of blood samples at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
In times of special circumstances, refer to Section 8 for study procedures. 
Note: 
Contact may be via telephone, SMS, email, video-telephone/telemedicine or other means, depending on local best practice. If the study site is the participant’s primary healthcare 
facility, contact with study personnel may also be made in the context of a visit for routine or event-driven care. 
The timing of an event-driven visit cannot be defined with precision in the protocol. 


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Table 3 
Allowed windows for study visits (Amended 15 March 2022) 
Visit 
Study Day a 
Allowed visit window b 
Maternal participants 
Screening 
Up to 28 days prior to Visit 1 
Day (-28) - Day 1 
Visit 1 
Day 1 
Day 1 
Contact 1 
Day 8 
Day 8 – Day 12 
Visit 2 c 
Day 31 
Day 21 – Day 46 
Monthly contacts until delivery 
every 30 days 
every 25 – 35 days 
Visit 3 (Delivery) d 
- 
1 day before to 3 days after 
deliveryG  
Visit 4 
Day 43 
after delivery 
Day 31 - Day 61 
after delivery 
Contact 2 
Day 181 
after delivery 
Day 166 - Day 201 
after delivery 
Infant participants 
Visit 1-NB (Birth) d, e 
Birth 
- 
Recommended safefy contact 
Day 8 
Day 7 - Day 10 
Visit 2-NB 
Day 43 
after birth 
Day 31 – Day 61 
after birth  
Contact 1-NB 
Day 91 
after birth 
Day 84 - Day 98 
after birth 
Visit 3-NB f 
Day 121 
after birth 
Day 111 – Day 141 
after birth 
Visit 4-NB f 
Day 181 
after birth 
Day 166 – Day 201 
after birth 
Contact 2-NB 
Day 271 
after birth 
Day 257 – Day 287 
after birth 
Visit 5-NB 
Day 366 
after birth 
Day 331 – Day 401 
after birth 
a Whenever possible the Investigator should arrange study visits at study days. 
b The investigator should endeavor to have the participants come in for the visits within this window. 
c Visit 2 (Day 31) may be replaced by Visit 3 (Delivery) in case of premature delivery. If the delivery date occurs prior to 
Day 31 post-study intervention, there will be no Visit 2 (Day 31). 
d If no cord blood was collected, an infant blood sample must be collected within 72 hours after birth. 
e If consent is not obtained within the allowed interval, but the parent(s) /LAR(s) still wish the infant to participate, 
consent may be obtained at any time until the Day 43 post-delivery/birth visit. 
f Visit may coincide with infant participant’s routine care visit. 
G For participants in whom a cesarean section is performed, the sample may be collected as soon as the 
participant arrives at the clinic and the intravenous line is inserted to prepare them for the cesarean 
section. 
Note: In times of special circumstances, refer to Section 8 for study procedures. 
2. 
INTRODUCTION 
2.1. 
Study rationale 
GSK is developing an investigational respiratory syncytial virus (RSV) vaccine for 
administration to pregnant women in their late second and third trimester of pregnancy, 
with the aim of preventing RSV-associated lower respiratory tract illnesses (LRTIs) in 
their infants by transfer of maternal antibodies. 


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The investigational vaccine is an engineered version of the RSV fusion (F) surface 
glycoprotein, stabilized in the pre-fusion conformation. The F protein has been selected 
because it is a major surface antigen of the RSV virus that is well conserved among RSV-
A and RSV-B subgroups. The RSV F protein is the main target of the neutralizing 
antibody response to RSV, which is considered essential for protection against RSV-
associated severe disease [Magro, 2012]. Vaccination of pregnant women with the RSV F 
protein is expected to protect the baby against RSV (subtypes A and B) LRTI from birth 
up to 6 months of age. 
In the RSV maternal program RSV preF3 vaccine safety, reactogenicity and 
immunogenicity has been studied in healthy non-pregnant women, 18-45 yoa (study RSV 
MAT-001 [NCT 03674177] tested 30, 60 and 120 µg dose-levels, completed; study RSV 
MAT-011[NCT 04138056] tested 60 and 120 µg dose-levels in co-administration with 
dTpa vaccine, ongoing) and in healthy pregnant women 18-40 yoa (study RSV MAT-004 
[NCT 04126213], tested 60 and 120 µg dose-levels, ongoing) and in infants born to 
vaccinated mothers. 
The 120 µg dose has demonstrated robust immunogenicity with no safety concerns 
identified. It was, therefore, selected for evaluation in the Phase III studies: the RSV 
MAT-009 confirmatory efficacy trial is ongoing and the RSV MAT-012 trial is planned 
to assess the safety, reactogenicity and immunogenicity in the high risk obstetric 
population. 
High risk pregnancies represent up to 33% in the overall population of pregnant women 
[Holness, 2018]; however, women with high risk pregnancies will not be part of the 
pivotal RSV MAT-009 study, which will enroll healthy pregnant women. In order to 
collect proper information in this population, RSV MAT-012 study will enroll pregnant 
adult participants with prevalent obstetric complications or conditions which increase the 
risk of adverse pregnancy and neonatal outcomes: gestational diabetes, gestational 
hypertension, pre-eclampsia, fetal growth restriction, history of preterm labor in the 
current pregnancy, HIV infection or uncomplicated twin gestation.[ACOG, 2019; EPI-
RSV-015, 2019; Kachikis, 2017]. This study will also enroll healthy pregnant adolescent 
participants, considered as a potential high risk group. 
The objective of the RSV MAT-012 study is to evaluate the safety, reactogenicity, and 
immunogenicity of the single intramuscular 120 µg dose of the study RSV maternal 
vaccine compared to placebo, when administered in the second or third trimester of 
pregnancy in women with high risk pregnancies and in the infants born to the vaccinated 
mothers. 
2.2. 
Background 
Please refer to the current Investigator’s Brochure (IB) for background information on 
RSV infection, the rationale for the maternal immunization approach described in this 
protocol, and information regarding pre-clinical and clinical studies of the RSV Maternal 
(RSVPreF3) vaccine and epidemiology studies of RSV infection. 


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2.3. 
Benefit/Risk assessment (Amended 15 March 2022) 
The Sponsor has included provisions in this trial to ensure participant’s safety. Safety 
monitoring has been and will be conducted throughout this study by an unblinded 
Independent Data Monitoring Committee (IDMC) and by the Sponsor. The study 
includes the establishment of a surveillance system which may facilitate detection of 
respiratory tract infections, in particular lower respiratory tract infections (LRTIs) in 
infants enrolled in the study. Measures to suspend the study should a potential safety 
issue be identified are described in Section 8.2.3. 
Following a recommendation from the IDMC, the Sponsor made the decision to pause 
the enrollment, randomization and vaccination of participants in our active pregnant 
women studies, including RSV MAT-012, based on an observation of imbalance of the 
proportion of preterm births between the vaccine group and the placebo group in the 
RSV MAT-009 study. This pause was to allow for an evaluation of the available data in 
RSV MAT-009 to better understand the safety signal observed. Following a review of 
additional unblinded data from this trial in which a higher proportion of neonatal 
deaths reported in the treatment group compared to the placebo group was also 
observed, the Sponsor decided to STOP enrollment and vaccination in these studies. 
The safety signals are being investigated and, although at this time a cause has not 
been determined, the Sponsor stopped active enrollment and further vaccination of 
participants in the RSV MAT studies enrolling pregnant women on February 25, 2022 
as a precautionary measure. The study remains ongoing for safety follow-up. 
Participants already vaccinated and their infants will continue to be monitored until 
the end of the study. 


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3. 
OBJECTIVES AND ENDPOINTS (AMENDED 15 MARCH 
2022) 
Table 4 
Study objectives and endpoints (Amended 15 March 2022) 
Objectives 
Endpoints 
Primary 
Safety assessment: 
Maternal participants: 
• 
To evaluate the safety and reactogenicity of a single 
IM dose of study intervention (RSV maternal vaccine 
or placebo) administered to maternal participants up 
to 42 days post-delivery.  
• 
Number and percentage of maternal participants 
reporting: 
− 
Solicited administration site and systemic 
events during a 7-day follow-up period after 
dosing (i.e. Day 1 to Day 7 included). 
− 
Unsolicited AEs that occur during a 30-day 
follow-up period after dosing (i.e. Day 1 to Day 
30 included). 
− 
SAEs, (S)AEs leading to study withdrawal and 
MAEs from Day 1 up to 42 days post-delivery. 
• 
To evaluate the pregnancy outcomes and 
pregnancy-related AESIs up to 42 days post-
delivery, in maternal participants who received a 
single IM dose of study intervention (RSV maternal 
vaccine or placebo).  
• 
Number and percentage of maternal participants 
reporting: 
− 
Pregnancy outcomes * from Day 1 up to 42 
days post-delivery. 
* These include live birth with no congenital 
anomalies, live birth with minor congenital 
anomaly(ies) only; live birth with at least one 
major congenital anomaly, fetal death/still birth 
(antepartum or intrapartum) with no congenital 
anomalies, fetal death/still birth (antepartum or 
intrapartum) with only minor congenital 
anomalies, fetal death/still birth (antepartum or 
intrapartum) with at least 1 major congenital 
anomaly; elective/therapeutic termination with 
no congenital anomalies; elective/therapeutic 
termination with only minor congenital 
anomalies, and elective/therapeutic 
termination with at least 1 major congenital 
anomaly 1. 
− 
Pregnancy-related AESIs * and worsening of 
pre-existing medical conditions and/or 
obstetric complications from Day 1 up to 42 
days post-delivery. 
* These include maternal death, hypertensive 
disorders of pregnancy (gestational 
hypertension, pre-eclampsia, pre-eclampsia 
with severe features including eclampsia), 
fetal growth restriction, gestational diabetes 
mellitus, pathways to preterm birth (premature 
preterm rupture of membranes, preterm labor, 
provider-initiated preterm birth) and 
chorioamnionitis.1 


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Objectives 
Endpoints 
Infant participants: 
• 
To evaluate safety up to 42 days post-birth in infants 
born to maternal participants who received a single 
IM dose of study intervention (RSV maternal vaccine 
or placebo). 
• 
Number and percentage of infant participants 
reporting: 
− 
Neonatal / infant AESIs * from birth up to 42 
days post-birth. 
* These include small for gestational age, low 
birth weight including very low and extremely 
low birth weight (<2500 g, <1500g, <1000g), 
congenital anomalies (major external 
structural defects, internal structural defects, 
functional defects), neonatal death (in an 
extremely preterm birth [22<GA<28 weeks], in 
a preterm live birth [28<GA<37 weeks], or in a 
term live birth) and preterm birth.1 
− 
SAEs, (S)AEs leading to study withdrawal and 
MAEs from birth up to 42 days post-birth. 
• 
To evaluate safety up to 365 days post-birth (1 
year of age) in infants born to maternal 
participants who received a single IM dose of 
study intervention (RSV maternal vaccine or 
placebo). 
• 
Number and percentage of infant participants 
reporting: 
− 
SAEs, (S)AEs leading to study withdrawal 
and MAEs from birth up to 180 days post-
birth. 
− 
SAEs, (S)AEs leading to study withdrawal 
and MAEs from birth up to 365 days post-
birth. 
Immunogenicity assessment: 
Maternal participants: 
• 
To evaluate the immunogenicity of a single IM dose 
of study intervention (RSV maternal vaccine or 
placebo) administered to maternal participants, at 
delivery. 
• 
Humoral immune responses at pre-dosing (Day 1) 
and at delivery: 
− 
RSVPreF3 IgG-specific antibody 
concentrations 
− 
Neutralizing antibody titers against RSV-A 
Cord blood/ placental transfer: 
• 
To evaluate the transfer of RSV-specific antibodies 
from maternal participants who received a single IM 
dose of study intervention (RSV maternal vaccine or 
placebo) to their infants at delivery. 
• 
Ratio between cord blood* and maternal RSVPreF3 
IgG-specific antibody concentrations at delivery 
*or infant blood sample collected within 72 hours after 
birth (if no cord blood sample can be obtained). 
Infant participants: 
• 
To evaluate the RSV-specific antibody levels at birth 
in infants born to maternal participants who received 
a single IM dose of study intervention (RSV 
maternal vaccine or placebo). 
• 
Humoral immune responses at delivery*: 
− 
RSVPreF3 IgG-specific antibody 
concentrations 
− 
Neutralizing antibody titers against RSV-A 
*Measured in cord blood sample collected at delivery or in 
infant blood sample collected within 72 hours after birth (if 
no cord blood sample can be obtained). 


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Objectives 
Endpoints 
Secondary 
Safety assessment: 
Maternal participants: 
• 
To evaluate the safety of a single IM dose of study 
intervention (RSV maternal vaccine and placebo) 
administered to maternal participants, up to 180 
days post-delivery. 
• 
Number and percentage of maternal participants 
reporting: 
− 
SAEs, (S)AEs leading to study withdrawal and 
MAEs from Day 1 up to 180 days post-
delivery. 
• 
To evaluate the worsening of pre-existing medical 
conditions and/or obstetric complications up to 180 
days post-delivery, in maternal participants who 
received a single IM dose of study intervention (RSV 
maternal vaccine or placebo). 
• 
Number and percentage of maternal participants 
reporting: 
− 
Worsening of pre-existing medical conditions 
and/or obstetric complications from Day 1 up 
to 180 days post-delivery. 
• 
To evaluate the occurrence of RSV-associated MA-
RTIs in maternal participants who received a single 
IM dose of study intervention (RSV maternal vaccine 
and placebo) up to 180 days post-delivery. 
• 
Number and percentage of maternal participants 
reporting: 
− 
RSV-associated MA-RTIs from Day 1 up 
to180 days post-delivery. 
Infant participants: 
• 
To evaluate the occurrence of medically assessed, 
RSV-associated LRTIs up to 365 days post-birth (12 
months of age) in infants born to maternal 
participants who received a single IM dose of study 
intervention (RSV maternal vaccine or placebo). 
 
• 
From birth up to 365 days post-birth (12 months of 
age), number and percentage of infant participants 
reporting medically assessed, RSV-associated 
LRTIs of any severity and severe RSV-associated 
LRTIs (according to the cases definitions). 
• 
To evaluate the occurrence of medically assessed, 
RSV-associated hospitalization up to 365 days post-
birth (12 months of age) in infants born to maternal 
participants who received a single IM dose of study 
intervention (RSV maternal vaccine or placebo). 
• 
From birth up to 365 days post-birth (12 months of 
age), number and percentage of infant participants 
reporting medically assessed, RSV-associated 
hospitalizations (according to the cases definitions). 
Immunogenicity assessment: 
Maternal participants: 
• 
To evaluate the immunogenicity of a single IM dose 
of study intervention (RSV maternal vaccine or 
placebo) administered to maternal participants up to 
delivery. 
• 
Humoral immune responses at Day 31 post-dosing: 
− 
RSVPreF3 IgG-specific antibody 
concentrations 
− 
Neutralizing antibody titers against RSV-A 
• 
Humoral immune responses at pre-dosing (Day 1), 
at Day 31 post-dosing and at delivery: 
− 
Neutralizing antibody titers against RSV-B 
Infant participants: 
• 
To evaluate neutralizing antibody titers against RSV-
B at birth in infants born to maternal participants 
who received a single IM dose of study intervention 
(RSV maternal vaccine or placebo). 
• 
Humoral immune responses at delivery*: 
− 
Neutralizing antibody titers against RSV-B 
* Measured in cord blood sample collected at delivery or 
infant blood sample collected within 72 hours after birth (if 
no cord blood sample can be obtained). 
• 
To evaluate RSV-specific antibodies up to Day 181 
post-birth (6 months of age) in infants born to 
• 
Humoral immune responses at Day 43*, at Day 121* 
and at Day 181*: 


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Objectives 
Endpoints 
maternal participants who received a single IM dose 
of study intervention (RSV maternal vaccine or 
placebo).  
− 
RSVPreF3 IgG-specific antibody 
concentrations 
− 
Neutralizing antibody titers against RSV-A and 
RSV-B 
* Measured in infant blood samples collected at Day 43 
(sub-cohort 1, V2-NB), at Day 121 (sub-cohort 2, V3-NB) 
and at Day 181 (sub-cohort 3, V4-NB) post-birth. Each 
infant will be randomly assigned (1:1:1) to one of 3 sub-
cohorts. 
Tertiary 
AE = adverse event; IM = intramuscular; AESI = adverse event of special interest; LRTI = lower respiratory tract 
illness; MAE = medically attended adverse event; NB = newborn; RSV = respiratory syncytial virus; RSV-A/B = 
respiratory syncytial virus subtype A/B; MA-RTI = medically attended respiratory tract illness; RSVPreF3 IgG = 
respiratory syncytial virus PreF3 immunoglobulin G; SAE = serious adverse event 
1 Maternal and neonatal AESI and pregnancy outcomes should be recorded in the eCRF along with assessment of 
level of diagnostic certainty by Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) 
definitions when applicable. Of note, some events of interest fall under a single category but have multiple 
subcategories. For example, hypertensive disorders of pregnancy is an event with 3 subcategories that include: 
1) gestational hypertension; 2) pre-eclampsia; and 3) pre-eclampsia with severe features (including eclampsia). 
For each event, the investigator should identify the event and select the applicable sub-category. 
4. 
STUDY DESIGN 
4.1. 
Overall design 
Figure 1 and Figure 2 provide overviews of the study design for maternal and infant 
participants, respectively. 
Section 1.3 provides SoAs for maternal and infant participants. In times of special 
circumstances, refer to Section 8 for study procedures. 
Section 9.5.1 describes the sequence of analyses for maternal and infant participant data. 
CCI


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Figure 1 
Study design overview – Maternal participants (Amended 15 March 
2022) 
 
MAE = medically attended adverse event; MA-RTI = medically attended respiratory tract illness; (S)AE = (serious) 
adverse event; SCR = screening 
1 Visit 2 (Day 31) may be replaced by Visit 3 (Delivery) in case of premature delivery. If the delivery date occurs prior to 
Day 31 post-study intervention, there will be no Visit 2 (Day 31). 
2 SAEs related to study participation are to be collected from screening to Visit 1 (Day 1 pre-study intervention). 
3 Following study invervention (RSV maternal vaccine or placebo) administration, SAEs and (S)AEs leading to study 
withdrawal are to be collected from Day 1 (Visit 1) up to 180 days post-delivery (Contact 2). 
4 If not performed as part of the routine care, the blood and urine samples for screening should be collected within 15 
days prior to study intervention administration. 
5 Due to the recent safety signal, there will be no further enrollment and vaccination of maternal participants. 
Refer to section 2.3 for further details. 
6 Due to the change in the study requirements, MA-RTIs experienced by the maternal pariticipants will no 
longer be collected. 
7 In addition to the monthly contacts between Visit-2 and the Delivery visit, additional not pre-specified 
contacts and/or visits can be made more often (at any desired frequency), as per investigator’s, maternal 
participant’s or LAR’s discretion. 
Note: Placenta samples will be collected at delivery from all maternal participants, whenever feasible. These 
samples may be tested to support possible safety assessments, if necessary. Additional details are 
provided in the study procedures manual (SPM). 


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Figure 2 
Study design overview – Infant participants (Amended 15 March 
2022) 
 
AESI = adverse event of special interest; MAE = medically attended adverse event; RTI = respiratory tract 
illness;(S)AE = (serious) adverse event 
Infant sub-cohorts are abbreviated “BS1”, “BS2” and “BS3” correspond to Visit 2-NB (Day 43 post-birth), Visit 3-NB 
(Day 121 post-birth) and Visit 4-NB (Day 181 post-birth), respectively. 
RSV_MAT_BS1, _BS2, _BS3 = infants born to women in the RSV_MAT group and evaluated for immunogenicity at 
the designated timepoint (Day 43, Day 121 or Day 181 post-birth). 
Control_BS1, _BS2, _BS3 = infants born to women in the Control group evaluated for immunogenicity at the 
designated timepoint (Day 43, Day 121 or Day 181 post-birth) 
1 If cord blood was not collected at delivery/birth, a blood sample should be collected from the infant within 72 hours 
post-birth. 
2 Any neonatal / infant AESIs identified after 42 days post-birth should also be reported. 
3 Due to the change in the study requirements, there will no longer be collection of blood samples at Visit 2-
NB, Visit 3-NB and Visit 4-NB.  
Note:  
An additional recommended safety contact may be performed ~7 days post-birth if deemed necessary by the 
investigator or by the parent/ LAR(s). 
• 
Study Type: self-contained. 
• 
Experimental design: Phase III, double-blind*, randomized, placebo-controlled, 
multi-center, multi-country study with 1 investigational RSV MAT vaccine group in 
a parallel design. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
• 
Duration of the study: The intended duration of the study for maternal participant is 
approximately 10 to 11 months (including screening visit, from informed 
consent/assent until 180 days post-delivery) and approximately 12 months for infant 


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participants (from birth until 365 days post-birth), which is expected to cover at least 
1 complete RSV season. 
• 
Control: Placebo control. 
• 
Blinding: Double-blind*, as described in Table 5. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
• 
Study (intervention) groups are single 120 µg dose of the investigational RSV 
vaccine and Placebo control, as described in Table 5. 
• 
Study intervention schedule*: 1 single dose administered IM between 24 and 36 
weeks of gestation (at Visit 1, Day 1) to maternal participants. 
* Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants. 
• 
Randomized study intervention allocation* is 2:1 (investigational vaccine : 
placebo), as described in Table 5 and Section 6.3. 
* Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants. 
• 
Sampling schedule: 
− 
Blood and urine samples for assessing eligibility criteria will be taken, if not 
performed locally as per standard of care, from all maternal participants at 
screening. Refer to section 10.2.1 for details. 
− 
Blood samples for immunogenicity assessment will be taken from all maternal 
participants at Days 1, 31 and delivery. 
− 
Placenta samples will be taken from all maternal participants at delivery visit, 
whenever feasible. These samples may be tested to support possible safety 
assessments, if necessary. Additional details are provided in the study 
procedures manual (SPM). 
− 
Cord blood samples for immunogenicity assessment will be taken from all 
maternal participants at delivery. If no cord blood sample can be obtained, the 
infant blood sample will be collected within 72 hours days after birth. 
− 
Blood samples for immunogenicity* analysis will be taken from sub-cohorts of 
infant participants at one of 3 timepoints (Day 43, Day 121 or Day 181 post-
birth). 
* Due to the change in the study requirements, there will no longer be 
collection of blood samples at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
− 
Nasal swab for confirmation of RSV-A/B infection will be taken from 
participants* clinically diagnosed as having a suspected case of RSV-associated 
RTIs at an event-driven timepoint. 
* Due to the change in the study requirements, nasal swab samples from the 
maternal participants will no longer be collected. 


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• 
Primary completion Date (PCD): Visit 5-NB (Day 366 post-birth). 
Refer to Section 10.7.2 for the definition of PCD. 
• 
Data collection: standardized Electronic Case Report Form (eCRF). 
e-Diaries will be used to collect solicited event data. Unsolicited AEs data will be 
collected through questioning at study visits/contacts and reported into the eCRF, as 
appropriate. 
Parent(s) / LAR(s) will use a Paper Diary to record RTI symptoms experienced by 
infant participants; these data will be transcribed into the eCRF as appropriate. 
• 
Safety monitoring will be conducted by an external IDMC and an internal SRT. 
Safety precautions such as study holding rules have been pre-defined. 
Refer to Sections 8.2.3 and 10.1.5 for detailed description safety monitoring and 
holding rules. 
 


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Table 5 
Study groups, intervention and blinding (Amended 15 March 2022) 
Study 
groups 
Maternal participants 
Infant participants 
 
Blinding 
 
~Number 
Age 
in 
years 
(Min-
Max) 
Intervention 
name 
Study groups 
for 
randomization 
(Allocation 
2:1) 
Infant Blood Sampling 
sub-cohorts 
Sub-cohorts 
for 
randomization 
(Allocation 
1:1:1) 
M + I 
M + I 
I only 
Up to Day 43 
post-
delivery/birth 
Up to Day 181 
post-
delivery/birth 
From Day 182 to 
Day 366 
post-
delivery/birth  
 
 
 
 
 
Name 
~Number 
 
Double-blind** 
Single-blind** 
Single-blind** 
RSV_MAT 
~252 * 
15 – 
49 
RSV MAT 
RSV_MAT 
RSV_MAT_BS1 
~84 
RSV_MAT_BS1  
● 
● 
● 
RSV_MAT_BS2 
~84 
RSV_MAT_BS2  
RSV_MAT_BS3 
~84 
RSV_MAT_BS3 
Control 
~126 * 
15 – 
49 
Control 
Control 
Control_BS1 
~42 
Control_BS1 
● 
● 
● 
Control_BS2  
~42 
Control_BS2 
Control_BS3 
~42 
Control_BS3 
Control = Placebo; M = maternal participants; I = infant participants 
Infant sub-cohorts are abbreviated “BS1”, “BS2” and “BS3” correspond to Visit 2-NB (Day 43 post-birth), Visit 3-NB (Day 121 post-birth) and Visit 4-NB (Day 181 post-birth), 
respectively. 
RSV_MAT_BS1, _BS2, _BS3 = infants born to women in the RSV_MAT group and evaluated for immunogenicity at the designated timepoint (Day 43, Day 121 or Day 181 post-birth). 
Control_BS1, _BS2, _BS3 = infants born to women in the Control group evaluated for immunogenicity at the designated timepoint (Day 43, Day 121 or Day 181 post-birth) 
* Due to the recent safety signal, there will be no further enrollment and vaccination of maternal participants. 
** Due to the recent safety signal, the study was fully unblinded to ensure the safety monitoring of the participants 


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4.2. 
Scientific rationale for study design 
4.2.1. 
Study population 
The study population will include pregnant women with prevalent obstetric complications 
and risk factors for adverse pregnancy outcome, including healthy pregnant adolescent 
participants. 
4.2.2. 
Use of placebo 
The placebo group serves as a control for safety, reactogenicity, and immunogenicity 
assessments. No licensed vaccine against RSV is currently available. 
4.2.3. 
Randomization ratio 
A 2:1 randomization ratio was chosen to permit efficient evaluation of vaccine safety, 
reactogenicity and immunogenicity without compromising statistical rigor. Ratios greater 
than 1:1 for vaccinated vs. placebo recipients increase the likelihood that reported events 
may occur among vaccine recipients. It is possible that a higher number of reported 
events among vaccine recipients may be attributed to the greater randomization ratio, the 
vaccine itself, or due to chance. GSK plans to mitigate the potential risk associated with 
unbalanced randomization by: a) improving standardization of reporting of pre-defined 
pregnancy-related and neonatal AESI using Global Alignment of Immunization Safety 
Assessment in pregnancy [GAIA] definitions; b) referring to the background rates for 
events available in the literature in the epidemiological study [EPI-RSV-008, 2020] and 
observational natural history studies [EPI-RSV-015, 2019; EPI-RSV-015, 2020]; and c) 
establishing processes for continuous review of safety data by the SRT and IDMC. 
4.2.4. 
Sub-cohorts for infant blood sampling 
Sub-cohorts for infant blood sampling have been defined to limit discomfort and risk 
while ensuring enough observations to support robust evaluation of immune response in 
infants. 
4.2.5. 
Case definition (Amended 15 March 2022) 
RTI cases will be classified (during data analyses) according to the definitions provided 
in Sections 4.2.5.1*, 4.2.5.2 and 4.2.5.3. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 


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4.2.5.1. 
Maternal, medically attended respiratory tract illness (MA-RTI) 
(Amended 15 March 2022) 
Table 6 
MA-RTI case definitions for data analysis in maternal participants 
(Amended 15 March 2022) 
RSV-MA-RTI 
Medically attended visit for RTI symptoms AND Confirmed RSV infection 1, 2 
RSV hospitalization 
Confirmed RSV infection AND Hospitalized for acute medical condition 3 
All-cause MA- RTI 
Medically attended visit for RTI symptoms 
1 Confirmed RSV infection defined in Section 4.2.5.3 
2 RSV (nasal swab) sampling and testing as specified in Table 10. 
3 Hospitalization is defined as admission for observation or treatment based on the judgment of a health care provider. 
Note: Due to the change in the study requirements, RTI surveillance of the maternal participants will no longer 
be performed. 
4.2.5.2. 
Respiratory tract illness (RTI) / Lower respiratory tract illness (LRTI) in 
infants 
Table 7 
RTI/LRTI case definitions for data analysis in infants 
RSV-RTI 
Runny nose, OR Blocked nose, OR Cough 
AND 
Confirmed RSV infection 4 
RSV-LRTI 
History of cough OR difficulty in breathing 1 
AND 
SpO2 < 95%2, OR RR increase 3 
AND 
Confirmed RSV infection 4 
RSV-severe LRTI 
Meeting the case definition of RSV-LRTI 
AND 
SpO2 < 93%2, OR lower chest wall in-drawing, OR inability to feed, OR failure 
to respond / unconscious 
RSV hospitalization 
Confirmed RSV infection 5 
AND 
Hospitalized for acute medical condition 6 
All-cause RTI 
Runny nose, OR Blocked nose, OR Cough 
All-cause LRTI 
History of cough OR difficulty in breathing 1 
AND 
SpO2 < 95% 2, OR RR increase 3  
All-cause LRTI hospitalization 
Hospitalized due to all-cause LRTI as defined above 
Definitions are modified from [Modjarrad, 2016]; RTI = respiratory tract illness; LRTI = lower respiratory tract illness; 
RR = respiratory rate; SpO2 = blood oxygen saturation by pulse oximetry. 
1 Based on history reported by parents/LARs and includes difficulty in breathing (e.g. showing signs of wheezing or 
stridor, tachypnoea, flaring [of nostrils], chest in-drawing, apnea). 
2 For blood oxygen saturation (SpO2), the lowest value monitored will be used. In high altitudes (>2500m), SpO2 <92% 
for LRTI, <90% for severe LRTI. 
3 RR increase defined as: 
> 60/minute (< 2 months of age) 
> 50/minute (2 to < 12 months of age) 
> 40/minute (12 to 24 months of age) 
4 Confirmed RSV infection defined in Section 4.2.5.3 
5 RSV (nasal swab) sampling and testing as specified in Table 12. 
6 Hospitalization is defined as admission for observation or treatment based on the judgment of a health care provider. 


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4.2.5.3. 
RSV infection (Amended 15 March 2022) 
The sponsor will analyse nasal swabs by quantitative reverse transcription polymerase 
chain reaction (qRT-PCR) for the presence of RSV-A/B. A positive (RSV-A or B) test 
result constitutes a case of RSV infection. Refer to Table 10, Table 12 and Section 8.4. 
In the event the collection of a nasal swab for testing by the sponsor is impossible, results 
from locally collected samples, tested with locally approved tests, may also be considered 
for the determination of a case of RSV infection. 
Note: Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
4.3. 
Justification for dose (Amended 15 March 2022) 
A single formulation of the investigational RSV maternal vaccine (containing 120 µg of 
the RSVPreF3 antigen) was planned. Available data suggested that the 120 µg 
formulation had an acceptable safety profile and tends to elicit stronger immune 
responses, which is likely to result in higher placental transfer of antibodies to the fetus 
than formulations containing 30 or 60 µg of the RSVPreF3 antigen. Available results 
from RSV MAT-001 and RSV MAT-004 studies are included in the IB to support RSV 
MAT-012. 
Infection with RSV occurs in almost all participants by the time of reproductive age and 
it is extremely unlikely that a maternal participant would not have been naturally infected 
with RSV before. Results of study RSV MAT-001 in non-pregnant women and RSV 
MAT-004 in pregnant women indicate that a single dose of the study vaccine is 
sufficient to boost the neutralizing antibodies induced by previous natural infections. 
The study vaccine will be administered* between 240/7 and 360/7 weeks of gestation 
(inclusive). This gestational age range is considered optimal for both immunogenicity and 
safety. It allows enough time to (a) induce high neutralizing antibody levels in maternal 
participants before term delivery and (b) ensure these antibody levels are elevated during 
the period of greatest placental antibody transfer to the fetus. Moreover, it is after the 
critical period for organogenesis (i.e. after the period when most congenital abnormalities 
develop). 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. For details, refer to Section 2.3. 
4.4. 
End of Study definition 
A participant is considered to have completed the study if he/she returns for the last visit 
or is available for the last scheduled contact as described in the protocol. Refer to Section 
10.7.2 for the definition of EoS. 
EoS: Last subject last visit (LSLV) of infant participants (Visit 5-NB, Day 366 post-birth) 


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5. 
STUDY POPULATION 
Adherence to the inclusion and exclusion criteria specified in the protocol is essential. 
Deviations from these criteria are not allowed because they can jeopardize the scientific 
integrity, regulatory acceptability of the study or safety of the participant. 
5.1. 
Inclusion criteria 
5.1.1. 
Maternal participants 
Maternal participants must satisfy ALL the following criteria at study entry: 
• 
Participants who, in the opinion of the investigator, can and will comply with the 
requirements of the protocol (e.g. completion of diaries, return for follow-up visits). 
• 
Participants and legally acceptable representatives (LARs) who give written or 
witnessed/thumb printed informed consent after the study has been explained 
according to local regulatory requirements, and before any study specific procedures 
are performed. The informed consent given at screening should (consistent with local 
regulations / guidelines) either: 
− 
include consent for both the maternal participant’s participation* and 
participation of the infant after the infant’s birth, or 
− 
include consent for the maternal participant’s participation* and expressed 
willingness to consider permitting the infant to take part after the infant’s birth 
(if local regulations/guidelines require parent(s) to provide an additional 
informed consent after the infant’s birth). 
* Written informed consent obtained from parents/LARs and written informed assent 
obtained from the maternal participant if she is less than legal age, or written 
informed consent obtained from the participant if the participant has achieved legal 
age. The legal age is determined according to local regulations in each participating 
country. 
In case the legal age is achieved during the conduct of the study, an additional 
written informed consent from the maternal participant should be obtained at the 
time of the legal age. 
− 
both mother and father should consent if local regulations / guidelines require it. 
• 
Pre-pregnancy Body Mass Index (BMI) (based on participant’s report) 18.5 to 39.9 
kg/m2, inclusive. 
• 
Healthy (as established by medical history and clinical examination) adolescent 
pregnant women, 15 to 17 YOA, inclusive, at the time of study intervention 
administration. 
OR 
• 
Pregnant women, 18 to 49 YOA, inclusive, at the time of study intervention 
administration with: 


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− 
HIV infection (as confirmed by local standard of care serologic tests) 
AND/OR 
− 
Obstetric complications or risk factors during the current pregnancy, where the 
expectant management of the pregnancy is possible and without evidence of 
non-reassuring fetal status (only cases for which fetal heart rate can be 
ascertained) as follows: 
− 
Gestational diabetes, well-controlled on medications (with or without diet or 
exercise): i.e. when normoglycemia is maintained (fasting or preprandial 
blood glucose values <95 mg/dL [5.3 mmol/L], and/or postprandial blood 
glucose concentration <140 mg/dL [7.8 mmol/L] at 1 hour and/or 
postprandial blood glucose concentration: <120 mg/dL [6.7 mmol/L] at 2 
hours). 
− 
Gestational hypertension, well-controlled on diet or medications below 
160/110 mmHg. 
− 
Pre-eclampsia without severe features (i.e. eclampsia, severe hypertension 
[>160/110 mmHg], organ dysfunction, unstable or complicated by 
Hemolysis, Elevated Liver enzymes, and Low Platelets [HELLP] 
syndrome). 
− 
Fetal Growth Restriction in singleton pregnancies, with normal umbilical 
artery (UA) Doppler and estimated fetal weight 3 to 10th percentile for 
gestational age. 
− 
History of threatened preterm labor in the current pregnancy, with no 
cervical dilation greater than 2 cm or effacement exceeding 50%, and/or no 
progressive change in cervical dilation or effacement detected by serial 
examinations, when maternal participant is asymptomatic (i.e. no vaginal 
bleeding or uterine contractions or amniotic fluid loss). 
− 
Uncomplicated twin gestation. 
• 
Pregnant females at 24 0/7 to 36 0/7 weeks of gestation at the time of study 
intervention administration (Day 1), as established by: 
− 
Last menstrual period (LMP) date corroborated by first or second trimester 
ultrasound examination (U/S) (i.e. at or before 28 weeks of gestation). 
− 
first or second trimester U/S only, if LMP is unknown/uncertain. 
− 
Certain LMP, corroborated by an U/S performed after 28 weeks of gestation is 
also acceptable. 
Notes: If pregnancy resulted from assisted reproductive technologies, LMP date may 
be replaced by intrauterine insemination (IUI) or embryo-transfer (ET) date. Refer to 
Section 10.8 for guidance on gestational age assessment. 
The level of diagnostic certainty of the gestational age should be established by using 
the GAIA gestation age assessment tool (Section 10.8). 
• 
Participants who are willing to provide cord blood. 


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• 
Willing to have their offspring followed-up after delivery for a period of 12 months. 
• 
Participants who do not plan to give their offspring for adoption or place the child in 
care. 
Note that women whose pregnancies resulted from assisted reproductive technologies 
may be enrolled if they meet all inclusion criteria and none of the exclusion criteria. 
5.1.2. 
Infant participants 
Infant participants must satisfy all the following criteria at study entry: 
• 
Live-born from the study pregnancy. 
• 
If required per local regulations / guidelines, re-signed (confirmed) written or 
witnessed/thumb printed informed consent for study participation of the infant 
obtained from the infant’s mother and/or father and/or LAR, before performing any 
infant study specific procedure. To comply with RTI surveillance and other protocol-
required procedures that begin immediately after birth: if written consent cannot be 
provided by the parent(s)/LAR(s) readily post-birth, verbal consent – if permitted per 
local regulation -- may be sought from the parent(s) / LAR(s) instead. Verbal consent 
should be documented in the source data by the investigator or delegate. The 
parent(s) / LAR(s) will provide additional, written informed consent by (or before) 
Visit 2-NB. 
5.2. 
Exclusion criteria 
The following criteria should be checked at the time of study entry. The potential 
participant MUST NOT be included in the study if ANY exclusion criterion applies: 
5.2.1. 
Maternal participants 
5.2.1.1. 
Medical conditions 
• 
History of any reaction or hypersensitivity likely to be exacerbated by any 
component of the study intervention. 
• 
Hypersensitivity to latex. 
• 
Any pre-existing medical conditions or obstetric complications in the current 
pregnancy that, based on the investigator’s clinical judgment, are poorly controlled 
and/or with clinical evidence of a non-reassuring fetal status and/or are likely to 
result in delivery within 7 days after study intervention administration and/or when 
the timing of planned delivery is within 7 days after study intervention 
administration and/or acute conditions requiring immediate medical attention for 
maternal stabilization and/or treatment. 
• 
A multiple pregnancy with 3 or more fetuses. 


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• 
Complicated twin gestation (e.g twin to twin transfusion syndrome or fetal growth 
restriction). 
• 
Placenta Accreta Spectrum, including placenta increta, percreta, and accreta. 
• 
Fetal structural defects or genetic abnormalities that affect (or are likely to affect) 
fetal health or survival during the first year of life. 
• 
Known or suspected impairment of the immune system or immunodeficiency 
syndrome other than HIV. 
• 
Lymphoproliferative disorder or malignancy within 5 years before study dose 
administration (excluding effectively treated non-melanoma skin cancer). 
• 
Any illness of the mother or conditions of the fetus that, in the investigator’s 
judgment, may substantially interfere with the maternal participant’s ability to 
comply with study procedures, or could increase the risks to the mother or the fetus, 
or could preclude the evaluation of the participant's data. 
• 
Any other clinical condition that, in the opinion of the investigator, might pose 
additional risk to the participant due to participation in the study, as determined by 
medical history, physical examination or laboratory screening tests. 
• 
Women with any diagnosis, condition, treatment, or other factor that, in the opinion 
of the investigator, has the potential to affect or confound assessments of 
immunogenicity or safety 
• 
Any conditions which, in the investigator’s opinion, would increase the risks of 
study participation to the unborn infant. 
5.2.1.2. 
Prior/Concomitant therapy (Amended 15 March 2022) 
• 
Prior receipt of an RSV maternal vaccine. 
• 
Use of any investigational or non-registered product (drug, vaccine or medical 
device) other than the study intervention(s) during the period beginning: 
− 
For a drug, vaccine or medical device: 29 days before the dose of study 
intervention(s) (Day -28 to Day 1), or their planned use during the study period. 
− 
For immunoglobulins: 90 days before the dose of study intervention(s), or their 
planned use during the study period. 
The exception to this is investigational products (drugs / vaccines / 
immunoglobulins) administered in the setting of a pandemic. Administration in this 
case should respect the same period outlined above prior to study intervention 
administration, but may be allowed following delivery. 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 29 days before the study Day 1 and ending at delivery, 
with the exception of seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap – 
alone vaccines, dTpa/Tdap vaccines that also contain other antigens and Hepatitis B 
vaccines, all of which may be administered according to standard of care ≥ 15 days 
before or after study intervention (Day 1). 


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Note: In case an emergency mass vaccination for an unforeseen public health threat 
(e.g.: a pandemic) is recommended and/or organized by the public health 
authorities, outside the routine immunization program, the time period described 
above can be reduced if necessary for that vaccine provided it is used according to 
the local governmental recommendations and that the Sponsor is notified 
accordingly. In that sense, COVID-19 vaccines may be allowed, when administered 
≥ 15 days before or after study vaccination. 
• 
Receipt of blood or plasma products or immunoglobulin, from 90 days before study 
intervention administration, or planned receipt through delivery, with the exception 
of Rho(D) immunoglobulin, which can be given at any time. In that sense, antibody 
therapy received against COVID-19 disease should be recorded. 
• 
Administration of immune-modifying therapy within 6 months before study 
intervention administration, or planned administration through delivery, except if it 
is part of management of HIV infection. This includes but is not limited to: 
− 
Azathioprine, mycophenolate mofetil, 6-mercaptopurine, cyclosporine, 
tacrolimus, monoclonal or polyclonal antibodies; 
− 
Prednisone  5 mg/day or equivalent for ≥ 14 days. Inhaled, intra-articular/intra-
bursal and topical steroids are allowed. 
5.2.1.3. 
Prior/Concurrent clinical study experience 
• 
Concurrently participating in another clinical study, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational intervention (drug, vaccine or invasive medical device). 
Note: European Economic Community (EEC) directive 93/42/EEC defines an 
invasive medical device as ‘A device which, in whole or in part, penetrates inside the 
body, either through a body orifice or through the surface of the body’. 
5.2.1.4. 
Other exclusions 
• 
Alcoholism or substance use disorder within the past 24 months based on the 
presence of 2 or more of the following abuse criteria: hazardous use, 
social/interpersonal problems related to use, neglect of major roles to use, 
withdrawal, tolerance, use of larger amounts or longer, repeated attempts to quit or 
control use, much time spent using, physical or psychological problems related to 
use, activities given up to use, craving [Hasin, 2013]. 
• 
A local condition that in the opinion of the Investigator precludes injection of the 
study vaccine/product or precludes assessment of local (administration site) 
reactogenicity. 
• 
Consanguinity of maternal participant and her partner (second degree cousins or 
closer). 
• 
Any study personnel or their immediate dependants, family, or household members. 


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5.2.2. 
Infant participants 
• 
Concurrently participating in another clinical trial, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational vaccine/product (drug or invasive medical device). 
• 
Any condition which, in the investigator’s opinion, would increase the risks of study 
participation to the infant. 
• 
Child in care. Please refer to Section 10.7.2 for the definition of child in care. 
5.3. 
Lifestyle considerations 
5.3.1. 
Demographic data 
Demographic data for maternal and infant participants including geographic ancestry 
(race)*, ethnicity*, month of birth (if allowed per local regulation) and year of birth, will 
be collected. 
*Differences in the safety and efficacy of certain medical products, including vaccines 
[Haralambieva, 2013; Pérez-Losada, 2009; Kollmann, 2013] have been observed in 
racially and ethnically distinct subgroups. These differences may be attributable to 
intrinsic factors (e.g., genetics, metabolism, elimination), extrinsic factors (e.g., diet, 
environmental exposure, sociocultural issues), or interactions between these factors. 
Therefore, both geographic ancestry (race) and ethnicity will be collected for all study 
participants. 
5.3.2. 
Lifestyle characteristics 
5.3.2.1. 
Maternal participants 
Lifestyle characteristics that should be collected may include highest level of education, 
smoking status/exposure, illicit drug use, household environment, and other factors that 
could place study participants at risk of adverse study outcomes. 
5.3.2.2. 
Infant participants 
Lifestyle characteristics that should be collected may include living environment, 
household composition, breastfeeding (breastfeeding only / breastfeeding with 
supplementation / no breastfeeding), passive smoking, and extent of contact with children 
less than 6 YOA. 
5.4. 
Screen failures 
Screen failures are maternal participants who consent to take part in this study but are not 
subsequently randomly assigned to a study intervention due to not meeting all of the 
eligibility criteria. 


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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. 
5.5. 
Criteria for temporarily delaying study intervention 
administration (Amended 15 March 2022) 
Study intervention administration may be postponed* within the permitted time interval 
until transient conditions cited below are resolved: 
• 
Acute disease and/or fever within 48 hours before study intervention administration. 
Refer to Section 1.3 for definition of fever and preferred location for measuring 
temperature in this study. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be dosed at the discretion of the investigator. 
• 
Use of systemic antibiotic or antiviral (except for HIV+ participants) treatment 
within 48 hours before study intervention administration. 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY 
Refer to Section 10.7.2 for the definition of study intervention. 
Refer to Section 4 for the study intervention administration schedule. 
Refer to the SPM for additional details. 
6.1. 
Study interventions administered (Amended 15 March 2022) 
Table 8 
Study interventions administered (Amended 15 March 2022) 
Study Interventions 
Name: 
RSV MAT 
Control 
Vaccine/product name 
RSVPreF3 
NaCl Solution 
Sucrose 
NaCl Solution 
Study intervention 
formulation: 
RSVPreF3  
(120 µg) 
Sodium chloride 
(NaCl) (0.9%); 
Water for 
injections**  
Sucrose 
Sodium chloride 
(NaCl) (0.9%); 
Water for 
injections**  
Presentation 
Powder for solution 
for injection, vial 
Solution for 
solution for 
injection; syringe 
Powder for solution 
for injection, vial 
Solution for 
solution for 
injection; syringe 
Type: 
Biologic 
Not applicable 
Route of administration 
Intramuscular injection 
Intramuscular injection 
Administration site: 
 
 
• 
Location 
Deltoid  
Deltoid 
• 
Laterality * 
Non-dominant  
Non-dominant  


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Study Interventions 
Name: 
RSV MAT 
Control 
Number of doses to be 
administered: 
1 
1 
Volume to be 
administered** 
Whole content 
Whole content 
Packaging and labeling 
Refer to the SPM 
Refer to the SPM 
Manufacturer 
GSK 
GSK 
SPM = study procedure manual 
* The non-dominant arm is the preferred arm of injection. In case it is not possible to administer the vaccine / product in 
the non-dominant arm, an injection in the dominant arm may be performed. 
** The entire contents of the pre-filled NaCl syringe will be transferred into the vial for reconstitution. The entire 
contents of the reconstituted vaccine/product will be withdrawn for administration. Refer to the SPM for additional 
information. 
Note: Due to the recent safety signal, there will be no further enrollment and vaccination of maternal 
participants.  
Maternal participants must be observed closely for at least 30 minutes after the 
administration* of the study intervention. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis, syncope. 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
6.2. 
Preparation/Handling/Storage/Accountability 
The study interventions must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s). 
Only authorized study personnel should be allowed access to the study interventions. 
Storage conditions will be assessed by a sponsor study contact during pre-study activities. 
Refer to the SPM for more details on storage and handling of the study interventions. 
6.3. 
Measures to minimize bias: randomization and blinding 
6.3.1. 
Participant identification 
Maternal identification numbers will be assigned sequentially to pregnant women who 
have consented to participate in the study, according to the range of participant 
identification numbers allocated to each study center. 
Maternal participants who have provided informed consent/assent will be registered into 
an automated internet-based system (SBIR) at the time of screening. SBIR will be further 
used to confirm eligibility to participate in the study, to randomize each maternal 
participant to an intervention, and to confirm that an intervention has been administered 
(Refer to Section 6.3.3). 


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The maternal participant’s infant (as yet unborn) will be assigned an identification 
number, according to the range of numbers allocated to each study center, AFTER the 
maternal participant has been randomized and has received the study intervention at 
Visit 1. 
Maternal and infant identification numbers will be linked. 
6.3.2. 
Randomization to study intervention (Amended 15 March 2022) 
Approximately 378 maternal participants will be enrolled* and randomized (2:1) to 
receive either the RSV maternal vaccine or the placebo control at Day 1 (Visit 1). At the 
same time, infant participants (as yet unborn) will be further randomized (1:1:1) into sub-
cohorts for blood sample collection for the assessment of immunogenicity at one of 3 
timepoints (Day 43, Day 121 or Day 181 post-birth). 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
6.3.3. 
Intervention allocation to the participant (Amended 15 March 
2022) 
The randomization algorithm will use a stratification procedure accounting for maternal 
age at the time of study intervention administration (<18, ≥18 YOA) and a minimization 
procedure accounting for (a) gestational age at the time of study intervention 
administration (<28 0/7; ≥ 28 0/7 weeks), (b) pre-existing HIV infection and obstetric 
complication status (HIV present and obstetric complication present, HIV present and 
obstetric complication absent, or HIV absent and obstetric complication present) for 
participants ≥18 YOA only, and (c) center. Minimization factors will have equal weight 
in the minimization algorithm. 
Once a participant identification number is allocated, the randomization system will 
determine study group and will provide the study intervention number to be used for the 
dose. 
When an automated, internet-based system (SBIR) is not available, please refer to the 
SBIR user guide or SPM for specific instructions. 
Refer to the SPM for additional information about the study intervention number 
allocation. 
Note: Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants 
6.3.4. 
Allocation of participants to assay subsets 
Not applicable. 


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6.3.5. 
Blinding and unblinding (Amended 15 March 2022) 
To minimize the introduction of bias, this study will be double-blinded* from Day 1 pre-
study intervention to Day 43 post-delivery/birth visit after which the first analysis will be 
conducted and treatment-level unblinded* summaries will be provided to GSK and 
regulatory agency for review. No individual treatment code will be shared with 
investigators, site staff and participants until the end of the study. After Day 43 
delivery/birth visit, the study will be conducted as a single-blind* study. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
The laboratory in charge of sample testing will be blinded to the study intervention 
assignment. Codes will be used to link the participant and study to each sample. There 
will be no link between the study intervention and the identity of the participant. 
6.3.5.1. 
Emergency unblinding (Amended 15 March 2022) 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information is essential for the clinical 
management or welfare of the participant. 
A participant may continue in the study even if that participant’s intervention assignment 
is unblinded. 
The emergency unblinding process enables the investigator to have unrestricted, 
immediate and direct access to the participant’s individual study intervention via an 
automated internet-based system (SBIR). Investigators are cautioned not to share this 
knowledge with sponsor staff, or with site staff who do not need it, in order to ensure that 
other members of the study team remain blinded. 
A physician other than the investigator (e.g. an emergency room physician) or 
participant/care giver/family member may also request emergency unblinding either via 
the investigator (preferred option) or via the GSK Helpdesk (back up option). The 
subject/participant card provides contact information for the investigator, his/her back up 
and GSK Helpdesk. 
The investigator may contact a GSK Helpdesk (refer to the Table 9) if he/she needs help 
to perform the unblinding process (i.e., if the investigator is unable to access the 
automated Internet-based system). 
Note: Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 


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Table 9 
Contact information for emergency unblinding 
GSK Helpdesk 
Available 24/24 hours and 7/7 days 
The Helpdesk is available by phone, fax and email 
Phone:  
 
+32 2 656 68 04 
Fax:   
 
+32 2 401 25 75 
Email:  
 
rix.ugrdehelpdesk@gsk.com 
Toll-free numbers are available for the following countries.  
Country 
Toll-free number 
Canada 
1 833 541 0263 
United States 
1 844 446 3133 
Spain 
00 800 4344 1111 
Italy 
800 879 197 
Finland 
999 800 4344 1111 
Brazil 
0800 891 2906 
India 
000800 919 0928 
South Africa 
0800 984 003 
6.3.5.2. 
Unblinding prior to regulatory reporting of SAEs (Amended 15 March 
2022) 
GSK policy requires unblinding of any unexpected SAE which is attributable/suspected 
to be attributable to the study intervention(s), prior to regulatory reporting. Vaccines 
Clinical Safety and Pharmacovigilance (VCSP) is responsible for unblinding the study 
intervention assignment within the timeframes defined for expedited reporting of SAEs 
(Refer to the Section 10.3.10.1). 
In addition, GSK VCSP staff may unblind the intervention assignment for any participant 
with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or a SAE that is fatal 
or life-threatening. For SAEs requiring expedited reporting to 1 or more regulatory 
agencies, a copy of the report containing participant’s intervention assignment may be 
sent to investigators in accordance with local regulations and/or GSK policy. 
Note: Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
6.4. 
Study intervention compliance (Amended 15 March 2022) 
Before dosing, a qualified member of the site staff other than the person administering 
the dose will confirm that the intervention number is correct. The intervention number 
administered, and the administration date and time will be recorded in the source 
documents. 


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Note: Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants. 
6.5. 
Dose modification 
Section is not applicable. 
6.6. 
Continued access to study intervention after the end of the 
study (Amended 15 March 2022) 
There will be no access to RSV MAT vaccine after the end of the study. Please refer to 
Section 2.3 for details. 
6.7. 
Treatment of overdose 
Section is not applicable. 
6.8. 
Concomitant therapy 
At the timepoints indicated in the SoA, the investigator or his/her delegate should 
question the participant and/or the infant participant’s parent(s)/LAR(s) about all 
medications/products taken, and vaccinations received by the participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF. 
The Local Medical Lead (LML) should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.8.1. 
Maternal participants (Amended 15 March 2022) 
• 
All folate and iron supplements beginning the month before the estimated date of 
conception and continuing through delivery (i.e., through Visit 3). These 
supplements should be reported when taken independently and/or when included in a 
multivitamin mineral supplement. 
• 
All antibiotics, antivirals, analgesics, and anti-pyretics taken within 7 days before 
dose administration. 
• 
All concomitant vaccines beginning the month before the estimated date of 
conception and throughout the study (i.e., through Contact 2). 
• 
Prophylactic medication related to the effects (actual or anticipated) of study 
vaccine/product administration (e.g., medication administered either in the absence 
of ANY symptom and in anticipation of a reaction to the study vaccine, or to prevent 
re-occurrence of one or more post-study intervention AEs such as headache). 
• 
Any concomitant medications/products given for pre-existing medical conditions, 
beginning at Visit 1 and ending at Contact 2 (Day 1 to Day 181). 


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• 
Any concomitant medications/products associated with a solicited event or with an 
unsolicited AE, beginning at Visit 1 and ending at Visit 2 (Day 1 to Day 31). 
• 
Any corticosteroids for fetal lung maturation administered prior to/during labor or 
delivery, as well as any antibiotics administered in the last week prior to delivery 
and/or during labor. Note: Standard of care medications/products administered 
routinely during labor/delivery (eg. general/regional/local anesthetics, analgesics, 
etc) do not need to be reported. 
• 
Any concomitant medications/products associated with a MAE other than an MA-
RTI beginning at Visit 1 and ending at Visit 4 (Day 1 to Day 43 post-delivery). 
• 
Any concomitant medications/products associated with an MA-RTI beginning at 
Visit 1 and ending at Contact 2 (Day 1 to Day 181 post-delivery). 
6.8.2. 
Infant participants 
• 
Vaccinations administered from birth (Visit 1-NB) through the Day 181 post-birth 
visit (Visit 4-NB). 
• 
Medications administered in relation to RTIs/LRTIs from birth (Visit 1-NB) through 
the Day 366 post-birth visit (Visit 5-NB). 
• 
Medications/products administered in relation to MAEs from birth (Visit 1-NB) 
through Day 366 post-birth visit (Visit 5-NB). 
6.8.3. 
Maternal and Infant participants 
• 
Any concomitant medications/products/vaccines leading to a participant’s non-
eligibility (Sections 5.2.1 and 5.2.2) or potential non-evaluability (Section 9.3.1.1), 
or to a participant’s withdrawal from the study. 
• 
Any concomitant medications/products/vaccines relevant to an SAE/Adverse Event 
of Special interest (AESI) to be reported as per protocol or administered at any time 
during the study period for the treatment of an SAE/AESI.  
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of study intervention 
Criteria for discontinuation of study interventions do not apply since this is a single dose 
study. However, administration of the study’s single dose may be delayed if the criteria 
presented in Section 5.5 are met. 


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7.2. 
Participant discontinuation/withdrawal from the study 
A participant is considered to have withdrawn from the study if no new study procedure 
has been performed or no new information has been collected for him/her since the date 
of withdrawal/last contact. 
From an analysis perspective, a study ‘withdrawal’ refers to any participant who did not 
return for the concluding visit/was not available for the concluding contact planned in the 
protocol. 
Investigators will attempt to contact participants who do not return for scheduled visits or 
follow-up. 
All data and samples collected up to and including the date of withdrawal of /last contact 
with the participant will be included in the study analyses. 
The primary reason for study withdrawal will be documented in the eCRF, based on the 
list below: 
• 
AEs requiring expedited reporting to GSK (Section 10.3.10.1) 
• 
Unsolicited non-SAEs 
• 
Solicited AE (maternal participants) 
• 
Withdrawal by participant, not due to an AE* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 
• 
Other (specify) 
*If a participant is withdrawn from the study because she/the participant’s 
parent(s)/LAR(s) has withdrawn consent and the reason for withdrawal was provided, the 
investigator must document this reason in the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved (see Section 10.3.8.2). 
7.3. 
Lost to follow-up 
A maternal participant will be considered ‘lost to follow-up’ if she fails to return for 
scheduled visits and cannot be contacted by the study site. 
An infant participant will be considered ‘lost to follow-up’ if his or her parent(s)/LAR(s) 
fail to return for scheduled visits and are unable to be contacted by the study site. 


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Please refer to the SPM for a description of actions to be taken before considering the 
participant lost to follow-up. 
8. 
STUDY ASSESSMENTS AND PROCEDURES (AMENDED 
15 MARCH 2022) 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant. 
Immediate safety concerns should be discussed with the sponsor as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarized in the SoA (Section 1.3). 
All screening evaluations must be completed and the results reviewed before confirming 
that potential participants meet all eligibility criteria. 
The investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for screening failure will be mentioned in 
this screening log. 
Procedures conducted as part of routine clinical management (e.g. hematologic profiles, 
Ultrasounds, HIV testing, etc.), and obtained before the participant/participant’s 
parent(s)/LAR(s) signed the Informed Consent Form (ICF), may be used for screening 
and/or for establishing a clinical baseline, provided the procedure met protocol-specified 
criteria and was performed within the time frame defined in the SoA (Section 1.3) and/or 
the eligibility criteria (Section 5.1 and 5.2). 
The SPM provides the investigator and site personnel with detailed administrative and 
technical information that does not impact participant safety. 
Study procedures during special circumstances (Amended 15 March 2022) 
During special circumstances (e.g., the COVID-19 pandemic), the resulting limitations 
may affect the sites’ ability to conduct the study procedures. 
Enrollment* of ADDITIONAL maternal participants may be placed on hold. Decisions 
on re-starting enrollment* to achieve the planned sample size will be made in a manner 
consistent with guidance from public health and other competent authorities. 
For guidance regarding the temporary delay of study intervention administration because 
of exposure to COVID-19, please refer to the SPM for details. 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 


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The following measures may be implemented for enrolled participants: 
• 
If it is not possible to conduct a protocol-specified, scheduled or event-driven visit as 
described in Section 1.3, the visit may be replaced with a contact conducted by SMS, 
email, telephone, video-telephone or telemedicine. In such cases: 
− 
Protocol-specified clinical data that cannot be collected by site staff during the 
contact (e.g., physical examination results; SpO2 results) BUT are available 
within the allowed visit window (Table 3) in the participant’s medical records 
and can be obtained by site staff (as allowed by local law), may be recorded in 
the participant’s source document and entered into the eCRF. 
• 
Whenever possible, as appropriate per the judgment of the investigator and as 
allowed by local law, arrangements should be made for qualified personnel to collect 
any protocol-specified safety data/safety assessment(s) and/or biological samples at 
an alternate location* or at participant’s home within the allowed visit window 
(Table 3). 
− 
Samples should not be collected if they cannot be processed in a timely manner 
and / or appropriately stored until the intended use. 
− 
Nasal swabs for central testing must be collected using GSK-provided supplies. 
(note: if collection at either the study site, participant’s home or an alternate 
location is not possible, participants may be instructed to collect nasal swab 
samples by themselves*/for their infant. Collection will be done using GSK-
provided supplies and all the corresponding detailed instructions to allow such 
collection will be provided along with the nasal swab sampling kit). 
* Due to the change in the study requirements, nasal swab samples will no 
longer be collected from any maternal participant. 
− 
Blood / cord blood samples for assessment of immune response must be 
retrieved, processed and stored in accordance with the Investigator Laboratory 
Manual. 
• 
“Medically attended visits” will include instances where, due to the special 
circumstances, the participant 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, video-telephone or telemedicine, or other means. 
Additional details of how these visits can be conducted are outlined in the SPM. 
Impact on the analysis sets 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 (CSR). 
The specific guidance from local public health and other competent authorities regarding 
the protection of individuals’ welfare must be applied. 
*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 


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delegation of responsibilities in this location. This alternate location should be covered by 
proper insurance for the conduct of study on participants by investigator and staff at a site 
other than the designated study site. 
8.1. 
Immunogenicity assessments 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol. 
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subject to prior 
IEC/IRB approval, if required by local legislation. 
Information on further research and its rationale can be obtained from GSK. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant/participant’s parent(s)/LAR(s). 
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed and agreed 
with GSK. 


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8.1.1. 
Biological samples (Amended 15 March 2022) 
Table 10 
Biological samples - Maternal participants (Amended 15 March 2022) 
Maternal Sample 
type 
Collected to evaluate 
Minimum 
Quantity per 
participant 
Unit 
Time point 
Additional information 
Whole blood 
Hematology, Biochemistry 
~5.5 
mL 
Screening 
Blood sample to be collected and analyzed locally 
only if not performed as per standard of care. 5 
Immune response 1 
~10 
mL 
Visit 1 (Day 1) pre-Dose 
- 
Visit 2 (Day 31) 4 
Visit 3 (Delivery) 
Urine 
Protein, Glucose 
Dipstick 
NA 
Screening 
Urine sample to be collected and analyzed locally 
only if not performed as per standard of care. 5 
Nasal Swab 2, 3, 6 
Presence of RSV-A/B 
- 
- 
MA-RTI Visit (Event-
Driven) 
Collect a nasal swab from any maternal participant 
who reports a MA-RTI. 
 
 
 
 
RTI hospitalization 
(Event-Driven) 
Collect a nasal swab (if possible) from any 
participant hospitalized with RTI (or soon after 
discharge, as long as symptoms are ongoing). 
1 Volume of the blood sample collected for immune response assessment may be reduced to ~5 ml at investigator’s discretion. Refer to the laboratory manual for additional 
information. 
2 Collection of a nasal swab for sponsor testing is additional to and DOES NOT REPLACE any specimen collection (per local standard of care) for testing by the local laboratory to 
establish a fast and accurate diagnosis for the hospitalization. In the case of hospitalization, local testing for RSV infection should be performed if feasible. 
3 If other nasal swab specimens are collected and tested locally as per local standard of care, results will be recorded in the eCRF. In principle only the sponsor laboratory results will 
be used when applying the case definitions for data analysis in Section 4.2.5.3. Thus, where mandated by the protocol, every effort should be made to obtain nasal swab 
samples that can be analyzed by the sponsor (or sponsor-designated) laboratory. Results of locally tested samples, with locally approved tests may be used when applying 
case definitions only in the event the nasal swab for central testing was impossible to collect. 
4. Blood sample at Visit 2 (Day 31) will not be collected if the delivery occurs prior to Day 31 post-study intervention. 
5 Blood sample for hematology, biochemistry evaluation should be tested and analyzed locally. 
6 Due to the change in the study requirements, nasal swab samples will no longer be collected from any maternal participant for RTI assessment. 


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Table 11 
Biological samples - Cord blood 
Sample type 
Collected to evaluate 
Minimum Quantity per 
participant 
Unit 
Time point 
Additional information 
Cord blood  
Immune Response 
~5, up to ~10 
ml 
Visit 3 (Delivery) 
- 
Table 12 
Biological samples – Infant participants (Amended 15 March 2022) 
Infant Sample 
type 
Collected to 
evaluate 
Minimum 
Quantity per 
participant 
Unit 
Time point 
Additional information 
Whole Blood 
Immune 
response - IF 
cord blood not 
collected 
~2.5  
mL 
Visit 1-NB 
(Within 72 hours after birth) 
Volume must be reduced if weight ≤ 2.5 kg. 
[Trial-related blood loss for infant participants should be ≤ 1 % at each 
timepoint. Total blood volume is estimated at 80 to 90 ml/kg body 
weight, and venipuncture should not exceed ~ 1.6 ml for a 2 kg baby or 
2.0 ml for a 2.5 kg baby.] 
Refer to the Laboratory Manual for additional information. 
All minimum totals given below assume a body weight > 2.5 kg.  
Immune 
response – 
sub-cohort 4 
~2.5 1 
mL 
Either 
Visit 2-NB (Day 43 post-birth) or 
Visit 3-NB (Day 121 post-birth) or 
Visit 4-NB (Day 181 post-birth) 
Nasal swab 2, 3 
Presence of 
RSV-A/B 
- 
- 
RTI Surveillance Visit - LRTIs 
(Event-Driven) 
Collect at least one nasal swab for each potential LRTI reported. 
If more than one follow-up assessment visit is conducted, additional 
nasal swabs may be collected at the Investigator’s discretion. 
RTI Surveillance Visit - RTI 
hospitalization (Event-Driven) 
Collect (if possible) from any participant hospitalized with a RTI (or 
soon after release, as long as symptoms are ongoing). 
1 Only from infant participants in the sample collection sub-cohort for the visit. Each infant is assigned to a single sub-cohort. 
2 Collection of a nasal swab for sponsor testing is additional to and DOES NOT REPLACE any specimen collection (per local standard of care) for testing by the local laboratory to 
establish a fast and accurate diagnosis for the hospitalization. In the case of hospitalization, local testing for RSV infection should be performed if feasible. 
3 If other nasal swab specimens are collected and tested locally as per local standard of care, results will be recorded in the eCRF. In principle only the sponsor laboratory results will 
be used when applying the case definitions for data analysis in Section 4.2.5.3. Thus, where mandated by the protocol, every effort should be made to obtain nasal swab samples 
that can be analyzed by the sponsor (or sponsor-designated) laboratory. Results of locally tested samples, with locally approved tests may be used when applying case definitions 
only in the event the nasal swab for central testing was impossible to collect. 
4 Due to the change in the study requirements, there will no longer be collection of blood samples at Visit 2-NB, Visit 3-NB and Visit 4-NB. 


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• 
An overall blood volume of approximately 30 mL will be collected from maternal 
participants during the entire study period, if blood sample for assessing eligibility 
criteria should not be taken at screening. 
• 
An overall blood volume of approximately 35.5 mL will be collected from maternal 
participants during the entire study period, if blood sample for assessing eligibility 
criteria must be taken at screening. 
• 
An overall blood volume of approximately 2.5 mL will be collected from infant 
participants during the entire study period*. If cord blood sample cannot be 
collected, then an overall volume of 5 mL will be collected*. 
* Due to the change in the study requirements, there will no longer be collection of 
blood samples from infant participants at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
• 
Refer to Table 10 and SoA (Setion 1.3) for details of volumes collected for different 
assessments. 
8.1.2. 
Laboratory assays (Amended 15 March 2022) 
Following laboratory assays will be performed (Table 13): 
• 
Serological assays for the determination of RSV-A/B neutralizing antibodies (nAbs) 
will be performed by neutralization assay with wild type virus. Further 
characterization of the humoral immune response will be performed using enzyme-
linked immunosorbent assay (ELISA) based assays for measurement of IgG 
antibodies binding to the RSV PreF3 protein. 
• 
RSV-A/B qRT-PCR assay is the core assay on nasal swab samples to confirm RSV 
cases in RSV program. The assay is able to identify, and discriminate RSV-A and 
RSV-B subtypes extracted from the nasal swabs. 
Table 13 
Laboratory assays (Amended 15 March 2022) 
Assay type 
System 
Component 
Method 
Laboratory 1 
Humoral Immunity 
(Antibody 
determination) 
SERUM 
RSV-A NAb 
NEUT 
GSK 2 or GSK 
designated lab 
SERUM 
RSV-B NAb  
NEUT 
GSK 2 or GSK 
designated lab 
SERUM 
RSV PreF3 Ab.IgG 
ELISA 
GSK 2 or GSK 
designated lab 
Molecular Biology 3 
NASMUC 
(Nasal swab) 
Respiratory Syncytial 
Virus A RNA  
qRT-PCR  
GSK 2 or GSK 
designated lab 
 
NASMUC 
(Nasal swab) 
Respiratory Syncytial 
Virus B RNA  
qRT-PCR 
GSK 2 or GSK 
designated lab 
ELISA = enzyme-linked immunosorbent assay; NEUT = Neutralization; qRT-PCR = Quantitative Reverse Transcription 
PCR; RSV-A Nab = RSV-A neutralizing antibody; RSV-B Nab = RSV-B neutralizing antibody; RSVPreF3 Ab.IgG 
= RSV PreF3 antibody.immunoglobulin G; SOP = Standard operating procedure 
1 Refer to the list of clinical laboratories for details. 
2 GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium; Marburg, 
Germany. CLS may delegate testing to GSK Research laboratories in Rixensart, Belgium; Rockville, USA; 
Sienna, Italy.  
3 RSV-A/B quantitative reverse transcription PCR will be performed on all specimens collected to evaluate RTI as 
specified in Section 8.4.4. To evaluate tertiary objectives, an Allplex Respiratory Viruses Panel or alternative may 


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be performed for RSV-A/B-positive samples, and (if deemed necessary) for RSV-A/B-negative samples. The 
panel may include testing for SARS-COV-2. Please note that SARS-COV-2 testing is not intended to be 
diagnostic and results will not be provided to the investigator. Testing for SARS-COV-2 in any suspected infected 
participant should be performed as per the standard of care. 
Please refer to the Section 10.2 for a detailed description of the assays performed in the 
study. 
Additional exploratory testing on the disease under study and/or other RTIs or infections 
of relevance to pregnant women and their newborns may be performed within the 
framework of the study if deemed necessary for accurate interpretation of the data/ 
should such assay(s) become available at GSK. These assays may not be represented in 
the objectives/ endpoints of the study protocol. 
The addresses of clinical laboratories used for sample analysis are provided in a separate 
document accompanying this study protocol. 
GSK clinical laboratories have established a Quality System supported by procedures. 
The activities of GSK clinical laboratories are audited regularly for quality assessment by 
an internal (sponsor-dependent) but laboratory-independent Quality Department. 
8.1.3. 
Immunological read-outs (Amended 15 March 2022) 
Table 14 
Immunological read-outs (Amended 15 March 2022) 
Blood sampling timepoint 
Study group 
Approximate 
No. 
participants 
Component 
Type of contact and 
timepoint 
Sampling timepoint 
Maternal participants*  
Visit 1 (Day 1) 
pre-study intervention All study groups 378 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Visit 2 (Day 31) 1 
post-study 
intervention 
All study groups 378 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Visit 3 (Delivery) 
post-study 
intervention  
Whole blood: 
All study groups 
Cord blood: 
All study groups 
378 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Infant participants* 
 
 
Visit 1-NB (Birth) 
birth (only if cord 
blood cannot be 
collected) 
Event-driven 
Event-driven 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Visit 2-NB (Day 43) 2 
post-birth 
RSV_MAT_BS1 84 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Control_BS1 
42 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Visit 3-NB (Day 121) 2 post-birth 
RSV_MAT_BS2 84 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 


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Blood sampling timepoint 
Study group 
Approximate 
No. 
participants 
Component 
Type of contact and 
timepoint 
Sampling timepoint 
Control_BS2 
42 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Visit 4-NB (Day 181) 2 post-birth 
RSV_MAT_BS3 84 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Control_BS3 
42 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
RSV-A Nab = RSV-A neutralizing antibody; RSV-B Nab = RSV-B neutralizing antibody; RSVPreF3 Ab.IgG = RSV 
PreF3 antibody.immunoglobulin G. 
1 Blood sample at Visit 2 (Day 31) wil not be collected if the delivery occurs prior to Day 31 post-study intervention. 
2 Due to the change in the study requirements, there will no longer be collection of blood samples from infant 
participants at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
* Refer to Table 10, Table 11, and Table 12 
Table 15 
Molecular biology tests (Amended 15 March 2022) 
Nasal swab sampling timepoint 
No. 
participants 
Component 3 
Type of contact (timepoint) 
Sampling timepoint 
Maternal MA-RTI 1, 4 
Event-driven 
Event-driven 
RSV-A RNA  
 
 
 
RSV-B RNA  
Infant RTI 2 
Event-driven 
Event-driven 
RSV-A RNA  
 
 
 
RSV-B RNA 
1 Includes maternal RTI hospitalizations 
2 Includes infant RTI hospitalizations 
3 Quantitative reverse transcription PCR will be performed on all specimens collected to evaluate RTI as specified in 
Section 8.4.4. To evaluate tertiary objectives, an Allplex Respiratory Viruses Panel or alternative, may be 
performed for RSV-A/B-positive samples, and (if deemed necessary) for RSV-A/B-negative samples. The panel 
may include testing for SARS-COV-2. Please note that SARS-COV-2 testing is not intended to be diagnostic and 
results will not be provided to the investigator. Testing for SARS-COV-2 in any suspected infected participant 
should be performed as the standard of care. 
4 Due to the change in the study requirements, nasal swab samples will no longer be collected from any 
maternal participant for MA-RTI assessment. 
8.1.4. 
Clinical safety laboratory assessments 
Refer to the Section 10.2 for the list of clinical laboratory safety assessments required by 
the protocol.  
These assessments must be conducted according to the clinical laboratory manual and the 
SoA. 
8.1.5. 
Immunological correlates of protection 
No generally accepted immunological correlate of protection has been demonstrated so 
far for the antigen(s) used in the RSV maternal (RSVPreF3) vaccine. 


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8.2. 
Safety assessments 
The investigator and his/her designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE. The investigator and designees 
are responsible for following up AEs that are serious, considered related to the study 
intervention or the study, or that caused the participant’s withdrawal from the study. 
Surveillance for evaluation of RTI is described in Section 8.4. 
8.2.1. 
Procedures for maternal participants 
Additional details are provided in the SPM. 
8.2.1.1. 
Collection of demographic data 
At screening, record demographic data such as date of birth, sex, race and ethnicity in the 
participant’s eCRF. 
8.2.1.2. 
Collection of worsening of the pre-existing medical condition and/or 
obstetric complication 
Worsening of the pre-existing medical condition and/or obstetric complication should be 
considered by the investigator, using clinical judgment and the following criteria: 
• 
Change in medication and/or medication dose 
• 
Medically attended event in relation to pre-existing condition and/or obstetric 
complication that are outside the routine management of the condition/complication 
• 
SAE and/or hospitalization in relation to pre-existing condition and/or obstetric 
complication 
Worsening of the pre-existing medical condition and/or obstetric complication will be 
collected from Day 1 (Visit 1) up to Day 181 post-delivery as AESI. 
8.2.1.3. 
Medical/vaccination history 
Obtain the maternal participant’s medical/vaccination history by interviewing her and/or 
review her medical records. Record any pre-existing conditions, signs and/or symptoms 
present prior to the study intervention in the eCRF. 
• 
Record outcome of the comprehensive detailed fetal morphology ultrasound 
assessment (also known as a Level 2 ultrasound scan or fetal morphology 
assessment). Please see Section 10.7.2 for a description. If results are not available at 
screening, then the ultrasound can be performed as a study procedure under certain 
conditions and results should be available prior to participant’s study randomization 
and study intervention administration. Refer to the SPM for further details. If 
abnormal, participants will be referred, as/if applicable, per local standard of care. 


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• 
Information from additional routine standard of care antenatal / medical evaluations 
(external to study visits/procedures) are not to be reported in the eCRF. If an 
unscheduled visit is performed post-study intervention, for safety reasons, results of 
procedures performed, per investigators discretion (eg. hematology/biochemistry 
testing, urinalysis, etc) will be recorded in the “Unscheduled Safety visit” eCRF. 
• 
Record number of past pregnancies, their outcome(s) and any pregnancy-related 
complications. 
• 
For the current pregnancy, record: 
− 
the participant’s pre-pregnancy BMI (i.e., BMI during the months before the 
participant became pregnant or at the very first maternal visit [if occurred early 
in the 1st pregnancy trimester]). This information can be obtained either via 
medical record review or participant interview. If BMI is not directly available, 
investigators will obtain participant’s pre-pregnancy weight (i.e. weight during 
the months before the participant became pregnant or are the very first maternal 
visit [if occurred early in the 1st trimester]) and calculate pre-pregnancy BMI 
from it, in order to report it in the eCRF. 
− 
gestational age, along with GAIA level of certainty as defined in Section 5.1.1 
and 10.8. 
− 
date of: LMP or ET or IUI, as applicable. 
− 
expected date of delivery (EDD) and method of estimation. 
− 
number of prenatal visits attended up to the date of the study screening visit. 
− 
approximate date of first prenatal visit. 
− 
results of any clinically significant, abnormal pregnancy screening laboratory 
tests. 
− 
any pregnancy-related complications. 
− 
results of any procedures intended to screen for congenital anomalies. 
− 
record all vaccination received by the maternal participant since the month prior 
to the estimated date of conception and before study intervention administration. 
Note: Medical / vaccination history and past pregnancy history will be captured in the 
source document as part of screening, but recorded in eCRF only at Visit 1 if the 
maternal participant is eligible. 
8.2.1.4. 
Physical examination (General and obstetric examination) 
Screening and Visit 1 to Visit 3 
• 
Height (only at screening). 
• 
Weight (at screening and Visits 1-2). 


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• 
Temperature at screening and Visits 1-3. At Visit 1, temperature need only be 
measured once, pre-study intervention. At Visit 3 (Delivery) temperature should be 
measured if/as per standard of care. 
• 
Systolic/diastolic blood pressure, heart rate and respiratory rate (after at least 10 
minutes rest) at screening and at Visits 1-2; and on admission for delivery at Visit 3. 
Respiratory rate should be measured at Visit 3 (Delivery) if/as per SoC. 
• 
Pulmonary examination including measurement of blood oxygen saturation and chest 
auscultation (at Visit 1). 
Obstetric examination should include: 
• 
Fetal heart tones. 
• 
Fetal movement and fundal height (at screening and Visits 1 – 2). No specific test 
required for fetal movement, unless part of standard of care, information reported by 
the maternal participant while at the visit will be acceptable. 
• 
Presence of edema (at screening and Visits 1 – 2). 
• 
Vaginal examination (manual and/or speculum) will be performed ONLY if 
warranted by participant's symptoms or as per investigator's clinical discretion. If 
done, results will be recorded (normal or abnormal; if abnormal, specify). 
Note: At delivery visit, the results of the general and obstetric examination can be 
obtained from the medical chart as activity performed as part of standard of care and 
transcribed into the eCRF. 
If the screening visit and Visit 1/study intervention are performed on the same day: 
• 
Physical examination (general and obstetric examination) procedures required both at 
screening and at Visit 1/study intervention should be performed once; they do not need 
to be repeated. 
• 
Temperature will only be measured once, but will need to be recorded twice in the 
eCRF. 
• 
The Pulmonary examination foreseen at Visit 1 should be performed. 
Visit 4 
• 
Vital signs (systolic/diastolic blood pressure, heart rate and respiratory rate after at 
least 10 minutes of rest) 
• 
History and/or symptom-directed physical and obstetrical exam as per standard of 
care (eg. check of c-section scar / episiotomy scar, any specific checks based on 
eventual complaints raised by the mother, etc. as applicable). Clinically significant 
abnormalities will be recorded 
All unscheduled visits 
General and obstetric examination should be symptom-directed. 


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Any unscheduled visit for a medically attended RTI must include the maternal 
participant assessments listed in Section 8.4.4. 
8.2.1.4.1. Pulse oximetry 
Measurement of blood oxygen saturation by trained site personnel, using pulse oximeters 
provided by GSK, is strongly preferred. The SPM presents additional information about 
GSK-provided pulse oximeters and their use. 
8.2.1.4.2. Monthly contacts (Amended 15 March 2022) 
At least 3 attempts should be made within the week of a scheduled contact. If these 
attempts are unsuccessful, that monthly contact is considered a missed contact. The next 
scheduled contact will be made the following month. 
In addition to the monthly contacts between Visit-2 and the Delivery visit, additional 
not pre-specified contacts and/or visits can be made more often (at any desired 
frequency), as per investigator’s, maternal participant’s or LAR’s discretion. 
8.2.1.5. 
Warnings and precautions to administration of study intervention 
Warnings and precautions to administration of study intervention must be checked at the 
visit with planned administration of study intervention. 
8.2.2. 
Procedures for infant participants 
Additional details are provided in the SPM. 
8.2.2.1. 
Physical examination at Visit 1-NB to Visit 5-NB 
A physical examination will be performed at each protocol-specified visit (Visit 1-NB to 
Visit 5-NB). 
The examination will include assessment of the following: 
• 
Weight*, length, head circumference. 
* At Visit 1-NB, body weight should be taken within 24 hours after the birth. 
• 
Temperature, heart rate and respiratory rate. 
• 
Age-appropriate organ system examination including: eyes, ears, musculoskeletal, 
reflexes (motor/visual/sound), pulmonary (chest auscultation), cardiovascular, 
neurological, skin and genitourinary. 
• 
Presence of congenital anomalies. 


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8.2.3. 
Study holding rules and safety monitoring (Amended 15 March 
2022) 
An internal SRT and an external IDMC (external to GSK) will review available maternal 
and infant safety data on a regular basis throughout the study. Any potential safety 
concern identified will be escalated to the GSK Global Safety Board (GSB). 
8.2.3.1. 
Safety evaluation by the Safety Review Team (SRT) (Amended 15 
March 2022) 
The SRT includes as core members the GSK’ Central Safety physician, Safety scientist, 
Clinical Research & Development Lead (CRDL), Epidemiologist, Global Regulatory 
Lead and Biostatistician of the project. The SRT is responsible for ongoing safety 
monitoring of the entire study and will review on a regular, ongoing basis the safety data. 
Continuous monitoring throughout the study will allow for ad-hoc data review meetings 
if deemed necessary by the SRT. 
The SRT will inform the IDMC about any potential safety concern or study holds at any 
point during the study and may request ad-hoc safety evaluations by the IDMC. 
Note: Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants 
8.2.3.2. 
Independent data monitoring committee (IDMC) evaluation (Amended 
15 March 2022) 
An unblinded IDMC will be established by GSK. The IDMC will monitor the safety data 
and the scientific validity of the study. 
The IDMC will conduct unblinded reviews of all available safety data on an ongoing 
basis. The unblinded analyses will be done by an independent statistician from an 
Independent Data Analysis Center (IDAC) outside GSK to maintain the study blind* and 
will be documented in a statistical analysis report. No unblinded data* will be shared 
with the study team. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
In addition, there will be at least 3 planned IDMC data review meetings. The first will 
take place after ~63 active vaccine recipients have completed the Day 43 post-delivery 
visit (Visit 4 for maternal participants; Visit 2-NB for their enrolled infants). The second 
planned IDMC meeting will occur after all participants have completed follow-up to the 
Day 43 post-delivery/birth visit (Visit 4 for maternal participants; Visit 2-NB for their 
enrolled infants). The third planned IDMC meeting will occur when all data up to study 
end (Visit 5-NB, 12 months post-birth) are available. For each review, the IDMC will be 
provided with unblinded safety data as described above. Ad-hoc data reviews or meetings 
may be organized, if deemed necessary by the IDMC. 


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As part of ongoing review, the IDMC will monitor the rates of SAEs, pregnancy-related 
outcomes, pregnancy-related and neonatal /infant AESIs, medically attended RTIs in 
maternal participants and LRTIs in infants. 
Additional details concerning the IDMC’s structure and processes will be provided in the 
IDMC charter. 
8.2.3.3. 
Study holding rules (Amended 15 March 2022) 
The safety holding rules are defined in Table 16. 
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 study intervention administration and 
consenting of new participants irrespective of number of participants enrolled and/or 
timing of the event relative to study dose administration. 
Of note, all available safety data will also be reviewed by the SRT/IDMC to allow an 
overall assessment of the benefit/risk ratio of study intervention administration. 
Table 16 
Holding rules assessed by the investigator 
Holding 
Rule 
Event 
Number of 
mothers/infants 
1a 
Any maternal or fetal death within 30 days from study dose administration that 
cannot be reasonably attributed to a cause other than vaccination as per 
Investigator assessment. 
 1 
1b 
Any life-threatening SAE in a maternal participant or fetus within 30 days from 
study dose administration that cannot be reasonably attributed to a cause other than 
vaccination as per Investigator assessment. 
 1 
If the investigator becomes aware of a holding rule being met, he/she must suspend 
administration of the study intervention and inform GSK immediately (e.g. holding rules 
1a-b).Refer to the Table 19 for contact information). 
The following communication sequence must be followed: 
• 
Investigator (or a designee) informs their local sponsor contact as soon as possible (no 
later than within 24 hours). (Table 19). 
• 
The local sponsor contact informs the central sponsor contact (e.g., the Study Delivery 
Lead [SDL]; the CRDL) as soon as possible (no later than within 24 hours). 
• 
The central sponsor team ensures that SBIR is blocked, all sites administering study 
vaccine/product are informed, and all country or region- specific regulatory authorities 
are informed. 
• 
Study sites confirm that they have been notified and have taken appropriate action, 
providing appropriate documentation to their local sponsor contact. 
• 
The GSK GSB evaluates the case after receipt of the IDMC’s recommendations / and 
takes the decision to stop or to re-start dose administration. 


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• 
Where required per local / regional regulation, the central sponsor team submits a 
substantial amendment to the local/regional authority requesting authorization to re-
start the study. 
• 
When all required authorizations to re-start the study in a country / region have been 
provided, the central sponsor team provides written notification to local sponsor 
contacts; local sponsor contacts then provide written notification to study sites. 
Risk assessment: 
Figure 3 presents the probability of not meeting the defined holding rules 1 (a-b) for the 
entire study population (n = 378 maternal participants). 
For holding rules 1 (a-b), using a cut-off of 1/378, there is around 85% chance that the 
holding rule is met if the corresponding event has a true incidence rate of 0.5% and 
around 70% chance the holding rule is not met if the corresponding event has a true 
incidence rate of 0.1%. 
Figure 3 
Risk assessment curve for the defined safety holding rules 
 


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8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and other safety reporting 
8.3.1. 
Time period and frequency for collecting AE, SAE and other safety information (Amended 15 March 2022) 
Table 17 
Timeframes for collecting and reporting of safety information (including RTI information) (Amended 15 March 
2022) 
 
Before delivery 1, 5 
Delivery/Birth 
Post-delivery/birth  
Timepoint 
D-28 
D1 
D8 
D31 
 
D 43 
D91 
D121 
D181 
D271 
D366 
Maternal participant visits/contacts 
Pre-2 
V1 
C1 
V2 
V3 
V4 
 
 
C2 
 
 
Infant participant visits/contacts 
 
 
 
 
V1-NB 
V2-
NB 
C1-NB 
V3-
NB 
V4-NB 
C2-
NB 
V5-NB  
Event 
Administration site and systemic solicited events 
 
 
 
 
 
 
 
 
 
 
 
 
M (Days 1-7) 
 
 
 
 
 
 
 
 
Unsolicited AEs that are neither SAEs, MAEs or 
AESIs  
 
 
 
 
 
 
 
 
 
 
 
 
M (Days 1-30) 
 
 
 
 
 
 
 
Worsening of pre-existing medical conditions 
and/or obstetric complications (reported as AESIs) 
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 180 days post-delivery) 
 
 
Pregnancy-related AESIs  
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 42 days post-delivery) 
 
 
 
 
 
Pregnancy outcomes 
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 42 days post-delivery) 
 
 
 
 
 
Suspected, probable and confirmed cases of 
COVID-19 infection (depending on the 
epidemiological COVID-19 situation)  
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 180 days post-delivery) 
 
 
 
 
 
 
I (Birth to 365 days post-birth) 
MA-RTIs 6 
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 180 days post-delivery) 
 
 
SAEs, AEs/SAEs leading to Withdrawal from the 
study and MAEs  
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 180 days post-delivery) 
 
 


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Before delivery 1, 5 
Delivery/Birth 
Post-delivery/birth  
Timepoint 
D-28 
D1 
D8 
D31 
 
D 43 
D91 
D121 
D181 
D271 
D366 
Maternal participant visits/contacts 
Pre-2 
V1 
C1 
V2 
V3 
V4 
 
 
C2 
 
 
Infant participant visits/contacts 
 
 
 
 
V1-NB 
V2-
NB 
C1-NB 
V3-
NB 
V4-NB 
C2-
NB 
V5-NB  
 
 
 
 
I (Birth to 365 days post-birth) 
Subsequent Pregnancies 3  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 180 days post-delivery) 
 
 
SAEs related to study participation  
 
 
 
 
 
 
 
 
 
 
 
M (Screening to 
Day 1 pre-study 
intervention) 
 
 
 
 
 
 
 
 
 
Neonatal / Infant AESIs 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I (Birth to 42 days post-
birth) 
 
 
 
 
 
LRTIs (including medically assessed, RSV-
associated LRTIs)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I (Birth to 365 days post-birth) 
Medically assessed, RSV-associated 
hospitalizations  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I (Birth to 365 days post-birth) 
Pre = pre-study intervention; V =visit; D = Day; M = Maternal participants; I= Infant participants; RTI = Respiratory tract infection; LRTI 
1 Approximately monthly contacts pre- delivery also occur within the timeframes described above and are described in Section 1.2. 
2 i.e. consent obtained. 
3 If subsequent pregnancy occurs during the study, follow-up may extend up to 8 weeks post-birth of the infant from that subsequent pregnancy. 
4 Neonatal AEs of special interest identified after Visit 2-NB (e.g., congenital anomalies) will continue to be reported as such. 
5 SAEs and/or AESIs experienced by an infant born to the exposed mother will be reported (if become known to the site staff), even if the re-consent for infant participants is not 
provided. 
6 Due to the change in the study requirements, RTI surveillance of the maternal participants will no longer be performed. 
 


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The investigator or designee will record and immediately report all SAEs (including RTIs 
associated with hospitalization of a maternal or infant participant and serious adverse 
pregnancy outcomes), as well as all pregnancy-related AESIs and neonatal AESIs to the 
sponsor or designee via the Adverse Events Form and the corresponding Expedited 
Adverse Event Form. Reporting should, under no circumstances, occur later than 24 
hours after the investigator becomes aware of an SAE, as indicated in Section 10.3.10 
and Table 18. The investigator will submit any updated SAE/AESI data to the sponsor 
within 24 hours of it being available. 
A post-study SAE is defined as any event that occurs after the end of the study. 
Investigators are not obligated to actively seek SAEs from former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a 
participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention, the investigator will promptly notify the 
study contact for reporting SAEs mentioned in the Table 19. 
8.3.2. 
Method of detecting AEs and SAEs, pregnancies and other 
events 
Detection and recording of AE/SAE/AESI/subsequent pregnancies are detailed in Section 
10.3.8. 
Assessment of AE/SAE intensity, causality and outcome are described in Section 10.3.9. 
Open-ended and non-leading verbal questioning of participants/participants’ 
parent(s)/LAR(s) is the preferred method of acquiring information related to an 
AE/SAE/AESI/ subsequent pregnancy. 
8.3.2.1. 
Clinically significant abnormal laboratory findings 
The investigator must review the laboratory report, document that he/she did so, and 
record any clinically relevant changes occurring during the study in the AE section of the 
eCRF. Clinically significant abnormal laboratory findings are those which are not 
associated with an underlying disease, unless judged by the investigator to be more 
severe than expected for the participant's condition. 
• 
All clinically significant abnormal laboratory test values associated with an AE 
reported during the study or within 30 days after the study intervention 
administration should be repeated until the values return to normal/baseline, or until 
they are no longer considered significantly abnormal by the investigator or LML. 
Refer to the Section 10.3.6 for more information on clinically abnormal laboratory 
assessments that qualify as an AE or SAE. 
• 
If such values do not return to normal/baseline after an interval judged reasonable by 
the investigator, the etiology of the abnormal value should be identified and the 
sponsor notified. 


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8.3.3. 
Regulatory reporting requirements for SAEs, subsequent 
pregnancies and other events (Amended 15 March 2022) 
Once an investigator (or designee) becomes aware that a study participant has 
experienced an SAE/AESI/subsequent pregnancy, he/she must report it to GSK using the 
required documentation and within the timeframes mentioned in Table 18. This is 
essential for meeting GSK legal obligations and ethical responsibilities for participant 
safety and the safety of a study intervention under clinical investigation. 
For SAEs/AESIs, the investigator must always provide an assessment of causality at the 
time of the initial report, as defined in the Section 10.3.9.2. 
Local regulatory requirements and sponsor policy for the preparation of an investigator 
safety report for SUSAR must be followed. These reports will be forwarded to 
investigators as necessary. 
The sponsor has the legal responsibility to notify local authorities and other regulatory 
agencies about the safety of an investigational study intervention. The sponsor will 
comply with country-specific regulatory requirements related to safety reporting to the 
regulatory authority, IRB/IEC and investigators. 
Please refer to the Section 10.3.10 for further details regarding the reporting of 
SAEs/AESIs/subsequent pregnancies. 
Table 18 
Timeframes for submitting SAE, subsequent pregnancy and other 
events reports to GSK (Amended 15 March 2022) 
Type of Event 
Initial Reports 
Follow-up of Relevant Information on 
a Previous Report 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs (including adverse 
outcomes for the study 
pregnancy and RSV-associated 
hospitalizations) 
24 hours* ‡ 
electronic Adverse 
Events Form and 
the corresponding 
Expedited Adverse 
Event Form 
24 hours*¥ 
electronic Adverse 
Events Form and the 
corresponding 
Expedited Adverse 
Event Form 
Subsequent Pregnancies 
24 hours* 
electronic 
pregnancy report 
24 hours* 
electronic pregnancy 
report 
AESIs 
24 hours** ‡,  
Adverse Events 
Form and the 
corresponding 
Expedited Adverse 
Event Form 
24 hours* ¥ 
electronic Adverse 
Events Form and the 
corresponding 
Expedited Adverse 
Event Form 
Maternal participants: MA-RTIs 
Infant participants: Medically 
assessed, RSV-associated 
LRTIs 
72 hours 
eCRF 
1 week 
eCRF 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
**Timeframe allowed once the investigator determines that the event meets the protocol definition of an AESI. 
‡ The investigator will be required to confirm review of the SAE/AESI causality within 72 hours of submission of the 
SAE/AESI. 
¥ The assessment of causality should be included in the initial report to be submitted within 24 hours. 


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8.3.3.1. 
Contact information for reporting SAEs, AESIs, pregnancies and study 
holding rules (Amended 15 March 2022) 
Table 19 
Contact information for reporting SAEs, AESIs, subsequent 
pregnancies and study holding rules (Amended 15 March 2022) 
Study contact for questions regarding 
SAEs, AESIs, subsequent pregnancies  
Study contact for reporting of study 
holding rules 
Refer to the local study contact information 
document 
As soon as the investigator is aware that 
a holding rule is met, he/she must 
immediately inform the LML.  
Back up study contact for reporting 
SAEs, AESIs, subsequent pregnancies 
Available 24/24 hours and 7/7 days 
Back up study contact for escalation 
of holding rules 
Refer to the local study contact 
information document. 
GSK Clinical Safety & 
Pharmacovigilance 
 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: ogm28723@gsk.com 
US sites only: 
Fax: 1 610 787 7053 
Canadian sites only: 
Fax: 1 866 903 4718 
 
8.3.4. 
Additional reporting guidance for the study pregnancy 
8.3.4.1. 
Labor and delivery 
• 
An uncomplicated vaginal delivery or planned caesarian section expected to occur in 
a hospital setting should NOT be reported as an AE, MAE or SAE. 
• 
A medical complication that requires a caesarian section or an emergency induction 
may be reported as an SAE/AESI (as applicable), using the corresponding Adverse 
Events Form and the corresponding Expedited Adverse Event Form. 
8.3.4.2. 
Pregnancy outcomes 
Pregnancy outcomes include: 
• 
Live birth with no congenital anomalies 
• 
Live birth with minor congenital anomalyies only 
• 
Live birth with at least 1 major congenital anomaly 
• 
Fetal death/still birth (antepartum or intrapartum) with no congenital anomalies 
• 
Fetal death/still birth (antepartum or intrapartum) with only minor congenital 
anomalies 


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• 
Fetal death/still birth (antepartum or intrapartum) with at least 1 major congenital 
anomaly 
• 
Elective/therapeutic termination with no congenital anomalies 
• 
Elective/therapeutic termination with only minor congenital anomalies 
• 
Elective/therapeutic termination with at least 1 major congenital anomaly 
8.3.4.3. 
Reporting of congenital anomalies in relation to pregnancy outcomes 
and SAEs and/or AESIs 
For characterization and reporting of the congenital anomalies, which will be captured 
during the study, the following classifications should be used: 
• 
Congenital anomaly as an SAE OR Congenital anomaly as not an SAE 
− 
The characterization of congenital anomalies as an SAE should be based on the 
Metropolitan Atlanta Congenital Defects Program (MACDP) guidelines, as 
oulined in [MACDP]. 
− 
Congenital anomalies that are included in the MACDP 6-Digit Code Defect List 
should be reported as SAEs. 
− 
Congenital anomalies that are not included in MACDP 6-Digit Code Defect List 
should not be reported as SAEs, unless they are fatal, life-threatening, led to 
hospitalization, prolongation of hospitalization, disability or permanent damage 
or are other medically significant events. 
− 
Congenital anomalies that are not included in MACDP 6-Digit Code Defect List 
may be also reported as MAEs, as appropriate. 
− 
If minor congenital anomalies are not reportable either as SAEs or MAEs, they 
should be recorded in the infant physical examination eCRF. 
• 
Major congenital anomaly OR Minor congenital anomaly 
− 
The characterization of congenital anomalies as major or minor should be based 
on the Centers for disease Control and Prevention (CDC) definitions, as outlined 
in [CDC]. 
− 
Major congenital anomalies are structural or functional defects that require 
surgical and/or medical treatment and that have serious adverse effects on health 
or development (functional) or have significant cosmetic impact. 
− 
Minor congenital anomalies are anatomic variants or defects that do not have 
serious medical, functional or cosmetic consequences for the child. 
• 
Congenital anomaly as an AESI OR Congenital anomaly as not an AESI 
− 
All major congenital anomalies should be reported as AESIs. Minor congenital 
anomalies should not be reported as AESIs. 
Refer to the SPM for additional information and guidance. 


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8.3.5. 
Treatment of adverse events (AEs) 
Any medication administered for the treatment of an SAE/AESI should be recorded in 
the eCRF and linked to the corresponding electronic Expedited Adverse Event Form 
(refer to the Section 10.3.10.1). 
8.3.6. 
Participant card 
At screening or at Visit 1, the investigator (or designee) must provide the maternal 
participant/ infant participant’s parent(s)/LAR(s) with a “participant card” containing 
information about the clinical study. One card will be provided to each maternal 
participant who enters the study. Another card will be provided for each infant participant 
who enters the study. 
The maternal participant/infant participant’s parent(s)/LAR(s) must be instructed to 
always keep the participant card in his/her/their possession for the duration of the study. 
In an emergency, this card serves to inform the responsible attending physician/LAR/care 
giver/family member that the maternal / infant participant is in a clinical study and that 
relevant information may be obtained by contacting the investigator or his/her back up. 
8.4. 
Respiratory tract illnesses (RTIs) 
The definitions provided in Sections 8.4.1.1 and 8.4.1.2 are for use by site personnel. 
They are designed to provide GSK with the information needed to apply case definitions 
during data analyses. They are related but not identical to the case definitions themselves 
(Section 4.2.5). For additional details regarding maternal MA-RTI and infant RTI 
surveillance and assessment, refer to the SPM. 
8.4.1. 
Definitions 
8.4.1.1. 
Medically attended respiratory tract illnesses (MA-RTIs) in maternal 
participants (Amended 15 March 2022) 
A maternal MA-RTI* occurs when the maternal participant visits a healthcare 
professional (e.g., a General Practitioner) for any respiratory symptom, including (but not 
limited to) cough, sore throat, sputum production and difficulty breathing. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
8.4.1.2. 
Respiratory tract illnesses (RTIs) in infant participants 
RTI symptoms include: 
• 
Nasal discharge running freely out of the infant’s nose (runny nose), 
• 
Breathing through the mouth because the infant’s nose is blocked (blocked nose), 
• 
Regular bursts of cough, 


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• 
Difficulty in breathing (fast breathing, poor feeding, working hard to breathe, or 
making unusual sounds when breathing), and 
• 
Wheezing (a whistling sound when the infant breathes out, and thus another sign of 
potential difficulty in breathing). 
Worsening means any clinically observed/diagnosed symptoms and signs that are 
reported during the same RTI and reflect a deterioration in the infant’s respiratory tract 
functions. 
A potential LRTI is one in which the infant’s RTI symptoms include at least one of the 
following: 
• 
Difficulty in breathing (fast breathing, poor feeding, working hard to breathe, or 
making unusual sounds when breathing); 
• 
Wheezing (a whistling sound when the infant breathes out); 
• 
Parental concern (the parent(s)/LAR(s) or their designate(s) are concerned about the 
infant’s RTI, or general health in the context of the RTI and intend to seek medical 
care). 
8.4.2. 
Surveillance 
8.4.2.1. 
Maternal participants (Amended 15 March 2022) 
MA-RTI surveillance* begins at Day 1 post-study intervention and ends 180 days after 
delivery (Contact 2). It will be accomplished via 2 types of contact. 
• 
For a Passive contact, each maternal participant will be instructed at study entry to 
contact the site should she 
− 
Visit (or plan to visit) a healthcare professional for any respiratory symptoms; 
− 
Be hospitalized because of her respiratory symptoms. 
If the study site is the primary treating facility for the maternal participant, a “contact” 
may also be made by going directly to the study site. 
Site personnel will use a script to guide data collection once a contact has been made. 
• 
For an Active contact, site personnel contact the maternal participant monthly in 
addition to the scheduled visits/contacts as per Table 1. Active contacts will be 
scripted. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 


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8.4.2.2. 
Infant participants 
RTI surveillance in infant participants begins at birth (Visit 1-NB) and ends 366 days 
after birth (Visit 5-NB) which is expected to cover at least 1 complete RSV season (i.e. 
the majority of the infant participants). 
It will be accomplished via 2 types of contact and completion of diary cards. 
8.4.2.2.1. RTI surveillance contacts 
• 
In a Passive contact, the participant’s parent(s) / LAR(s) contact site personnel if: 
− 
they observe cold-like respiratory tract symptoms such as cough, runny nose, 
blocked nose, difficulty in breathing and wheezing. 
− 
they intend to seek medical care because of concern about the infant’s RTI, or 
general health in the context of the infant’s RTI. 
Site personnel will use a script to guide data collection once a passive contact has 
been made. 
• 
In an Active contact, site personnel contact the participant’s parent(s) / LAR(s). 
Active contacts will be scripted. 
− 
In regions where RSV transmission is seasonal, contacts should occur every 
week during the RSV season and every month outside the RSV season. 
− 
In regions with year-round RSV transmission, contacts will occur every 2 
weeks. 
− 
At least 3 attempts should be made within the week of a scheduled contact. If 
these attempts are unsuccessful, that active contact is considered a missed 
contact. The next active contact will be made according to schedule. 
Further details are provided in the SPM. 
Site staff will use information gathered during each active or passive surveillance contact 
to determine whether a visit to assess a potential LRTI (Section 8.4.4) should be 
scheduled. 
8.4.2.2.2. RTI Diary cards 
Infant RTI diary cards will be provided to the infant participant’s parent(s)/LAR(s) at 
Day 31 post-study intervention (Visit 2). Parents will use the diary card to document 
symptoms of the RTI. 
Parent(s)/LAR(s) will be asked to bring any completed or partly completed diary cards 
with them to the infant participant’s study visits (including any RTI assessment visits). 
At each study visit (including any assessment visits), RTI symptoms may have ended or 
may be ongoing. This will be evaluated in order to determine whether to retrieve the 
Diary Card and replenish the parent(s)/LAR(s)/designate(s) supply of blank cards as 


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needed or, instruct them to continue collecting information until the corresponding 
symptom(s) have ended. 
Completed RTI diary cards may be collected by site staff during a site visit, home visit, 
or via postal mail, whichever is most effective based on local practice. 
Refer to the SPM for additional details. 
8.4.2.3. 
Maternal and infant participants (Amended 15 March 2022) 
If the maternal participant* visited / the infant participant was taken to a healthcare 
provider not affiliated with the study, site personnel should (if permitted by local 
regulation) contact that healthcare provider to obtain the medical record(s) for the visit. 
* Due to the change in the study requirement, RTI surveillance of the maternal 
participants will no longer be performed. 
8.4.3. 
When to conduct an assessment visit 
8.4.3.1. 
For a maternal MA-RTI (Amended 15 March 2022) 
Conduct an assessment visit (Section 8.4.4), ideally within 72 hours after a medically 
attended visit due to RTI symptoms* occurs during the surveillance period. However, a 
visit may be conducted even beyond the 72 hours window if symptoms are ongoing. 
If a maternal participant informs the site that she has RTI symptoms and (a) would seek / 
have sought medical advice for them and (b) is already scheduled for a study visit within 
the timeframes described above, then the site should perform the MA-RTI assessment 
visit procedures (including nasal swab) during the already scheduled study visit. 
A decision tree is provided in Figure 4. 
Refer to the SPM for additional details regarding maternal MA-RTI surveillance. 
* Due to the change in the study requirement, RTI surveillance of the maternal 
participants will no longer be performed. 


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Figure 4 
Decision Tree for site personnel – maternal surveillance and 
assessment 
 
 
RR: Respiratory rate: SpO2: Blood oxygen saturation by pulse oximetry. 
1Includes cases where symptoms would have resulted in a medically attended visit if participant were not already 
scheduled for a study visit 
2Details regarding the RTI assessment visit are provided in Section 8.4.4 and the SPM. 
Participant notifies site that
she has RTI symptoms
Yes
Perform assessment 2 visit within 3 
days:
•
Document signs and symptoms
•
Record RR and SpO2 
•
Record health care utilization
•
Nasal swab
And (as applicable)
•
Document details from medical
records
Participant plans to 
seek medical care 
for the RTI1
Remind to report any future 
medically attended RTIs by 
contacting site personnel
Symptoms have 
already resulted in 
a medically
attended visit
No
No
Yes


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8.4.3.2. 
For an infant RTI (Amended 15 March 2022) 
Conduct an assessment visit, as described in Section 8.4.4, as soon as possible after at 
least one of the following has been reported during the surveillance period: 
• 
Difficulty in breathing. 
• 
Wheezing. 
• 
The maternal participant/LAR intends to seek medical care because of concern about 
the infant’s RTI, or general health in the context of the infant’s RTI. 
The visit should take place as soon as possible; ideally within 72 hours. However, a visit 
may be conducted even beyond the specified ideal window if symptoms are ongoing. 
• 
After the first assessment visit, site personnel should use results of additional contacts 
to assess the development of new and worsening of previously reported symptoms. 
• 
Site personnel should conduct a follow-up assessment visit as soon as possible after 
learning: 
− 
that any symptom present at the first assessment visit has worsened, OR 
− 
that there are new symptoms of difficulty in breathing or wheezing, OR 
− 
that there is new or increased parental concern in the context of the RTI. 
The timing of the follow-up visit should be consistent with the guidance given above. 
A decision tree is provided in Figure 5. Refer to the SPM for additional details regarding 
infant RTI surveillance. 


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Figure 5 
Decision Tree for site personnel - infant surveillance and 
assessment (Amended 15 March 2022) 
 
RR: Respiratory rate: SpO2: Blood oxygen saturation by pulse oximetry. 
1Details regarding Surveillance are provided in Section 8.4.2.2 and the SPM. 
2Cough, runny nose, blocked nose, difficulty in breathing, wheezing are described in Section 8.4.1.2 
3Details regarding the RTI assessment visit are provided in Section 8.4.4 and the SPM. 
4 Post-visit follow-up is described in Sections 8.4.6 and in the SPM. 
5If a follow-up assessment visit is conducted, collection of additional nasal swabs is as described in Table 12. 
Active or Passive surveillance 
contact 1
Yes
Yes
No
Yes
No
No
Perform assessment visit 3, 4 ideally
within 3 days:
•
Document signs and symptoms
•
Record RR and SpO2 
•
Record health care utilization
•
Nasal swab 5
AND (as applicable)
•
Document details from medical records
Difficulty in breathing OR 
wheezing OR parental 
concern? 2
Any RTI symptom
(Cough OR runny nose
OR blocked nose OR 
difficulty in breathing OR 
wheezing)? 2
Remind to report any worsening 
of symptoms, any new 
symptoms, or parental concern
Remind to report any future 
symptoms
Worsening of 
symptoms, new 
symptoms, or parental 
concern? 4


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8.4.4. 
Assessment visit procedures (Amended 15 March 2022) 
The purpose of each assessment visit is to objectively document signs and symptoms of a 
RTI by an appropriately qualified person (i.e. medical or nursing), provide medical 
advice or referral as appropriate, and collect specimens for detection of RSV infection. 
An assessment visit may take place at the investigator’s clinical facility or another 
medical facility, or via a home visit by qualified site staff (or a designated third party), as 
appropriate per the judgment of the investigator (and as allowed by local law). 
Unless otherwise specified, assessment visit procedures will be the same for maternal 
participants with MA-RTIs* and for infant participants with RTIs. 
Note that if the reported symptoms are severe enough to warrant urgent care, the 
participant / parent(s)/LAR(s) should be advised to seek such care (e.g. Emergency 
Room). 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
8.4.4.1. 
Clinical evaluation (Amended 15 March 2022) 
At every assessment visit, the investigator/site staff/designated third party will evaluate 
the clinical signs and symptoms of the RTI. Data to be collected and recorded include 
(but are not limited to): 
For maternal participants*: 
• 
Temperature 
• 
Respiratory rate 
• 
Blood oxygen saturation measured by pulse oximetry (Section 8.2.1.4.1), in room 
air, if feasible 
• 
Results of chest auscultation 
• 
Signs of difficulty in breathing (wheezing and tachypnoea in maternal participants) 
* Due to the stop on RTI surveillance for maternal participants, these checks will no 
longer be performed. 
For infant participants: 
• 
Temperature 
• 
Respiratory rate 
• 
Blood oxygen saturation measured by pulse oximetry (Section 8.2.1.4.1), in room 
air, if feasible 
• 
Results of chest auscultation 
• 
Presence of cough, runny nose or blocked nose 


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• 
Signs of difficulty in breathing (wheezing, tachypnoea, nasal flaring, chest in-
drawing and apnea) 
• 
Irritability/agitation 
• 
Lethargy/excessive sleepiness 
• 
Cyanosis 
• 
Feeding poorly 
8.4.4.2. 
Nasal swab collection (Amended 15 March 2022) 
Refer to Table 10 (maternal participants)* and Table 12 (infant participants). Additional 
details are provided in the Central Laboratory Manual. 
* Due to the change in the study requirements, nasal swab samples of the maternal 
participants will no longer be collected for RTI assessment. 
8.4.4.3. 
Missed assessment visit (Amended 15 March 2022) 
If the criteria for an assessment visit have been met but the visit cannot take place while 
symptoms are ongoing, it is a missed assessment visit. 
If it is truly not possible to perform an assessment visit (for example, if the participant 
develops a MA-RTI* or potential RTI/LRTI while the family is traveling, and all 
symptoms have resolved by the time the family returns), then the corresponding 
assessment visit page of the eCRF should be filled in as completely as possible using 
available medical history and medical records. 
Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
8.4.5. 
RTI hospitalization during the surveillance interval (Amended 15 
March 2022) 
Whenever a participant is admitted to hospital for observation or treatment of an acute 
respiratory illness during the surveillance interval for that participant, a nasal swab 
should be collected using GSK-provided supplies and sent to GSK for analysis. as 
described in Table 10* and Table 12. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed.  
8.4.6. 
Follow-up of infant respiratory tract illnesses (RTIs) 
Any infant RTI documented as ongoing at a previous visit/contact will be reviewed at 
subsequent visits/contacts during the surveillance interval until (a) all symptoms have 
resolved (except runny nose, often chronic in infants), or (b) the participant completes 
Contact 2-NB or (c) the participant is lost to follow-up. 


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8.4.7. 
Covid-19 Infection 
Maternal and infant COVID-19 cases identified during the study (as per standard of care) 
will be captured and reported using standard AE, MAE or SAE criteria, as outlined in 
Section 10.3. 
COVID-19 cases should be reported in the eCRF according to the WHO Case Definition 
using one of the following terms: 
• 
Suspected COVID-19 infection 
• 
Probable COVID-19 infection 
• 
Confirmed COVID-19 infection 
8.5. 
Pharmacokinetics 
Section is not applicable. 
8.6. 
Genetics and/or Pharmacogenomics 
Section is not applicable. 
8.7. 
Biomarkers 
Section is not applicable. 
8.8. 
Immunogenicity 
Refer to Section 8.1. 
8.9. 
Health outcomes 
Section is not applicable. 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical hypotheses 
No hypothesis driven sample size calculation was conducted since the evaluation of the 
study objectives are descriptive. 
9.2. 
Sample size determination (Amended 15 March 2022) 
Approximately 378 maternal participants* will be randomized in a 2:1 ratio to achieve at 
least 340 evaluable maternal participants (including at least 16 evaluable adolescents 
from 15 to less than 18 YOA). 


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Participants who withdraw from the study will not be replaced. 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
9.2.1. 
Safety 
A sample size of 252 participants in RSV-MAT vaccine group will provide a probability 
of 72%, 92% or 98% to observe at least one participant with AE, if the true AE rate is 
0.5%, 1% or 1.5%, respectively. 
Table 20 presents the precision one can get on the percentage of participants with AEs 
following dosing in study vaccine group. 
If no AE was observed in RSV-MAT vaccine group, the exact, two-sided 95% 
confidence interval (CI) would rule out an AE rate of 1.5% or more. The current sample 
size also provides the precision on estimating the probability of observing AEs following 
dosing in RSV-MAT vaccine group. If 5% of the participants experienced an AE among 
252 participants following vaccination with the RSV-MAT vaccine, an exact 95% CI 
would be (2.7%, 8.5%). 
Table 20 
Exact 95% confidence interval (CI) on the percentage of participants 
with adverse events (AEs) following dosing in RSV-MAT vaccine 
group 
252 participants in RSV-MAT vaccine group 
Number (%) of 
participants 
with an AE 
Exact 95% CI 
Lower Limit 
Upper Limit 
0 (0) 
0.0 
1.5 
3 (1) 
0.2 
3.2 
5 (2) 
0.7 
4.6 
8 (3) 
1.3 
5.9 
10 (4) 
1.9 
7.2 
13 (5) 
2.7 
8.5 
15 (6) 
3.4 
9.7 
18 (7) 
4.2 
10.9 
20 (8) 
5 
12.1 
23 (9) 
5.8 
13.2 
25 (10) 
6.6 
14.4 
38 (15) 
10.8 
20.0 
50 (20) 
15.2 
25.5 
63 (25) 
19.8 
30.8 
75 (30) 
24.4 
36.1 
Note: Precision estimation using PASS2019 19.0.1 (Confidence Interval [CI] for one proportion) [Hahn, 1991] 
Exact 95% CI computed based on Clopper/ Pearson formula [Newcombe, 1998] 


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9.2.2. 
Immunogenicity 
With at least 226 evaluable maternal participants for immunogenicity in the RSV-MAT 
vaccine group (assuming a 10% non-evaluable rate), the current sample size can provide 
an adequate precision for estimating the fold increase. 
Table 21 presents the precision estimation of the fold increase from Day 1 to delivery 
based on standard deviation (SD) of log10 transformed titer for neutralizing antibody 
RSV-A and half width of the fold increase. 
If at least a 9-12 fold increase from Day 1 to delivery in terms of RSV-A neutralizing 
antibody is anticipated, then assuming a log 10 SD of 0.4, a 95% CI for a 9-fold increase 
would be (7.6, 10.7), and a 95% CI for a 12-fold increase would be (10.1, 14.2). 
Table 21 
Precision estimation on fold increase and its 95% CI with 226 
participants in RSV-MAT vaccine group 
Standard 
Deviation1 
Fold Increase 
from Day 1 to 
delivery 
No. of participants 
in RSV-MAT vaccine 
group 
Half 
Width2 
95% LL 
95% UL 
Log10 Fold 
0.3 
5 
226 
0.056 
4.4 
5.7 
0.699 
0.3 
6 
226 
0.056 
5.3 
6.8 
0.778 
0.3 
7 
226 
0.056 
6.2 
8.0 
0.845 
0.3 
8 
226 
0.056 
7.0 
9.1 
0.903 
0.3 
9 
226 
0.056 
7.9 
10.2 
0.954 
0.3 
10 
226 
0.056 
8.8 
11.4 
1 
0.3 
11 
226 
0.056 
9.7 
12.5 
1.041 
0.3 
12 
226 
0.056 
10.5 
13.7 
1.079 
0.4 
5 
226 
0.074 
4.2 
5.9 
0.699 
0.4 
6 
226 
0.074 
5.1 
7.1 
0.778 
0.4 
7 
226 
0.074 
5.9 
8.3 
0.845 
0.4 
8 
226 
0.074 
6.7 
9.5 
0.903 
0.4 
9 
226 
0.074 
7.6 
10.7 
0.954 
0.4 
10 
226 
0.074 
8.4 
11.9 
1 
0.4 
11 
226 
0.074 
9.3 
13.0 
1.041 
0.4 
12 
226 
0.074 
10.1 
14.2 
1.079 
1 Standard deviation on log10 transformed RSV-A neutralizing antibody titer based on previous studies on PreF2 
vaccine. 
2 Precision estimation using PASS2019 19.0.1 (Confidence Interval [CI] for one mean) [Hahn, 1991] 
LL=10^(log10(fold increase)-half width); UL=10^(log10(fold increase)+half width) 


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9.3. 
Analysis sets (Amended 15 March 2022) 
Table 22 
Maternal Participants (Amended 15 March 2022) 
Analysis set 
Description 
Enrolled  
All maternal participants who completed the informed consent process and signed the 
informed consent form and was determined as eligible for study participation. 
Exposed  
All maternal participants who received 1 dose of a study intervention. The allocation in a 
group is done in function of the administered intervention. 
Full Analysis - 
Immunogenicity 
All maternal participants in the Exposed set who have at least one post-dosing 
immunogenicity data. The allocation in a group is done in function of the randomized 
intervention.  
Per Protocol - 
Immunogenicity 
All maternal participants in the Full Analysis (Immunogenicity) minus participants with 
protocol deviations that lead to exclusion. The analysis will be done according to the study 
interventions that participants received at Dose 1. 
Solicited Safety  
All maternal participants in the Exposed set who have solicited safety data. 
Table 23 
Infant participants 
Analysis Set 
Description 
Exposed 
Infants live-born to exposed maternal participants, whose parents/LARs completed the 
informed consent process and signed the informed consent form. 
Full Analysis - 
Immunogenicity 
All infant participants in the Exposed set who have at least one post-delivery/birth 
immunogenicity data. The analysis will be done according to the study intervention that 
maternal participants received at Dose 1. 
Per Protocol - 
Immunogenicity 
All infant participants in the Full Analysis (Immunogenicity) set minus those who (a) were 
born less than 4 weeks post-maternal participant dosing and/ or (b) have protocol 
deviations that lead to exclusion. 
9.3.1. 
Criteria for elimination from analysis 
The Statistical Analysis Plan (SAP) will provide a complete list of criteria for elimination 
from the analysis sets. Criteria may include, but are not limited to, those in Sections 
9.3.1.1 and 9.3.1.2. 
9.3.1.1. 
Intercurrent medical conditions and concomitant medications / 
products / vaccines that may lead to elimination of a participant 
(maternal/infant) from per protocol analyses (immunogenicity) 
9.3.1.1.1. Maternal participants 
• 
Any of the medications listed in Section 5.2.1.2 if administered up to delivery (Visit 
3). 
9.3.1.1.2. Infant participants 
• 
Systemic immunosuppressants or other immune-modifying drugs administered 
chronically (i.e. for more than 14 consecutive days), except if it is part of 
management of HIV infection. 
− 
For corticosteroids, this will mean prednisone or equivalent, ≥ 0.5 mg/kg/day. 


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− 
Topical steroids are allowed. 
− 
Inhaled steroids are allowed if used in accordance with local labeling 
information (e.g. for budesonide). 
• 
RSV-specific immunoglobulins at any time during the study. 
• 
Immunoglobulins and/or any blood or plasma derivatives administered up to Day 43 
post-birth (Visit 2-NB), or Day 121 post-birth (Visit 3-NB), or Day 181 post-birth 
(Visit 4-NB), depending on the infant’s assigned sub-cohort for blood sampling. 
9.3.1.1.3. Maternal and Infant participants 
• 
Diagnosis during the study with an immunological disorder or occurrence during the 
study of a condition (other than the study pregnancy) capable of altering immune 
response. For evaluation of immunogenicity endpoints in maternal and infant 
participants, this includes RSV infection confirmed either locally or by GSK during 
the specified analysis interval. 
• 
Any investigational or non-registered product (drug or vaccine) other than the study 
vaccine/product administered during the specified analysis interval. 
9.3.1.2. 
Other situations that may lead to elimination of a participant (maternal / 
infant) from per protocol analyses (immunogenicity) 
• 
Protocol violation(s) linked to the inclusion/ exclusion criteria, including maternal 
age at Visit 1 (study intervention). 
• 
Study intervention not administered as specified by the protocol. 
• 
Failure to comply with the post-dose immunogenicity blood sampling schedule at a 
given time point (Table 3). 
9.4. 
Statistical analyses 
9.4.1. 
General considerations 
The SAP will be finalized before database lock and will include a more technical and 
detailed description of the statistical analyses to be performed. This section summarizes 
planned statistical analyses of primary and secondary endpoints. 
All statistical analyses are descriptive. Besides the primary analyses, sub-group analyses 
may be conducted based on age group, gestational age at birth (as assessed by the GAIA 
gestational age definition)*, pre-existing HIV infection, pre-existing obstetric 
complications and/or breastfeading status. 
* Additional statistical analyses may also be perfomed by using the Intergrowth-21st (IG-
21) standard definition [Villar, 2014]. 
The SAP will describe how missing data will be handled during analyses. 


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9.4.1.1. 
Safety 
Safety analyses in maternal participants will include summaries by study group and age 
category (<18 years; ≥ 18 years; overall) of solicited administration site and systemic 
events, unsolicited AEs, MAEs, SAEs, MA-RTIs, RSV-associated MA-RTIs, (S)AEs 
leading to study withdrawal, worsening of pre-existing medical conditions and/or 
obstetric complications, pregnancy outcomes and pregnancy-related AESIs. 
Safety analyses in infant participants will include summaries by study group and 
mother’s age category (<18 years; ≥ 18 years; overall) of neonatal AESIs, MAEs, SAEs, 
(S)AEs leading to study withdrawal, and occurrence of RSV- associated LRTIs, severe 
LRTIs, RSV-associated hospitalization. 
Case definition for MA-RTIs in maternal participants, RTIs and LRTIs in infant 
participants are described in Section 4.2.5. 
All safety analyses will be performed on the Solicited Safety and Exposed sets. 
9.4.1.2. 
Immunogenicity 
The primary analysis will be based on the PPS for analysis of immunogenicity. If, in any 
study group and at any timepoint, the percentage of exposed participants with serological 
results excluded from the PPS for analysis of immunogenicity is 5% or more, a second 
analysis based on the FAS will be performed to complement the per protocol analysis. 
9.4.2. 
Participant disposition 
Number of screened, randomized, exposed and withdrawn maternal participants in each 
group and overall will be described. 
Number of infant participants enrolled and withdrawn (by group and sub-cohort, and 
overall) will be described. Additional analyses by country and/or by site may be 
performed 


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9.4.3. 
Primary endpoints 
9.4.3.1. 
Safety (Amended 15 March 2022) 
 
Primary Safety Endpoints  
Statistical Analysis Methods 
Maternal 
participants 
Number and percentage of 
maternal participants reporting 
solicited administration site and 
systemic events during a 7-day 
(i.e. Day 1 to Day 7 included) 
follow-up period after dosing. 
The number and percentage with exact 95% CI of maternal 
participants reporting each solicited administration site event 
(any grade, each grade,) and solicited systemic event (any, 
each grade) during the 7-day (Day 1 to 7 days post-study 
intervention) follow-up period after dosing will be tabulated by 
maximum intensity per participant for each study group.  
The number and percentage of maternal participants reporting: 
• 
at least one administration site AE (solicited and 
unsolicited) 
• 
at least one systemic AE (solicited and unsolicited) 
• 
any AE 
during the 7-day (Day 1 to 7 days post-study intervention) 
follow-up period after dosing will be tabulated with exact 95% 
CI by group. 
The same computations will be done for Grade 3 solicited and 
unsolicited AEs, for any unsolicited AEs considered related to 
study intervention, for any Grade 3 unsolicited AEs considered 
related to study intervention and for any solicited and 
unsolicited AEs resulting in a medically attended visit (i.e., 
MAEs). 
Number and percentage of 
maternal participants reporting 
unsolicited AEs that occur during 
a 30-day (i.e. Day 1 to Day 30 
included) follow-up period after 
dosing. 
The number and percentage of maternal participants reporting 
unsolicited AEs within 30 days (Day 1 to 30 days post-study 
intervention) after dosing with exact 95% CIs will be tabulated 
by group and by MedDRA preferred term. 
Similar tabulations will be done for Grade 3 unsolicited AEs, for 
any causally related unsolicited AEs, for Grade 3 related 
unsolicited AEs and for MAEs. 
Number and percentage of 
maternal participants reporting 
SAEs, (S)AEs leading to study 
withdrawal, and MAEs from Day 
1 up to 42 days post-delivery. 
The number and percentage of maternal participants reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 42 days post-delivery with exact 95% CIs will 
be tabulated by group and by Medical MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal, and MAEs will be prepared. 
Number and percentage of 
maternal participants reporting 
pregnancy outcomes * from Day 
1 up to 42 days post-delivery. 
*These include live birth with no 
congenital anomalies, live birth 
with minor congenital anomalies 
only; live birth with at least one 
major congenital anomaly, fetal 
death/still birth (antepartum or 
intrapartum) with no congenital 
anomalies, fetal death/still birth 
The number and percentage of maternal participants reporting 
each pregnancy outcome from Day 1 up to 42 days post-
delivery will be tabulated with its exact 95% CI by group. 
By participant listings of adverse pregnancy outcomes will be 
prepared . 


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Primary Safety Endpoints  
Statistical Analysis Methods 
(antepartum or intrapartum) with 
only minor congenital anomalies, 
fetal death/still birth (antepartum 
or intrapartum) with at least 1 
major congenital anomaly; 
elective/therapeutic termination 
with no congenital anomalies; 
elective/therapeutic termination 
with only minor congenital 
anomalies, and 
elective/therapeutic termination 
with at least 1 major congenital 
anomaly. 
Number and percentage of 
maternal participants reporting 
pregnancy-related AESIs * and 
worsening of pre-existing medical 
conditions and/or obstetric 
complications from Day 1 up to 
42 days post-delivery. 
* These include maternal death, 
hypertensive disorders of 
pregnancy (gestational 
hypertension, pre-eclampsia, pre-
eclampsia with severe features 
including eclampsia), fetal growth 
restriction, gestational diabetes 
mellitus, pathways to preterm 
birth (premature preterm rupture 
of membranes, preterm labor, 
provider-initiated preterm birth) 
and chorioamnionitis. 
The number and percentage of maternal participants reporting 
each pregnancy-related AESI and worsening of pre-existing 
medical conditions and/or obstetric complications from Day 1 
up to 42 days post-delivery will be tabulated with its exact 95% 
CI by group. 
By participant listings of pregnancy-related AESIs and 
worsening of pre-existing medical conditions and/or obstetric 
complications will be prepared.  
Infant 
participants 
Number and percentage of infant 
participants reporting neonatal / 
infant AESIs * from birth up to 42 
days post-birth. 
* These include small for 
gestational age, low birth weight 
including very low and extremely 
low birth weight (<2500 g, 
<1500g, <1000g), congenital 
anomalies (major external 
structural defects, internal 
structural defects, functional 
defects), neonatal death (in an 
extremely preterm birth 
[22<GA<28 weeks], in a preterm 
live birth [28<GA<37 weeks], or 
in a term live birth) and preterm 
birth. 
The number and percentage of infant participants reporting 
each neonatal / infant AESI from birth up to 42 days post-birth 
will be tabulated with its exact 95% CI by group. 
By participant listings of neonatal / infant AESIs will be 
prepared. 


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Primary Safety Endpoints  
Statistical Analysis Methods 
 
Number and percentage of infant 
participants reporting SAE, 
(S)AEs leading to study 
withdrawal, and MAEs from birth 
up to 42 days post-birth. 
The number and percentage of infant participants reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 42 days post-birth with exact 95% CIs will be 
tabulated by group and by MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
 
Number and percentage of 
infant participants reporting 
SAEs, (S)AEs leading to study 
withdrawal, and MAEs from 
birth up to 180 days post-birth. 
The number and percentage of infant participants 
reporting at least one SAE, (S)AE leading to study 
withdrawal, and MAE from birth up to 180 days post-birth 
will be tabulated with 95% CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared.  
 
Number and percentage of 
infant participants reporting 
SAEs, (S)AEs leading to study 
withdrawal, and MAEs from 
birth up to 365 days post-birth. 
The number and percentage of infant participants 
reporting at least one SAE, (S)AE leading to study 
withdrawal, and MAE from birth up to 365 days post-birth 
will be tabulated with 95% CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
AE= Adverse event; CI= Confidence interval; MAE = medically attended adverse event; MedRA = Medical dictionary 
for regulatory activities; SPM = study procedure manual 
9.4.3.2. 
Immunogenicity 
 
Primary Immunogenicity 
Endpoints 
Statistical Analysis Methods 
Maternal 
participants 
• 
Humoral immune 
responses at pre-dosing 
(Day 1) and at delivery: 
− 
RSVPreF3 IgG-
specific antibody 
concentrations 
− 
Neutralizing antibody 
titers against RSV-A 
For each assay, at each timepoint and by study group and age 
category (<18 years; ≥ 18 years; overall): 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
• 
Individual post-dosing versus pre-dosing results will be 
plotted using scatter plots. Results of the control group 
will be used as a reference. 
• 
GMR of antibody titers/concentrations at delivery over 
pre-dosing will be tabulated with 95% CI. 
• 
Distribution of antibody titers/concentration will be 
tabulated by pre-specified pre-dosing titer category. 
• 
Distribution of the fold increase of the antibody 
titers/concentrations (post- versus pre-dosing) will be 
tabulated by pre-specified pre-dosing titer category. 
Relationship between maternal RSVPreF3 IgG-specific 
antibody concentration and RSV-A neutralizing antibody at 
baseline and at delivery will be explored using scatter plots of 
individual values. 
Between group evaluation in terms of RSVPreF3 IgG-specific 
antibody concentrations and neutralizing antibody titers against 
RSV-A will be performed at delivery using an ANCOVA model 


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Endpoints 
Statistical Analysis Methods 
on the logarithm10 transformation of the concentrations/titers, 
and including the pre-dosing logarithm10 transformation of the 
concentrations/titers, the study intervention, gestational age at 
the time of study intervention administration (<28 0/7; ≥ 28 0/7 
weeks), and the interval between dosing and delivery as 
covariates if needed. 
Cord blood/ 
placental 
transfer 
Ratio between cord blood* and 
maternal RSVPreF3 IgG-specific 
antibody concentrations at 
delivery. 
*or infant blood sample collected 
within 72 hours after birth (if no 
cord blood sample can be 
obtained). 
• 
Geometric mean of placental transfer ratio will be 
tabulated with 95% CI by study group. 
• 
Percentage of infants with placental transfer ratio ≥ 1 will 
be tabulated with exact 95 % CI by study group. 
Infant 
participants 
• 
Humoral immune 
responses at delivery*: 
− 
RSVPreF3 IgG-
specific antibody 
concentrations 
− 
Neutralizing antibody 
titers against RSV-A 
*Measured in cord blood sample 
collected at delivery or infant 
blood sample collected within 72 
hours after birth (if no cord blood 
sample can be obtained). 
For each assay, the following analysis will be performed by 
study group 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
• 
Distribution of RSV-A and RSVPreF3 IgG-specific 
antibody titers/concentration from cord blood will be 
tabulated. 
For each assay, relationship between maternal antibody titers 
and infant antibody titers at delivery will be evaluated 
graphically using scatter plots of individual results. 
Between group evaluation in terms of RSVPreF3 IgG-specific 
antibody concentrations and neutralizing antibody titers against 
RSV-A will be performed at delivery using an ANCOVA model 
on the logarithm10 transformation of the concentrations/titers, 
and including the pre-dosing logarithm10 transformation of the 
concentrations/titers, the study intervention, gestational age at 
the time of study intervention administration (<28 0/7; ≥ 28 0/7 
weeks), and the interval between dosing and delivery as 
covariates if needed. 
In addition, if cord blood samples are missing in 20% or more 
of infants in a single study group, and if the data permit: RSV 
antibody concentrations/titers in infants through time will be 
evaluated separately in infants with cord blood samples and in 
infants from whom, instead, a blood sample was obtained 
within 72 hours after birth.  
ANCOVA = Analysis of covariance; CI = Confidence interval; GMR = Geometric mean of ratio; GMT/ C = Geometric 
mean titer/ concentration; RSV-A = Respiratory syncytial virus subtype A; RSVPreF3 IgG = Respiratory syncytial 
virus PreF3 immunoglobulin G 


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9.4.4. 
Secondary endpoints 
9.4.4.1. 
Safety (Amended 15 March 2022) 
 
Secondary Safety Endpoints 
Statistical Analysis Methods 
Maternal 
participants 
Number and percentage of 
maternal participants reporting 
SAEs, (S)AEs leading to study 
withdrawal and MAEs from Day 1 
up to 180 days post-delivery. 
The number and percentage of maternal participants 
reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 180 days post-delivery with exact 95% CIs 
will be tabulated by group and by MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
 
Number and percentage of 
maternal participants reporting 
worsening of pre-existing medical 
conditions and/or obstetric 
complications from Day 1 up to 180 
days post-delivery. 
The number and percentage of maternal participants 
reporting each worsening of pre-existing medical conditions 
and/or obstetric complications from Day 1 up to 180 days 
post-delivery will be tabulated with its exact 95% CI by 
group. 
By participant listings of worsening of pre-existing medical 
conditions and/or obstetric complications will be prepared. 
 
Number and percentage of 
maternal participants reporting 
RSV-associated MA-RTIs from 
Day 1 up to 180 days post-
delivery. 
The number and proportion of participants reporting at least 
one RSV-associated MA-RTI from Day 1 up to 180 days 
post-delivery with exact 95% CIs will be calculated and 
tabulated. 
Infant 
participants 
From birth up to 365 days post-
birth (12 months of age), number 
and percentage of infant 
participants reporting medically 
assessed, RSV-associated LRTIs 
of any severity and severe RSV-
associated LRTIs (according to the 
case definitions). 
The number and percentage of infant participants reporting: 
• 
at least one medically assessed, RSV-associated 
LRTI of any severity 
• 
at least one medically assessed, severe RSV-
associated LRTI 
from birth up to 365 days post-birth (12 months of age) will 
be calculated and tabulated by group.  
 
From birth up to 365 days post-
birth (12 months of age), number 
and percentage of infant 
participants reporting medically 
assessed, RSV-associated 
hospitalizations (according to the 
cases definitions). 
The number and percentage of infant participants reporting 
at least one medically assessed, RSV-associated 
hospitalization from birth up to 365 days post-birth (12 
months of age) will be calculated and tabulated by group. 
AE = Adverse event; LRTI = Lower respiratory tract illness; MAE = medically attended adverse event; NB = Newborn; 
RSV-MA-RTI = respiratory syncytial virus associated medically attended respiratory tract illness; SAE = serious 
adverse event 


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9.4.4.2. 
Immunogenicity 
 
Secondary Immunogenicity 
Endpoints 
Statistical Analysis Methods 
Maternal 
participants 
• 
Humoral immune responses at 
Day 31 post-dosing: 
− 
RSVPreF3 IgG-specific 
antibody concentrations 
− 
Neutralizing antibody 
titers against RSV-A 
• 
Humoral immune responses at 
pre-dosing (Day 1), at Day 31 
post-dosing and at delivery: 
− 
Neutralizing antibody 
titers against RSV-B. 
For each assay, at each timepoint and by study group and 
age category (<18 years; ≥ 18 years; overall): 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
• 
Individual post-dosing versus pre-dosing results will 
be plotted using scatter plots. Results of the control 
group will be used as a reference. 
• 
GMR of antibody titers/concentrations at each post-
dosing timepoint over pre-dosing will be tabulated with 
95% CI. 
• 
Distribution of antibody titers/concentration will be 
tabulated by pre-specified pre-dosing titer category. 
• 
Distribution of the fold increase of the antibody 
titers/concentrations (post- versus pre-dosing) will be 
tabulated by pre-specified pre-dosing titer category. 
Relationship between maternal RSVPreF3 IgG-specific 
antibody concentration and RSV-A neutralizing antibody at 
Day 31 post-dosing, between RSV-A neutralizing antibody 
and RSV-B neutralizing antibody, and between RSVPreF3 
IgG-specific antibody concentration and RSV-B neutralizing 
antibody at baseline, at Day 31 post-dosing and at delivery 
will be explored using scatter plots of individual values. 
Between group evaluation in terms of RSVPreF3 IgG-
specific antibody concentrations and neutralizing antibody 
titers against RSV-A will be performed at Day 31 post-
dosing, and against RSV-B at Day 31 post-dosing and at 
delivery using an ANCOVA model on the logarithm10 
transformation of the concentrations/titers, and including the 
pre-dosing logarithm10 transformation of the 
concentrations/titers, the study intervention, gestational age 
at the time of study intervention administration (<28 0/7; ≥ 28 
0/7 weeks), and the interval between dosing and delivery as 
covariates if needed. 
Infant 
participants 
• 
Humoral immune responses at 
delivery*: 
− 
Neutralizing antibody 
titers against RSV-B 
* Measured in cord blood sample 
collected at delivery or infant blood 
sample collected within 72 hours 
after birth (if no cord blood sample 
can be obtained). 
For each assay, the following analysis will be performed by 
study group: 
• 
Antibody titers will be displayed using reverse 
cumulative curves. 
• 
GMTs will be tabulated with 95% CI and represented 
graphically. 
• 
Distribution of RSV-B antibody titers from cord blood 
will be tabulated. 
For each assay, relationship between maternal antibody 
titers and infant antibody titers at delivery will be evaluated 
graphically using scatter plots of individual results. 
Between group evaluation in terms of neutralizing antibody 
titers against RSV-B will be performed at delivery using an 


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Secondary Immunogenicity 
Endpoints 
Statistical Analysis Methods 
ANCOVA model on the logarithm10 transformation of the 
concentrations/titers, and including the pre-dosing 
logarithm10 transformation of the concentrations/titers, the 
study intervention, gestational age at the time of study 
intervention administration (<28 0/7; ≥ 28 0/7 weeks), and the 
interval between dosing and delivery as covariates if 
needed. 
In addition, if cord blood samples are missing in 20% or 
more of infants in a single study group, and if the data 
permit: RSV antibody concentrations/titers in infants through 
time will be evaluated separately in infants with cord blood 
samples and in infants from whom, instead, a blood sample 
was obtained within 72 hours after birth.  
• 
Humoral immune responses at 
Day 43*, at Day 121* and at 
Day 181* after birth: 
− 
RSVPreF3 IgG-specific 
antibody concentrations 
− 
Neutralizing antibody 
titers against RSV-A and 
RSV-B 
* Measured in infant blood samples 
collected at Day 43 (sub-cohort 1, 
V2-NB), at Day 121 (sub-cohort 2, 
V3-NB) and at Day 181 (sub-cohort 
3, V4-NB) after birth. Each infant will 
be randomly assigned (1:1:1) to one 
of 3 sub-cohorts. 
For each assay, at each timepoint and by study group: 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
• 
Distribution of RSV-A, RSV-B and RSVPreF3 IgG-
specific antibody titers/concentration from cord blood 
will be tabulated. 
Between group evaluation in terms of RSVPreF3 IgG-
specific antibody concentrations and neutralizing antibody 
titers against RSV-A and RSV-B at Day 43 (sub-cohort 1, 
V2-NB), at Day 121 (sub-cohort 2, V3-NB) and at Day 181 
(sub-cohort 3, V4-NB) after birth using an ANCOVA model 
on the logarithm10 transformation of the 
concentrations/titers, and including the pre-dosing 
logarithm10 transformation of the concentrations/titers, the 
study intervention, gestational age at the time of study 
intervention administration (<28 0/7; ≥ 28 0/7 weeks), and the 
interval between dosing and delivery as covariates if 
needed. 
ANCOVA = Analysis of covariance; CI = Confidence interval; GMR = Geometric mean of ratio; GMT/ C = Geometric 
mean titer/ concentration; NB = Newborn; RSV-A / B = Respiratory syncytial virus subtype A / B; RSVPreF3 IgG 
= Respiratory syncytial virus PreF3 immunoglobulin G 
9.4.5. 
Tertiary endpoints 
 
 
 
CCI


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9.4.6. 
Other analyses 
9.4.6.1. 
Demography and baseline characteristics analyses 
These analyses will be performed on the ES and on the FAS for immunogenicity. 
For all maternal participants, demographic characteristics (e.g., age at study intervention 
administration (<18 years; ≥ 18 years; overall), gestational age at study intervention 
administration (<28 0/7; ≥ 28 0/7 weeks), geographic ancestry) will be summarized by 
group using descriptive statistics. The interval in days between maternal study 
intervention and delivery will be calculated and summarized by group using descriptive 
statistics. 
For their infants, demographic characteristics (e.g., gestational age at time of delivery (> 
37 weeks; ≤ 37 weeks), sex, weight, length, head circumference, geographic ancestry, 
APGAR score), and lifestyle characteristics (e.g., living environment, household 
composition, breastfeeding, passive smoking and extent of contact with children less than 
6 YOA) will be summarized by group, and for each immunogenicity sub-cohort within 
each group, using descriptive statistics. 
• 
Frequency tables will be generated for categorical variable such as geographic 
ancestry. 
• 
Mean, median, SD and range will be provided for continuous data such as age. 
9.4.6.2. 
Other analyses for adolescent maternal participants 
Sub-analyses to evaluate objectives and endpoints will be performed on the 15-17 YOA 
sub-group. 
9.4.6.2.1. Safety 
Due to small number of adolescent maternal participants in this trial, a Bayesian approach 
will be applied to predict the probability of AEs in this population. It is assumed a 
specific AE in an adolescent maternal participant receiving the RSV-MAT vaccine is a 
binary outcome (yes/no) with p as a probability that the outcome is “yes”; it is further 
assumed that p is a random variable having beta distribution as a prior, which will be 
estimated from other data sources. The prior beta distribution will be developed based on 
data collected in RSV-MAT vaccine recipients above 17 YOA in this trial. With the data 
observed in RSV-MAT vaccine recipients 15-17 YOA, a Bayesian approach will be 
applied to estimate the posterior distribution of p. Similar procedures will be used for 
estimating the posterior distribution of p0 (the probability of having this AE for an 
adolescent maternal participant in placebo group). However, the prior distribution for p0 
will be assumed as a mixture of beta distributions based on both the data collected in 
participants above 17 YOA in the placebo group in this trial and the adolescents younger 
than 17 YOA in EPI-RSV-015 study [EPI-RSV-015, 2020]. Lastly, the predictive 
probability of the occurrence of this AE in an adolescent maternal participant 15-17 YOA 
will be calculated separately in the RSV-MAT vaccine group and the placebo group. A 
predictive probability in an adolescent maternal participant in RSV-MAT vaccine group 


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no worse than that in placebo group will provide reassurance that vaccination does not 
result in higher risk of AE. The detailed analysis plan will be described in the protocol 
and SAP. 
9.4.6.2.2. Immunogenicity 
The immunogenicity data collected in adolescent maternal participants 15 to 17 YOA in 
this trial will be descriptively summarized by treatment group. In addition, a Bayesian 
approach will be used for further extrapolation of the immune response. It is assumed that 
the log transformed immune response (for example neutralizing antibody titers) in 
adolescent maternal participants follows a normal distribution with the mean µ and SD of 
σ; it is further assumed that the mean µ is a random variable and has a normal distribution 
as a prior. The prior normal distribution for the mean µ will be developed based on data 
collected in maternal participants above 17 YOA in this trial. With the data observed in 
adolescent maternal participants 15-17 YOA in this trial, a Bayesian approach will be 
applied to estimate the posterior distribution of the mean µ and the predictive probability 
of observing a high immune response (for instance, 6 fold increase) for an adolescent 
maternal participant 15-17 YOA in the RSV-MAT vaccine group. A high predictive 
probability of having at least 6-fold increase 1 month post-study intervention from 
baseline in a pregnant adolescent RSV-MAT vaccine recipient will provide reassurance 
of immune response for an adolescent maternal participant 15-17 YOA receiving the 
RSV-MAT vaccine. The detailed analysis plan will be described in the protocol and SAP. 
9.5. 
Conduct of analyses (Amended 15 March 2022) 
No analysis requiring statistical adjustment will be performed. 
9.5.1. 
Sequence of analyses (Amended 15 March 2022) 
The final analysis will be performed when all data up to study end are available. A CSR 
including all available data will be written and made available to the investigators at that 
time. 
If the data for tertiary endpoints become available at a later stage, (an) additional 
analysis/ analyses may be performed. These data will be documented in annex(es) to the 
study report and will be made available to the investigators at that time. 
9.5.2. 
Statistical consideration for interim analysis 
Not applicable. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1. 
Regulatory and ethical considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
− 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF 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 substantial protocol amendments will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• 
GSK will provide full details of the above procedures to the investigator, either 
verbally, in writing, or both. 
• 
The investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC. 
− 
Notifying the IRB/IEC of SAE(s) or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
Financial disclosure 
Investigators and sub-investigators must provide the sponsor with full and accurate 
financial disclosure, as requested, to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators must provide their financial interest information before initiation of the 
study center and again at the end of the study. Investigators are responsible for providing 


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a financial disclosure update if their financial interests change at any point during study 
participation and for 1 year after completion of the study. 
10.1.3. 
Informed consent process 
The investigator or his/her representative must fully explain the nature of the study to the 
participant/participant’s parent(s) or his/her LAR(s) and answer all questions regarding 
the study. 
Participants/participants’ parent(s)/LAR(s) must be informed that their participation is 
voluntary. 
Freely given and written/witnessed/thumb printed informed consent must be obtained 
from each participant and/or each participant’s parent(s)/LAR(s)/witness and participant 
informed assent, as appropriate, prior to participation in the study. 
SAEs and/or AESIs experienced by an infant born to the exposed mothers will be 
reported (if become known to the site staff), even if the re-consent for infant participants 
is not provided. 
The content of the ICF must meet the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written or witnessed/thumb printed 
informed consent was obtained before the participant was enrolled in the study and the 
date the consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
Participants must be re-consented to the most current version of the ICF(s) or an ICF 
addendum during their participation in the study. 
A copy of the ICF(s) must be provided to the participants/participants’ parent(s)/LAR(s). 
Participants who are rescreened are required to sign a new ICF. 
The study investigator is encouraged to obtain assent from the minor in addition to the 
consent provided by the LAR(s) when a minor can assent to decisions about his/her 
participation in a study. The investigator is also accountable for determining a minor's 
capacity to assent to participation in a research study according to the local laws and 
regulations. 
10.1.4. 
Data protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets transferred to the sponsor will contain only the identifier. Name and any other 
information which would identify the participant will not be transferred. 


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The participants/participants’ parent(s)/LAR(s) must be informed that: 
• 
Her personal/their child’s study-related data will be used by the sponsor in 
accordance with local data protection law. 
• 
Her medical records/their child’s may be examined by Clinical Quality Assurance 
auditors or other authorized personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
• 
GSK will ensure protection of the personal data of the investigator and site staff 
which is collected within the framework of and for the purpose of the study, in 
accordance with the Data Privacy Notice that will be sent to the site staff. 
The participants/participants’ parent(s)/LAR(s) must be notified about their rights 
regarding the use of their personal data in accordance with the data privacy section of the 
ICF. 
10.1.5. 
Committees structure (Amended 15 March 2022) 
The protocol will be reviewed and approved by an IEC/IRB before initiation (Refer to 
Section 10.1.1 for further details). 
Safety oversight will be provided by the SRT composed of GSK RSV team members, 
and by the IDMC (Refer to Section 8.2.3 for further details). 
The GSB includes relevant members of the GSK study team and is responsible for 
ongoing safety monitoring of the entire project. The SRT will inform the GSB about any 
potential safety concern relevant to the study (Refer to Section 8.2.3). 
10.1.6. 
Dissemination of clinical study data (Amended 15 March 2022) 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocol summaries prior to 
study start and target results summaries submission within 12 months of primary/ study 
completion date. Where external regulations require earlier disclosure, GSK will follow 
those timelines. 
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical trial registers. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the investigator 
with the full summary of the study results. The investigator is encouraged to share the 
summary results with the study participants, as appropriate. 
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis*. 


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* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
GSK intends to make anonymized patient-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by trial 
participants are used to maximum effect in the creation of knowledge and understanding. 
10.1.7. 
Data quality assurance 
The investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents (see Section 10.7.2 for the exact definition of 
source documents). The document storage system used during the trial and for archiving 
(irrespective of the type of media used) should provide for document identification, 
version history, search, and retrieval. 
Essential trial documents may be added or removed where justified (in advance of trial 
initiation) based on their importance and relevance to the trial. When a copy is used to 
replace an original document (e.g. source documents, case report form [CRF]), the copy 
should fulfill the requirements for certified copies (see Section 10.7.2 for the exact 
definition of certified copies). 
All participant data related to the study will be recorded on printed or electronic CRF 
unless transmitted to the sponsor or designee electronically (e.g. laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
The investigator must maintain adequate and accurate source documents and trial records 
that include all pertinent observations on each of the site’s trial participants (see Section 
10.7.2 for the exact definition of source documents) that supports information entered in 
the eCRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies for such review and inspection. 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the source data (see Section 10.7.2 for the exact definition of source 
data). 
Study monitors will perform ongoing source data verification to confirm that data entered 
in the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (e.g. via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
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Quality tolerance limits (QTLs) will be pre-defined in the Study Management Plan to 
identify systematic issues that can impact participant safety and/or the reliability of study 
results. These pre-defined parameters will be monitored during the study. Important 
deviations from the QTLs and remedial actions taken will be summarized in the CSR. 
Trial records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the investigator for 25 years from issuance of the final 
CSR/equivalent summary unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor. 
10.1.8. 
Source documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The investigator should maintain a record of 
the location(s) of their source documents. 
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
Definitions of what constitutes source data and documents can be found in Section 
10.7.2. 
10.1.9. 
Study and site start and closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at its sole discretion, provided there is sufficient notice given to 
account for all participants safe exit from study. 
Regular closure of study sites will occur upon study completion. A study site is 
considered closed when all required data/documents and study supplies have been 
collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable 
cause and enough notice in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 


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At the end of the study, the investigator will: 
• 
Review data collected to ensure accuracy and completeness 
• 
Complete the study conclusion screen in the eCRF 
10.1.10. 
Publication policy 
GSK aims to submit the results of the study for publication in searchable, peer reviewed 
scientific literature within 18 months from the LSLV for interventional studies and 
follows the guidance from the International Committee of Medical Journal Editors 
(ICMJE). 
10.2. 
Appendix 2: Clinical laboratory tests 
10.2.1. 
Protocol-required safety laboratory assessments (Amended 15 
March 2022) 
Laboratory assessments detailed in Table 24 should either be available as part of the 
routine care within 15 days prior to study intervention administration or be performed 
within the same interval at the local laboratory as part of screening. 
Table 24 
Protocol-Required Safety Laboratory Assessments 
Laboratory assessments Parameters 
Hematology  
Leukocytes (White Blood Cells) 
Lymphocytes 
Eosinophils 
Basophils 
Hemoglobin 
Hematocrit 
Platelets 
Neutrophils 
Clinical chemistry 
Alanine Aminotransferase (ALT) 
Aspartate Aminotransferase (AST) 
Creatinine 
Blood Urea Nitrogen (BUN)/urea]* 
Urinalysis by dipstick 
Glucose 
 
Protein 
Notes: 
* 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). 
Laboratory assessments (e.g., placenta pathology) may be performed on the placental 
tissue samples collected from maternal participants at delivery visit to support possible 
safety assessments, if necessary. Additional details are provided in the study SPM. 
Additional assessments on the placental sample can be performed depending on local 
standard of practice, site capability and the investigators’ medical judgment. 


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10.2.2. 
Descriptions of the assays to be performed in the study 
(Amended 15 March 2022) 
Assay descriptions could be subject to change, due to assay re-development and/or 
qualification. 
RSV-A and RSV-B neutralization assays 
The serum neutralization assay is a functional assay that measures the ability of serum 
antibodies to neutralize RSV entry and replication in a host cell line. 
Virus neutralization is performed by incubating a fixed amount of RSV-A strain (Long, 
ATCC No. VR-26) or RSV-B strain (18537, ATCC No. VR-1580) with serial dilutions of 
the test serum. The serum-virus mixture is then transferred onto a monolayer of Vero 
cells (African Green Monkey, kidney, Cercopitheus aethiops, ATCC CCL-81) and 
incubated for 2 days to allow infection of the Vero cells by non-neutralized virus and the 
formation of plaques in the cell monolayer. Following a fixation step, RSV-infected cells 
are detected using a primary antibody directed against RSV (anti-RSV IgG) and a 
secondary antibody conjugated to horse-radish peroxidase (HRP), allowing the 
visualization of plaques by immunofluorescence after coloration with TrueBlueTM 
peroxidase substrate. Viral plaques are counted using an automated microscope coupled 
to an image analyzer (Scanlab system with reading software). For each serum dilution, a 
ratio, expressed as a percentage, is calculated between the number of plaques at that 
dilution and the number of plaques in the virus control wells (no serum added). The 
serum neutralizing antibody titer is expressed in ED60 (Estimated Dilution 60) and 
corresponds to the inverse of the interpolated serum dilution that yields a 60% reduction 
in the number of plaques compared to the virus control wells, as described by others 
[Barbas, 1992; Bates, 2014]. 
For RSV, NIBSC16/284 sample has been identified as an international reference. For 
RSV-A and RSV-B [McDonald, 2018; McDonald, 2020], GSK internal standards have 
been calibrated against the international standard and are used to convert ED60 in IU/mL 
in each run. 
Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) able to 
discriminate RSV-A and RSV-B subtypes 
Quantitative RT-PCR able to discriminate RSV-A and RSV-B subtypes: Briefly, RSV-A 
and RSV-B RNAs extracted from the nasal swabs are detected in a duplex PCR format 
using specific amplification primers and fluorescent probes designed in the RSV N gene, 
encoding the RSV nucleocapsid protein. The process involves nucleic acids extraction, 
conversion of RNA to complementary deoxyribonucleic acid by reverse transcription and 
detection by real- time PCR reaction using a calibration curve (absolute quantitation). 
The RSV viral load is reported as copies of RSV RNA per mL of sample. 


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RSVPreF3 IgG ELISA 
The RSVPreF3 IgG ELISAs will be based on an indirect ELISA allowing the detection 
and the quantification of specific IgG antibodies directed against RSVPreF3 in human 
serum samples. 
The principle of these assays will be as follows. RSVPreF3 antigen will be adsorbed onto 
a 96-well polystyrene microplate. After a washing and a blocking step, dilutions of serum 
samples, controls and standards will be added to the coated microplate. A reference 
standard curve will be prepared using a pool of commercial human serum containing 
anti-RSV antibodies. After incubation, the microplate will be washed to remove unbound 
primary antibodies. Bound IgG will be detected by the addition of a secondary anti-
human antibody (total IgG or IgG1-specific), conjugated to HRP. Bound antibodies are 
quantified by the addition of the HRP substrate, tetramethylbenzidine and hydrogen 
peroxide, whereby a colored product develops proportionally to the amount of anti-
RSVPreF3 IgG or IgG1 antibodies present in the serum sample. The optical density of 
each sample dilution is then interpolated on the reference standard. The corresponding 
antibody concentration, corrected for the dilution factor, is expressed in arbitrary ELISA 
Laboratory Units per milliliter (ELU/mL). 
Hematocrit assay 
The hematocrit is the proportion of the volume occupied by the red blood cells 
compared to the whole volume of the blood cells. The hematocrit value is determined 
by drawing blood sample into a capillary tube then centrifuged, the lengths of the 
columns for the red blood cells and the whole blood cells are measured using a graphic 
reading device. Thereafter, the proportion of the red blood cells to that of the whole 
blood cells is determined and expressed as a decimal or percentage fraction. 
Hematocrit will be tested at Visits 1, 2 and 3 for all participants until the current 
Protocol Amendment 1 is approved (unless IEC/IRB allows for immediate 
implementation of this measure to reduce participant’s burden, prior to full 
Amendment 1 being approved) in the respective study country(ies). Testing will be 
performed by a central laboratory. Results will be used to help evaluate changes over 
time in antibody titers / concentrations that may be related to volumetric changes 
during pregnancy, if deemed necessary. 
10.3. 
Appendix 3: Adverse Events: definitions and procedures for 
recording, evaluating, follow-up, and reporting Definition of 
AE 
10.3.1. 
Definition of an adverse event (AE) 
An AE is any untoward medical occurrence (an unfavorable/unintended sign - including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical 
study participant that is temporally associated with the study intervention. The AE may or 
may not be considered related to the study intervention. 


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10.3.1.1. 
Events meeting the AE definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication 
under study. 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after administration of the study 
intervention even though they may have been present before study start. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either the 
study intervention or a concurrent medication. 
• 
Signs or symptoms temporally associated with administration of the study 
intervention. 
• 
Signs, symptoms that require medical attention (e.g. hospital stays, physician visits 
and emergency room visits) 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated 
procedures (i.e. invasive procedures, modification of participant’s previous 
therapeutic regimen). 
• 
Clinically significant abnormal laboratory findings or other abnormal assessments 
that are present at baseline and significantly worsen following the start of the study 
will also be reported as AEs or SAEs. 
• 
AEs to be recorded as solicited AEs are described in the Section 10.3.3. All other 
AEs will be recorded as UNSOLICITED AEs. 
10.3.1.2. 
Events NOT meeting the AE definition 
• 
Situations where an untoward medical occurrence did not occur (e.g. social and/or 
convenience admission to a hospital, admission for routine examination). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
• 
Pre-existing conditions or signs and/or symptoms present in a participant before 
the study intervention. These events will be recorded in the medical history section 
of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent/assent) that did not worsen from 
baseline. 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 


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• 
Disease-related events (DRE), typically associated with the disease under study. 
These events will be recorded in the participant’s eCRF and will be monitored by 
the IDMC on a routine basis. 
However, if 1 or both of the following conditions apply, then the event should be 
reported promptly to GSK as an SAE (see Section 10.3.8): 
− 
The event is, in the investigator’s opinion, of greater intensity, frequency, or 
duration than expected for the individual participant, or 
− 
The investigator considers that there is a reasonable possibility that the event 
was related to the administration of the study intervention 
10.3.2. 
Definition of an SAE 
An SAE is any untoward medical occurrence that: 
a. 
Results in death 
b. Is life-threatening 
Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the participant was at risk of death at the time of the event. It does not refer 
to an event, which hypothetically might have caused death, had it been more 
severe. 
c. 
Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the participant has been admitted at 
the hospital or emergency ward for observation and/or treatment that would not 
have been appropriate in the physician’s office or in an out-patient setting. 
Complications that occur during hospitalization are also considered AEs. The 
event will also be considered serious if a complication prolongs hospitalization or 
fulfills any other serious criteria. When in doubt as to whether ‘hospitalization’ 
occurred or was necessary, the AE should be considered serious. 
d. Results in disability/incapacity 
Note: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include 
experiences of relatively minor medical significance such as uncomplicated 
headache, nausea, vomiting, diarrhea, influenza like illness, and accidental trauma 
(e.g. sprained ankle) which may interfere or prevent everyday life functions but do 
not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect in the offspring of a study participant 
Refer to Section 8.3.4 for additional information. 
f. 
Abnormal pregnancy outcomes (e.g. spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy). 


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g. Other situations 
Medical or scientific judgment must be exercised in deciding whether reporting is 
appropriate in other situations. Important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition should be considered serious. 
Examples of such events are invasive or malignant cancers; intensive treatment in 
an emergency room or at home for allergic bronchospasm; blood dyscrasias; and 
convulsions that do not result in hospitalization. 
10.3.3. 
Solicited events 
a. Solicited administration site events 
The following administration site events will be solicited for maternal participants: 
Table 25 
Solicited administration site events 
All age groups 
Pain  
Redness  
Swelling  
b. Solicited systemic events 
The following systemic events will be solicited for maternal participants: 
Table 26 
Solicited systemic events 
Adult 
Fatigue 
Fever 
Nausea 
Vomiting 
Diarrhea 
Abdominal pain 
Headache 
Note: maternal participants will be instructed to measure and record the temperature by 
an age-appropriate route (preferably oral) at least once each day, at approximately the 
same time each day. If additional temperature measurements are taken at other times of 
the day, maternal participants will be instructed to record the highest temperature in the 
electronic Participant Diary (eDiary). 
10.3.4. 
Unsolicited adverse events (AEs) 
An unsolicited AE is an AE that was not included in a list of solicited events using a 
Participant Diary. Unsolicited events must have been spontaneously communicated by a 
maternal participant who has signed the informed consent/assent. Unsolicited AEs 
include both serious and non-serious AEs. 


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Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, or an emergency room visit, or visit to/by a health care 
provider). The maternal participants will be instructed to contact the site as soon as 
possible to report medically attended event(s), as well as any events that, though not 
medically attended, are of participant’s concern. Detailed information about reported 
unsolicited AEs will be collected by qualified site personnel and documented in the 
participant’s records. 
Unsolicited AEs that are not medically attended or perceived as a concern by the 
maternal participant will be collected during an interview with the maternal participants 
and by review of available medical records at the next visit/contact. 
10.3.5. 
Adverse events of special interest (AESIs) 
AESIs include: 
• 
Worsening of pre-existing medical conditions and/or obstetric complications as 
defined in section 8.2.1.2. 
• 
The following pregnancy-related AESIs (collected as AESI if developed after 
study intervention administration and were not pre-existing): 
− 
Maternal death 
− 
Hypertensive disorders of pregnancy (gestational hypertension, pre-eclampsia, 
pre-eclampsia with severe features including eclampsia) 
− 
Fetal growth restriction 
− 
Gestational diabetes mellitus 
− 
Pathways to preterm birth (premature preterm rupture of membranes, preterm 
labor, provider-initiated preterm birth), and 
− 
Chorioamnionitis. 
• 
The following neonatal AESIs: 
− 
Small for gestational age 
− 
Low birth weight including very low and extremely low birth weight (<2500 g, 
<1500g, <1000g) 
− 
Congenital anomalies (major external structural defects, internal structural 
defects, functional defects) 
− 
Neonatal death (in an extremely preterm birth [22<GA<28 weeks], in a preterm 
live birth [28<GA<37 weeks], or in a term live birth), and preterm birth. 
Refer to Section 8.3.4 for additional information about categorizing and reporting 
congenital anomalies. 
When there is enough evidence to make any of the above diagnoses, the AE must be 
reported as AESI. Symptoms, signs or conditions which might (or might not) lead to one 
of the above diagnoses, should be recorded and reported as AEs but not as AESI until the 


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final or definitive diagnosis has been made, and alternative diagnoses eliminated or 
shown to be less likely. 
Note: AESIs experienced by an infant born to the exposed mother will be reported (if 
become known to the site staff), even if the re-consent for infant participants is not 
provided. 
10.3.6. 
Clinical laboratory parameters and other abnormal assessments 
qualifying as AEs or SAEs 
In the absence of a diagnosis, abnormal laboratory findings assessments (e.g. clinical 
chemistry, hematology, urinalysis) or other abnormal results the investigator considers 
clinically significant will be recorded as an AE or SAE, if they meet the definition of an 
AE or SAE (refer to the Sections 10.3.1 and 10.3.2). 
The investigator must exercise his or her medical and scientific judgment in deciding 
whether an abnormal laboratory finding, or other abnormal assessment is clinically 
significant. 
10.3.7. 
Events or outcomes not qualifying as AEs or SAEs 
10.3.7.1. 
Subsequent Pregnancy 
All maternal participants will be in the second or third trimester of pregnancy at 
enrollment and are expected to deliver while participating in the study. 
Maternal participants who become pregnant again after administration of the study 
intervention may continue the study at the discretion of the investigator. 
While subsequent pregnancy itself is not considered an AE or SAE, any abnormal 
subsequent pregnancy outcome or complication or elective termination of a subsequent 
pregnancy for medical reasons will be recorded and reported as an SAE. Please refer to 
the Section 10.3.2 for definition of SAE. 
10.3.8. 
Recording and follow-up of AEs, SAEs, AESIs and subsequent 
pregnancies 
The maternal participants/infant participants’ parent(s)/LAR(s) will be instructed to 
contact the investigator immediately should the maternal or infant participants experience 
any signs or symptoms the maternal participants/infant participants’ parent(s)/LAR(s) 
perceive as serious. 
When an AE/SAE occurs, it is the investigator’s responsibility to review all 
documentation (e.g. hospital progress notes, laboratory and diagnostics reports) related to 
the event. The investigator will then record all relevant information regarding an AE/SAE 
on the eCRF. The investigator may not send photocopies of the participant’s medical 
records to GSK instead of appropriately completing the eCRF. 


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There may be instances when copies of medical records for certain cases are requested by 
GSK. In this case, all participant identifiers will be blinded on copies of the medical 
records prior to submission to GSK. 
The investigator will attempt to establish a diagnosis pertaining to the event, based on 
signs, symptoms, and/or other clinical information. In such cases, the diagnosis should be 
documented as the AE/SAE instead of individual signs/symptoms. 
An Electronic Diary (eDiary), hereafter referred to as Participant Diary, will be used in 
this study to capture solicited administration site or systemic events for maternal 
participants. The maternal participant should be trained on how and when to complete the 
Participant Diary. 
Anyone who measures administration site or systemic events and who will record the 
event in the Participant Diary should be trained on using the Diary. This training must be 
documented in the maternal participant’s source record. If any individual other than the 
maternal participant is making entries in the Participant Diary, their identity must be 
documented in the Participant Diary/maternal participant’s source record. 
Refer to the SPM for more information regarding the use of eDiary. 
Note: SAEs and/or AESIs experienced by an infant born to the exposed mother will be 
reported (if become known to the site staff), even if the re-consent for infant participants 
is not provided. 
10.3.8.1. 
Time period for collecting and recording AEs, SAEs, AESIs and 
subsequent pregnancies 
For time period and frequency for collecting AE, SAE and other safety information, refer 
to Section 8.3.1. 
All solicited events that occur during 7 days following administration of the dose of study 
intervention (Day 1 to Day 7) must be recorded into the eDiary, irrespective of intensity 
or whether or not they are considered related to the study intervention. 
All other AEs should be recorded into the appropriate section of the eCRF, irrespective of 
their intensity or whether or not they are considered related to the study intervention. 
10.3.8.2. 
Follow-up of AEs, SAEs, AESIs, subsequent pregnancies or any other 
events of interest 
10.3.8.2.1. Follow-up during the study 
After the initial AE/SAE/AESI/subsequent pregnancy or any other event of interest, the 
investigator is required to proactively follow each participant at subsequent 
visits/contacts. 


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All SAEs and AESIs (serious or non-serious as defined in the Section 10.3.5), will be 
followed until the event is resolved, stabilized, otherwise explained, or the participant is 
lost to follow-up. 
Non-serious MAEs must be followed until recovered / resolved, or until the participant’s 
last study visit, or until the participant is lost to follow-up. 
Other non-serious AEs (maternal participants) must be followed until they are resolved, 
stabilized or until the participant is lost to follow-up. 
AEs/AESIs documented at a previous visit/contact and defined as not recovered/not 
resolved or recovering/resolving will be reviewed at subsequent visits/contacts until they 
are resolved, stabilized or until the participant is lost to follow-up. 
If a participant dies during their participation in the study or during a recognized follow-
up period, GSK will be provided with any available post-mortem findings, including 
histopathology. 
10.3.8.2.2. Follow-up after the participant is discharged from the study 
The investigator will provide any new or updated relevant information to GSK on a 
previously reported SAEs/AESIs using a paper/electronic Adverse Events Form and 
corresponding Expedited Adverse Event Form and/or pregnancy report as applicable. The 
investigator is obliged to perform or arrange for the conduct of supplemental clinical 
examinations/tests and/or evaluations to elucidate the nature and/or causality of the 
SAE/AESI as fully as possible. 
10.3.8.2.3. Follow-up of subsequent pregnancies 
Maternal participants who become pregnant again while participating in the study will be 
followed to determine the outcome of the subsequent pregnancy. At the end of the 
subsequent 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 
Adverse Events Form and corresponding Expedited Adverse Event Form if applicable. 
Generally, the follow-up period does not need to be longer than 6 to 8 weeks after the 
estimated date of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is an 
SAE, it should always be reported as such. 
Furthermore, if the investigator becomes aware of any SAE occurring as a result of a 
post-study pregnancy AND it is considered by the investigator to be reasonably related to 
the study intervention, he/she must report this information to GSK as described in the 
Section 10.3.10. 


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10.3.8.3. 
Updating of SAE, AESI and subsequent pregnancy information after 
removal of write access to the participant’s eCRF 
When additional SAE, AESI or subsequent pregnancy information is received after write 
access to the participant’s eCRF is removed, new or updated information should be 
recorded on the appropriate paper report, with all changes signed and dated by the 
investigator. The updated report should be faxed to the Study contact for reporting SAEs 
(refer to the Section 8.3.3.1 or to GSK VCSP department within the defined reporting 
time frames specified in the Table 18. 
10.3.9. 
Assessment of intensity and toxicity 
10.3.9.1. 
Assessment of intensity 
The intensity of the following solicited AEs will be assessed as described: 
Table 27 
Intensity scales for solicited events in adults 
Adults 
Event 
Intensity grade 
Parameter 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor preventing 
normal everyday activities. 
 
2 
Moderate: Painful when limb is moved and interferes with 
every day activities. 
 
3 
Severe: Significant pain at rest. Prevents normal every 
day activities. 
Redness at administration site 
Greatest surface diameter in mm 
Swelling at administration site 
Greatest surface diameter in mm  
Temperature* 
 
Record temperature in °C/°F with 1 decimal 
Temperature will be analyzed in 0.5°C increments from ≥ 
38.0°C /100.4°F) 
Grade 3 fever is defined as > 39.0°C /102.2°F 
Headache 
 
 
Fatigue 
0 
Normal 
Nausea 
1 
Mild: Easily tolerated 
Vomiting 
2 
Moderate: Interferes with normal activity 
Diarrhea 
3 
Severe: Prevents normal activity 
Abdominal pain 
 
 
* Refer to Section 1.3 for the definition of fever and the preferred location for temperature measurement. 
The maximum intensity of local injection site redness/swelling will be scored at GSK as 
follows: 
• 
0: ≤ 20 mm 
• 
1: > 20 mm to ≤ 50 mm 
• 
2: > 50 mm to ≤ 100 mm 
• 
3: > 100 mm 


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The investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the investigator’s clinical judgment. 
The intensity should be assigned to 1 of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the participant, causing 
minimal discomfort and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with 
normal everyday activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities 
(in a young child, such an AE would, for example, prevent 
attendance at school/kindergarten/a day-care center and would 
cause the parent(s)/LAR(s) to seek medical advice. In 
adults/adolescents, such an AE would, for example, prevent 
attendance at work/school and would necessitate the 
administration of corrective therapy.) 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. Grade 3 
is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. An event is defined as ‘serious’ when it meets 1 of the pre-defined 
outcomes as described in the Section 10.3.2. 
10.3.9.2. 
Assessment of causality 
The investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgment. Where several different 
interventions were administered, the investigator should specify, when possible, if the 
unsolicited AE/SAE could be causally related to a specific intervention. When a causal 
relationship to a specific study intervention cannot be determined, the investigator should 
indicate the unsolicited AE/SAE to be related to all interventions. 
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The investigator will also consult 
the IB to assist in making his/her assessment. 
Causality should be assessed by the investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study intervention? 
YES 
: 
There is a reasonable possibility that the study intervention 
contributed to the AE.  
NO 
: 
There is no reasonable possibility that the AE is causally related to 
the administration of the study intervention. There are other, more 
likely causes and administration of the study intervention is not 
suspected to have contributed to the AE. 


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If an event meets the criteria to be determined ‘serious’ (see Section 10.3.2), additional 
examinations/tests will be performed by the investigator to determine ALL possible 
contributing factors for each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol-required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the study intervention, if applicable. 
• 
An error in study intervention administration. 
• 
Other cause (specify). 
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Adverse Events 
Form and corresponding Expedited Adverse Event Form to GSK. 
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. The investigator may change his/her opinion of causality after receiving 
additional information and update the SAE information accordingly. 
10.3.9.3. 
Medically attended visits 
For each solicited and unsolicited AE the participant experiences, the maternal 
participant/infant participant’s parent(s)/LAR(s) will be asked if she/the infant participant 
received medical attention (defined as hospitalization, or an otherwise unscheduled visit 
to or from medical personnel for any reason, including emergency room visits). This 
information will be recorded in the in the eCRF. 
10.3.9.4. 
Assessment of outcomes 
The investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 


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10.3.10. 
Reporting of SAEs, AESIs, subsequent pregnancies and other 
events 
10.3.10.1. Events requiring expedited reporting to GSK 
Once an investigator becomes aware that an SAE has occurred, the investigator (or 
designee) must complete information in the electronic Adverse Events Form and 
corresponding Expedited Adverse Event Form WITHIN 24 HOURS, even if the 
investigator does not have complete information on the SAE. It must be completed as 
thoroughly as possible, with all available details of the event. 
The SAE report must be updated WITHIN 24 HOURS of the receipt of updated 
information on the SAE. The investigator will always provide an assessment of causality 
at the time of the initial report. 
Refer to the Table 18 for the details on timeframes for reporting of 
SAEs/AESIs/subsequent pregnancies. 
The investigator will be required to confirm the review of SAE/AESI causality within 72 
hours of submission of the SAE/AESI. 
Refer to the Section 10.3.10.2 for information on back up systems in case the electronic 
reporting system does not work. 
10.3.10.2. Back up system in case the electronic reporting system does not work 
If the electronic reporting system does not work, the investigator (or designee) must fax a 
completed, dated and signed paper Expedited Adverse Events Report to the study contact 
for reporting SAEs (refer to the Sponsor Information) or to GSK VCSP department 
within 24 hours of becoming aware of the SAE. 
Investigator (or designee) must complete the electronic Adverse Events Form and 
corresponding Expedited Adverse Event Form within 24 hours after the electronic 
reporting system is working again. The information reported through the electronic SAE 
reporting system will be considered valid for regulatory reporting purposes. 
10.4. 
Appendix 4: Contraceptive guidance and collection of 
subsequent pregnancy information 
Contraceptive guidance does not apply in this study. 
Refer to the Sections 8.3.1, 8.3.2, 10.3.8.1 and 10.3.8.3 for further information on 
detection, recording, reporting and follow-up of pregnancies. 
10.5. 
Appendix 5: Genetics 
Not applicable. 


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10.6. 
Appendix 6: Country-specific requirements 
Not applicable. 
10.7. 
Appendix 7: Abbreviations and glossary of terms 
10.7.1. 
List of abbreviations (Amended 15 March 2022) 
AE: 
Adverse Event 
AESI: 
Adverse Event of Special interest 
ANCOVA: 
Analysis of Covariance 
BMI: 
Body Mass Index 
CI: 
Confidence Interval 
CLS: 
Clinical Laboratory Sciences 
COVID-19: 
Corona Virus Disease 2019 
CRDL: 
Clinical Research & Development Lead 
CRF: 
Case Report Form 
CSR: 
Clinical Study Report 
DRE: 
Disease-related event 
eCRF: 
electronic Case Report Form 
EDD: 
Expected Date of Delivery 
ELISA: 
Enzyme-Linked Immunosorbent Assay 
EoS: 
End of Study 
ES: 
Exposed set 
ET: 
Embryo-Transfer 
FAS: 
Full Analysis Set 
FU: 
Follow-up 
GAIA: 
Global Alignment of Immunization Safety Assessment 
in pregnancy 


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GCP: 
Good Clinical Practice 
GDM: 
Gestational Diabetes Mellitus 
GMC: 
Geometric Mean Concentration 
GMT: 
Geometric Mean Titer 
GSB: 
Global Safety Board 
GSK: 
GlaxoSmithKline 
HIV: 
Human Immunodeficiency Virus 
HRP: 
Horse-radish peroxidase 
IAF: 
Informed Assent Form 
IB: 
Investigator Brochure 
ICF: 
Informed Consent Form 
ICH: 
International Council on Harmonization 
IDMC: 
Independent Data Monitoring Committee 
IEC: 
Independent Ethics Committee 
IND: 
Investigational New Drug 
IRB: 
Institutional Review Board 
IUI: 
Intrauterine insemination 
LAR: 
Legally Acceptable Representative 
LML: 
Local Medical lead 
LMP: 
Last Menstrual Period 
LRTI: 
Lower Respiratory Tract illness 
LSLV: 
Last Participant Last Visit 
MACDP: 
Metropolitan Atlanta Congenital Defects Program 
MAE: 
Medically attended adverse event 
MA-RTI: 
Medically attended respiratory tract illness 


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MedDRA: 
Medical Dictionary for Regulatory Activities 
nAb: 
Neutralizing antibody 
NB: 
Newborn 
PCD: 
Primary Completion Date 
PCR: 
Polymerase Chain Reaction 
PPS: 
Per Protocol Set 
QTL: 
Quality Tolerance Limit 
RR: 
Respiratory Rate 
RSV: 
Respiratory Syncytial Virus 
RTI: 
Respiratory Tract Illness 
SAE: 
Serious Adverse Event 
SAP: 
Statistical Analysis Plan 
SARS-COV-2: 
The corona virus that is the causative agent of COVID-
19. 
SBIR: 
Source data Base for Internet Randomization  
SD: 
Standard deviation 
SoA: 
Schedule of Activities 
SPM: 
Study Procedures Manual 
SpO2: 
Blood oxygen saturation as measured by pulse oximetry 
SRT: 
Safety Review Team 
SUSAR: 
Suspected Unexpected Serious Adverse Reaction 
VCSP: 
Vaccines Clinical Safety and Pharmacovigilance 
WHO: 
World Health Organization 
YOA: 
Years Of Age 


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10.7.2. 
Glossary of terms (Amended 15 March 2022) 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product. 
An adverse event (AE) can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal 
product. For marketed medicinal products, this also 
includes failure to produce expected benefits (i.e. lack of 
efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
trial, and only when the data are cleaned to an acceptable 
level of quality will appropriate personnel be unblinded 
or when required in case of a serious adverse event 
In an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned. 
In a single-blind study, the investigator and/or his staff 
are aware of the intervention assignment but the 
participant is not. 
In a double-blind study, the participant, the investigator 
and sponsor staff who are involved in the treatment or 
clinical evaluation of the participants and the review or 
analysis of data are all unaware of the intervention 
assignment. 
Body Mass Index 
A key index for relating weight to height. Calculated as 
follows: Weight (kg) / Height (m)2 
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. 


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Child in care: 
A child who has been placed under the control or 
protection of an agency, organization, 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. 
Child: 
A young human being below the legal age of majority 
(generally < 18 years of age). 
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
End of Study (EoS) 
(Synonym of End of Trial)  
EoS occurs with the last infant participant last visit 
(LSLV; Visit 5-NB).  
Enrolled participant 
‘Enrolled’ means a maternal participant’s/infant 
parent’s/LAR’s agreement to participate in a clinical 
study following completion of the informed consent 
process. Potential maternal participants who are 
screened for determining eligibility for the study, but do 
not participate in the study, are not considered enrolled, 
unless otherwise specified by the protocol. 
Refer to the Section 9.3 of the protocol for the definition 
of ‘enrolled set’ applicable to the study.  
Essential documents 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced. 
eTrack: 
GSK’s tracking tool for clinical trials. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per protocol analysis (see Section 9.3 for 
details on criteria for evaluability). 
GAIA 
Global Alignment of Immunization Safety Assessment 
in pregnancy. A project that aims to improve the quality 
of outcome data from clinical vaccine trials in pregnant 
women with a specific focus on the needs and 
requirements for safety monitoring in low to middle 
income countries.  


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Gestational age: 
A measure of the age of a pregnancy where the origin is 
the first day of the woman's last normal menstrual 
period, or the corresponding age as estimated by other 
methods. Gestational age will be described in weeks of 
pregnancy completed + number of days completed of the 
following week. For example: 28 0/7 means completed 
28 weeks of pregnancy + 0 days of the 29th week and 28 
6/7 means completed 28 weeks of pregnancy + 6 days of 
the 29th week. 
Immunological correlate 
of protection: 
A correlate of risk that has been validated to predict a 
certain level of protection from the targeted endpoint. 
Infant 
A child younger than 1 year of age  
Intervention 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Investigational vaccine: 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorization when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use. 
Synonym: Investigational Medicinal Product 
Investigator 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the investigator is the 
responsible leader of the team and may be called the 
principal investigator. 
The investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
and functions. 
Legally acceptable 
representative 
An individual, judicial or other body authorized under 
applicable law to consent on behalf of a prospective 
participant to the participant's participation in the 
clinical trial. 
The terms legal representative or legally authorized 
representative are used in some settings. 


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Level 2 ultrasound (also 
known as a fetal anomaly 
ultrasound scan or fetal 
morphology assessment)  
Comprehensive, detailed evaluation of fetal anatomy and 
development that is usually performed at approximately 
20 weeks of gestational age. In addition to standard 
ultrasound parameters such as fetal heart activity and 
gestational age estimation, a Level 2 ultrasound usually 
includes assessment of amniotic fluid levels; assessment 
of the condition of the placenta, cervix, and uterus; and 
detection of fetal anomalies.  
Local healthcare provider 
A healthcare provider who provides participants with 
medical care per local standards. This individual may or 
may not be a member of the site staff.  
Neonatal adverse events of 
special interest 
Adverse events that occur from birth through 42 days of 
age and are to be reported as neonatal AESIs are listed in 
Table 4 and Section 10.3.5. It is anticipated that most 
neonatal AESIs will be identified (and thus may be 
reported in the eCRF) by or before the Day 43 visit 
(Visit2-NB). However, as indicated in Table 17, any 
neonatal AESIs identified after Visit 2-NB should also 
be reported in the eCRF. 
Neonate (or Newborn) 
An infant 28 days old or younger. 
Parental concern 
The parent(s) / Legally Acceptable Representative(s) are 
concerned about the infant’s respiratory tract illness (or 
general health in the context of the respiratory tract 
illness) and intend to seek medical care 
Participant number: 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Participant: 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control) or an 
infant born from participants who received the study 
intervention. 
Synonym: subject 
Pregnancy outcomes 
Pregnancy outcomes that occur up to 42 days after 
delivery are listed in Table 4 and Section 8.3.4.2. 
Pregnancy related adverse 
events of special interest: 
Pregnancy related events that occur up to 42 days after 
delivery are to be reported as AESIs and are listed in 
Table 4 and Section 10.3.5.  


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Primary completion date: 
The date that the final participant was examined or 
received an intervention for the purpose of final 
collection of data for all primary outcomes, whether the 
clinical trial was concluded according to the pre-
specified protocol or was terminated. 
Randomization: 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Site Monitor: 
An individual assigned by the sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Solicited event: 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified follow-up period following study 
intervention administration. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data 
are contained in source documents (original records or 
certified copies). 
Source documents: 
Original legible documents, data, and records (e.g. 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participants' diaries or evaluation 
checklists, pharmacy dispensing records, recorded data 
from automated instruments, copies or transcriptions 
certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, participant files, and records 
kept at the pharmacy, laboratories and at medico-
technical departments involved in the clinical trial). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Study population: 
Sample of population of interest. 


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Sub-cohort: 
A group of participants for whom specific study 
procedures are planned as compared to other participants 
or a group of participants who share a common 
characteristic (e.g. ages, vaccination/ study intervention 
schedule, etc.) at the time of enrollment. 
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. 
10.8. 
Appendix 8: Gestational Age Assessment 
10.8.1. 
GAIA gestational age assessment form 
Based on Quinn, JA, Munoz FM, Gonik B et al. Preterm birth: Case definition & 
guidelines for data collection, analysis, and presentation of immunization safety data. 
Vaccine. 2016; 34: 6047 – 6056. 
LEVELS OF CERTAINTY OF GESTATIONAL AGE ASSESSMENT 
Level 
Description 
Level 1 
Highest level of 
certainty 
Certain LMP or IUI date or ET WITH confirmatory 1st trimester U/S 1 
or 
1st trimester U/S 
Level 2A 
Certain LMP WITH 2nd trimester U/S 1 
or 
Certain LMP WITH 1st trimester physical examination2 
Level 2B 
Uncertain LMP WITH 2nd trimester U/S 1 
Level 3A 
Certain LMP WITH 3rd trimester U/S3, 
or 
Certain LMP WITH confirmatory 2nd trimester FH, 
or 
Certain LMP WITH birth weight, 
or 
Uncertain LMP WITH 1st trimester physical examination 
Level 3B 
Lowest level of 
certainty 
Uncertain LMP WITH FH, 
or 
Uncertain LMP WITH neonatal physical assessment (New Ballard score), 
or 
Uncertain LMP WITH birth weight 
1st trimester U/S: ≤136/7 weeks, 2nd trimester U/S: 140/7 to 276/7 weeks, 3rd trimester U/S: ≥280/7 weeks. 
GA: gestational age; U/S: ultrasound examination; LMP: last menstrual period; IUI: intrauterine insemination; ET: 
embryo-transfer, FH: fundal height; 
Boldface = Applicable for enrollment in this study. 
1 If LMP and U/S do not correlate, default to U/S GA assessment. 
2 For singleton pregnancies only. Unreliable if obesity, or uterine anomalies. 
3 May be enrolled provided gestational age is within the limits specified for eligibility Refer.to Section 5.1.1 for further 
details. 


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10.8.2. 
Methods of gestational age assessment and estimation of due 
date 
Adapted from: The American College of Obstetricians and Gynecologists (ACOG) 
Committee on Obstetric Practice, American Institute of Ultrasound in Medicine and 
Society for Maternal-Fetal. Committee Opinions: Method for estimating Due Date. 
Number 700, May 2017 (accessed on-line on 05/Mar/2020 at: 
https://www.acog.org/clinical/clinical-guidance/committee-
opinion/articles/2017/05/methods-for-estimating-the-due-date). 
Gestational age range 
Method of measurement 
Discrepancy between U/S dating and LMP (or 
IUI or ET dating) prompting re-dating of EDD 
considering U/S 
1st trimester ≤136/7 weeks 
≤86/7 weeks 
90/7 to 136/7 weeks 
CRL 
> 5 days 
> 7 days 
2nd trimester 140/7 to 276/7 weeks 
140/7 to 156/7 weeks 
BPD, HC, AC, FL 
> 7 days 
160/7 to 216/7 weeks 
> 10 days 
220/7 to 276/7 weeks 
> 14 days 
3rd trimester 
280//7 weeks and beyond 
BPD, HC, AC, FL 
> 21 days 
U/S: ultrasound examination; LMP: last menstrual period; IUI: intrauterine insemination; ET: embryo-transfer; CRL: 
crown-rump length; BPD: biparietal diameter; HC: head circumference; AC: abdominal circumference; FL: femur 
length;, EDD: estimated date of delivery 
* Based on LMP (or, if applicable, IUI/ET date) 


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10.9. 
Appendix 9: Definitions of study AESIs and pregnancy 
outcomes 
• 
Table 4 and Section 10.3.5 list events of interest that must be reported as AESIs. 
• 
Worsening of pre-existing medical conditions and/or obstetric complications should 
be collected as maternal AESI and reported with enough information to support 
worsening from baseline condition (Section 8.2.1.2). 
• 
Diagnosis of pregnancy-related AESIs, pregnancy outcomes (Section 8.3.4.2) and 
neonatal AESIs should be assessed using the GAIA case definitions below. AESIs 
should be reported as non-serious or SAE as appropriate. The narrative for each of 
the cases must include enough details to permit assessment of the level of diagnostic 
certainty by GAIA case definition 
• 
Articles that discuss GAIA case definitions in detail can be found in the following 
issues of Vaccine: 
− 
Bauwens J, Bonhoeffer J, Chen RT, editors. Harmonising Immunization Safety 
Assessment in Pregnancy. Vaccine. 2016. 34 (49): 5991 – 6110. 
− 
Kochhar S, Bauwens J, Bonhoeffer J, editors. Harmonising Immunization Safety 
Assessment in Pregnancy – Part II. Vaccine. 2017. 35 (48): 6469-6582. 
• 
Definitions and Levels of Diagnostic Certainty are presented in the following Tables. 
References specific to each event of interest are given at the end of the relevant Table. 
Pregnancy Outcomes 
Fetal Death / Stillbirth 
Table 28 
Maternal Events of Interest 
Maternal Death 
Table 29 
Hypertensive Disorders of Pregnancy 
Table 30 
Fetal Growth restriction 
Table 31 
Gestational Diabetes Mellitus 
Table 32 
Pathways to Preterm Birth 
Table 33 
Chorioamnionitis 
Table 34 
Neonatal Events of Interest 
Small for Gestational Age 
Table 35 
Low Birth Weight 
Table 36 
Congenital Anomalies 
Table 37 
Neonatal Death 
Table 38 
Preterm Birth 
Table 39 


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Table 28 
Fetal death / Stillbirth 
Fetal death occurring before birth after 20 to 28 weeks of gestation (variation due to 
country definitions). 
Antepartum Stillbirth (Fetal death occurs prior to the evidence of labor.) 
Level 
Description 
1 
Delivery of an infant with no of signs of life at birth (No spontaneous movements, no umbilical cord pulse, 
no heartbeat, no respirations, Apgar score of 0 at 1 and 5 min) determined by physical examination after 
delivery (with or without electronic monitoring of heart rate, respiratory rate, and pulse oximetry). 
AND 
1. 
Prenatal ultrasound examination documenting lack of fetal cardiac activity or movement before the 
onset of labor. 
OR 
2. 
Auscultation for fetal heart tones (using electronic devices or non-electronic devices) documenting 
lack of fetal heartbeat. 
AND 
3. 
Maternal report of lack of fetal movement for 24 h or more. 
OR 
4. 
Maternal physical examination confirming lack of fetal movement. 
OR 
5. 
Radiology findings consistent with intrauterine fetal death. 
AND 
6. 
Attended delivery followed by fetal physical examination afterbirth consistent with antepartum 
death, by obstetrician, neonatologist, pediatrician, maternal-fetal medicine specialist, or pathologist. 
In the setting where access to a specialist is not feasible, diagnosis by a health care provider 
trained or experienced to make the diagnosis is acceptable (e.g. general practice physician, mid-
wife, nurse practitioner, a physician’s assistant or other qualified trained practitioner). 
OR 
7. 
Fetal/placental pathology report consistent with antepartum death. 
AND 
Gestational age within pre-defined range for selected stillbirth definition as assessed by maternal and/or 
fetal parameters (Level1 or 2 in GA assessment algorithm). 
2 
Delivery of an infant with no of signs of life at birth (No spontaneous movements, no umbilical cord pulse, 
no heartbeat, no respirations, Apgar score of 0 at 1 and 5 min) determined physical examination after 
delivery. 
AND 
1. 
Maternal report of lack of fetal movement for 24 h or more. 
OR 
2. 
Maternal physical examination confirming lack of fetal movement. 
OR 
3. 
Auscultation for fetal heart tones (using electronic or non-electronic devices) documenting lack of 
fetal heartbeat. 
AND 
4. 
Attended delivery followed by physical examination after birth consistent with antepartum death, by 
specialist or qualified trained practitioner appropriate to the health care setting. 
OR 
5. 
Fetal/placental pathology report consistent with antepartum death. 
AND 
Gestational age within pre-defined range for selected stillbirth definition as assessed by maternal and/or 
fetal parameters (Level1–2 in GA assessment algorithm). 


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Antepartum Stillbirth (Fetal death occurs prior to the evidence of labor.) (continued) 
Level 
Description 
3 
Delivery of an infant reported to have no of signs of life at birth (No spontaneous movements, no umbilical 
cord pulse, no heartbeat, no cry or spontaneous respirations, no chest movement, and whole body 
cyanosis). AND 
1. 
Maternal report of lack of fetal movement for 24 h or more prior to delivery. 
OR 
2. 
Report of auscultation for fetal heart tones (using electronic or non-electronic devices) documenting 
lack of fetal heartbeat. 
AND 
3. 
Non-attended delivery followed by physical examination of the fetus after birth consistent with 
antepartum death by a healthcare professional appropriate to the level of standard of care in the 
health care setting. 
OR 
4. 
Verbal history by a trained health care provider, non-medical witness or the mother of a fetus born 
with no signs of life or unresponsive to resuscitation efforts immediately after birth and with physical 
features consistent with antepartum death. 
AND 
Gestational age within pre-defined range for selected stillbirth definition as assessed by maternal and/or 
fetal parameters (Level2–3 in GA assessment algorithm). 
4 
Report of stillbirth but fetus is not available for physical examination after birth (no objective assessment 
can be made) 
Maternal information insufficient to assess gestational age 
Intrapartum stillbirth (Fetal death occurs during labor and before delivery) 
Level 
Description 
1 
Delivery of an infant with no of signs of life at birth, including: No spontaneous movements, no umbilical 
cord pulse, no heartbeat, no respirations, and Apgar score of 0 at 1 and 5 min 
Determination of the absence of signs of life is made by physical examination after delivery, with or 
without electronic monitoring of heart rate, respiratory rate, and pulse oximetry. 
AND 
Evidence of live fetus prior to onset of labor (documentation of fetal movement and of fetal heart tones by 
ultrasound prior to onset of labor) (Note: in the absence of evidence of a live fetus prior to the onset of 
labor, the fetal death should be reported as a stillbirth or an antepartum stillbirth). 
AND 
Attended delivery followed by physical examination afterbirth consistent with intrapartum death by 
obstetrician, neonatologist, pediatrician, maternal-fetal medicine specialist, pathologist. In the setting 
where access to a specialist is not feasible, diagnosis by a health care provider trained or experienced to 
make the diagnosis is acceptable (e.g. general practice physician, mid-wife, or other qualified trained 
practitioner). 
AND 
Gestational age within pre-defined range for selected stillbirth definition as assessed by maternal and/or 
fetal-neonatal parameters (Level 1 in GA assessment algorithm) 


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Intrapartum stillbirth (Fetal death occurs during labor and before delivery) (continued) 
Level 
Description 
2 
Delivery of an infant with no of signs of life at birth, including: No spontaneous movements, no umbilical 
cord pulse, no heartbeat, no respirations, and Apgar score of 0 at 1 and 5 min. 
Determination of the absence of signs of life is made by physical examination after delivery, with or 
without electronic monitoring of heart rate, respiratory rate, and pulse oximetry OR documentation of lack 
of response to resuscitation efforts. 
AND 
Evidence of live fetus prior to onset of labor (maternal report of fetal movement prior to onset of labor and 
documentation of fetal heart tones by auscultation or hand held Doppler) (Note: in the absence of 
evidence of a live fetus prior to the onset of labor, the fetal death should be reported as a stillbirth or an 
antepartum stillbirth). 
AND 
Attended delivery followed by physical examination after birth consistent with intrapartum death by a 
health care professional appropriate to the level of standard of care in the health care setting. 
AND 
Gestational age within pre-defined range for selected stillbirth definition as assessed by maternal and/or 
fetal parameters (Level1–2 in GA assessment algorithm). 
3 
Delivery of an infant reported to have no of signs of life at birth, including: No spontaneous movements, 
no umbilical cord pulse, no heartbeat, no cry, no spontaneous respirations or chest movement, and whole 
body cyanosis. AND 
Evidence of live fetus prior to onset of labor (maternal report of fetal movement prior to onset of labor OR 
auscultation of fetal heart tones) (Note: in the absence of evidence of a live fetus prior to the onset of 
labor, the fetal death should be reported as a stillbirth or an antepartum stillbirth). AND 
Non-attended delivery followed by physical examination of the fetus after birth consistent with intrapartum 
death by a healthcare professional appropriate to the level of standard of care in the health care setting 
OR verbal history by a trained health care provider, non-medical witness or the mother of a fetus born 
with no signs of life or unresponsive to resuscitation efforts immediately after birth. AND 
Gestational age within pre-defined range for selected stillbirth definition as assessed by maternal and/or 
fetal parameters (Level2–3 in GA assessment algorithm). 
4 
Report of stillbirth but fetus is not available for physical examination after birth (no objective assessment 
can be made). 
Maternal information insufficient to assess gestational age. 
Reference: DaSilva FT, Gonik B, McMillan M, et al. Stillbirth: Case definition and guidelines for data collection, 
analysis, and presentation of maternal immunization safety data. Vaccine. 2016; 34(49):6057-6068. 


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Table 29 
Maternal Death 
The death of a woman while pregnant or within 42 days of termination of pregnancy, 
irrespective of the duration and site of the pregnancy, from any cause related to or 
aggravated by the pregnancy or its management but not from accidental or incidental 
causes. (As ICD-10 terminology). 
In the context of immunization: Death of a woman during pregnancy, childbirth and the 
puerperium that is closely related temporally to an immunization event of the mother 
which is likely the single or contributory cause 
Levels of Diagnostic Certainty 
(Highest level (1) to lowest level of certainty) 
Level 
Description 
1 
Diagnosis of pregnancy established by any of the following documented criteria: 
1. 
Ultrasound examination 
2. 
Fetal heart tones 
3. 
Positive serum or urine human chorionic gonadotropin pregnancy test 
4. 
Delivery of a neonate or other products of conception (abortus, stillborn) 
AND 
5. 
Death of the mother while pregnant or within 42 days of termination of pregnancy, irrespective of the 
duration and site of the pregnancy 
AND 
Documentation of Cause of death as: 
6. 
Direct: abortive outcome, hypertensive disorder, obstetric hemorrhage, pregnancy-related infection, 
other obstetric complications, unanticipated complications 
7. 
Indirect: non-obstetric complications 
8. 
Death during pregnancy, childbirth and the puerperium: other or coincidental 
2 
Diagnosis of pregnancy established by any of the following criteria in the absence of Level 1 criteria: 
1. 
LMP date 
2. 
Serial Symphysio Fundal Height examinations 
AND 
Death of the mother while pregnant or within 42 days of termination of pregnancy, irrespective of the 
duration and site of the pregnancy And 
Documentation of Cause of death as: 
3. 
Direct: abortive outcome, hypertensive disorder, obstetric hemorrhage, pregnancy-related infection, 
other obstetric complications, unanticipated complications 
4. 
Indirect: non-obstetric complications 
5. 
Death during pregnancy, childbirth and the puerperium: other or coincidental 
6. 
Unspecified: unknown or undetermined 
3 
Absence of Level 1 or 2 criteria for establishing diagnosis of pregnancy and: 
1. 
Unsure LMP 
2. 
No clinical examination documented 
AND 
Death of the mother temporal to pregnancy, childbirth or the postpartum period when exact timing of 
death is unknown 
AND 
Documentation of cause of death as: 
3. 
Direct: abortive outcome, hypertensive disorder, obstetric hemorrhage, pregnancy-related infection, 
other obstetric complications, unanticipated complications 
4. 
Indirect: non-obstetric complications 
5. 
Death during pregnancy, childbirth and the puerperium: other or coincidental 
6. 
Unspecified: unknown or undetermined. 
Reference: Patwardhan M, Eckert LO, Spiegel H, et al. Maternal death: Case definition and guidelines for data 
collection, analysis, and presentation of immunization safety data. Vaccine. 2016;34(49):6077-6083. 


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Table 30 
Hypertensive disorders of pregnancy (Gestational hypertension, 
Pre-eclampsia, Pre-eclampsia with severe features including 
eclampsia) 
Levels of Diagnostic Certainty (Highest level (1) to lowest level of certainty) 
Gestational hypertension  
Level 
Description 
All 
Clinical syndrome characterized by pregnancy ≥20 weeks 
AND 
New onset hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) 
sustained on 2 measurements over a minimum of 1 h 
WITHOUT severe features (see pre-eclampsia with severe features category) and WITHOUT proteinuria 
1 
No proteinuria (as defined by 24 h urine collection < 300 mg, spot protein:creatinine ratio <0.3) 
2 
No proteinuria (as defined by urine dipstick negative or trace)  
In Ev 
Blood pressure cannot be measured OR 
No proteinuria evaluation is available 
Pre-eclampsia  
Level 
Description 
All 
Clinical syndrome characterized by pregnancy ≥20 weeks 
AND 
New onset hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) 
sustained on 2 measurements over a minimum of 1 h 
AND 
New onset proteinuria  
1 
Proteinuria diagnosed with ≥300 mg of protein on 24 h urine collection OR ≥0.3 on spot protein:creatinine 
ratio  
2 
Proteinuria diagnosed with ≥1+ protein on urine dipstick 
In Ev. 
Blood pressure cannot be measured 
OR 
no proteinuria evaluation is available (note diagnosis of pre-eclampsia with severe features does not 
require proteinuria, see definition below) 
In Ev = Insufficient Evidence 


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Hypertensive Disorders of Pregnancy Continued 
Pre-eclampsia with severe features NOTE :can be diagnosed in the presence or absence of proteinuria. 
Vascular: 
Severely elevated blood pressures, with systolic blood pressure≥160 mmHg and/or diastolic blood pressure ≥110 
mmHg, which is confirmed after only minutes (to facilitate timely anti-hypertensive treatment) 
Neurologic: 
Development of a severe headache (which can be diffuse, frontal, temporal or occipital) that generally does not 
improve with over the counter pain medications (such as acetaminophen/paracetamol) 
Eclampsia 
Development of visual changes (including photopsia, scotomata, cortical blindness) 
Hematologic: 
New onset thrombocytopenia, with platelet count <100,000/L 
Gastrointestinal: 
New onset of nausea, vomiting, epigastric pain 
Transaminitis (AST and ALT elevated to twice the upper limit of normal) 
Liver capsular hemorrhage or liver rupture 
Renal: 
Worsening renal function, as evidenced by serum creatinine level greater than 1.1 mg/dL or a doubling of the serum 
creatinine (absent other renal disease) 
Oliguria (urine output <500 mL/24 h) 
Respiratory: 
Pulmonary edema (confirmed on clinical exam or imaging) 
Level 
Description 
All 
Clinical syndrome characterized by pregnancy ≥20 weeks 
AND 
New onset hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) 
sustained on 2 measurements over a minimum of 1 h 
AND 
At least one of the criteria for severe disease: 
1 
At least one of the following: 
1. 
Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110mmHg, which is confirmed 
after only minutes OR 
2. 
Development of severe, persistent headache OR 
3. 
Development of visual changes OR 
4. 
Eclampsia* OR 
5. 
New onset thrombocytopenia (platelets <100,000/L) OR 
6. 
New onset unremitting epigastric pain OR 
7. 
AST and ALT elevated to twice upper limit of normal OR 
8. 
Evidence of liver capsular hematoma or liver rupture (diagnosed on clinical exam or with imaging) OR 
9. 
Worsening renal function, as evidenced by serum creatinine level greater than 1.1 mg/dL or a doubling 
of the serum creatinine (absent other renal disease) or oliguria (<500 cc/24 h) OR 
Pulmonary edema (confirmed on imaging with chest X-ray, or on clinical exam) 
2 
New onset nausea and vomiting  
In Ev 
Blood pressure cannot be measured 
◦* ECLAMPSIA, or new onset grand mal seizures in a patient with pre-eclampsia, without other provoking factors (such 
as evidence of cerebral malaria or pre-existing seizure disorder). Seizures are often preceded by headaches, 
visual changes or altered mental status: 
In Ev = Insufficient Evidence 
Reference: Rouse CE, Eckert LO, Wylie BJ, et al. Hypertensive disorders of pregnancy: Case definitions & guidelines 
for data collection, analysis, and presentation of immunization safety data. Vaccine. 2016;34(49):6069-6076 


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Table 31 
Fetal growth restriction 
A fetus with a sonographic estimation of fetal weight below the tenth percentile for a 
given gestational age with increasing specificity for adverse perinatal outcomes below the 
third percentile. 
Levels of Diagnostic Certainty (Highest level (1) to lowest level of certainty) 
Level 
Description 
 
Fetal growth restriction is a sonographic finding characterized by: 
1a 
Level 1* evidence of pregnancy dating 
AND 
• 
Estimated fetal weight below 3% using locally-accepted growth curve 
OR 
• 
Estimated fetal weight below 10% using locally-accepted growth curve 
AND 
• 
Absent or reversed end-diastolic flow of the umbilical artery Doppler 
OR 
• 
Oligohydramnios as defined as amniotic fluid index (AFI) < 8 cm or deepest vertical pocket (DVP) < 
2 cm in the presence of intact membranes without concern for fetal anomalies contributing to its 
etiology 
1b 
Level 1* evidence of pregnancy dating 
AND 
Estimated fetal weight below 10%ile using locally-accepted growth curve 
AND 
Lack of absent or reversed end-diastolic flow of the umbilical artery or oligohydramnios (as defined above, 
cfr. Level 1a) 
2a  
Level 2 evidence of pregnancy dating 
AND 
• 
Estimated fetal weight below 3% using locally-accepted growth curve 
OR 
• 
Estimated fetal below 10% using locally-accepted growth curve 
AND 
• 
Absent or reversed end-diastolic flow of the umbilical artery Doppler. 
OR 
• 
Oligohydramnios (as defined above, cfr. Level 1a). 
2b 
• 
Level 2 evidence of pregnancy dating 
AND 
Estimated fetal weight below 10%ile using locally-accepted growth curve 
AND 
No findings of absent or reversed end-diastolic flow of the umbilical artery or oligohydramnios (as defined 
above, cfr Level 1a). 
OR 
• 
Level 1* evidence of pregnancy dating 
AND 
Estimated fetal weight below 10% using locally-accepted growth curve with no findings of oligohydramnios 
(as defined above, cfr. Level 1a) with inability to assess umbilical artery Doppler. 
In Ev 
Absence of ultrasound for use in assessment of estimated fetal weight 
*Level 1 evidence of pregnancy dating as defined by the Preterm Birth Working Group of the Brighton Collaboration. 
Level 1 pregnancy dating depends on a confirmatory ultrasound performed ≤13 6/7 weeks gestation 
In Ev = Insufficient Evidence 
Reference: Easter SR, Eckert LO, Boghossian N, et al. Fetal growth restriction: Case definition & guidelines for data 
collection, analysis, and presentation of immunization safety data. Vaccine. 2017; 35: 6546-6554. 


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Table 32 
Gestational diabetes mellitus (pregnancy induced hyperglycemia) 
Gestational diabetes mellitus (GDM) is a clinical syndrome characterized by the absence 
of pre-gestational diabetes diagnosis, defined by 
• 
Previous diagnosis of diabetes while not pregnant 
OR 
• 
First trimester hemoglobin A1c level of ≥ 6.5% (47.5 mmol/mol) 
OR 
• 
First trimester fasting blood glucose 126 mg/dL / ≥ 7mmol/L 
AND 
• 
Identification of sustained hyperglycemia during pregnancy not due to other known 
causes (i.e. corticosteroids, beta-mimetics, etc.) 
Levels of Diagnostic Certainty (Highest level (1) to lowest level of certainty) 
Level 
Description 
1 
Absence of pre-gestational diabetes mellitus diagnosis in the first trimester as defined above with level 1-
2 certainty for gestational age using GAIA definition for gestational age (Section 10.8) 
AND 
Diagnosis of gestational diabetes based on a positive internationally recognized oral glucose tolerance 
test (“major criteria” 1,2) using venous blood sample/samples 
2 
Absence of pre-gestational diabetes mellitus diagnosis in the first trimester as defined above with at least 
level 1-2 certainty for gestational age using GAIA definition for gestational age (Section 10.8) 
AND 
Diagnosis of gestational diabetes based on positive internationally recognized oral glucose tolerance test 
(“major criteria” 1,2) using capillary blood sample/samples 
3 
Absence of pre-gestational diabetes mellitus diagnosis in the first trimester as defined above with at least 
level 3 certainty for gestational age using GAIA definition for gestational age 
AND 
Diagnosis of gestational diabetes based on positive internationally recognized oral glucose tolerance test 
(see below ‘‘major criteria”1,2) using venous blood or capillary blood sample/samples 
OR 
Diagnosis of gestational diabetes based on fasting plasma glucose of 5.1-6.9 mmol/l (92-125 mg/dL) 
using venous or capillary blood samples. 
In Ev 
Blood glucose cannot be measured 
OR 
Elevated postprandial blood glucose level without confirmatory 
fasting venous blood or capillary glucose level 
OR 
Use of Hemoglobin A1c alone for the diagnosis of GDM without a diagnostic oral glucose tolerance test 
(OGTT) or elevated fasting plasma glucose level. 
OR 
Clinical and laboratory findings such as glucosuria, fundal height greater than dates, obesity, prior history 
of GDM or family history for the diagnosis of gestational diabetes mellitus without a diagnostic test. 
In Ev = Insufficient Evidence 
Reference(s): Kachikis A, Eckert LO, Walker C, et al. Gestational diabetes mellitus: Case definition & guidelines for 
data collection, analysis, and presentation of immunization safety data. Vaccine. 2017; 35:6555-6562. 


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1 Major criteria (presented in Kachikis op cit) 
 
2 Further details regarding oral glucose tolerance tests presented in footnote 1 (Major Criteria); also presented in 
Kachikis (op cit) 
 


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Table 33 
Pathways to preterm birth 
Premature preterm rupture of membranes; Preterm labor; Insufficient cervix (not 
applicable to this study, as women with insufficient cervix are ineligible); Provider-
initiated preterm birth 
Preterm = Birth at less than 37 gestation-completed weeks (less than 259 days). 
Levels of Diagnostic Certainty (Highest level (1) to lowest level of certainty) 
Premature preterm rupture of membranes 
Level 
Description 
All 
Patient is determined to be preterm as defined above. 
• 
On presentation, patient is determined to not be in preterm labor, having ≤4 contractions per hour 
documented clinically or on tocodynometer, with <2 cm cervical dilation (greater than 4 contractions 
per hour would qualify the patient as having preterm labor) 
• 
Fluid can be noted to be clear, blood-tinged, meconium-tinged (fetal stool), purulent-tinged 
(yellowish, suggesting infection) 
1 
• 
Clinical history of rupture of membranes 
AND 
• 
Visible leakage of fluid on vaginal speculum exam 
AND 
• 
Visible arborization (ferning) on microscopy of amniotic fluid 
OR 
• 
Ultrasound with oligohydramnios (AFI <5 or MVP <2) 
AND 
• 
Documented membrane rupture by a diagnostic test (one of the below options): 
1. 
Positive intra-amniotic dye-injection method 
2. 
Positive result on amniotic fluid alpha-fetoprotein test kit 
3. 
Amniotic fluid pH measurement (nitrazine paper test) 
4. 
Amniotic fluid placental alpha macroglobulin-1 protein assay (PAMG-1) test (AmniSure test) 
5. 
Amniotic fluid insulin-like growth factor binding protein (IGFBP-1) test (Actim PROM test) 
2 
• 
Clinical history of rupture of membranes 
AND 
• 
Visible leakage of fluid on vaginal speculum examination 
AND 
• 
Visible arborization (ferning) on microscopy of amniotic fluid 
OR 
• 
Documented membrane rupture by a diagnostic test (one of those listed above) 
OR 
• 
Ultrasound with oligohydramnios (AFI <5 or MVP <2) 
3 
• 
Clinical history of rupture of membranes 
AND 
• 
Visible leakage of presumed amniotic fluid; this may be on vaginal speculum examination (pooling 
in vagina), on inspection of the perineum (wet perineum due to leakage of fluid from the vagina), or 
fluid soaked cloth/clothes/sanitary pad. 
 


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Preterm labor 
Level 
Description 
All 
Patient is determined to be have delivered preterm (at less than 37 gestation-completed weeks (less than 
259 days)).  
1 
• 
On presentation, >4 documented uterine contractions per hour as determined by a tocodynometer 
AND 
• 
Documented change in length or dilation of cervix by physical examination or transvaginal 
ultrasound over a 2 hour period, with clinical criteria for documenting cervical change by exam 
including: 
− 
Cervical dilation 2 cm or greater at the internal os by digital examination 
− 
Cervical length of 1 cm or less by digital examination 
− 
50% or greater effacement by digital examination 
2 
• 
Greater than 4 uterine contractions per hour as determined by a tocodynometer or clinical 
assessment 
AND 
• 
Documented change in length or dilation of cervix by physical examination, with clinical criteria 
including: 
− 
Cervical dilation 2 cm or greater at the internal os by digital examination 
− 
Cervical length of 1 cm or less by digital examination 
− 
50% or greater effacement by digital examination 
3 
• 
Greater than 4 documented uterine contractions per hour determined by clinical assessment 
AND 
• 
Documented change in cervical examination (change in dilation or effacement) over a 2 hour period 
Provider-initiated preterm birth 
Level 
Description 
All 
Patient is determined to be preterm (birth at less than 37 gestation-completed weeks [less than 259 
days]).  
1 
• 
Documentation in the healthcare record by a patient’s delivering provider that there were no signs 
or symptoms of the spontaneous onset of preterm labor 
AND 
• 
Documentation in the healthcare record by a patient’s delivering provider that the patient needed to 
undergo induction of labor or cesarean delivery which led to the preterm delivery  
2 
• 
From recall, delivering provider confirms that there was an absence of any signs or symptoms of 
the spontaneous onset of preterm labor 
AND 
• 
Delivering provider reports from recall that he or she decided that the patient needed to undergo 
induction of labor or cesarean delivery 
3 
• 
From recall, patient confirms that there was an absence of any signs or symptoms of the 
spontaneous onset of preterm labor 
AND 
• 
Patient reports from recall that the healthcare provider indicated that she needed to undergo 
induction of labor or cesarean delivery 
Reference: Harrison MS, Eckert LO, Cutland C, et al. Pathways to preterm birth: Case definition and guidelines for 
data collection, analysis, and presentation of immunization safety data. Vaccine. 2016;34(49):6093-6101. 


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Table 34 
Chorioamnionitis 
Chorioamnionitis encompasses a broad spectrum of disease during pregnancy that is 
characterized by inflammation and/or infection of intrauterine structures such as the 
placenta, the chorion and amnion. 
This case definition focuses on the infectious manifestation of chorioamnionitis, intra-
amniotic infection. Four definitions of chorioamnionitis have been developed based on 
systematic literature review, are summarized below, and must be considered when 
applying the case definitions. 
It is important to rule out other obvious sources of acute systemic infection (i.e. 
pyelonephritis) prior to chorioamnionitis diagnosis. 
Level 
Description 
All 
levels 
Clinical Definition A: 
Maternal fever ≥ 38 degrees Celsius on one occasion plus one or more of: 
• 
Baseline fetal tachycardia (FHR > 160 bpm for 10 min or longer, excluding accelerations, 
decelerations and periods of marked variability or, where continuous monitoring is not available, an 
FHR exceeding 160 bpm during and after at least 3 consecutive contractions) 
• 
Maternal WBC ≥ 15,000 per mm3 in the absence of corticosteroids. 
• 
Definite purulent fluid from the cervical os. 
Clinical Definition B 
Maternal fever ≥ 38 degrees Celsius on one occasion plus 2 of: 
• 
Maternal tachycardia (HR > 100 bpm) 
• 
Baseline fetal tachycardia (FHR > 160 bpm for 10 min or longer, excluding accelerations, 
decelerations and periods of marked variability or, where continuous monitoring is not available, an 
FHR exceeding 160 bpm during and after at least 3 consecutive contractions) 
• 
Purulent fluid from the cervical os. 
• 
Uterine tenderness 
• 
Maternal WBC ≥ 15,000 per mm3 in the absence of corticosteroids 
Histologic diagnosis: 
• 
Positive finding of invasion of maternal polymorphonuclear leukocytes into the placental plate, the 
chorion and/or amnion which meets criteria based on a widely accepted histopathologic staging and 
grading system [such as Blanc1 Redline2, or Salafia3 criteria]. 
Culture criteria: 
• 
Positive culture of amniotic fluid (via amniocentesis), and/or 
• 
Positive culture of placental membranes (between chorion/amnion) 
GAIA gestational age level 1–2 criteria denote higher gestational age certainty including a combination 
of certain last menstrual period (LMP), first or second trimester ultrasound or first trimester exam 
confirmation. Level 3 diagnostic certainty for gestational age has a lower accuracy compared to levels 1–
2. (see Section 10.8) 
1a 
Clinical Definition A 
AND 
Confirmation via histopathology or culture 
AND 
Gestational age  22–0/7 weeks by GAIA gestational age level 1–2 criteria  
1b 
Clinical Definition A 
AND 
Confirmation via histopathology or culture 
AND 
Gestational age  22–0/7 weeks by ANY GAIA gestational age criteria 


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Level 
Description 
2a 
Clinical Definition A 
OR 
Chorioamnionitis via histopathology or culture 
AND 
Gestational age  22–0/7 weeks by GAIA gestational age level 1–2 criteria  
2b 
Clinical Definition B 
AND 
Gestational age  22–0/7 weeks by GAIA gestational age level 1–2 criteria 
2c 
Clinical Definition A or B 
OR 
Chorioamnionitis via histopathology or culture 
AND 
Gestational age  22–0/7 weeks by any GAIA gestational age criteria 
3a 
Clinical definition A or B with report of fever or maternal feeling of ‘‘feverishness”. 
AND 
Gestational age  22–0/7 weeks by any GAIA gestational age criteria  
3b 
Clinical definition B without fever (documented or reported) 
AND 
Gestational age  22–0/7 weeks by any GAIA gestational age criteria 
1W.A. Blanc Pathology of the placenta, membranes, and umbilical cord in bacterial, fungal, and viral infections in man. 
Monogr Pathol, 22 (1981), pp. 67-132 
2R.W. Redline, O. Faye-Petersen, D. Heller, F. Qureshi, V. Savell, C. Vogler Amniotic infection syndrome: nosology 
and reproducibility of placental reaction patterns. Pediatric Dev Pathol: Off J Soc Pediatric Pathol Paediatric 
Pathol Soc, 6 (5) (2003), pp. 435-448 
3C.M. Salafia, C. Weigl, L. Silberman The prevalence and distribution of acute placental inflammation in uncomplicated 
term pregnancies. Obstet Gynecol, 73 (3 Pt 1) (1989), pp. 383-389 
Reference: Kachikis, A, Eckart L, Walker C et al. Chorioamnionitis: Case definition & guidelines for data collection, 
analysis, and presentation of immunization safety data. Vaccine. 2019; 7610–7622 


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Table 35 
Small for gestational age 
Weight below 10th percentile for gestational age as assessed against a validated global, 
regional or local standard. 
Levels of Diagnostic Certainty (1 highest level to 4 lowest level of certainty) 
Level 
Description 
1 
• 
Weight below 10th percentile for gestational age 
AND 
• 
The following used in assessment of weight: 
− 
Newborn weighed within 24 hours of birth 
− 
Weight assessed using a calibrated electronic scale with 10 g resolution 
AND 
• 
The following for assessment of gestational age: 
− 
Certain LMP or IUI or ET date AND confirmatory ultrasound in first trimester 
OR 
− 
First trimester ultrasound 
2a 
• 
Weight below 10th percentile for gestational age 
AND 
• 
The following used in assessment of weight: 
− 
Newborn weighed within 24 hours of birth on any scale with a < 50 g resolution, tared to zero 
and calibrated 
AND 
• 
The following for assessment of gestational age: 
− 
Certain LMP with first or second trimester ultrasound 
OR 
− 
Certain LMP with first trimester physical exam 
2b 
• 
Weight below 10th percentile for gestational age 
AND 
• 
The following used in assessment of weight: 
− 
Newborn weighed within 24 hours of birth on any scale with a < 50 g resolution, tared to zero 
and calibrated 
AND 
• 
The following assessment of gestational age: 
− 
Uncertain LMP with second trimester ultrasound 
3a 
• 
Weight below 10th percentile for gestational age 
AND 
• 
The following used in assessment of weight: 
− 
Infant weighed within the first 48 hours of life 
− 
Newborn weighed on any scale with a < 50 g resolution, tared to zero and calibrated 
AND 
• 
The following assessment of gestational age: 
− 
Certain LMP with third trimester ultrasound 
OR 
− 
Certain LMP with confirmatory 2nd trimester fundal height 
OR 
− 
Certain LMP with birthweight 
OR 
− 
Uncertain LMP with first trimester physical exam  
 


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Small for Gestational Age (continued) 
Level 
Description 
3b 
• 
Weight below 10th percentile for gestational age 
AND 
• 
The following used in assessment of weight: 
− 
Infant weighed within the first 48 hours of life 
− 
Newborn weight assessed by measuring the difference between an adult holding the infant 
and the adult being weighed alone on any scale 
AND 
• 
The following assessment of gestational age: 
− 
Uncertain LMP with fundal height 
OR 
− 
Uncertain LMP with newborn physical assessment 
OR 
− 
Uncertain LMP with birthweight 
4 
• 
Baby noted to be small, but no actual weight 
• 
Baby with GA assessed only by infant examination 
• 
Diagnosis extracted from billing codes or chart, with no documentation of actual birth weight or GA 
Reference: Schlaudecker EP, Munoz FM, Bardají A, et al. Small for gestational age: Case definition & guidelines for 
data collection, analysis, and presentation of maternal immunization safety data. Vaccine. 2017; 35:6518-6528. 


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Table 36 
Low Birth Weight (LBW) 
Regardless of gestational age: 
• 
Low birth weight (LBW): <2500 grams 
• 
Very low birth weight (VLBW): <1500 grams 
• 
Extremely low birth weight (ELBW): <1000grams 
Levels of Diagnostic Certainty (1 highest level to 4 lowest level of certainty) 
Level 
Description 
1 
Newborn infant weighed within 24 hours of birth 
AND 
Use electronic scale which is graduated to 10 grams 
AND 
Scale is calibrated at least once a year 
AND 
Scale placed on level, hard surface 
AND 
Scale tared to zero grams 
AND 
Weight recorded as <2500 grams 
OR 
Birth weight recorded as <2500 grams 
AND 
Birth weight assessed as per health care facility’s standard operating procedure, which fulfills criteria 1 to 
5 above. 
2 
Newborn infant weighed within 24 hours of birth 
AND 
Scale (electronic/spring) is graduated to at least 50 grams 
AND 
Scale is calibrated at least once a year, or more often if moved 
AND 
Scale tared to zero grams or 0.00kg 
AND 
Weight recorded as <2500 grams 
OR 
Birth weight recorded as <2500 grams AND 
Birth weight assessed as per health care facility’s standard operating procedure, which fulfills criteria 1 to 
4 above. 
(Scale used could be electronic or spring scale, including color-coded scale) 
3 
Newborn infant weighed on day 1 or 2 of life (first 48 hours of life) 
AND 
Weight measured using dial/spring/color-coded scale 
AND 
Weight assessed as <2500 grams 
4 
Newborn weight assessed between day 1 and 2 of life (first 48 hours) 
AND 
Proxy measure (newborn foot length, chest circumference, mid-upper arm circumference) of birth weight 
used 
AND 
Weight CATEGORY assessed as <2500 grams 
Reference: Cutland CL, Lackritz EM, Mallett-Moore T, et al. Low birth weight: Case definition & guidelines for data 
collection, analysis, and presentation of maternal immunization safety data. Vaccine. 2017; 35:6492-6500. 


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Table 37 
Major Congenital anomalies 
Congenital anomalies, also commonly referred to as birth defects, congenital disorders, 
congenital malformations, or congenital abnormalities. Major congenital anomalies are 
events of prenatal origin that are represent at birth, potentially impacting an infant’s 
health, development and/or survival. 
Major and minor characterization of congenital anomalies are assessed based on CDC 
classification [CDC]. 
Only major congenital anomalies are reported as AESIs based on the CDC classification 
[CDC]. 
Levels of Diagnostic Certainty (1 highest level to 4 lowest level of certainty) 
Major External Structural Defects 
Level 
Description 
1 
Alterations in external anatomy visible: 
• 
at the time of live birth and persistent beyond the immediate peripartum period unless surgically 
repaired 
OR 
• 
in a stillbirth or in the products of conception of a spontaneous or therapeutic abortion 
AND 
Confirmed by documentation of a diagnosis made by a clinician experienced in diagnosing congenital 
anomalies and with the highest level of morphology training for the specific setting 
2 
Alterations in external anatomy visible: 
• 
at the time of live birth and persistent beyond the immediate peripartum period unless surgically 
repaired 
OR 
• 
in a stillbirth or in the products of conception of a spontaneous or therapeutic abortion 
AND 
Confirmed by documentation of a diagnosis made by a clinician with some experience diagnosing 
congenital anomalies 
3 
Alterations in external anatomy visible: 
• 
at the time of live birth and persistent beyond the immediate peripartum period unless surgically 
repaired 
OR 
• 
in a stillbirth or in the products of conception of a spontaneous or therapeutic abortion 
AND 
Confirmed: 
• 
by documentation of a diagnosis made by a trained maternal or child health care provider with at 
least minimal experience diagnosing congenital anomalies 
OR 
• 
For live births, by using individual (ICD-9/ICD-10) codes or as part of an ICD-9/ICD-10 code based 
algorithm, where the outcome (individual code or algorithm) has been validated 
4 
(Insufficient evidence to confirm) 
Alterations in external anatomy visible: 
• 
at the time of live birth and persistent beyond the immediate peripartum period unless surgically 
repaired 
OR 
• 
in a stillbirth or in the products of conception of a spontaneous or therapeutic abortion 
AND 
Confirmed: 
• 
by medical record review 
OR 
• 
in claims data (ICD-9/ICD-10 diagnoses)  


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Internal Structural Defects 
Level 
Description 
1 
Alterations in internal anatomy present at the time of live birth and persistent beyond the immediate 
peripartum period unless surgically repaired 
AND 
Confirmed by definitive imaging study or intraoperative diagnosis 
OR 
Alterations in internal anatomy detected during autopsy for a stillbirth, spontaneous or therapeutic 
abortion confirmed by documentation by a pathologist or other relevant subspecialist  
2 
Alterations in internal anatomy present at the time of live birth and persistent beyond the immediate 
peripartum period unless surgically repaired 
AND 
Confirmed by documentation of a diagnosis made by a clinician experienced in diagnosing congenital 
anomalies and with the highest level of morphology training for the specific setting without definitive 
imaging or intraoperative evaluation 
OR 
For stillbirth, spontaneous or therapeutic abortion, internal structural defect is visible by ultrasound or 
other imaging modality prenatally 
3 
Alterations in internal anatomy present at the time of live birth and persistent beyond the immediate 
peripartum period unless surgically repaired 
AND 
Confirmed: 
• 
by documentation of a diagnosis made by a clinician with some experience diagnosing congenital 
anomalies 
OR 
• 
using individual (ICD-9/ICD-10) codes or as part of an ICD-9/ICD-10 code based algorithm, where 
the outcome (individual code or algorithm) has been validated 
4 
(Insufficient evidence to confirm) 
Alterations in internal anatomy present: 
• 
at the time of live birth and persistent beyond the immediate peripartum period unless surgically 
repaired 
OR 
• 
at time of stillbirth, spontaneous abortion, or induced abortion 
AND 
Confirmed: 
• 
through medical record review, with the medical record demonstrating that the anomaly was 
present at the time of live birth or time of fetal demise, and that the anomaly was diagnosed by a 
trained maternal or child health care provider with minimal experience diagnosing congenital 
anomalies 
OR 
• 
by claims data (ICD-9/ICD-10 diagnoses) 


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Functional Defects 
Level 
Description 
1 
For live births, alterations in functioning of one or more organs or body parts not due to a structural 
defect, present at the time of birth (or propensity to develop alteration present at live birth), and persistent 
beyond the immediate peripartum period, unless treated through gene therapy or stem cell 
transplantation 
OR 
For stillbirths, spontaneous or therapeutic abortions, alterations in functioning of one or more organs or 
body parts, not due to a structural defect 
AND 
Confirmed by definitive diagnostic study 
2 
For live births, alterations in functioning of one or more organs or body parts not due to a structural 
defect, present at livebirth (or propensity to develop alteration present at live birth), and persistent beyond 
the immediate peripartum period, unless treated through gene therapy or stem cell transplantation 
OR 
For stillbirths, spontaneous or therapeutic abortions, alterations in functioning of one or more organs or 
body parts, not due to a structural defect 
AND 
Confirmed by documentation of a diagnosis made by a clinician experienced in diagnosing congenital 
anomalies and with the highest level of training in the diagnosis of functional defects for the specific 
setting 
3 
For live births, alterations in functioning of one or more organs or body parts not due to a structural 
defect, present at livebirth (or propensity to develop alteration present at live birth), and persistent beyond 
the immediate peripartum period, unless treated through gene therapy or stem cell transplantation OR 
For stillbirths, spontaneous or therapeutic abortions, alterations in functioning of one or more organs or 
body parts, not due to a structural defect 
AND 
Confirmed: 
• 
by documentation of a diagnosis made by a clinician with some experience diagnosing functional 
defects 
OR 
• 
using individual (ICD-9/ICD-10) codes or as part of an ICD-9/ICD-10 code based algorithm, where 
the outcome (individual code or algorithm) has been validated 
4 
(Insufficient evidence to confirm) 
For live births, alterations in functioning of one or more organs or body parts not due to a structural 
defect, present at the time of live birth (or propensity to develop alteration present at livebirth), and 
persistent beyond the immediate peripartum period, unless treated through gene therapy or stem cell 
transplantation 
OR 
For stillbirths, spontaneous or therapeutic abortions, alterations in functioning of one or more organs or 
body parts, not due to a structural defect 
AND 
Confirmed: 
• 
through medical record review, with the medical record demonstrating that the anomaly was 
present at the time of live birth or time of fetal demise, and that the anomaly was diagnosed by a 
trained maternal or child healthcare provider who is not a qualified geneticist, neonatologist, 
pathologist, subspecialist, pediatrician, obstetrician, or family medicine practitioner 
OR 
• 
by claims data (ICD-9/ICD-10 diagnoses) 
Reference: DeSilva M, Munoz FM, Mcmillan M, et al. Congenital anomalies: Case definition and guidelines for data 
collection, analysis, and presentation of immunization safety data. Vaccine. 2016;34(49):6015-6026. 


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Table 38 
Neonatal Death 
Death of a live-born infant regardless of gestational age at birth, within the first 28 
completed days of life 
Levels of Diagnostic Certainty (1 highest level to 4 lowest level of certainty) 
Neonatal death in a non-viable live birth 
Level 
Description 
1 
Live-born infant 
AND 
• 
Gestational age <22 weeks (GA level of certainty = 1) 
OR 
• 
Birth weight <500 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death 
2 
Live-born infant 
AND 
Gestational age/size of newborn assessed as at least one of: 
• 
Gestational age <22 weeks (GA Level of Certainty = 1 OR 2) 
• 
Birth weight <500 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death OR non-medically-confirmed death 
3 
Live-born infant 
AND 
Gestational age <5 months according to parent/family member/delivery attendant (GA Level of Certainty 
= 2 OR 3) 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death OR non-medically-confirmed death 
Neonatal death in an extremely preterm live birth 
Level 
Description 
1 
Live-born infant 
AND 
• 
Gestational age ≥22 and <28 weeks (GA Level of Certainty = 1) 
OR 
• 
Birth weight ≥500 g but <1000 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death 
2 
Live-born infant 
AND 
Gestational age/size of newborn assesses as one or more of: 
• 
Gestational age ≥22 and <28 weeks (GA Level of Certainty = 1 OR 2) 
• 
Birth weight ≥500 g but <1000 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death OR non-medically-confirmed death 


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Neonatal death in an extremely preterm live birth (continued) 
Level 
Description 
3 
Live-born infant 
AND 
Gestational age ≥5 months but <7 months according to neonate’s parent (mother/father)/family 
member/delivery attendant (GA Level of Certainty = 2 OR 3) 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death OR non-medically-confirmed death 
Neonatal death in a preterm live birth (gestational age ≥28to <37 weeks) 
Level 
Description 
1 
Live-born infant 
AND 
• 
Gestational age ≥28 and <37 weeks (Level of Certainty = 1) 
OR 
• 
Birth weight ≥1000 g but <2500 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death 
2 
Live-born infant 
AND 
Gestational age/size of newborn assesses as one or more of: 
• 
Gestational age ≥28 and <37 weeks (GA Level of Certainty = 1 OR 2) 
• 
Birth weight ≥1000 g but <2500 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death OR non-medically-confirmed death 
3 
(MAY apply to LMIC- or may be non-viable in LMIC) 
Live-born infant 
AND 
Gestational age ≥7 months but <9 months according to parent/family member/delivery attendant (GA 
Level of Certainty = 2 OR 3) 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death OR non-medically-confirmed death 
Neonatal death in a term live birth 
Level 
Description 
1 
Live-born infant AND 
Gestational age ≥37 weeks (GA Level of Certainty = 1) AND 
• 
Birth weight >2500 g 
OR 
• 
Documented intrauterine growth retardation if ≤2500 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death 


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Neonatal death in a term live birth (continued) 
Level 
Description 
2 
Live-born infant 
AND 
Gestational age/size of newborn assesses as one or more of: 
• 
Gestational age ≥37 weeks (GA Level of Certainty = 1 OR 2) 
• 
Birth weight ≥2500 g 
AND 
Death of infant in first 28 days of life 
AND 
Medically-confirmed death OR non-medically-confirmed death which is confirmed by examination by (by 
at least) non-medically-trained attendant (e.g. undertaker, community member) 
3 
(apply to Lower Middle Income Countries) 
Live-born infant AND 2. Gestational age ≥9 months according to parent/family member/delivery attendant 
(GA Level of Certainty = 2 OR 3) AND 
• 
Death of infant in first 28 days of life 
AND 
• 
Medically-confirmed death OR non-medically-confirmed death 
Reference: Pathirana J, Munoz FM, Abbing-Karahagopian V, et al. Neonatal death: Case definition & guidelines for 
data collection, analysis, and presentation of immunization safety data. Vaccine. 2016;34(49):6027-6037. 
Table 39 
Preterm Birth 
Birth in less than 37 gestation-completed weeks (less than 259 days). 
Prematurity and assessment of gestational age  
Level 
Description 
1 
Certain last menstrual period date (LMP) LMP or intrauterine insemination (IUI) date or embryo-transfer 
(ET) date with confirmatory 1st trimester scan (≤13 6/7 weeks). 
OR 
1st trimester scan (≤13 6/7 weeks) 
2a 
Certain LMP* with 2nd trimester scan (14 0/7 weeks to 27 6/7weeks). 
Note: If LMP and U/S do not correlate, default to U/S GA assessment. 
OR 
Certain LMP* with 1st trimester physical examination. 
2b 
Uncertain LMP with 2nd trimester scan (14 0/7 weeks to 27 6/7 weeks). 
3a 
Certain LMP with 3rd trimester scan ≥ 28 0/7 weeks.  
* 
Definitions of LMP, birth weight and physical assessment in referenced article. 
Adapted from Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: Case definition &amp; guidelines for data collection, 
analysis, and presentation of immunization safety data. Vaccine. 2016;34(49):6047-6056. 


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10.10. 
Appendix 10: Protocol Amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment 
is located directly before the Table of Contents (TOC). 
DOCUMENT HISTORY 
Document 
Date of Issue 
Protocol 
12 March 2021 
Protocol Amendment 1 
15 March 2022 
Detailed description of the current Protocol amendment changes: 
In this section, deleted text is indicated in strikethrough and changed text in bold italics. 
• 
Section 1.1, Synopsis 
The objective of the study is to evaluate the safety, reactogenicity, and immunogenicity * 
of the single intramuscular 120 µg dose of the study RSV maternal vaccine compared to 
placebo, in women with high risk pregnancies in the late second or third trimester of 
pregnancy and in the infants born to the vaccinated mothers. 
* Based on all available safety information following vaccination with RSV MAT 
vaccine, there will be no further enrollment and vaccination of maternal participants. 
However, monitoring will continue for rest of the study. All planned objectives will be 
assessed for the participants enrolled so far. 
• 
Section 1.2, Schema 
The study is a Phase III, double-blind*, randomized, placebo-controlled, multi-center, 
multi-country study. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
[...] 
Approximately 378 eligible maternal participants will be enrolled *and randomized (2:1) 
to receive either RSV MAT vaccine or the placebo control. At least eighteen (5%) of the 
enrolled and randomized maternal participants will be between 15 and 17 YOA, 
inclusive. At the same time, infant participants (as yet unborn) will be further randomized 
(1:1:1) into sub-cohorts for blood sample collection for the assessment of 
immunogenicity at one of 3 timepoints (Day 43, Day 121 or Day 181 post-birth). 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 


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[...] 
All maternal participants who receive the study intervention (exposed set [ES]) will be 
followed for safety and reactogenicity and evaluated for: solicited administration site and 
systemic adverse events (AEs) within 7 days of study intervention, unsolicited AEs 
within 30 days of study intervention, pregnancy outcomes and pregnancy-related adverse 
events of special interest (AESIs) within 42 days of delivery, serious adverse events 
(SAEs), medically attended respiratory tract illnesses (MA-RTIs)* and medically 
attended adverse events (MAEs) throughout the study period and up to the time of the 
last contact. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
[…] 
Blood samples for humoral immunogenicity will be collected from sub-cohorts of infant 
participants at Day 43, Day 121 and Day 181 post-birth*. A second analysis of 
immunogenicity based on the FAS may be performed to complement the PPS analysis 
(Refer to Sections 9.3 and 9.4.1.2 for details). 
* Due to the change in the study requirements, there will no longer be collection of 
blood samples at Visit-2NB, Visit-3NB and Visit-4NB. 


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• 
Section 1.3, Schedule of Activities (SoA) 
Table 1 
Schedule of Activities (SoA) – Maternal participants 
Visit / 
Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associa
ted MA-
RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoin
t 
D (-28) 
– D 1 
D1 
(24 0/7 
- 36 0/7 
weeks 
of 
gestati
on) 
D8 
D31 
 
Delivery 
D43 
Post
-
deliv
ery 
D181 
Post-
delive
ry 
 
 
For monthly 
contacts: 
Section 
8.4.2.1 
Additional 
contacts 
and/or visits 
can be 
made 
between 
Visit-2 and 
the Delivery 
visit if 
deemed 
necessary. 
Informed 
consent/a
ssent 
● 
 
 
 
 
 
 
 
 
 
Section 
10.1.3 
Due to the 
recent 
safety 
signal, there 
will be no 
further 
enrollment 
and 
vaccination 
of maternal 
participants
. 
[…] 
 
 
 
 
 
 
 
 
 
 
 
Blood 
sample 
(hematocr
it: ~ 3.0 
ml) 
 
● 
 
● 
 
● 
 
 
 
 
Sections 
8.1.1 and 
8.1.3 
[…] 
 
 
 
 
 
 
 
 
 
 
 
Nasal 
swab 7 
 
 
 
 
 
 
 
 
 
● 
Sections 
8.1.1, 8.1.3, 
and 8.4.4 
Nasal swab 
samples will 
no longer 
be 
collected. 


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Visit / 
Contact 
Screening 
V1 
C1 
V2 1  
Monthly 
contacts 
until 
delivery 6 
V3 
V4 
C2 
Safety 
Visit - 
Event-
driven 
RSV-
associa
ted MA-
RTI 
Visit - 
Event-
driven 7 
Notes 
Timepoin
t 
D (-28) 
– D 1 
D1 
(24 0/7 
- 36 0/7 
weeks 
of 
gestati
on) 
D8 
D31 
 
Delivery 
D43 
Post
-
deliv
ery 
D181 
Post-
delive
ry 
 
 
For monthly 
contacts: 
Section 
8.4.2.1 
Additional 
contacts 
and/or visits 
can be 
made 
between 
Visit-2 and 
the Delivery 
visit if 
deemed 
necessary. 
Placental 
tissue 
sample 8 
 
 
 
 
 
● 
 
 
 
 
Section 
10.2.1  
Samples 
will be 
collected at 
delivery 
from all 
participants
, if feasible. 
[…] 
 
 
 
 
 
 
 
 
 
 
 
MA-RTIs 
(Day 1 
post-study 
interventio
n to 180 
days post-
delivery) 7 
 
O 5 
O 5 
O 5 
O 5 
O 5 
O 5 
O 5 
 
● 
Sections 
8.3.1, 8.3.3, 
8.4 and 
10.3.8 
MA-RTIs for 
the 
maternal 
participants 
will no 
longer be 
performed. 
 
 
 
 
 
 
 
 
 
 
 
 
V = visit; C = Contact; D = day; MA-RTI = medically attended respiratory tract illness; Hct = hematocrit; LAR = Legally 
acceptable representative 
[…] 
6 In addition to the monthly contacts between Visit-2 and the Delivery visit, additional not pre-specified 
contacts and/or visits can be made more often (at any desired frequency), as per investigator’s, maternal 
participant’s or LAR’s discretion. 
7 Due to the change in the study requirements, RTI surveillance/ assessment for the maternal participants will 
no longer be performed  
8 Placental tissue samples will be collected at delivery from all maternal participants, whenever feasible. These 
samples may be tested to support possible safety assessments, if necessary. Additional details are 
provided in the study procedures manual (SPM). 


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Note: 
The double-line border following Day 43 post-delivery indicates the analyses which will be performed on all data 
obtained up to Day 43 post-delivery (Visit 4). 
Table 2 
Schedule of activities (SoA) – Infant participants 
Visit / 
Contact 
V1
-
NB 
Recommen
ded safety 
contact 5 
V2-
NB 
C1-
NB 
V3-
NB 
V4-
NB 
C2-
NB 
V5-
NB 
RTI 
Surveillance 
Notes 
 
Contac
ts 
(Sectio
n 
8.4.2.2
.1) 
Visit 
Age of 
infant 
 
8 days 
6 
wee
ks 
3 
mont
hs 
4 
mont
hs 
6 
mont
hs 
9 
mont
hs 
12 
mont
hs 
 
 
Visit Day 
Birt
h 
D87  
Post-birth 
D43 
Post
-
birth 
D91 
Post-
birth 
D121 
Post-
birth 
D181 
Post-
birth 
D271 
Post-
birth 
D366 
Post-
birth 
Birth to 
Day 
366 
Post-
birth 
Eve
nt-
Driv
en 
[…] 
 
 
 
 
 
 
 
 
 
 
 
Review 
infant RTI 
diary card 
 
O 
O 
O 
O 
O 
O 
O 
O 
O 
 
[…] 
 
 
 
 
 
 
 
 
 
 
 
Transcribe 
applicable 
infant RTI 
diary card 
data to 
eCRF 
 
O 
● 
● 
● 
● 
● 
● 
● 
● 
 
[…] 
 
 
 
 
 
 
 
 
 
 
 
Lifestyle 
characterist
ics 1  
● 
O 
● 
● 
● 
● 
● 
● 
 
 
 
[…] 
 
 
 
 
 
 
 
 
 
 
 
Blood 
sample 
(immunolo
gy, infants) 
~2.5 ml 3, 6  
 
 
● 
Sub-
coh
ort 1 
 
● 
Sub-
coho
rt 2 
● 
Sub-
coho
rt 3 
 
 
 
 
Table 12 
Samples 
will no 
longer be 
collected 
at Visit 2-
NB, Visit 
3-NB and 
Visit 4-NB 
Concomita
nt 
vaccination
s 
● 
O 
● 
● 
● 
● 
 
 
 
 
Sections 
6.8.2 and 
6.8.3 
Concomita
nt 
medication
s  
● 
O 
● 
● 
● 
● 
● 
● 
● 
● 
[…] 
 
 
 
 
 
 
 
 
 
 
 


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Visit / 
Contact 
V1
-
NB 
Recommen
ded safety 
contact 5 
V2-
NB 
C1-
NB 
V3-
NB 
V4-
NB 
C2-
NB 
V5-
NB 
RTI 
Surveillance 
Notes 
 
Contac
ts 
(Sectio
n 
8.4.2.2
.1) 
Visit 
Age of 
infant 
 
8 days 
6 
wee
ks 
3 
mont
hs 
4 
mont
hs 
6 
mont
hs 
9 
mont
hs 
12 
mont
hs 
 
 
Visit Day 
Birt
h 
D87  
Post-birth 
D43 
Post
-
birth 
D91 
Post-
birth 
D121 
Post-
birth 
D181 
Post-
birth 
D271 
Post-
birth 
D366 
Post-
birth 
Birth to 
Day 
366 
Post-
birth 
Eve
nt-
Driv
en 
[…] 
 
 
 
 
 
 
 
 
 
 
 
Suspected, 
probable 
and 
confirmed 
cases of 
COVID-19 
infection 
(depending 
on the 
epidemiolo
gical 
COVID-19 
situation) 
(Birth to 
365 days 
post-birth) 
● 
O 
● 
● 
● 
● 
● 
● 
● 
● 
Sections 
8.4.7 
LRTIs 
(including 
medically 
assessed, 
RSV-
associated 
LRTIs) 
(Birth to 
365 days 
post-birth) 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
● 
Sections8.
3.1, 8.3.3, 
8.4and 
10.3.8. 
Medically 
assessed, 
RSV-
associated 
hospitalizat
ions (Birth 
to 365 days 
post-birth) 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
O 4 
● 
Sections 
8.3.1, 
8.3.3, 8.4 
and 
10.3.8. 
SAEs, 
(S)AEs 
leading to 
study 
withdrawal, 
MAEs 
● 
O 
● 
● 
● 
● 
● 
● 
● 
● 
Sections7.
2, 
8.3.1and 
10.3.8 


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Visit / 
Contact 
V1
-
NB 
Recommen
ded safety 
contact 5 
V2-
NB 
C1-
NB 
V3-
NB 
V4-
NB 
C2-
NB 
V5-
NB 
RTI 
Surveillance 
Notes 
 
Contac
ts 
(Sectio
n 
8.4.2.2
.1) 
Visit 
Age of 
infant 
 
8 days 
6 
wee
ks 
3 
mont
hs 
4 
mont
hs 
6 
mont
hs 
9 
mont
hs 
12 
mont
hs 
 
 
Visit Day 
Birt
h 
D87  
Post-birth 
D43 
Post
-
birth 
D91 
Post-
birth 
D121 
Post-
birth 
D181 
Post-
birth 
D271 
Post-
birth 
D366 
Post-
birth 
Birth to 
Day 
366 
Post-
birth 
Eve
nt-
Driv
en 
[…] 
 
 
 
 
 
 
 
 
 
 
 
(Birth to 
365 days 
post-birth) 
[…] 
5 An additional recommended safety contact may be performed ~7 days post-birth if deemed necessary by the 
investigator or by the parent/ LAR(s). 
6 Due to the change in the study requirements, there will no longer be collection of blood samples at Visit 2-
NB, Visit 3-NB and Visit 4-NB. 
Note  
The double-line border following Day 43 post-birth indicates the analyses which will be performed on all data obtained 
up to Day 43 post-birth (Visit 2-NB). 
Table 3 
Allowed windows for study visits 
Visit 
Study Day a 
Allowed visit window b 
Maternal participants 
[…] 
 
 
Visit 3 (Delivery) d 
- 
1 day before to 3 days after 
deliveryG  
[…] 
 
 
Infant participants 
[…] 
 
 
Recommended safety contact 
Day 8 
Day 7 - Day 10 
[…] 
G For participants in whom a cesarean section is performed, the sample may be collected as soon as the 
participant arrives at the clinic and the intravenous line is inserted to prepare them for the cesarean 
section. 
• 
Section 2.3, Benefit/Risk assessment 
The Sponsor has included provisions in this trial to ensure participant’s safety. Safety 
monitoring has been and will be conducted throughout this study by an unblinded 
Independent Data Monitoring Committee (IDMC) and by the Sponsor. The study 
includes the establishment of a surveillance system which may facilitate detection of 
respiratory tract infections, in particular lower respiratory tract infections (LRTIs) in 
infants enrolled in the study. Measures to suspend the study should a potential safety 
issue be identified are described in Section 8.2.3. 


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Following a recommendation from the IDMC, the Sponsor made the decision to pause 
the enrollment, randomization and vaccination of participants in our active pregnant 
women studies, including RSV MAT-012, based on an observation of imbalance of the 
proportion of preterm births between the vaccine group and the placebo group in the 
RSV MAT-009 study. This pause was to allow for an evaluation of the available data in 
RSV MAT-009 to better understand the safety signal observed. Following a review of 
additional unblinded data from this trial in which a higher proportion of neonatal 
deaths reported in the treatment group compared to the placebo group was also 
observed, the Sponsor decided to STOP enrollment and vaccination in these studies. 
The safety signals are being investigated and, although at this time a cause has not 
been determined, the Sponsor stopped active enrollment and further vaccination of 
participants in the RSV MAT studies enrolling pregnant women on February 25, 2022 
as a precautionary measure. The study remains ongoing for safety follow-up. 
Participants already vaccinated and their infants will continue to be monitored until 
the end of the study. 
Detailed information about the known and expected benefits and risks and expected AEs 
of the RSV Maternal (RSVPreF3) vaccine can be found in the IB. 
GSK has included provisions in this trial to ensure participant’s safety. Maternal 
participants will remain under observation for 30 minutes after administration of the 
study intervention to ensure that immediate treatment may be provided in the event of a 
hypersensitivity reaction, or syncope. Safety monitoring will be conducted throughout 
this study by an external IDMC and an internal SRT. 
The study includes the establishment of a surveillance system which may facilitate 
detection of respiratory tract infections (RTIs), in particular LRTIs in women and infants 
enrolled in the study. Measures to suspend the study should a potential safety issue be 
identified are described in Section 8.2.3. 
Taking into account the measures to minimize potential risks for participants 
participating in this study, the potential or identified risks are justified by the potential 
benefits of enhanced surveillance for the participants, and by the potential future benefits 
an RSV vaccine for maternal immunization may provide in preventing LRTIs in the 
infants of vaccinated mothers. 
Based on ongoing systematic review of the safety data from the ongoing study in 
pregnant women, the benefit-risk profile of the RSV Maternal vaccine (RSVPreF3) 
continues to be favorable and justifies unaltered continuation of the development 
program. 


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• 
Section 3, Objectives and endpoints 
Table 4 
Study objectives and endpoints 
Objectives 
Endpoints 
Primary 
Safety assessment: 
[…] 
 
Infant participants: 
• 
To evaluate safety up to 365 days post-birth (1 
year of age) in infants born to maternal 
participants who received a single IM dose of 
study intervention (RSV maternal vaccine or 
placebo). 
 
• 
Number and percentage of infant participants 
reporting: 
− 
SAEs, (S)AEs leading to study withdrawal 
and MAEs from birth up to 180 days post-
birth. 
− 
SAEs, (S)AEs leading to study withdrawal 
and MAEs from birth up to 365 days post-
birth. 
Secondary 
Safety assessment: 
[…] 
• 
 
Infant participants: 
• 
To evaluate safety up to 365 days post-birth (1 year 
of age) in infants born to maternal participants who 
received a single IM dose of study intervention (RSV 
maternal vaccine or placebo). 
• 
Number and percentage of infant participants 
reporting: 
− 
SAEs, (S)AEs leading to study withdrawal and 
MAEs from birth up to 180 days post-birth. 
− 
SAEs, (S)AEs leading to study withdrawal and 
MAEs from birth up to 365 days post-birth. 
 


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• 
Section 4.1, Overall design 
Figure 1 
Study design overview – Maternal participants 
 
[…] 
5 Due to the recent safety signal, there will be no further enrollment and vaccination of maternal participants. 
Refer to section 2.3 for further details. 
6 Due to the change in the study requirements, MA-RTIs experienced by the maternal pariticipants will no 
longer be collected. 
7 In addition to the monthly contacts between Visit-2 and the Delivery visit, additional not pre-specified 
contacts and/or visits can be made more often (at any desired frequency), as per investigator’s, maternal 
participant’s or LAR’s discretion. 
Note: Placenta samples will be collected at delivery from all maternal participants, whenever feasible. These 
samples may be tested to support possible safety assessments, if necessary. Additional details are 
provided in the study procedures manual (SPM). 


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Figure 2 
Study design overview – Infant participants 
 
[…] 
3 Due to the change in the study requirements, there will no longer be collection of blood samples at Visit-2NB, 
Visit-3NB and Visit-4NB.  
Note:  
An additional recommended safety contact may be performed ~7 days post-birth if deemed necessary by the 
investigator or by the parent/ LAR(s). 
• 
[…] 
• 
Experimental design: Phase III, double-blind*, randomized, placebo-controlled, 
multi-center, multi-country study with 1 investigational RSV MAT vaccine group in 
a parallel design. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants 
• 
[…] 
• 
Blinding: Double-blind*, as described in Table 5. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
• 
[…] 
• 
Study intervention schedule*: 1 single dose administered IM between 24 and 36 
weeks of gestation (at Visit 1, Day 1) to maternal participants. 
* Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants. 
• 
Randomized study intervention allocation* is 2:1 (investigational vaccine : placebo), 
as described in Table 5 and Section 6.3. 


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* Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants. 
• 
Sampling schedule: 
• 
Blood samples for immunogenicity/hematocrit assessment will be taken from all 
maternal participants at Days 1, 31 and delivery. 
• 
Placenta samples will be taken from all maternal participants at delivery Visit, 
whenever feasible. These samples may be tested to support possible safety 
assessments, if necessary. Additional details are provided in the study procedures 
manual (SPM). 
• 
[…] 
• 
Blood samples for immunogenicity* analysis will be taken from sub-cohorts of 
infant participants at one of 3 timepoints (Day 43, Day 121 or Day 181 post-birth). 
* Due to the change in the study requirements, there will no longer be collection of 
blood samples at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
• 
Nasal swab for confirmation of RSV-A/B infection will be taken from participants* 
clinically diagnosed as having a suspected case of RSV-associated RTIs at an event-
driven timepoint. 
* Due to the change in the study requirements, nasal swab samples from the 
maternal participants will no longer be collected. 
• 
Primary completion Date (PCD): Visit 4 (Day 43 post-delivery for maternal 
participants and Visit 2-NB (Day 43 post-birth)Visit 5-NB (Day 366 post-birth). 


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Table 5 
Study groups, intervention and blinding 
Study 
group
s 
Maternal participants 
Infant participants 
 
Blinding 
 
~Nu
mber 
Ag
e 
in 
ye
ars 
(Mi
n-
Ma
x) 
Interve
ntion 
name 
Study 
groups 
for 
randomi
zation 
(Allocati
on 2:1) 
Infant Blood 
Sampling sub-
cohorts 
Sub-
cohorts 
for 
randomiz
ation 
(Allocatio
n 1:1:1) 
M 
only 
M + I 
M + I 
I only 
Scree
ning 
Up to 
Day 43 
post-
deliver
y/birth 
Up to 
Day 
181 
post-
deliver
y/birth 
From 
Day 
182 to 
Day 
366 
post-
deliver
y/birth  
 
 
 
 
 
Name 
~Nu
mber 
 
Open 
Double
-blind** 
Single-
blind** 
Single-
blind** 
RSV_
MAT 
~252 
* 
15 
– 
49 
RSV 
MAT 
RSV_M
AT 
RSV_MA
T_BS1 
~84 
RSV_MA
T_BS1  
 
● 
● 
● 
RSV_MA
T_BS2 
~84 
RSV_MA
T_BS2  
RSV_MA
T_BS3 
~84 
RSV_MA
T_BS3 
Contr
ol 
~126 
* 
15 
– 
49 
Contro
l 
Control 
Control_
BS1 
~42 
Control_
BS1 
 
● 
● 
● 
* Due to the recent safety signal, there will be no further enrollment and vaccination of maternal participants. 
** Due to the recent safety signal, the study was fully unblinded to ensure the safety monitoring of the 
participants 
* The double-blinding will apply from Day 1 pre-study intervention to Day 43 post-delivery/birth visit after which the first 
analysis will be conducted and treatment-level unblinded summaries will be provided to GSK and regulatory 
agency for review. No individual treatment code will be shared with investigators, site staff and participants until 
the end of the study. 
• 
Section 4.2.5, Case definition 
RTI cases will be classified (during data analyses) according to the definitions provided 
in Sections 4.2.5.1*, 4.2.5.2 and 4.2.5.3. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
• 
Section 4.2.5.1, Maternal, medically attended respiratory tract illness (MA-RTI) 
Table 6 
MA-RTI case definitions for data analysis in maternal participants 
RSV-MA-RTI 
Medically attended visit for RTI symptoms AND Confirmed RSV infection 1, 2 
RSV hospitalization 
Confirmed RSV infection AND Hospitalized for acute medical condition 3 
All-cause MA- RTI 
Medically attended visit for RTI symptoms 
Note: Due to the change in the study requirements, RTI surveillance of the maternal participants will no longer 
be performed. 


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• 
Section 4.2.5.3, RSV infection 
Note: Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
• 
Section 4.3, Justification for dose 
A single formulation of the investigational RSV maternal vaccine (containing 120 µg of 
the RSVPreF3 antigen) was is planned. Available data suggested that the 120 µg 
formulation hads an acceptable safety profile and tends to elicit stronger immune 
responses, which is likely to result in higher placental transfer of antibodies to the fetus 
than formulations containing 30 or 60 µg of the RSVPreF3 antigen. Available results 
from RSV MAT-001 and RSV MAT-004 studies are included in the IB to support RSV 
MAT-012. 
Infection with RSV occurs in almost all participants by the time of reproductive age and 
it is extremely unlikely that a maternal participant would not have been naturally infected 
with RSV before. Results of study RSV MAT-001 in non-pregnant women and RSV 
MAT-004 in pregnant women indicate that a single dose of the study vaccine is 
sufficient to boost the neutralizing antibodies induced by previous natural infections. 
The study vaccine will be administered* between 240/7 and 360/7 weeks of gestation 
(inclusive). This gestational age range is considered optimal for both immunogenicity and 
safety. It allows enough time to (a) induce high neutralizing antibody levels in maternal 
participants before term delivery and (b) ensure these antibody levels are elevated during 
the period of greatest placental antibody transfer to the fetus. Moreover, it is after the 
critical period for organogenesis (i.e. after the period when most congenital abnormalities 
develop). 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. For details, refer to Section 2.3. 
• 
Section 5.2.1.2, Prior/Concomitant therapy 
• 
[…] 
• 
Planned administration/administration of a vaccine not foreseen by the study 
protocol in the period starting 29 days before the study Day 1 and ending at delivery, 
with the exception of seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap – 
alone vaccines, dTpa/Tdap vaccines that also contain other antigens and Hepatitis B 
vaccines, all of which may be administered according to standard of care ≥ 15 days 
before or after study intervention (Day 1). 
Note: In case an emergency mass vaccination for an unforeseen public health threat 
(e.g.: a pandemic) is recommended and/or organized by the public health authorities, 
outside the routine immunization program, the time period described above can be 
reduced if necessary for that vaccine provided it is used according to the local 
governmental recommendations and that the Sponsor is notified accordingly. In that 
sense, COVID-19 vaccines may be allowed, when administered ≥ 15 days before or 
after study vaccination. 


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• 
Receipt of blood or plasma products or immunoglobulin, from 90 days before study 
intervention administration, or planned receipt through delivery, with the exception 
of Rho(D) immunoglobulin, which can be given at any time. In that sense, antibody 
therapy received against COVID-19 disease should be recorded. 
• 
Section 5.5, Criteria for temporarily delaying study intervention administration 
Study intervention administration may be postponed* within the permitted time interval 
until transient conditions cited below are resolved: 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
• 
Section 6.1, Study interventions administrated  
Table 8 
Study interventions administered  
[…] 
 
 
Study Interventions 
Name: 
RSV MAT 
Control 
[…] 
 
 
[…] 
Note: Due to the recent safety signal, there will be no further enrollment and vaccination of maternal 
participants.  
Maternal participants must be observed closely for at least 30 minutes after the 
administration* of the study intervention. Appropriate medical treatment must be readily 
available during the observation period in case of anaphylaxis, syncope. 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
• 
Section 6.3.2, Randomization to study intervention 
Approximately 378 maternal participants will be enrolled* and randomized (2:1) to 
receive either the RSV maternal vaccine or the placebo control at Day 1 (Visit 1). At the 
same time, infant participants (as yet unborn) will be further randomized (1:1:1) into sub-
cohorts for blood sample collection for the assessment of immunogenicity at one of 3 
timepoints (Day 43, Day 121 or Day 181 post-birth). 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
• 
Section 6.3.3, Intervention allocation to the participant 
[…] 
Note: Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants 


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• 
Section 6.3.5, Blinding and unblinding 
To minimize the introduction of bias, this study will be double-blinded* from Day 1 pre-
study intervention to Day 43 post-delivery/birth visit after which the first analysis will be 
conducted and treatment-level unblinded* summaries will be provided to GSK and 
regulatory agency for review. No individual treatment code will be shared with 
investigators, site staff and participants until the end of the study. After Day 43 
delivery/birth visit, the study will be conducted as a single-blind* study. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
Section 6.3.5.1, Emergency unblinding 
[…] 
Note: Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
Section 6.3.5.2, Unblinding prior to regulatory reporting of SAEs 
[…] 
Note: Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
Section 6.4, Study intervention compliance 
[…] 
Note: Due to the recent safety signal, there will be no further enrollment and 
vaccination of maternal participants. 
Section 6.6, Continued access to study intervention after the end of the study 
There will be no access to RSV MAT vaccine after the end of the study. Please refer to 
Section 2.3 for details. 
It is likely that the RSV antibodies elicited by the vaccine may wane during the period 
between pregnancies, therefore there may be a need to administer the investigational 
vaccine during each pregnancy to achieve optimal anti-RSV antibody levels in the 
newborn. 
Therefore, during the conclusion visit of the current study, the investigator will ask each 
maternal participant if she is interested in participating in a study in which the second 
dose of the study intervention will be administered during the subsequent pregnancy. If a 
participant is not interested in joining the study the reason for refusal will be documented, 
when available, in the participant’s eCRF 


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Section 6.8.1, Maternal participants 
• 
[…] 
• 
All antibiotics, antivirals, analgesics, and anti-pyretics taken within 7 days before 
dose administration. 
Section 8, Study assessments and procedures 
Study procedures during special circumstances 
During special circumstances (e.g., the COVID-19 pandemic), the resulting limitations 
may affect the sites’ ability to conduct the study procedures. 
Enrollment* of ADDITIONAL maternal participants may be placed on hold. Decisions 
on re-starting enrollment* to achieve the planned sample size will be made in a manner 
consistent with guidance from public health and other competent authorities. 
For guidance regarding the temporary delay of study intervention administration because 
of exposure to COVID-19, please refer to the SPM for details. 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
The following measures may be implemented for enrolled participants: 
• 
[…] 
• 
Whenever possible, as appropriate per the judgment of the investigator and as 
allowed by local law, arrangements should be made for qualified personnel to collect 
any protocol-specified safety data/safety assessment(s) and/or biological samples at 
an alternate location* or at participant’s home within the allowed visit window 
(Table 3). 
− 
Samples should not be collected if they cannot be processed in a timely manner 
and / or appropriately stored until the intended use. 
− 
Nasal swabs for central testing must be collected using GSK-provided supplies. 
(note: if collection at either the study site, participant’s home or an alternate 
location is not possible, participants may be instructed to collect nasal swab 
samples by themselves*/for their infant. Collection will be done using GSK-
provided supplies and all the corresponding detailed instructions to allow such 
collection will be provided along with the nasal swab sampling kit). 
* Due to the change in the study requirements, nasal swab samples will no 
longer be collected from any maternal participant. 
Blood samples for central assessment of hematocrit related to immunogenicity 
evaluation must be collected using GSK-provided supplies. 


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Section 8.1.1, Biological samples 
Table 10 
Biological samples - Maternal participants 
Maternal 
Sample type 
Collected to evaluate 
Minimum 
Quantity 
per 
participant 
Unit 
Time point 
Additional information 
Whole blood 
Hematology, 
Biochemistry 
Hematocrit 
~5.5 
~3 
mL 
mL 
Screening 
Visit 1 (Day 1) 
pre-Dose 
Visit 2 
(Day 31) 4 
Visit 3 
(Delivery) 
Blood sample to be collected 
and analyzed locally only if not 
performed as per standard of 
care. 5 
Immune response 1 
~10 
mL 
Visit 1 (Day 1) 
pre-Dose 
- 
Urine 
Protein, Glucose 
Dipstick 
NA 
Screening 
Urine sample to be collected 
and analyzed locally only if not 
performed as per standard of 
care. 5 
Nasal Swab 
2, 3, 6 
Presence of RSV-A/B 
- 
- 
MA-RTI Visit 
(Event-Driven) 
Collect a nasal swab from any 
maternal participant who reports 
a MA-RTI. 
 
 
 
 
RTI 
hospitalization 
(Event-Driven) 
Collect a nasal swab (if 
possible) from any participant 
hospitalized with RTI (or soon 
after discharge, as long as 
symptoms are ongoing). 
[…] 
6 Due to the change in the study requirements, nasal swab samples will no longer be collected from any 
maternal participant for RTI assessment. 


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Table 12 
Biological samples Infant participants 
Infant 
Sample 
type 
Collected 
to 
evaluate 
Minimum 
Quantity 
per 
participant 
Unit 
Time point 
Additional information 
Whole 
Blood 
Immune 
response 
- IF cord 
blood not 
collected 
~2.5  
mL 
Visit 1-NB 
(Within 72 hours after 
birth) 
Volume must be reduced if weight ≤ 2.5 kg. 
[Trial-related blood loss for infant 
participants should be ≤ 1 % at each 
timepoint. Total blood volume is estimated at 
80 to 90 ml/kg body weight, and 
venipuncture should not exceed ~ 1.6 ml for 
a 2 kg baby or 2.0 ml for a 2.5 kg baby.] 
Refer to the Laboratory Manual for 
additional information. 
All minimum totals given below assume a 
body weight > 2.5 kg.  
Immune 
response 
– sub-
cohort 4 
~2.5 1 
mL 
Either 
Visit 2-NB (Day 43 
post-birth) or 
Visit 3-NB (Day 121 
post-birth) or 
Visit 4-NB (Day 181 
post-birth) 
Nasal 
swab 2, 3 
Presence 
of RSV-
A/B 
- 
- 
RTI Surveillance Visit 
- LRTIs (Event-
Driven) 
Collect at least one nasal swab for each 
potential LRTI reported. 
If more than one follow-up assessment visit 
is conducted, additional nasal swabs may be 
collected at the Investigator’s discretion. 
RTI Surveillance Visit 
- RTI hospitalization 
(Event-Driven) 
Collect (if possible) from any participant 
hospitalized with a RTI (or soon after 
release, as long as symptoms are ongoing). 
[…] 
4 Due to the change in the study requirements, nasal swab samples will no longer be collected from any 
maternal participant for RTI assessment. 
• 
An overall blood volume of approximately 309 mL will be collected from maternal 
participants during the entire study period, if blood sample for assessing eligibility 
criteria should not be taken at screening. 
• 
An overall blood volume of approximately 3544.5 mL will be collected from 
maternal participants during the entire study period, if blood sample for assessing 
eligibility criteria must be taken at screening. 
• 
An overall blood volume of approximately 2.5 mL will be collected from infant 
participants during the entire study period*. If cord blood sample cannot be 
collected, then an overall volume of 5 mL will be collected*. 
* Due to the change in the study requirements, there will no longer be collection of 
blood samples from infant participants at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
Section 8.1.2, Laboratory assays 
Following laboratory assays will be performed (Table 13): 
• 
Serological assays for the determination of RSV-A/B neutralizing antibodies (nAbs) 
will be performed by neutralization assay with wild type virus. Further 
characterization of the humoral immune response will be performed using enzyme-
linked immunosorbent assay (ELISA) based assays for measurement of IgG 
antibodies binding to the RSV PreF3 protein. 


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Hematocrit assay will be performed to evaluate changes over time in antibody titers / 
concentrations that may be related to volumetric changes during pregnancy. 
Table 13 
Laboratory assays 
Assay type 
System 
Component 
Method 
Laboratory 12 
Hematocrit 1 
Whole Blood 
Hematocrit 
Per Central 
Laboratory SOP 
Central Laboratory 
Humoral Immunity 
(Antibody 
determination) 
SERUM 
RSV-A NAb 
NEUT 
GSK 23 or GSK 
designated lab 
SERUM 
RSV-B NAb  
NEUT 
GSK 23 or GSK 
designated lab 
SERUM 
RSV PreF3 Ab.IgG 
ELISA 
GSK 23 or GSK 
designated lab 
Molecular Biology 34 
NASMUC 
(Nasal swab) 
Respiratory Syncytial 
Virus A RNA  
qRT-PCR  
GSK 23 or GSK 
designated lab 
 
NASMUC 
(Nasal swab) 
Respiratory Syncytial 
Virus B RNA  
qRT-PCR 
GSK 23 or GSK 
designated lab 
ELISA = enzyme-linked immunosorbent assay; NEUT = Neutralization; qRT-PCR = Quantitative Reverse Transcription 
PCR; RSV-A Nab = RSV-A neutralizing antibody; RSV-B Nab = RSV-B neutralizing antibody; RSVPreF3 Ab.IgG = 
RSV PreF3 antibody.immunoglobulin G; SOP = Standard operating procedure 
1 Hematocrit testing will be performed as part of immunogenicity assessment 
12 Refer to the list of clinical laboratories for details. 
23 GSK laboratory refers to the Clinical Laboratory Sciences (CLS) in Rixensart, Belgium; Wavre, Belgium; Marburg, 
Germany. CLS may delegate testing to GSK Research laboratories in Rixensart, Belgium; Rockville, USA; 
Sienna, Italy.  
34 RSV-A/B quantitative reverse transcription PCR will be performed on all specimens collected to evaluate RTI as 
specified in Section 8.4.4. To evaluate tertiary objectives, an Allplex Respiratory Viruses Panel or alternative may 
be performed for RSV-A/B-positive samples, and (if deemed necessary) for RSV-A/B-negative samples. The 
panel may include testing for SARS-COV-2. Please note that SARS-COV-2 testing is not intended to be 
diagnostic and results will not be provided to the investigator. Testing for SARS-COV-2 in any suspected infected 
participant should be performed as per the standard of care. 
Section 8.1.3, Immunological read-outs 
Table 14 
Immunological read-outs 
Infant participants 
 
 
Visit 2-NB (Day 43) 2 
post-birth 
RSV_MAT_BS1 84 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Control_BS1 
42 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Visit 3-NB (Day 121) 2 
post-birth 
RSV_MAT_BS2 84 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Control_BS2 
42 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Visit 4-NB (Day 181) 2 
post-birth 
RSV_MAT_BS3 84 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 
Control_BS3 
42 
RSV-A NAb 
RSV-B NAb 
RSV PreF3 Ab.IgG 


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[…] 
2 Due to the change in the study requirements, there will no longer be collection of blood samples from infant 
participants at Visit 2-NB, Visit 3-NB and Visit 4-NB. 
Table 15 
Hematocrit Readout (deleted and subsequent tables have been renumbered 
accordingly) 
Blood sampling timepoint 
Study group 
Approximate No. 
participants 
Component 
Type of contact and 
timepoint 
Sampling timepoint 
Maternal participants 
Visit 1 (Day 1) 
pre-study intervention 
All study groups 
378 
Hematocrit 
Visit 2 (Day 31) 1 
post-study intervention All study groups 
378 
Hematocrit 
Visit 3 (Delivery) 
post-study intervention All study groups 
378 
Hematocrit 
1 Blood sample at Visit 2 (Day 31) wil not be collected if the delivery occurs prior to Day 31 post-study intervention. 
Table 15 
Molecular biology tests 
Nasal swab sampling timepoint 
No. 
participants 
Component 3 
Type of contact (timepoint) 
Sampling timepoint 
Maternal MA-RTI 1, 4 
Event-driven 
Event-driven 
RSV-A RNA  
 
 
 
RSV-B RNA  
[…] 
4 Due to the change in the study requirements, nasal swab samples will no longer be collected from any 
maternal participant for MA-RTI assessment. 
Section 8.2.1.4.2, Monthly contacts 
[…] 
In addition to the monthly contacts between Visit-2 and the Delivery visit, additional 
not pre-specified contacts and/or visits can be made more often (at any desired 
frequency), as per investigator’s, maternal participant’s or LAR’s discretion. 
Section 8.2.3, Study holding rules and safety monitoring 
An internal SRT and an external IDMC (external to GSK) will review available maternal 
and infant safety data on a regular basis throughout the study. Any potential safety 
concern identified will be escalated to the GSK Global Safety Board (GSB)Vaccine 
Safety Monitoring Board (VSMB). 
Section 8.2.3.1, Safety evaluation by the Safety Review Team (SRT) 
The SRT includes as core members the GSK’ Central Safety physician, Safety scientist, 
Clinical Research & Development Lead (CRDL), Epidemiologist, Global Regulatory 
Lead and Biostatistician of the project. The SRT is responsible for ongoing safety 
monitoring of the entire study and will review on a regular, ongoing basis the safety data. 
The review will be blinded until Day 43 post-delivery/birth visit and may also be 
unblinded for later timepoints until study end, if required. Continuous monitoring 
throughout the study will allow for ad-hoc data review meetings if deemed necessary by 
the SRT. 


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Note: Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants 
Section 8.2.3.2, Independent data monitoring committee (IDMC) evaluation 
[…] 
The IDMC will conduct unblinded reviews of all available safety data on an ongoing 
basis. The unblinded analyses will be done by an independent statistician from an 
Independent Data Analysis Center (IDAC) outside GSK to maintain the study blind* and 
will be documented in a statistical analysis report. No unblinded data* will be shared 
with the study team. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
In addition, there will be at least 3 planned IDMC data review meetings. The first will 
take place after a quarter of the maternal participants (~63 active vaccine recipients) have 
completed the Day 43 post-delivery visit (Visit 4 for maternal participants; Visit 2-NB 
for their enrolled infants). The second planned IDMC meeting will occur after all 
participants have completed follow-up to the Day 43 post-delivery/birth visit (Visit 4 for 
maternal participants; Visit 2-NB for their enrolled infants). The third planned IDMC 
meeting will occur when all data up to study end (Visit 5-NB, 12 months post-birth) are 
available. For each review, the IDMC will be provided with unblinded safety data as 
described above. Ad-hoc data reviews or meetings may be organized, if deemed 
necessary by the IDMC. 
Section 8.2.3.3, Study holding rules 
[…] 
The following communication sequence must be followed: 
• 
[…] 
• 
The GSK GSBVSMB evaluates the case after receipt of the IDMC’s recommendations 
/ and takes the decision to stop or to re-start dose administration. 
Section 8.3.1, Time period and frequency for collecting AE, SAE and other safety 
information 
Table 17 
Timeframes for collecting and reporting of safety information (including 
RTI information) 
[…] 
 
 
 
 
 
 
 
 
 
 
 
MA-RTIs 6 
 
 
 
 
 
 
 
 
 
 
 
 
M (Day 1 to 180 days post-delivery) 
 
 
[…] 
6 Due to the change in the study requirements, RTI surveillance of the maternal participants will no longer be 
performed. 


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Section 8.3.3, Regulatory reporting requirements for SAEs, subsequent pregnancies 
and other events 
Table 18 
Timeframes for submitting SAE, subsequent 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 (including adverse 
outcomes for the study pregnancy 
and RSV-associated 
hospitalizations) 
24 hours* ‡ 
electronic Adverse 
Events Form and 
the corresponding 
Expedited Adverse 
Event Form 
24 hours*¥ 
electronic Adverse 
Events Form and the 
corresponding 
Expedited Adverse 
Event Form 
Subsequent Pregnancies 
24 hours 
weeks* 
electronic 
pregnancy report 
24 hours 
weeks* 
electronic pregnancy 
report 
Section 8.3.3.1, Contact information for reporting SAEs, AESIs, pregnancies and 
study holding rules 
Table 19 
Contact information for reporting SAEs, AESIs, subsequent pregnancies 
and study holding rules 
[…] 
 
GSK Clinical Safety & Pharmacovigilance 
 
Outside US & Canada sites: 
Fax: +32 2 656 51 16 or +32 2 656 80 09 
Email address: ogm28723@gsk.comRix.CT-
safety-vac@gsk.com 
US sites only: 
Fax: 1 610 787 7053 
Canadian sites only: 
Fax: 1 866 903 4718 
 
Section 8.4.1.1, Medically attended respiratory tract illnesses (MA-RTIs) in 
maternal participants 
A maternal MA-RTI* occurs when the maternal participant visits a healthcare 
professional (e.g., a General Practitioner) for any respiratory symptom, including (but not 
limited to) cough, sore throat, sputum production and difficulty breathing. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
Section 8.4.2.1, Maternal participants 
MA-RTI surveillance* begins at Day 1 post-study intervention and ends 180 days after 
delivery (Contact 2). It will be accomplished via 2 types of contact. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 


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Section 8.4.2.3, Maternal and infant participants 
If the maternal participant* visited / the infant participant was taken to a healthcare 
provider not affiliated with the study, site personnel should (if permitted by local 
regulation) contact that healthcare provider to obtain the medical record(s) for the visit. 
* Due to the change in the study requirement, RTI surveillance of the maternal 
participants will no longer be performed. 
Section 8.4.3.1, For a maternal MA-RTI 
Conduct an assessment visit (Section 8.4.4), ideally within 72 hours after a medically 
attended visit due to RTI symptoms* occurs during the surveillance period. However, a 
visit may be conducted even beyond the 72 hours window if symptoms are ongoing. 
* Due to the change in the study requirement, RTI surveillance of the maternal 
participants will no longer be performed. 
Section 8.4.3.2, For an infant RTI 
Figure 5 
Decision Tree for site personnel - infant surveillance and assessment 
(footnote) 
RR: Respiratory rate: SpO2: Blood oxygen saturation by pulse oximetry. 
1Details regarding Surveillance are provided in Section 8.4.2.2 and the SPM. 
2Cough, runny nose, blocked nose, difficulty in breathing, wheezing are described in Section 8.4.1.2. 
3Details regarding the RTI assessment visit are provided in Section 8.4.4 and the SPM. 
4 Post-visit follow-up is described in Sections 8.4.6 and in the SPM. 
5If a follow-up assessment visit is conducted, collection of additional nasal swabs is as described in Table 12. 
6Parental concern in the context of an RTI 
Section 8.4.4, Assessment visit procedures 
[…] 
Unless otherwise specified, assessment visit procedures will be the same for maternal 
participants with MA-RTIs* and for infant participants with RTIs. 
Note that if the reported symptoms are severe enough to warrant urgent care, the 
participant / parent(s)/LAR(s) should be advised to seek such care (e.g. Emergency 
Room). 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 


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Section 8.4.4.1, Clinical evaluation 
[…] 
For maternal participants*: 
• 
Temperature 
• 
Respiratory rate 
• 
Blood oxygen saturation measured by pulse oximetry (Section 8.2.1.4.1), in room 
air, if feasible 
• 
Results of chest auscultation 
• 
Signs of difficulty in breathing (wheezing and tachypnoea in maternal participants) 
* Due to the stop on RTI surveillance for maternal participants, these checks will no 
longer be performed. 
Section 8.4.4.2, Nasal swab collection 
Refer to Table 10 (maternal participants)* and Table 12 (infant participants). Additional 
details are provided in the Central Laboratory Manual. 
* Due to the change in the study requirements, nasal swab samples of the maternal 
participants will no longer be collected for RTI assessment. 
Section 8.4.4.3, Missed assessment visit 
If it is truly not possible to perform an assessment visit (for example, if the participant 
develops a MA-RTI* or potential RTI/LRTI while the family is traveling, and all 
symptoms have resolved by the time the family returns), then the corresponding 
assessment visit page of the eCRF should be filled in as completely as possible using 
available medical history and medical records. 
Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
Section 8.4.5, RTI hospitalization during the surveillance interval 
Whenever a participant is admitted to hospital for observation or treatment of an acute 
respiratory illness during the surveillance interval for that participant, a nasal swab 
should be collected using GSK-provided supplies and sent to GSK for analysis. as 
described in Table 10* and Table 12. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed.  


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Section 9.2, Sample size determination 
Approximately 378 maternal participants* will be randomized in a 2:1 ratio to achieve at 
least 340 evaluable maternal participants (including at least 16 evaluable adolescents 
from 15 to less than 18 YOA). 
Participants who withdraw from the study will not be replaced. 
* Due to the recent safety signal, there will be no further enrollment and vaccination of 
maternal participants. 
Section 9.3, Analysis sets 
Table 22 
Maternal Participants 
Analysis 
set 
Description 
Enrolled  
All maternal participants who completed the informed consent process, and signed the informed 
consent form and was determined as eligible for study participation. 
Section 9.4.3.1, Safety 
Maternal 
participants 
[…] 
[…] 
Number and percentage of 
maternal participants reporting 
SAEs, (S)AEs leading to study 
withdrawal, and MAEs from Day 
1 up to 42 days post-delivery. 
The number and percentage of maternal participants reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 42 days post-delivery with exact 95% CIs will 
be tabulated by group and by Medical MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal, and MAEs will be prepared (but will not be shared 
with investigators and site staff until the final, unblinded 
analysis has been completed). 
Number and percentage of 
maternal participants reporting 
pregnancy outcomes * from Day 
1 up to 42 days post-delivery. 
*These include live birth with no 
congenital anomalies, live birth 
with minor congenital anomalies 
only; live birth with at least one 
major congenital anomaly, fetal 
death/still birth (antepartum or 
intrapartum) with no congenital 
anomalies, fetal death/still birth 
(antepartum or intrapartum) with 
only minor congenital anomalies, 
fetal death/still birth (antepartum 
or intrapartum) with at least 1 
major congenital anomaly; 
elective/therapeutic termination 
with no congenital anomalies; 
The number and percentage of maternal participants reporting 
each pregnancy outcome from Day 1 up to 42 days post-
delivery will be tabulated with its exact 95% CI by group. 
By participant listings of adverse pregnancy outcomes will be 
prepared (but will not be shared with investigators and site staff 
until the final, unblinded analysis has been completed. 


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elective/therapeutic termination 
with only minor congenital 
anomalies, and 
elective/therapeutic termination 
with at least 1 major congenital 
anomaly. 
Number and percentage of 
maternal participants reporting 
pregnancy-related AESIs * and 
worsening of pre-existing medical 
conditions and/or obstetric 
complications from Day 1 up to 
42 days post-delivery. 
* These include maternal death, 
hypertensive disorders of 
pregnancy (gestational 
hypertension, pre-eclampsia, pre-
eclampsia with severe features 
including eclampsia), fetal growth 
restriction, gestational diabetes 
mellitus, pathways to preterm 
birth (premature preterm rupture 
of membranes, preterm labor, 
provider-initiated preterm birth) 
and chorioamnionitis. 
The number and percentage of maternal participants reporting 
each pregnancy-related AESI and worsening of pre-existing 
medical conditions and/or obstetric complications from Day 1 
up to 42 days post-delivery will be tabulated with its exact 95% 
CI by group. 
By participant listings of pregnancy-related AESIs and 
worsening of pre-existing medical conditions and/or obstetric 
complications will be prepared (but will not be shared with 
investigators and site staff until the final, unblinded analysis 
has been completed).  
Infant 
participants 
Number and percentage of infant 
participants reporting neonatal / 
infant AESIs * from birth up to 42 
days post-birth. 
* These include small for 
gestational age, low birth weight 
including very low and extremely 
low birth weight (<2500 g, 
<1500g, <1000g), congenital 
anomalies (major external 
structural defects, internal 
structural defects, functional 
defects), neonatal death (in an 
extremely preterm birth 
[22<GA<28 weeks], in a preterm 
live birth [28<GA<37 weeks], or 
in a term live birth) and preterm 
birth. 
The number and percentage of infant participants reporting 
each neonatal / infant AESI from birth up to 42 days post-birth 
will be tabulated with its exact 95% CI by group. 
By participant listings of neonatal / infant AESIs will be 
prepared but will not be shared with investigators and site staff 
until the final, unblinded analysis has been completed. 


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Number and percentage of infant 
participants reporting SAE, 
(S)AEs leading to study 
withdrawal, and MAEs from birth 
up to 42 days post-birth. 
The number and percentage of infant participants reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 42 days post-birth with exact 95% CIs will be 
tabulated by group and by MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared (but will not be shared 
with investigators and site staff until the final, unblinded 
analysis has been completed). 
 
Number and percentage of 
infant participants reporting 
SAEs, (S)AEs leading to study 
withdrawal, and MAEs from 
birth up to 180 days post-birth. 
The number and percentage of infant participants 
reporting at least one SAE, (S)AE leading to study 
withdrawal, and MAE from birth up to 180 days post-birth 
will be tabulated with 95% CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared.  
 
Number and percentage of 
infant participants reporting 
SAEs, (S)AEs leading to study 
withdrawal, and MAEs from 
birth up to 365 days post-birth. 
The number and percentage of infant participants 
reporting at least one SAE, (S)AE leading to study 
withdrawal, and MAE from birth up to 365 days post-birth 
will be tabulated with 95% CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
AE= Adverse event; CI= Confidence interval; MAE = medically attended adverse event; MedRA = Medical dictionary 
for regulatory activities; SPM = study procedure manual 
Section 9.4.4.1, Safety 
 
Secondary Safety Endpoints 
Statistical Analysis Methods 
Maternal 
participants 
Number and percentage of 
maternal participants reporting 
SAEs, (S)AEs leading to study 
withdrawal and MAEs from Day 1 
up to 180 days post-delivery. 
The number and percentage of maternal participants 
reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 180 days post-delivery with exact 95% CIs 
will be tabulated by group and by MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared but will not be shared 
with investigators and site staff until the final, unblinded, 
analysis has been completed. 
 
Number and percentage of 
maternal participants reporting 
worsening of pre-existing medical 
conditions and/or obstetric 
complications from Day 1 up to 180 
days post-delivery. 
The number and percentage of maternal participants 
reporting each worsening of pre-existing medical conditions 
and/or obstetric complications from Day 1 up to 180 days 
post-delivery will be tabulated with its exact 95% CI by 
group. 
By participant listings of worsening of pre-existing medical 
conditions and/or obstetric complications will be prepared 
but will not be shared with investigators and site staff until 
the final, unblinded analysis has been completed. 
 
[…] 
[…] 


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Secondary Safety Endpoints 
Statistical Analysis Methods 
Infant 
participants 
Number and percentage of infant 
participants reporting SAEs, (S)AEs 
leading to study withdrawal, and 
MAEs from birth up to 180 days 
post-birth. 
The number and percentage of infant participants reporting 
at least one SAE, (S)AE leading to study withdrawal, and 
MAE from birth up to 180 days post-birth will be tabulated 
with 95% CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared but will not be shared 
with investigators and site staff until the final, unblinded 
analysis has been completed.  
 
Number and percentage of infant 
participants reporting SAEs, (S)AEs 
leading to study withdrawal, and 
MAEs from birth up to 365 days 
post-birth. 
The number and percentage of infant participants reporting 
at least one SAE, (S)AE leading to study withdrawal, and 
MAE from birth up to 365 days post-birth will be tabulated 
with 95% CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
 
 
AE = Adverse event; LRTI = Lower respiratory tract illness; MAE = medically attended adverse event; NB = Newborn; 
RSV-MA-RTI = respiratory syncytial virus associated medically attended respiratory tract illness; SAE = serious 
adverse event 
Section 9.5, Conduct of analyses 
No analysis requiring statistical adjustment will be performed. However, analyses to 
evaluate objectives and endpoints will be performed in steps. The sequence of analyses is 
described in Section 9.5.1. 
Section 9.5, Sequence of analyses 
Analyses to evaluate objectives and endpoints are descriptive and will be performed in 
steps: 
• 
The first analysis to evaluate maternal and infant safety data up to (and if available/ 
needed beyond) the Day 43 post-delivery/birth visit (Visit 4 maternal participants/ 
Visit 2-NB infant participants), maternal immunogenicity data up to (and including) 
the delivery (Visit 3), and immunogenicity data based on analyses of cord blood 
(Visit 3) or an infant blood sample collected within 72 hours after delivery (Visit 1-
NB – if a cord blood sample could not be collected) will be performed when the 
respective visits are completed and the data are available. At this point, the central 
study team including the study statistician will be unblinded (i.e. will have access to 
the individual participant treatment assignments), but no individual listings will be 
provided to the investigators, site staff and participants until the end of study. An 
interim CSR will be written and made available to the investigators at that time. 
The final analysis will be performed when all data up to study end are available. A CSR 
including all available data will be written and made available to the investigators at that 
time. 


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214725 (RSV MAT-012) 
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Section 10.1.5, Committees structure 
The GSBVSMB includes relevant members of the GSK study team and is responsible for 
ongoing safety monitoring of the entire project. The SRT will inform the GSBVSMB 
about any potential safety concern relevant to the study (Refer to Section 8.2.3). 
Section 10.1.6, Dissemination of clinical study data 
[…] 
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis*. 
* Due to the recent safety signal, the study was fully unblinded to ensure the safety 
monitoring of the participants. 
Section 10.2.1, Protocol-required safety laboratory assessments 
[…] 
Laboratory assessments (e.g., placenta pathology) may be performed on the placental 
tissue samples collected from maternal participants at delivery visit to support possible 
safety assessments, if necessary. Additional details are provided in the SPM. 
Additional assessments on the placental sample can be performed depending on local 
standard of practice, site capability and the investigators’ medical judgment. 
Section 10.2.2, Descriptions of the assays to be performed in the study 
Hematocrit assay 
The hematocrit is the proportion of the volume occupied by the red blood cells 
compared to the whole volume of the blood cells. The hematocrit value is determined 
by drawing blood sample into a capillary tube then centrifuged, the lengths of the 
columns for the red blood cells and the whole blood cells are measured using a graphic 
reading device. Thereafter, the proportion of the red blood cells to that of the whole 
blood cells is determined and expressed as a decimal or percentage fraction. 
Hematocrit will be tested at Visits 1, 2 and 3 for all participants until the current 
Protocol Amendment 1 is approved (unless IEC/IRB allows for immediate 
implementation of this measure to reduce participant’s burden, prior to full 
Amendment 1 being approved) in the respective study country(ies). Testing will be 
performed by a central laboratory. Results will be used to help evaluate changes over 
time in antibody titers / concentrations that may be related to volumetric changes 
during pregnancy, if deemed necessary. 


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214725 (RSV MAT-012) 
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192 
Section 10.7.1, List of abbreviations 
[…] 
 
GSB: 
Global Safety Board 
[…] 
 
VSMB: 
Vaccine Safety Monitoring Board 
Section 10.7.2, Glossary of terms 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
trial, and only when the data are cleaned to an acceptable 
level of quality will appropriate personnel be unblinded 
or when required in case of a serious adverse event. 
In an open-label study, no blind is used. Both the 
investigator and the participant know the identity of the 
intervention assigned. 
In a single-blind study, the investigator and/or his staff 
are aware of the intervention assignment but the 
participant is not. 
In a double-blind study, the participant, the investigator 
and sponsor staff who are involved in the treatment or 
clinical evaluation of the participants and the review or 
analysis of data are all unaware of the intervention 
assignment. 
 


CONFIDENTIAL 
214725 (RSV MAT-012) 
Protocol Amendment 1 Final 
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193 
11. 
REFERENCES 
ACOG. Practice Bulletin No. 202 Summary: Gestational Hypertension and Preeclampsia. 
Obstetrics & Gynecology. 2019; 133 (1) 211-214. 
Barbas CF, Crowe JE, Cababa D, et al. Human monoclonal Fab fragments derived from a 
combinatorial library bind to respiratory syncytial virus F glycoprotein and neutralize 
infectivity. Proc Natl Acad Sci U S A. 1992;89(21):10164-8. 
Bates JT, Keefer CJ, Slaughter JC, et al. Escape from neutralization by the respiratory 
syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by 
changes in on-rate of binding to the fusion protein. Virology. 2014; 454-455:139-144. 
Centers for Disease Control and Prevention (CDC). Quick reference handbook of 
selected congenital anomalies and infections. Chapter 1.4: Congenital anomalies - 
Definitions. 
https://www.cdc.gov/ncbddd/birthdefects/surveillancemanual/chapters/chapter-
1/chapter1-4.html. Accessed 8 February 2021. 
GSK’s Clinical Study EPI-RSV-008 BOD (207636). A prospective epidemiological 
study of women between 24-27 weeks of pregnancy to describe pregnancy outcomes and 
events of interest in the mother and neonate, as well as determine incidence in infants of 
RSV LRTI and RSV hospitalization. Protocol Amendment 4 dated 29 May 2020. 
GSK’s Clinical Study EPI-RSV-015 BOD UK DB (207874). A retrospective cohort 
study using the Clinical Practice Research Datalink to assess the proportion of pregnancy 
outcomes, pregnancy-related events of interest, and infant events of interest in pregnant 
women and their infants. Clinical Study Report dated 12 November 2019. 
GSK’s Clinical Study EPI-RSV-015 BOD UK DB (207874). A retrospective cohort 
study using the Clinical Practice Research Datalink to assess the proportion of pregnancy 
outcomes, pregnancy-related events of interest, and infant events of interest in pregnant 
women and their infants. Protocol Amendment 2 dated 6 July 2020. 
Hahn, G. J. and Meeker, W.Q. Statistical intervals: a guide for practitioners. John Wiley 
& Sons, New York. 1991. 
Haralambieva IH, Ovsyannikova IG, Pankratz VS, Kennedy RB, Jacobson RM, Poland 
GA. The genetic basis for interindividual immune response variation to measles vaccine: 
new understanding and new vaccine approaches. Expert Rev Vaccines. 2013; 12(1):57–
70. 
Hasin DS, O’Brien CP, Auriacombe M, et al. DSM-5 Criteria for Substance Use 
Disorders: Recommendations and Rationale. The American journal of psychiatry. 
2013;170(8):834-851. 
Holness N High-Risk Pregnancy. Nurs Clin North Am. 2018 Jun;53(2):241-251 


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15 March 2022 
194 
Kachikis A, Eckert LO, Walker C, et al. Gestational diabetes mellitus: Case definition & 
guidelines for data collection, analysis, and presentation of immunization safety data. 
Vaccine. 2017; 35 (48): 6555-6562. 
Kollmann TR. Variation between Populations in the Innate Immune Response to Vaccine 
Adjuvants. Front Immunol. 2013; 4:81. 
Magro M, Mas V, Chappell K, et al., Neutralising antibodies against the preactive form 
of respiratory syncytial virus fusion protein offer unique possibilities for clinical 
intervention. Proc Natl Acad Sci USA. 2012; 109: 3089-94. 
McDonald J.U., Rigsby P et al., Establishment of the first WHO International Standard 
for antiserum to Respiratory Syncytical Virus: Report of an International collaborative 
study. Vaccine. 2018. 36. 7641-7649. 
McDonald J.U., Rigsby P et al., Expansion of the 1st WHO international standard for 
antiserum to respiratory syncytial virus to include neutralisation titres against RSV 
subtype B: An international collaborative study. Vaccine. 2020. 38. 800-807. 
Metropolitan Atlanta Congenital Defects Program (MACDP). 
https://www.cdc.gov/ncbddd/birthdefects/macdp.html. Accessed 8 February 2021. 
Modjarrad K, Giersing B, Kaslow DC, Smith PG, Moorthy VS; WHO RSV Vaccine 
Consultation Expert Group. WHO consultation on Respiratory Syncytial Virus Vaccine 
Development Report from a World Health Organization Meeting held on 23-24 March 
2015. Vaccine. 2016;34(2):190-7. 
Newcombe, R. G. Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Stat Med. 1998;17(8):857-72. 
Pérez-Losada M, Posada D, Arenas M, et al. Ethnic differences in the adaptation rate of 
HIV gp120 from a vaccine trial. Retrovirology. 2009; 6:67. 
Villar J, Cheikh Ismail L, Victora CG, et al. International standards for newborn weight, 
length, and head circumference by gestational age and sex: the Newborn Cross-Sectional 
Study of the INTERGROWTH-21st Project. Lancet 2014; 384: 857-68. 


Signature Page for  214725 TMF-14522268 v1.0
Signature Page for TMF-14522268 v1.0
Reason for signing: Approved
Name: 
Role: A
Date of signature: 16-Mar-2022 16:40:02 GMT+0000
PPD

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  214725
Official Title of Study: A Phase III, double-blind, randomized, placebo-controlled 
study to evaluate the safety, reactogenicity and immune response of a single 
intramuscular dose of unadjuvanted RSV Maternal vaccine, in high risk pregnant 
women aged 15 to 49 years and infants born to the vaccinated mothers. 
NCT ID: NCT04980391
Date of Document: 01 Jun 2022 


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
214725 (RSV MAT-012) 
XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021 
Page 1 of 52 
 
TITLE PAGE 
Protocol Title: 
A Phase III, double-blind, randomized, placebo-controlled 
study to evaluate the safety, reactogenicity and immune 
response of a single intramuscular dose of unadjuvanted RSV 
Maternal vaccine, in high risk pregnant women aged 15 to 49 
years and infants born to the vaccinated mothers. 
Study Number: 
214725 (RSV MAT-012) 
Compound Number: GSK3888550A  
Abbreviated Title: 
A study on the safety and immune response to an 
unadjuvanted RSV Maternal vaccine, in high risk pregnant 
women aged 15 to 49 years and infants born to the vaccinated 
mothers. 
 
Sponsor Name: GlaxoSmithKline Biologicals SA (GSK) 
Regulatory Agency Identifier Number(s): 2021-000994-96 
Registry 
ID 
Clintrials.gov 
NCT 04980391 
Copyright 2021 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
Information Type: 
Statistical Analysis Plan (SAP) 


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Page 2 of 52 
TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
1. 
INTRODUCTION ...................................................................................................... 7 
1.1. 
Objectives, Estimands and Endpoints ........................................................... 7 
1.2. 
Study Design .............................................................................................. 11 
2. 
STATISTICAL HYPOTHESES ............................................................................... 15 
2.1. 
Multiplicity Adjustment ................................................................................ 15 
3. 
ANALYSIS SETS ................................................................................................... 15 
3.1. 
Definition..................................................................................................... 15 
3.2. 
Criteria for eliminating data from Analysis Sets ........................................... 16 
3.2.1. 
Elimination from Exposed Set (ES) .............................................. 16 
3.2.2. 
Elimination from Full Analysis Set (FAS) - Immunogenicity .......... 17 
3.2.3. 
Elimination from Per-protocol analysis Set (PPS) - 
Immunogenicity............................................................................ 18 
3.2.4. 
Elimination from solicited safety set ............................................. 23 
4. 
STATISTICAL ANALYSES ..................................................................................... 24 
4.1. 
General Considerations .............................................................................. 24 
4.1.1. 
General Methodology .................................................................. 24 
4.1.2. 
Definition...................................................................................... 25 
4.2. 
Primary Endpoint(s) Analyses ..................................................................... 27 
4.2.1. 
Safety .......................................................................................... 27 
4.2.2. 
Immunogenicity............................................................................ 30 
4.2.3. 
Sensitivity analyses ..................................................................... 31 
4.3. 
Secondary Endpoint(s) Analyses ................................................................ 31 
4.3.1. 
Safety .......................................................................................... 31 
4.3.2. 
Immunogenicity............................................................................ 34 
4.3.3. 
Sensitivity analyses ..................................................................... 36 
4.4. 
Tertiary Endpoint(s) Analyses ..................................................................... 37 
4.5. 
Other Safety Analyses ................................................................................ 37 
4.5.1. 
COVID-19 Assessment and COVID-19 AEs ................................ 37 
4.5.2. 
Additional Safety Assessments (if applicable) .............................. 37 
4.5.3. 
Combined solicited and unsolicited events ................................... 38 
4.6. 
Other Analyses ........................................................................................... 38 
4.6.1. 
Other analyses for adolescent maternal participants .................... 38 
4.6.2. 
Subgroup analyses ...................................................................... 39 
4.7. 
Conduct of Analyses ................................................................................... 40 
4.7.1. 
Sequence of analyses.................................................................. 40 
4.8. 
Changes to Protocol Defined Analyses ....................................................... 40 
5. 
SAMPLE SIZE DETERMINATION ......................................................................... 41 
5.1. 
Safety ......................................................................................................... 41 
5.2. 
Immunogenicity........................................................................................... 42 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 44 
6.1. 
Appendix 1 Study Population Analyses ....................................................... 44 


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6.1.1. 
Participant Disposition ................................................................. 44 
6.1.2. 
Demographic and Baseline Characteristics .................................. 44 
6.1.3. 
Protocol Deviations ...................................................................... 45 
6.1.4. 
Concomitant Medications and Vaccinations ................................. 46 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic .................. 46 
6.2. 
Appendix 2 Data Derivations Rule .............................................................. 46 
6.2.1. 
Study Day and Reference Dates .................................................. 46 
6.2.2. 
Attributing events to vaccine doses .............................................. 46 
6.2.3. 
Handling of missing data .............................................................. 47 
6.2.4. 
Data derivation ............................................................................ 48 
6.2.5. 
Display of decimals ...................................................................... 50 
7. 
REFERENCES ....................................................................................................... 52 
 


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LIST OF TABLES 
PAGE 
Table 1 
Study objectives, estimands and endpoints .............................................. 7 
Table 2 
Study groups, intervention and blinding .................................................. 14 
Table 3 
Maternal Participants ............................................................................. 15 
Table 4 
Infant Participants .................................................................................. 16 
Table 5 
Elimination code and condition for maternal participants ........................ 17 
Table 6 
Elimination code and condition for infant participants ............................. 17 
Table 7 
Elimination code and condition for maternal participants ........................ 18 
Table 8 
Elimination code and condition for infant participants ............................. 20 
Table 9 
MA-RTI case definitions for data analysis in maternal participants ......... 26 
Table 10 
RTI/LRTI case definitions for data analysis in infants ............................. 26 
Table 11 
Intensity scales for solicited events in adults .......................................... 33 
Table 12 
Implausible Solicited Events ................................................................... 34 
Table 13 
Exact 95% confidence interval (CI) on the percentage of 
participants with adverse events (AEs) following dosing in RSV-
MAT vaccine group ................................................................................ 41 
Table 14 
Precision estimation on fold increase and its 95% CI with 226 
participants in RSV-MAT vaccine group ................................................. 42 
 


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LIST OF FIGURES 
PAGE 
Figure 1 
Study design overview – Maternal participants ....................................... 11 
Figure 2 
Study design overview – Infant participants ............................................ 12 
 


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Version history 
SAP Version 
Approval 
Date 
Protocol Version 
(Date) on which 
SAP is Based 
Change 
Rationale 
SAP 
17 August 
2021 
Final 
(12 March 2021) 
Not Applicable 
Original version 
SAP 
Amendment 1 
01 Jun 2022 
Amendment 1 
(15 March 2022) 
The SAP was amended 
to align to changes 
performed in the 
Protocol Amendment 1.  
This amendment is 
considered substantial based 
on the criteria defined in 
Article 10(a) of Directive 
2001/20/EC of the European 
Parliament and the Council of 
the European Union because 
it significantly impacts the 
safety of participants, conduct 
of the trial and scientific value 
of the trial. 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the CSR for 
Study 214725 (RSV MAT-012). Details of the planned interim analysis, as well as the 
final analyses, are provided. 
1.1. 
Objectives, Estimands and Endpoints  
Table 1 
Study objectives, estimands and endpoints  
Objectives 
Endpoints & Estimands 
Primary 
Safety assessment: 
Maternal participants: 
• 
To evaluate the safety and reactogenicity of 
a single IM dose of study intervention (RSV 
maternal vaccine or placebo) administered to 
maternal participants up to 42 days post-
delivery.  
• 
Number and percentage of maternal participants reporting: 
− 
Solicited administration site and systemic events 
during a 7-day follow-up period after dosing (i.e. Day 
1 to Day 7 included). 
− 
Unsolicited AEs that occur during a 30-day follow-up 
period after dosing (i.e. Day 1 to Day 30 included). 
− 
SAEs, (S)AEs leading to study withdrawal and MAEs 
from Day 1 up to 42 days post-delivery. 
• 
To evaluate the pregnancy outcomes and 
pregnancy-related AESIs up to 42 days post-
delivery, in maternal participants who 
received a single IM dose of study 
intervention (RSV maternal vaccine or 
placebo).  
• 
Number and percentage of maternal participants reporting: 
− 
Pregnancy outcomes * from Day 1 up to 42 days 
post-delivery. 
* These include live birth with no congenital 
anomalies, live birth with minor congenital 
anomaly(ies) only; live birth with at least one major 
congenital anomaly, fetal death/still birth (antepartum 
or intrapartum) with no congenital anomalies, fetal 
death/still birth (antepartum or intrapartum) with only 
minor congenital anomalies, fetal death/still birth 
(antepartum or intrapartum) with at least 1 major 
congenital anomaly; elective/therapeutic termination 
with no congenital anomalies; elective/therapeutic 
termination with only minor congenital anomalies, and 
elective/therapeutic termination with at least 1 major 
congenital anomaly 1. 
− 
Pregnancy-related AESIs * and worsening of pre-
existing medical conditions and/or obstetric 
complications from Day 1 up to 42 days post-delivery. 
* These include maternal death, hypertensive 
disorders of pregnancy (gestational hypertension, pre-
eclampsia, pre-eclampsia with severe features 
including eclampsia), fetal growth restriction, 
gestational diabetes mellitus, pathways to preterm 
birth (premature preterm rupture of membranes, 
preterm labor, provider-initiated preterm birth) and 
chorioamnionitis.1 


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Objectives 
Endpoints & Estimands 
Infant participants: 
• 
To evaluate safety up to 42 days post-birth in 
infants born to maternal participants who 
received a single IM dose of study 
intervention (RSV maternal vaccine or 
placebo). 
• 
Number and percentage of infant participants reporting: 
− 
Neonatal / infant AESIs * from birth up to 42 days 
post-birth. 
* These include small for gestational age, low birth 
weight including very low and extremely low birth 
weight (<2500 g, <1500g, <1000g), congenital 
anomalies (major external structural defects, internal 
structural defects, functional defects), neonatal death 
(in an extremely preterm birth [22<GA<28 weeks], in 
a preterm live birth [28<GA<37 weeks], or in a term 
live birth) and preterm birth.1 
− 
SAEs, (S)AEs leading to study withdrawal and MAEs 
from birth up to 42 days post-birth. 
• 
To evaluate safety up to 365 days post-birth 
(1 year of age) in infants born to maternal 
participants who received a single IM dose of 
study intervention (RSV maternal vaccine or 
placebo). 
• 
Number and percentage of infant participants reporting: 
− 
SAEs, (S)AEs leading to study withdrawal and MAEs 
from birth up to 180 days post-birth. 
− 
SAEs, (S)AEs leading to study withdrawal and MAEs 
from birth up to 365 days post-birth. 
Immunogenicity assessment: 
Maternal participants: 
• 
To evaluate the immunogenicity of a single 
IM dose of study intervention (RSV maternal 
vaccine or placebo) administered to maternal 
participants, at delivery. 
• 
Humoral immune responses at pre-dosing (Day 1) and at 
delivery: 
− 
RSVPreF3 IgG-specific antibody concentrations 
− 
Neutralizing antibody titers against RSV-A 
Cord blood/ placental transfer: 
• 
To evaluate the transfer of RSV-specific 
antibodies from maternal participants who 
received a single IM dose of study 
intervention (RSV maternal vaccine or 
placebo) to their infants at delivery. 
• 
Ratio between cord blood* and maternal RSVPreF3 IgG-
specific antibody concentrations at delivery 
*or infant blood sample collected within 72 hours after birth (if no 
cord blood sample can be obtained). 
Infant participants: 
• 
To evaluate the RSV-specific antibody levels 
at birth in infants born to maternal 
participants who received a single IM dose of 
study intervention (RSV maternal vaccine or 
placebo). 
• 
Humoral immune responses at delivery*: 
− 
RSVPreF3 IgG-specific antibody concentrations 
− 
Neutralizing antibody titers against RSV-A 
*Measured in cord blood sample collected at delivery or in infant 
blood sample collected within 72 hours after birth (if no cord 
blood sample can be obtained). 
Secondary 
Safety assessment: 
Maternal participants: 
• 
To evaluate the safety of a single IM dose of 
study intervention (RSV maternal vaccine 
and placebo) administered to maternal 
participants, up to 180 days post-delivery. 
• 
Number and percentage of maternal participants reporting: 
− 
SAEs, (S)AEs leading to study withdrawal and MAEs 
from Day 1 up to 180 days post-delivery. 


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Objectives 
Endpoints & Estimands 
• 
To evaluate the worsening of pre-existing 
medical conditions and/or obstetric 
complications up to 180 days post-delivery, 
in maternal participants who received a 
single IM dose of study intervention (RSV 
maternal vaccine or placebo). 
• 
Number and percentage of maternal participants reporting: 
− 
Worsening of pre-existing medical conditions and/or 
obstetric complications from Day 1 up to 180 days 
post-delivery. 
• 
To evaluate the occurrence of RSV-
associated MA-RTIs in maternal participants 
who received a single IM dose of study 
intervention (RSV maternal vaccine and 
placebo) up to 180 days post-delivery. 
• 
Number and percentage of maternal participants reporting: 
− 
RSV-associated MA-RTIs from Day 1 up to180 days 
post-delivery. 
Infant participants: 
• 
To evaluate the occurrence of medically 
assessed, RSV-associated LRTIs up to 365 
days post-birth (12 months of age) in infants 
born to maternal participants who received a 
single IM dose of study intervention (RSV 
maternal vaccine or placebo). 
• 
From birth up to 365 days post-birth (12 months of age), 
number and percentage of infant participants reporting 
medically assessed, RSV-associated LRTIs of any severity 
and severe RSV-associated LRTIs (according to the cases 
definitions). 
• 
To evaluate the occurrence of medically 
assessed, RSV-associated hospitalization up 
to 365 days post-birth (12 months of age) in 
infants born to maternal participants who 
received a single IM dose of study 
intervention (RSV maternal vaccine or 
placebo). 
• 
From birth up to 365 days post-birth (12 months of age), 
number and percentage of infant participants reporting 
medically assessed, RSV-associated hospitalizations 
(according to the cases definitions). 
Immunogenicity assessment: 
Maternal participants: 
• 
To evaluate the immunogenicity of a single 
IM dose of study intervention (RSV maternal 
vaccine or placebo) administered to maternal 
participants up to delivery. 
• 
Humoral immune responses at Day 31 post-dosing: 
− 
RSVPreF3 IgG-specific antibody concentrations 
− 
Neutralizing antibody titers against RSV-A 
• 
Humoral immune responses at pre-dosing (Day 1), at Day 
31 post-dosing and at delivery: 
− 
Neutralizing antibody titers against RSV-B 
Infant participants: 
• 
To evaluate neutralizing antibody titers 
against RSV-B at birth in infants born to 
maternal participants who received a single 
IM dose of study intervention (RSV maternal 
vaccine or placebo). 
• 
Humoral immune responses at delivery*: 
− 
Neutralizing antibody titers against RSV-B 
* Measured in cord blood sample collected at delivery or infant 
blood sample collected within 72 hours after birth (if no cord 
blood sample can be obtained). 


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Objectives 
Endpoints & Estimands 
• 
To evaluate RSV-specific antibodies up to 
Day 181 post-birth (6 months of age) in 
infants born to maternal participants who 
received a single IM dose of study 
intervention (RSV maternal vaccine or 
placebo).  
• 
Humoral immune responses at Day 43*, at Day 121* and at 
Day 181*: 
− 
RSVPreF3 IgG-specific antibody concentrations 
− 
Neutralizing antibody titers against RSV-A and RSV-B 
* Measured in infant blood samples collected at Day 43 (sub-
cohort 1, V2-NB), at Day 121 (sub-cohort 2, V3-NB) and at Day 
181 (sub-cohort 3, V4-NB) post-birth. Each infant will be 
randomly assigned (1:1:1) to one of 3 sub-cohorts. 
Tertiary 
AE = adverse event; IM = intramuscular; AESI = adverse event of special interest; LRTI = lower respiratory tract 
illness; MAE = medically attended adverse event; NB = newborn; RSV = respiratory syncytial virus; RSV-A/B = 
respiratory syncytial virus subtype A/B; MA-RTI = medically attended respiratory tract illness; RSVPreF3 IgG = 
respiratory syncytial virus PreF3 immunoglobulin G; SAE = serious adverse event; GMT = Geometric mean titer; GMC 
= Geometric mean concentration 
1 Maternal and neonatal AESI and pregnancy outcomes should be recorded in the eCRF along with assessment of 
level of diagnostic certainty by Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions 
when applicable. Of note, some events of interest fall under a single category but have multiple subcategories. For 
example, hypertensive disorders of pregnancy is an event with 3 subcategories that include: 1) gestational 
hypertension; 2) pre-eclampsia; and 3) pre-eclampsia with severe features (including eclampsia). For each event, the 
investigator should identify the event and select the applicable sub-category. 
CCI


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1.2. 
Study Design 
Overview of Study Design and Key Features 
Figure 1 and Figure 2 provide overviews of the study design for maternal and infant 
participants, respectively. 
Figure 1 
Study design overview – Maternal participants 
 
MAE = medically attended adverse event; MA-RTI = medically attended respiratory tract illness; (S)AE = (serious) 
adverse event; SCR = screening 
1 Visit 2 (Day 31) may be replaced by Visit 3 (Delivery) in case of premature delivery. If the delivery date occurs 
prior to Day 31 post-study intervention, there will be no Visit 2 (Day 31). 
2 SAEs related to study participation are to be collected from screening to Visit 1 (Day 1 pre-study intervention). 
3 Following study invervention (RSV maternal vaccine or placebo) administration, SAEs and (S)AEs leading to study 
withdrawal are to be collected from Day 1 (Visit 1) up to 180 days post-delivery (Contact 2). 
4 If not performed as part of the routine care, the blood and urine samples for screening should be collected within 
15 days prior to study intervention administration. 
5 Due to the recent safety signal in RSV-MAT-009, there will be no further enrollment and vaccination of 
maternal participants. Refer to Protocol section 2.3 for further details. 
6 Due to the change in the study requirements, MA-RTIs experienced by the maternal pariticipants will no 
longer be collected. 
7 In addition to the monthly contacts between Visit-2 and the Delivery visit, additional not pre-specified 
contacts and/or visits can be made more often (at any desired frequency), as per investigator’s, maternal 
participant’s or LAR’s discretion. 
Note: Placenta samples will be collected at delivery from all maternal participants, whenever feasible. 
These samples may be tested to support possible safety assessments, if necessary. Additional details are 
provided in the study procedures manual (SPM). 


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Overview of Study Design and Key Features 
Figure 2 
Study design overview – Infant participants 
 
AESI = adverse event of special interest; MAE = medically attended adverse event; RTI = respiratory tract 
illness;(S)AE = (serious) adverse event 
Infant sub-cohorts are abbreviated “BS1”, “BS2” and “BS3” correspond to Visit 2-NB (Day 43 post-birth), Visit 3-NB 
(Day 121 post-birth) and Visit 4-NB (Day 181 post-birth), respectively. 
RSV_MAT_BS1, _BS2, _BS3 = infants born to women in the RSV_MAT group and evaluated for immunogenicity at 
the designated timepoint (Day 43, Day 121 or Day 181 post-birth). 
Control_BS1, _BS2, _BS3 = infants born to women in the Control group evaluated for immunogenicity at the 
designated timepoint (Day 43, Day 121 or Day 181 post-birth) 
1 If cord blood was not collected at delivery/birth, a blood sample should be collected from the infant within 72 hours 
post-birth. 
2 Any neonatal / infant AESIs identified after 42 days post-birth should also be reported. 
3 Due to the change in the study requirements, there will no longer be collection of blood samples at Visit 2-
NB, Visit 3-NB and Visit 4-NB.  
Note:  
An additional recommended safety contact may be performed ~7 days post-birth if deemed necessary by 
the investigator or by the parent/ LAR(s). 
Design Features 
Study Type: self-contained. 
Experimental design: Phase III, double-blind*, randomized, 
placebo-controlled, multi-center, multi-country study with 1 
investigational RSV MAT vaccine group in a parallel design. 
* Due to the recent safety signal, the study was fully unblinded 
to ensure the safety monitoring of the participants. 
Study Population: High risk pregnant women aged 15 to 49 
years and infants born to the vaccinated mothers. 


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Overview of Study Design and Key Features 
Duration of the study: The intended duration of the study for 
maternal participant is approximately 10 to 11 months (including 
screening visit, from informed consent/assent until 180 days post-
delivery) and approximately 12 months for infant participants 
(from birth until 365 days post-birth), which is expected to cover 
at least 1 complete RSV season. 
Control: Placebo control. 
Blinding: Double-blind*, as described in Table 2. 
* Due to the recent safety signal, the study was fully unblinded 
to ensure the safety monitoring of the participants. 
Study 
intervention 
Study (intervention) groups are single 120 µg dose of the 
investigational RSV vaccine and Placebo control, as described in 
Table 2. 
Study 
intervention 
Assignment 
Study intervention schedule*: 1 single dose administered IM 
between 24 and 36 weeks of gestation (at Visit 1, Day 1) to 
maternal participants. 
* Due to the recent safety signal, there will be no further 
enrollment and vaccination of maternal participants. 
Randomized study intervention allocation* is 2:1 
(investigational vaccine: placebo), as described in Table 2. 
* Due to the recent safety signal, there will be no further 
enrollment and vaccination of maternal participants. 
Conduct of 
Analyses 
No analysis requiring statistical adjustment will be performed. 
However, analyses to evaluate objectives and endpoints will be 
performed in steps. Refer to Section 4.7 for details. 
 


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Table 2 
Study groups, intervention and blinding 
Study 
groups 
Maternal participants 
Infant participants 
 
Blinding 
 
~Number 
Age in 
years 
(Min-
Max) 
Intervention 
name 
Study groups 
for 
randomization 
(Allocation 2:1) 
Infant Blood Sampling 
sub-cohorts 
Sub-cohorts for 
randomization 
(Allocation 1:1:1) 
M + I 
M + I 
I only 
Up to Day 43 
post-
delivery/birth 
Up to Day 
181 post-
delivery/birth 
From Day 182 to 
Day 366 post-
delivery/birth  
 
 
 
 
 
Name 
~Number  
Double-blind** 
Single-blind** 
Single-blind** 
RSV_MAT 
~252 * 
15 – 49 
RSV MAT 
RSV_MAT 
RSV_MAT_BS1 
~84 
RSV_MAT_BS1  
● 
● 
● 
RSV_MAT_BS2 
~84 
RSV_MAT_BS2  
RSV_MAT_BS3 
~84 
RSV_MAT_BS3 
Control 
~126 * 
15 – 49 
Control 
Control 
Control_BS1 
~42 
Control_BS1 
● 
● 
● 
Control_BS2  
~42 
Control_BS2 
Control_BS3 
~42 
Control_BS3 
Control = Placebo; M = maternal participants; I = infant participants 
Infant sub-cohorts are abbreviated “BS1”, “BS2” and “BS3” correspond to Visit 2-NB (Day 43 post-birth), Visit 3-NB (Day 121 post-birth) and Visit 4-NB (Day 181 post-birth), 
respectively. 
RSV_MAT_BS1, _BS2, _BS3 = infants born to women in the RSV_MAT group and evaluated for immunogenicity at the designated timepoint (Day 43, Day 121 or Day 181 post-birth). 
Control_BS1, _BS2, _BS3 = infants born to women in the Control group evaluated for immunogenicity at the designated timepoint (Day 43, Day 121 or Day 181 post-birth) 
* The double-blinding will apply from Day 1 pre-study intervention to Day 43 post-delivery/birth visit after which the first analysis will be conducted and treatment-level unblinded 
summaries will be provided to GSK and regulatory agency for review. No individual treatment code will be shared with investigators, site staff and participants until the end of the study 
* Due to the recent safety signal in RSV-MAT-009, there will be no further enrollment and vaccination of maternal participants. 
** Due to the recent safety signal, the study was fully unblinded to ensure the safety monitoring of the participants 


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2. 
STATISTICAL HYPOTHESES  
No statistical hypotheses will be tested. All statistical analyses are descriptive. 
2.1. 
Multiplicity Adjustment 
No analysis requiring statistical adjustment will be performed.  
3. 
ANALYSIS SETS 
3.1. 
Definition 
Table 3 
Maternal Participants 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Enrolled 
All maternal participants who completed 
the informed consent process and signed 
the informed consent form and were 
determined as eligible for study 
participation. 
Study Population 
Exposed 
All maternal participants who received 1 
dose of a study intervention. The 
allocation in a group is done in function 
of the administered intervention. 
Safety 
Full Analysis 
Immunogenicity 
All maternal participants in the Exposed 
set who have at least one post-dosing 
immunogenicity data.  
It will be defined by timepoint, e,g. FAS 
at Day 31 
Immunogenicity 
Per-Protocol 
Immunogenicity 
All maternal participants in the Full 
Analysis (Immunogenicity) minus 
participants with protocol deviations that 
lead to exclusion.  
The analysis will be done according to 
the study interventions that participants 
received. 
It will be defined by timepoint, e.g. PPS 
at Day 31. 
Immunogenicity 
Solicited Safety 
All maternal participants in the Exposed 
set who have solicited safety data. 
Safety 
FAS = Full Analysis Set; PPS = Per Protocol Set 


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Table 4 
Infant Participants 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Exposed 
Infants live-born to exposed maternal 
participants, whose parents/LARs 
completed the informed consent process 
and signed the informed consent form. 
Safety 
Full Analysis 
Immunogenicity 
All infant participants in the Exposed set 
who have at least one post-delivery/birth 
immunogenicity data.  
The analysis will be done according to the 
study intervention that maternal 
participants received. 
It will be defined by timepoint, e.g. FAS 
at Day 31 
Immunogenicity 
Per-Protocol 
Immunogenicity 
All infant participants in the Full Analysis 
(Immunogenicity) set minus those who (a) 
were born less than 4 weeks post-maternal 
participant dosing and/ or (b) have 
protocol deviations that lead to exclusion. 
It will be defined by timepoint, e.g. PPS at 
Day 31 
Immunogenicity 
FAS = Full Analysis Set; PPS = Per Protocol Set 
3.2. 
Criteria for eliminating data from Analysis Sets 
Elimination codes are used to identify participants to be eliminated from analysis. Detail 
is provided below for each set.  
3.2.1. 
Elimination from Exposed Set (ES) 
Maternal participants: Code 1030 (Study vaccine not administered at all), 800 
(Fraudulent data) and code 900 (invalid informed consent) will be used for identifying 
maternal participants eliminated from ES. 
Infants: Code 1030 (Study vaccine not administered at all, carry forward elimination 
from mother to infant), 800 (Fraudulent data), code 900 (invalid informed consent) and 
code 901 (invalid informed consent due to mother) will be used for identifying infants 
eliminated from ES.  


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3.2.2. 
Elimination from Full Analysis Set (FAS) - Immunogenicity 
3.2.2.1. 
Excluded participants from FAS of maternal participants 
A maternal participant will be excluded from the FAS analysis under the following 
conditions.  
Table 5 
Elimination code and condition for maternal participants 
Code 
Condition under which 
the code is used 
Visit (timepoints) 
where the code is 
applicable 
Applicable for analysis 
set/endpoint 
800 
Fraudulent data 
All 
All 
900 
Invalid informed consent 
All 
All 
1030 
Study vaccine not 
administered at all 
All 
Safety, immunogenicity 
2100.Vx 
Serological results not 
available post-vaccination 
Visit 2/Day 31,  
Visit 3/Delivery 
Immunogenicity 
Vx indicates participants whose immunogenicity data will be eliminated from a specific visit. 
3.2.2.2. 
Excluded participants from FAS of infant participants 
An infant participant will be excluded from the FAS analysis under the following 
conditions.  
Table 6 
Elimination code and condition for infant participants 
Code 
Condition under 
which the code is 
used 
Visit (timepoints) where the 
code is applicable 
Applicable for 
analysis 
set/endpoint 
800 
Fraudulent data 
All 
All 
900 
Invalid informed 
consent 
All 
All 
901# 
Invalid informed 
consent - mother 
All 
All 
1030# 
Study vaccine not 
administered at 
all - mother 
All 
Safety, 
immunogenicity 
2100.Vx 
Serological 
results not 
available  
Visit 1-NB/Birth* 
Visit 2-NB/Day 43 post-birth 
Visit3-NB/Day 121 post-birth 
Visit4-NB/Day 181 post-birth 
Immunogenicity 
#Carry forward elimination from mother to infant 
Vx indicates participants whose immunogenicity data will be eliminated from a specific visit. 
*cord blood sample or blood sample collected within 72 hours after birth if cord blood sample is not collected 


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3.2.3. 
Elimination from Per-protocol analysis Set (PPS) - 
Immunogenicity 
3.2.3.1. 
Excluded participants from Per-protocol analysis set of maternal 
participants 
A maternal participant will be excluded from the PPS analysis under the following 
conditions.  
Table 7 
Elimination code and condition for maternal participants 
Code 
Condition under which the 
code is used 
Visit (timepoints) 
where the code is 
applicable 
Applicable for 
analysis 
set/endpoint 
800 
Fraudulent data 
All 
All 
900 
Invalid informed consent 
All 
All 
1030 
Study vaccine not 
administered at all 
All 
Safety, 
immunogenicity 
1040.Vx+* Administration of 
concomitant vaccine(s) 
forbidden in the protocol 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
1050 
Randomisation failure 
All 
Immunogenicity  
1060 
Randomisation code was 
broken 
All 
Immunogenicity  
1070** 
Participants got vaccinated 
with the correct vaccine but 
containing an incorrect 
volume 
All 
Immunogenicity 
1070** 
Vaccination not according to 
protocol (site of injection, 
route of administration, 
wrong replacement of study 
treatment administered) 
All 
Immunogenicity 
1070** 
Study treatment not prepared 
as per protocol (e.g. 
reconstitution) 
All 
Immunogenicity 
1070** 
Other deviations related to 
wrong study 
treatment/administration/dose 
All 
Immunogenicity 
1070** 
Study treatment administered 
while contraindication  
All 
Immunogenicity 
1080 
Vaccine temperature 
deviation 
All 
Immunogenicity 
1090 
Expired vaccine administered All 
Immunogenicity 


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Code 
Condition under which the 
code is used 
Visit (timepoints) 
where the code is 
applicable 
Applicable for 
analysis 
set/endpoint 
2010 
Protocol violation 
(inclusion/exclusion criteria) 
DOB – VAC – 15-49 years 
Gestational age at 
vaccination - 28 0/7 - 360/7 
All 
Immunogenicity 
2040.Vx+* Administration of any 
medication forbidden by the 
protocol 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2040.Vx+* Device, excluded by the 
protocol, was administered 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2050.Vx+* Intercurrent medical 
conditions which are 
exclusionary as per protocol 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2060.Vx+* Concomitant infection related 
to the vaccine which may 
influence immune response 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2070.Vx+* Concomitant infection not 
related to the vaccine but 
may influence immune 
response 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2090.Vx 
Subjects did not comply with 
blood sample schedule: 
• 
For PPS at Day 31, 
check the interval from 
vaccination to day 31 BS 
= 20 – 45 days; 
• 
For PPS at Delivery, 
check the interval from 
delivery to delivery BS = 
1 day before to 3 days 
after delivery; 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2100.Vx 
Serological results not 
available post-vaccination 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2120.Vx 
Obvious incoherence or 
abnormality or error in data 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
2130.Vx 
Testing performed on 
samples not aligned with ICF 
Visit 2/Day 31, 
Visit 3/Delivery 
Immunogenicity 
*Attribution of these elimination codes to subject need CRDL review of individual listing 
** Attribution of code 1070 to a subject requires CRDL confirmation 
Vx+ indicates subjects whose immunogenicity data will be eliminated from a specific visit onwards; Vx indicates 
subjects whose immunogenicity data will be eliminated from a specific visit. 
DOB-Date of Birth, VAC-Vaccination, BS- Blood Sample 
BS- Blood Sample. 


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3.2.3.2. 
Excluded participants from Per-protocol analysis set of infant 
participants 
An infant participant will be excluded from the PPS analysis under the following 
conditions.  
Table 8 
Elimination code and condition for infant participants 
Code 
Condition under which the 
code is used 
Visit (timepoints) 
where the code is 
applicable 
Applicable for 
analysis 
set/endpoint 
800 
Fraudulent data 
All 
All 
900 
Invalid informed consent - 
infant 
All 
All 
901# 
Invalid informed consent - 
mother 
All 
All 
1030# 
Study vaccine not 
administered at all 
All 
Safety, 
immunogenicity 
1040.Vx+* Administration of 
concomitant vaccine(s) 
forbidden in the protocol - 
infant 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
1041#* 
Maternal administration of 
concomitant vaccine(s) 
forbidden in the protocol up 
to Delivery 
All 
Immunogenicity 
1050# 
Maternal randomisation 
failure 
All 
Immunogenicity 
1060# 
Maternal randomisation code 
was broken 
All 
Immunogenicity 
1070# 
Maternal participants got 
vaccinated with the correct 
vaccine but containing an 
incorrect volume 
All 
Immunogenicity 
1070# 
Vaccination not according to 
protocol (site of injection, 
route of administration, 
wrong replacement of study 
treatment administered) 
All 
Immunogenicity 
1070# 
Study treatment not prepared 
as per protocol (e.g. 
reconstitution) 
All 
Immunogenicity 
1070# 
Other deviations related to 
wrong study 
treatment/administration/dose 
All 
Immunogenicity 


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Code 
Condition under which the 
code is used 
Visit (timepoints) 
where the code is 
applicable 
Applicable for 
analysis 
set/endpoint 
1070# 
Study treatment administered 
while contraindicated  
All 
Immunogenicity 
1080# 
Vaccine temperature 
deviation 
All 
Immunogenicity 
1090# 
Expired vaccine administered All 
Immunogenicity 
2010 
Protocol violation 
(inclusion/exclusion criteria) 
- infant 
All 
Immunogenicity 
2011# 
Protocol violation 
(inclusion/exclusion criteria) 
- mother 
All 
Immunogenicity 
2040.Vx+* Administration of any 
medication forbidden by the 
protocol - infant 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
2040.Vx+* Device, excluded by the 
protocol, was administered - 
infant 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
2041#* 
Maternal administration of 
any medication forbidden by 
the protocol up to Delivery 
All 
Immunogenicity 
2041#* 
Device, excluded by the 
protocol, was administered 
by mother up to Delivery 
All 
Immunogenicity 
2050.Vx+* Intercurrent medical 
conditions which are 
exclusionary as per protocol - 
infant 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
2060.Vx+* Concomitant infection related 
to the vaccine which may 
influence immune response - 
infant 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 


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Code 
Condition under which the 
code is used 
Visit (timepoints) 
where the code is 
applicable 
Applicable for 
analysis 
set/endpoint 
2070.Vx+* Concomitant infection not 
related to the vaccine but 
may influence immune 
response - infant 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
2050#* 
Maternal intercurrent medical 
conditions which are 
exclusionary as per protocol 
up to Delivery 
All 
Immunogenicity 
2060#* 
Maternal concomitant 
infection related to the 
vaccine which may influence 
immune response up to 
Delivery 
All 
Immunogenicity 
2070#* 
Maternal concomitant 
infection not related to the 
vaccine but may influence 
immune response up to 
Delivery 
All 
Immunogenicity 
2090.Vx 
Participants did not comply 
with blood sample schedule – 
infant: 
• 
For infants without cord 
blood, check the interval 
from birth to Visit 1-NB 
birth BS = 0 – 72 hours; 
• 
For PPS at Day 43 post-
birth, check the interval 
from birth to Day 43 BS 
= 30 – 60 days; 
• 
For PPS at Day 121 
post-birth, check the 
interval from birth to 
Day 121 BS = 110 – 140 
days; 
• 
For PPS at Day 181 
post-birth, check the 
interval from birth to 
Day 181 BS = 165 - 200 
days 
Visit 1-NB/Birth 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 


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Code 
Condition under which the 
code is used 
Visit (timepoints) 
where the code is 
applicable 
Applicable for 
analysis 
set/endpoint 
2100.Vx 
Serological results not 
available  
Visit 1-NB/Birth 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
2120.Vx 
Obvious incoherence or 
abnormality or error in data 
Visit 1-NB/Birth 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
2130.Vx 
Testing performed on 
samples not aligned with ICF 
Visit 1-NB/Birth 
Visit 2-NB/Day 43 
post-birth 
Visit3-NB/Day 121 
post-birth 
Visit4-NB/Day 181 
post-birth 
Immunogenicity 
3100 
Delivery happens less than 4 
weeks post vaccination 
All 
Immunogenicity 
*Attribution of these elimination codes to subject need CRDL review of individual listing 
#Carry forward elimination from mother to infant 
Vx+ indicates subjects whose immunogenicity data will be eliminated from a specific visit onwards; Vx indicates 
subjects whose immunogenicity data will be eliminated from a specific visit. 
BS- Blood Sample. 
3.2.4. 
Elimination from solicited safety set 
Code 1030 (Study vaccine not administered at all), code 800 (fraudulent data) and code 
900 (invalid informed consent) and code 1160 (no post-vaccination solicited safety data) 
will be used for identifying participants eliminated from the solicited safety set.  


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4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
Unless otherwise specified, reactogenicity analysis will be performed on Solicited Safety 
Set for maternal participants, and other safety analyses will be performed on Exposed 
Sets for both maternal and infant participants. 
In general, Immunogenicity analysis will be performed on the Per Protocol set. If, in any 
study group and at any timepoint, the percentage of exposed participants with 
immunogenicity results excluded from the Per Protocol set is 5% or more, a second 
analysis based on the Full Analysis Set will be performed to complement the Per Protocol 
analysis for primary and secondary immunogenicity analysis. 
4.1.1. 
General Methodology 
Participants who prematurely withdrew from study will not be replaced.  
Unless otherwise specified, continuous data will be summarized using descriptive 
statistics: n, mean, standard deviation (SD), median, minimum and maximum. 
Categorical data will be summarized as the number and percentage of participants in each 
category. 
95% confidence interval (CI) for proportion will be based on exact Clopper-Pearson 
confidence interval [Clopper, 1934]. 
95% CI for group difference in proportion will be based on Miettinen and Nurminen 
confidence interval [Miettinen, 1985].  
95% CI for GMT(C) will be based on a back transformation of student confidence 
interval for the mean of log-transformation. 
95% CI for GMT(C) ratio between groups will be based on a back transformation of 
confidence interval for the mean difference on log-transformation. 
For a given participant and given immunogenicity measurement, missing or non-
evaluable measurements will neither be imputed nor be replaced, and therefore will not 
be included in immunogenicity analysis. 
For between group statistical modelling analysis, participants having a result at both the 
baseline and the considered timepoint will be included in the analysis. 


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4.1.2. 
Definition 
4.1.2.1. 
Baseline definition 
For all endpoints the baseline value will be the latest pre-dose assessment with a non-
missing value, including those from unscheduled visits. If time is not collected, Day 1 
assessments are assumed to be taken prior to first dose and used as baseline. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
4.1.2.2. 
Worsening of pre-existing medical conditions and/or obstetric 
complications 
Worsening of the pre-existing medical condition and/or obstetric complication will be 
considered by the investigator, using clinical judgment and the following criteria: 
• 
Change in medication and/or medication dose 
• 
Medically attended event in relation to pre-existing condition and/or obstetric 
complication that are outside the routine management of the condition/complication 
• 
SAE and/or hospitalization in relation to pre-existing condition and/or obstetric 
complication 
Worsening of the pre-existing medical condition and/or obstetric complication will be 
collected from Day 1 (Visit 1) up to Day 181 post-delivery as AESI. 
4.1.2.3. 
RSV infection 
The sponsor will analyse nasal swabs by quantitative reverse transcription polymerase 
chain reaction (qRT-PCR) for the presence of RSV-A/B. A positive (RSV-A or B) test 
result constitutes a case of RSV infection. Refer to Table 10, Table 12 and section 8.4 of 
the Protocol. 
In the event the collection of a nasal swab for testing by the sponsor is impossible, results 
from locally collected samples, tested with locally approved tests, may also be considered 
for the determination of a case of RSV infection. 
Note: Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 
4.1.2.4. 
RTI and LRTI 
RTI cases will be classified (during data analyses) according to the definitions provided 
in Table 9* and Table 10. 
* Due to the change in the study requirements, RTI surveillance of the maternal 
participants will no longer be performed. 


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Table 9 
MA-RTI case definitions for data analysis in maternal participants 
RSV-MA-RTI 
Medically attended visit for RTI symptoms AND Confirmed RSV infection 1, 2 
RSV hospitalization 
Confirmed RSV infection AND Hospitalized for acute medical condition 3 
All-cause MA- RTI 
Medically attended visit for RTI symptoms 
1 Confirmed RSV infection defined in Section 4.2.5.3 of the Protocol 
2 RSV (nasal swab) sampling and testing as specified in Table 10 of the Protocol. 
3 Hospitalization is defined as admission for observation or treatment based on the judgment of a health care provider. 
MA-RTI = Maternal, medically attended respiratory tract illness 
Note: Due to the change in the study requirements, RTI surveillance of the maternal participants will no longer 
be performed. 
Table 10 
RTI/LRTI case definitions for data analysis in infants 
RSV-RTI 
Runny nose, OR Blocked nose, OR Cough 
AND 
Confirmed RSV infection 4 
RSV-LRTI 
History of cough OR difficulty in breathing 1 
AND 
SpO2 < 95%2, OR RR increase 3 
AND 
Confirmed RSV infection 4 
RSV-severe LRTI 
Meeting the case definition of RSV-LRTI 
AND 
SpO2 < 93%2, OR lower chest wall in-drawing, OR inability to feed, OR failure 
to respond / unconscious 
RSV hospitalization 
Confirmed RSV infection 5 
AND 
Hospitalized for acute medical condition 6 
All-cause RTI 
Runny nose, OR Blocked nose, OR Cough 
All-cause LRTI 
History of cough OR difficulty in breathing 1 
AND 
SpO2 < 95% 2, OR RR increase 3  
All-cause LRTI hospitalization 
Hospitalized due to all-cause LRTI as defined above 
Definitions are modified from [Modjarrad, 2016]; RTI = respiratory tract illness; LRTI = lower respiratory tract illness; 
RR = respiratory rate; SpO2 = blood oxygen saturation by pulse oximetry. 
1 Based on history reported by parents/LARs and includes difficulty in breathing (e.g. showing signs of wheezing or 
stridor, tachypnoea, flaring [of nostrils], chest in-drawing, apnea). 
2 For blood oxygen saturation (SpO2), the lowest value monitored will be used. In high altitudes (>2500m), SpO2 <92% 
for LRTI, <90% for severe LRTI. 
3 RR increase defined as: 
> 60/minute (< 2 months of age) 
> 50/minute (2 to < 12 months of age) 
> 40/minute (12 to 24 months of age) 
4 Confirmed RSV infection defined in Section 4.2.5.3 of the Protocol. 
5 RSV (nasal swab) sampling and testing as specified in Table 12 of the Protocol. 
6 Hospitalization is defined as admission for observation or treatment based on the judgment of a health care provider. 
For the analysis of RTI episode, a new RTI episode will be defined as any occurrence of 
cough, runny nose, blocked nose, wheezing or difficulty breathing with an interval of at 
least 7 symptom free days since the last episode of RTI that was diagnosed. 


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4.2. 
Primary Endpoint(s) Analyses 
4.2.1. 
Safety 
4.2.1.1. 
Analysis of safety and reactogenicity planned in the protocol 
Safety analyses in maternal participants will include summaries by study group and age 
category (<18 years; ≥ 18 years; overall) of solicited administration site and systemic 
events, unsolicited AEs, MAEs, SAEs, MA-RTIs, RSV-associated MA-RTIs, (S)AEs 
leading to study withdrawal, worsening of pre-existing medical conditions and/or 
obstetric complications, pregnancy outcomes and pregnancy-related AESIs. 
Safety analyses in infant participants will include summaries by study group and 
gestational age at birth (≥ 37 weeks; <37 weeks; overall) of neonatal AESIs, MAEs, 
SAEs, (S)AEs leading to study withdrawal, and occurrence of RSV- associated LRTIs, 
severe LRTIs, RSV-associated hospitalization. 
The reactogenicity analysis will be performed on Solicited Safety Set for maternal 
participants, and other safety analyses will be performed on the Exposed Sets for both 
maternal and infant participants. 
 
Primary Safety Endpoints  
Statistical Analysis Methods 
Maternal 
participants 
Number and percentage of 
maternal participants reporting 
solicited administration site and 
systemic events during a 7-day 
(i.e. Day 1 to Day 7 included) 
follow-up period after dosing. 
The number and percentage with exact 95% CI of maternal 
participants reporting each solicited administration site event 
(any grade, each grade,) and solicited systemic event (any, 
each grade) during the 7-day (7 days post-study intervention, 
Day 1 included) follow-up period after dosing will be tabulated 
by maximum intensity per participant for each study group.  
The number and percentage of maternal participants reporting: 
• 
at least one administration site AE (solicited and 
unsolicited) 
• 
at least one systemic AE (solicited and unsolicited) 
• 
any AE 
during the 7-day (7 days post-study intervention, Day 1 
included) follow-up period after dosing will be tabulated with 
exact 95% CI by group. 
The same computations will be done for Grade 3 solicited and 
unsolicited AEs, for any unsolicited AEs considered related to 
study intervention, for any Grade 3 unsolicited AEs considered 
related to study intervention and for any solicited and 
unsolicited AEs resulting in a medically attended visit (i.e., 
MAEs). 
Number and percentage of 
maternal participants reporting 
unsolicited AEs that occur during 
a 30-day (i.e. Day 1 to Day 30 
included) follow-up period after 
dosing. 
The number and percentage of maternal participants reporting 
unsolicited AEs within 30 days (30 days post-study 
intervention, Day 1 included) after dosing with exact 95% CIs 
will be tabulated by group and by MedDRA preferred term. 
Similar tabulations will be done for Grade 3 unsolicited AEs, for 
any causally related unsolicited AEs, for Grade 3 related 
unsolicited AEs and for MAEs. 


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Primary Safety Endpoints  
Statistical Analysis Methods 
Number and percentage of 
maternal participants reporting 
SAEs, (S)AEs leading to study 
withdrawal, and MAEs from Day 
1 up to 42 days post-delivery. 
The number and percentage of maternal participants reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 42 days post-delivery with exact 95% CIs will 
be tabulated by group and by Medical MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal, and MAEs will be prepared. 
Number and percentage of 
maternal participants reporting 
pregnancy outcomes * from Day 
1 up to 42 days post-delivery. 
*These include live birth with no 
congenital anomalies, live birth 
with minor congenital anomalies 
only; live birth with at least one 
major congenital anomaly, fetal 
death/still birth (antepartum or 
intrapartum) with no congenital 
anomalies, fetal death/still birth 
(antepartum or intrapartum) with 
only minor congenital anomalies, 
fetal death/still birth (antepartum 
or intrapartum) with at least 1 
major congenital anomaly; 
elective/therapeutic termination 
with no congenital anomalies; 
elective/therapeutic termination 
with only minor congenital 
anomalies, and 
elective/therapeutic termination 
with at least 1 major congenital 
anomaly. 
The number and percentage of maternal participants reporting 
each pregnancy outcome from Day 1 up to 42 days post-
delivery will be tabulated with its exact 95% CI by group. 
By participant listings of adverse pregnancy outcomes will be 
prepared. 
Number and percentage of 
maternal participants reporting 
pregnancy-related AESIs * and 
worsening of pre-existing medical 
conditions and/or obstetric 
complications from Day 1 up to 
42 days post-delivery. 
* These include maternal death, 
hypertensive disorders of 
pregnancy (gestational 
hypertension, pre-eclampsia, pre-
eclampsia with severe features 
including eclampsia), fetal growth 
restriction, gestational diabetes 
mellitus, pathways to preterm 
birth (premature preterm rupture 
of membranes, preterm labor, 
provider-initiated preterm birth) 
and chorioamnionitis. 
The number and percentage of maternal participants reporting 
each pregnancy-related AESI and worsening of pre-existing 
medical conditions and/or obstetric complications from Day 1 
up to 42 days post-delivery will be tabulated with its exact 95% 
CI by group. 
By participant listings of pregnancy-related AESIs and 
worsening of pre-existing medical conditions and/or obstetric 
complications will be prepared.  


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Primary Safety Endpoints  
Statistical Analysis Methods 
Infant 
participants 
Number and percentage of infant 
participants reporting neonatal / 
infant AESIs * from birth up to 42 
days post-birth. 
* These include small for 
gestational age, low birth weight 
including very low and extremely 
low birth weight (<2500 g, 
<1500g, <1000g), congenital 
anomalies (major external 
structural defects, internal 
structural defects, functional 
defects), neonatal death (in an 
extremely preterm birth 
[22<GA<28 weeks], in a preterm 
live birth [28<GA<37 weeks], or 
in a term live birth) and preterm 
birth. 
The number and percentage of infant participants reporting 
each neonatal / infant AESI from birth up to 42 days post-birth 
will be tabulated with its exact 95% CI by group. 
By participant listings of neonatal / infant AESIs will be 
prepared. 
 
Number and percentage of infant 
participants reporting SAE, 
(S)AEs leading to study 
withdrawal, and MAEs from birth 
up to 42 days post-birth. 
The number and percentage of infant participants reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 42 days post-birth with exact 95% CIs will be 
tabulated by group and by MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
 
Number and percentage of infant 
participants reporting SAEs, 
(S)AEs leading to study 
withdrawal, and MAEs from birth 
up to 180 days post-birth. 
The number and percentage of infant participants reporting at 
least one SAE, (S)AE leading to study withdrawal, and MAE 
from birth up to 180 days post-birth will be tabulated with 95% 
CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared.  
 
Number and percentage of infant 
participants reporting SAEs, 
(S)AEs leading to study 
withdrawal, and MAEs from birth 
up to 365 days post-birth. 
The number and percentage of infant participants reporting at 
least one SAE, (S)AE leading to study withdrawal, and MAE 
from birth up to 365 days post-birth will be tabulated with 95% 
CI by group. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
AE= Adverse event; CI= Confidence interval; MAE = medically attended adverse event; MedRA = Medical dictionary 
for regulatory activities; SPM = study procedure manual 
4.2.1.2. 
Additional considerations 
Refer to Section 4.3.1.2 


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4.2.2. 
Immunogenicity 
4.2.2.1. 
Analysis of immunogenicity planned in the protocol 
The primary analysis for immunogenicity will be based on the PPS for analysis of 
immunogenicity.  
 
Primary Immunogenicity 
Endpoints 
Statistical Analysis Methods 
Maternal 
participants 
• 
Humoral immune 
responses at pre-dosing 
(Day 1) and at delivery: 
− 
RSVPreF3 IgG-
specific antibody 
concentrations 
− 
Neutralizing antibody 
titers against RSV-A 
For each assay, at each timepoint and by study group and age 
category (<18 years; ≥ 18 years; overall): 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
• 
GMR of antibody titers/concentrations at delivery over 
pre-dosing will be tabulated with 95% CI. 
Between group evaluation in terms of RSVPreF3 IgG-specific 
antibody concentrations and neutralizing antibody titers against 
RSV-A will be performed at delivery using an ANCOVA model 
on the logarithm10 transformation of the concentrations/titers, 
and including the pre-dosing logarithm10 transformation of the 
concentrations/titers, the study intervention, gestational age at 
the time of study intervention administration (<28 0/7; ≥ 28 0/7 
weeks), and the interval between dosing and delivery as 
covariates if needed. 
Cord blood/ 
placental 
transfer 
Ratio between cord blood* and 
maternal RSVPreF3 IgG-specific 
antibody concentrations at 
delivery. 
*or infant blood sample collected 
within 72 hours after birth (if no 
cord blood sample can be 
obtained). 
• 
Geometric mean of placental transfer ratio will be 
tabulated with 95% CI by study group. 
• 
Percentage of infants with placental transfer ratio ≥ 1 will 
be tabulated with exact 95 % CI by study group. 


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Primary Immunogenicity 
Endpoints 
Statistical Analysis Methods 
Infant 
participants 
• 
Humoral immune 
responses at delivery*: 
− 
RSVPreF3 IgG-
specific antibody 
concentrations 
− 
Neutralizing antibody 
titers against RSV-A 
*Measured in cord blood sample 
collected at delivery or infant 
blood sample collected within 72 
hours after birth (if no cord blood 
sample can be obtained). 
For each assay, the following analysis will be performed by 
study group 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
Between group evaluation in terms of RSVPreF3 IgG-specific 
antibody concentrations and neutralizing antibody titers against 
RSV-A will be performed at delivery using an ANCOVA model 
on the logarithm10 transformation of the concentrations/titers, 
and including the pre-dosing logarithm10 transformation of the 
concentrations/titers, the study intervention, gestational age at 
the time of study intervention administration (<28 0/7; ≥ 28 0/7 
weeks), and the interval between dosing and delivery as 
covariates if needed. 
In addition, if cord blood samples are missing in 20% or more 
of infants in a single study group, and if the data permit: RSV 
antibody concentrations/titers in infants through time will be 
evaluated separately in infants with cord blood samples and in 
infants from whom, instead, a blood sample was obtained 
within 72 hours after birth.  
ANCOVA = Analysis of covariance; CI = Confidence interval; GMR = Geometric mean of ratio; GMT/ C = Geometric 
mean titer/ concentration; RSV-A = Respiratory syncytial virus subtype A; RSVPreF3 IgG = Respiratory syncytial virus 
PreF3 immunoglobulin G 
4.2.3. 
Sensitivity analyses 
Refer to Section 4.3.3 
4.3. 
Secondary Endpoint(s) Analyses 
4.3.1. 
Safety 
4.3.1.1. 
Analysis of safety and reactogenicity planned in the protocol 
Safety analyses in maternal participants will include summaries by study group and age 
category (<18 years; ≥ 18 years; overall) of solicited administration site and systemic 
events, unsolicited AEs, MAEs, SAEs, MA-RTIs, RSV-associated MA-RTIs, (S)AEs 
leading to study withdrawal, worsening of pre-existing medical conditions and/or 
obstetric complications, pregnancy outcomes and pregnancy-related AESIs. 
Safety analyses in infant participants will include summaries by study group and 
gestational age at birth (≥ 37 weeks; <37 weeks; overall) of neonatal AESIs, MAEs, 
SAEs, (S)AEs leading to study withdrawal, and occurrence of RSV- associated LRTIs, 
severe LRTIs, RSV-associated hospitalization. 


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The reactogenicity analysis will be performed on Solicited Safety Set for maternal 
participants, and other safety analyses will be performed on the Exposed Sets for both 
maternal and infant participants. 
 
Secondary Safety Endpoints 
Statistical Analysis Methods 
Maternal 
participants 
Number and percentage of 
maternal participants reporting 
SAEs, (S)AEs leading to study 
withdrawal and MAEs from Day 1 
up to 180 days post-delivery. 
The number and percentage of maternal participants 
reporting: 
• 
at least one SAE 
• 
at least one (S)AE leading to study withdrawal 
• 
at least one MAE 
from Day 1 up to 180 days post-delivery with exact 95% CIs 
will be tabulated by group and by MedDRA preferred term. 
By participant listings of SAEs, (S)AEs leading to study 
withdrawal and MAEs will be prepared. 
 
Number and percentage of 
maternal participants reporting 
worsening of pre-existing medical 
conditions and/or obstetric 
complications from Day 1 up to 180 
days post-delivery. 
The number and percentage of maternal participants 
reporting each worsening of pre-existing medical conditions 
and/or obstetric complications from Day 1 up to 180 days 
post-delivery will be tabulated with its exact 95% CI by 
group. 
By participant listings of worsening of pre-existing medical 
conditions and/or obstetric complications will be prepared. 
 
Number and percentage of 
maternal participants reporting 
RSV-associated MA-RTIs from 
Day 1 up to 180 days post-
delivery. 
The number and proportion of participants reporting at least 
one RSV-associated MA-RTI from Day 1 up to 180 days 
post-delivery with exact 95% CIs will be calculated and 
tabulated. 
Infant 
participants 
From birth up to 365 days post-
birth (12 months of age), number 
and percentage of infant 
participants reporting medically 
assessed, RSV-associated LRTIs 
of any severity and severe RSV-
associated LRTIs (according to the 
case definitions). 
The number and percentage of infant participants reporting: 
• 
at least one medically assessed, RSV-associated 
LRTI of any severity 
• 
at least one medically assessed, severe RSV-
associated LRTI 
from birth up to 365 days post-birth (12 months of age) will 
be calculated and tabulated by group.  
 
From birth up to 365 days post-
birth (12 months of age), number 
and percentage of infant 
participants reporting medically 
assessed, RSV-associated 
hospitalizations (according to the 
cases definitions). 
The number and percentage of infant participants reporting 
at least one medically assessed, RSV-associated 
hospitalization from birth up to 365 days post-birth (12 
months of age) will be calculated and tabulated by group. 
AE = Adverse event; LRTI = Lower respiratory tract illness; MAE = medically attended adverse event; NB = Newborn; 
RSV-MA-RTI = respiratory syncytial virus associated medically attended respiratory tract illness; SAE = serious 
adverse event 


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4.3.1.2. 
Additional considerations 
4.3.1.2.1. Analysis of solicited events 
The analysis of solicited events will be performed on Solicited Safety Set. The intensity 
of the solicited events will be assessed as described: 
Table 11 
Intensity scales for solicited events in adults  
Adults 
Event 
Intensity grade 
Parameter 
Solicited 
administration 
site events 
Pain at administration site 
0 
None 
 
1 
Mild: Any pain neither interfering with nor 
preventing normal everyday activities. 
 
2 
Moderate: Painful when limb is moved and 
interferes with every day activities. 
 
3 
Severe: Significant pain at rest. Prevents 
normal every day activities. 
Redness at administration site 
Greatest surface diameter in mm 
Swelling at administration site 
Greatest surface diameter in mm  
Solicited 
systemic 
events 
Temperature* 
 
Record temperature in °C/°F with 1 decimal 
Temperature will be analyzed in 0.5°C 
increments from ≥ 38.0°C /100.4°F) 
Grade 3 fever is defined as > 39.0°C /102.2°F 
Headache 
 
 
Fatigue 
0 
Normal 
Nausea 
1 
Mild: Easily tolerated 
Vomiting 
2 
Moderate: Interferes with normal activity 
Diarrhea 
3 
Severe: Prevents normal activity 
Abdominal pain 
 
 
* Refer to Section 1.3 of the Protocol for the definition of fever and the preferred location for temperature 
measurement. 
The maximum intensity of solicited administration site redness/swelling will be scored at 
GSK Biological as follows:  
0 
: 
≤ 20 mm 
1 
: 
> 20 mm to ≤ 50 mm 
2 
: 
> 50 mm to ≤ 100 mm 
3 
: 
> 100 mm 
Duration in days of solicited administration site and systemic events within 7 days after 
study intervention will be tabulated by study group and overall, and if needed by age 
group. The derivation rule of duration in days for solicited events is detailed in section 
6.2.4.9. 
4.3.1.2.2. Exclusion of implausible solicited events 
Some local and systemic events will be directly measured by the participant and will be 
subject to a reconciliation process, even if they are biologically implausible. Therefore, 
these implausible measurements will be removed from the analysis but included in 
listings. Implausible measurements are summarized in the table below: 


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Table 12 
Implausible Solicited Events 
Parameter 
Implausible measurements 
Body temperature 
≤ 33°C or ≥ 42°C 
Erythema 
Measurements < 0 mm 
For subjects ≥ 6 years: ≥ 900 mm 
Swelling 
Measurements < 0 mm 
For subjects ≥ 6 years: ≥ 500 mm 
4.3.1.2.3. Analysis of unsolicited adverse events 
The analysis of unsolicited events will be performed on Exposed Set. 
4.3.1.2.4. Analysis of pregnancy outcome 
The analysis of pregnancy outcome will be performed on Exposed Set.  
Still births, preterm births and spontaneous abortions will be counted per pregnancy, 
regardless of the number of fetuses in the concerned pregnancy.  
4.3.1.2.5. Analysis of RTI and LRTI 
The analysis of RTI and LRTI will be performed on Exposed Set according to the case 
definitions in section 4.1.2.4. Separate listings of maternal RSV associated MA-RTI and 
infant RSV associated LRTI/hospitalization will be provided. 
Further analysis with respect to the incidence of RSV LRTI by an exploratory case 
definition might be performed if deemed necessary. 
4.3.2. 
Immunogenicity 
4.3.2.1. 
Analysis of immunogenicity planned in the protocol 
The secondary analysis for immunogenicity will be based on the Per Protocol – 
Immunogenicity Set.  
 
Secondary Immunogenicity 
Endpoints 
Statistical Analysis Methods 
Maternal 
participants 
• 
Humoral immune responses at 
Day 31 post-dosing: 
− 
RSVPreF3 IgG-specific 
antibody concentrations 
− 
Neutralizing antibody 
titers against RSV-A 
• 
Humoral immune responses at 
pre-dosing (Day 1), at Day 31 
post-dosing and at delivery: 
For each assay, at each timepoint and by study group and 
age category (<18 years; ≥ 18 years; overall): 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
• 
GMR of antibody titers/concentrations at each post-
dosing timepoint over pre-dosing will be tabulated with 
95% CI. 
Between group evaluation in terms of RSVPreF3 IgG-
specific antibody concentrations and neutralizing antibody 


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Secondary Immunogenicity 
Endpoints 
Statistical Analysis Methods 
− 
Neutralizing antibody 
titers against RSV-B. 
titers against RSV-A will be performed at Day 31 post-
dosing, and against RSV-B at Day 31 post-dosing and at 
delivery using an ANCOVA model on the logarithm10 
transformation of the concentrations/titers, and including the 
pre-dosing logarithm10 transformation of the 
concentrations/titers, the study intervention, gestational age 
at the time of study intervention administration (<28 0/7; ≥ 28 
0/7 weeks), and the interval between dosing and delivery as 
covariates if needed. 
Infant 
participants 
• 
Humoral immune responses at 
delivery*: 
− 
Neutralizing antibody 
titers against RSV-B 
* Measured in cord blood sample 
collected at delivery or infant blood 
sample collected within 72 hours 
after birth (if no cord blood sample 
can be obtained). 
For each assay, the following analysis will be performed by 
study group: 
• 
Antibody titers will be displayed using reverse 
cumulative curves. 
• 
GMTs will be tabulated with 95% CI and represented 
graphically. 
Between group evaluation in terms of neutralizing antibody 
titers against RSV-B will be performed at delivery using an 
ANCOVA model on the logarithm10 transformation of the 
concentrations/titers, and including the pre-dosing 
logarithm10 transformation of the concentrations/titers, the 
study intervention, gestational age at the time of study 
intervention administration (<28 0/7; ≥ 28 0/7 weeks), and the 
interval between dosing and delivery as covariates if 
needed. 
In addition, if cord blood samples are missing in 20% or 
more of infants in a single study group, and if the data 
permit: RSV antibody concentrations/titers in infants through 
time will be evaluated separately in infants with cord blood 
samples and in infants from whom, instead, a blood sample 
was obtained within 72 hours after birth.  
• 
Humoral immune responses at 
Day 43*, at Day 121* and at 
Day 181* after birth: 
− 
RSVPreF3 IgG-specific 
antibody concentrations 
− 
Neutralizing antibody 
titers against RSV-A and 
RSV-B 
* Measured in infant blood samples 
collected at Day 43 (sub-cohort 1, 
V2-NB), at Day 121 (sub-cohort 2, 
V3-NB) and at Day 181 (sub-cohort 
3, V4-NB) after birth. Each infant will 
be randomly assigned (1:1:1) to one 
of 3 sub-cohorts. 
For each assay, at each timepoint and by study group: 
• 
Antibody titers/concentrations will be displayed using 
reverse cumulative curves. 
• 
GMTs/ GMCs will be tabulated with 95% CI and 
represented graphically. 
Between group evaluation in terms of RSVPreF3 IgG-
specific antibody concentrations and neutralizing antibody 
titers against RSV-A and RSV-B at Day 43 (sub-cohort 1, 
V2-NB), at Day 121 (sub-cohort 2, V3-NB) and at Day 181 
(sub-cohort 3, V4-NB) after birth using an ANCOVA model 
on the logarithm10 transformation of the 
concentrations/titers, and including the pre-dosing 
logarithm10 transformation of the concentrations/titers, the 
study intervention, gestational age at the time of study 
intervention administration (<28 0/7; ≥ 28 0/7 weeks), and the 
interval between dosing and delivery as covariates if 
needed. 
ANCOVA = Analysis of covariance; CI = Confidence interval; GMR = Geometric mean of ratio; GMT/ C = Geometric 
mean titer/ concentration; NB = Newborn; RSV-A / B = Respiratory syncytial virus subtype A / B; RSVPreF3 IgG = 
Respiratory syncytial virus PreF3 immunoglobulin G 


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4.3.3. 
Sensitivity analyses 
For primary and secondary immunogenicity endpoints, between study group comparisons 
will also be explored through statistical modelling. This analysis is exploratory. 
For the analysis of maternal participants at each time point (Day 31, Delivery), the 
ANCOVA model will be explored and fitted via the proc GML procedure according to 
the following code: 
PROC GLM data=adis_moth; 
   BY atptn atpt; 
   CLASS tr01aga gagevg1 agegr3; 
   MODEL aval = base tr01aga gagevg1 agegr3 vacdel; 
   LSMEANS tr01aga/pdiff cl alpha=0.05; 
RUN; 
where aval represents the log-transformed antibody value of the immunogenicity variable 
at a given post baseline timepoint, group indicates the study group, gagevg1 is the 
gestational age category at study intervention administration (<280/7, ≥ 28 0/7  weeks), 
agegr3 is the age category at study intervention administration (<18 years and ≥18 years), 
vacdel is the interval between vaccination and delivery (days). The inclusion of age 
category at study intervention administration, interaction term between age category and 
gestational age category and interval between study intervention administration and 
delivery in the model depends on the availability of the variables (vacdel may not be 
available at Day 31 analysis) and the necessity, therefore, the above SAS code serves as a 
reference and may be adjusted according to the analysis needs. Other possible co-variates 
which could be included in the model, but not limited to, are pre-existing HIV infection 
status, CD4 count, COVID-related complications. 
For the analysis of infants at each time point (cord blood at Delivery, Day 43 post-birth, 
Day 121 post-birth, and Day 181 post-birth), similar model will be explored: 
PROC GLM data=adis; 
   BY atptn atpt; 
   CLASS tr01aga gagevg1 gagebg1 agegr3; 
   MODEL aval = base tr01aga gagevg1 gagebg1 agegr3; 
   LSMEANS tr01aga/pdiff cl alpha=0.05; 
   RUN;  


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Baseline is pre-vaccination logarithm10 transformation of the concentrations/titers from 
maternal participants, gagebg1 is gestational age category at birth (> 37 weeks; ≤ 37 
weeks) for infant participants. With the inclusion of gestational age category at 
vaccination (gagevg1) in the model, this categorical variable gagebg1 provides similar 
information as continuous variable vacdel, therefore the inclusion of either variable in the 
model could be adjusted according to the analysis needs. Other possible co-variates 
which could be included in the model, but not limited to, are maternal pre-existing HIV 
infection status, CD4 count, COVID-related complications, infant HIV infection status. 
The ratio of GMTs/GMCs between study intervention groups and the corresponding 95% 
CI will then be constructed by exponentiating the mean difference and its confidence 
interval between study intervention groups on the logarithm10 scale estimated from the 
model. Summary tables will show adjusted GMT/GMC for study intervention groups, 
and ratios of GMTs/GMCs between study intervention groups along with the 95% CI. 
Summary tables will present number of observations included in the model, the model 
adjusted GMT/GMC for each group and between group adjusted GMT/GMC ratio with 
the corresponding 95% CIs at each timepoint. 
4.4. 
Tertiary Endpoint(s) Analyses 
 
 
 
4.5. 
Other Safety Analyses 
Other safety analyses will be based on the Exposed Set, unless otherwise specified.  
4.5.1. 
COVID-19 Assessment and COVID-19 AEs 
A participant is defined as having a suspected, probable or confirmed COVID-19 
infection during the study if the answer is “Confirmed”, “Probable” or “Suspected” to the 
case diagnosis question from the COVID-19 coronavirus infection assessment electronic 
Case Report Form (eCRF).  
Numbers and percentage of participants with a suspected, probable or confirmed COVID-
19 infection will be summarized by group based on Exposed Set. 
Number and percentage of participants who had a COVID-19 test performed and number 
and percentage of participants with positive, negative and indeterminate results will be 
summarized by group on Exposed Set. 
4.5.2. 
Additional Safety Assessments (if applicable) 
Vital signs will be summarized by group using descriptive statistics at all timepoint(s). 
The information is collected on Exposed Set and Per-protocol Set. The parameters 
include but may not be limited to systolic blood pressure (SBP), diastolic blood pressure 
CCI


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(DBP), temperature, heart rate, respiratory rate, height, weight and body mass index 
(BMI). 
4.5.3. 
Combined solicited and unsolicited events 
The combined analysis of solicited and unsolicited events will be performed on Exposed 
Set. A summary of participants with all combined solicited and unsolicited adverse 
events will be provided.  
Solicited adverse events will be coded by MedDRA as per the following codes 
Solicited symptom 
Lower level term code 
Corresponding Lower level term decode  
Pain 
Injection site pain 
10022086 
Redness 
Redness at injection site 
10022098 
Swelling 
Swelling at injection site 
10053425 
Fatigue 
Fatigue 
10016256 
Fever 
Fever 
10016558 
Nausea 
Nausea 
10028813 
Vomiting 
Vomiting 
10047700 
Diarrhea 
Diarrhea 
10012727 
Abdominal pain 
Abdominal pain 
10000081 
Headache 
Headache 
10019211 
Please note – to check for AE term in CDISC during dry run 
For clintrial.gov and EudraCT posting purposes, a summary of combined solicited and 
unsolicited adverse events will be produced by System Organ Class and preferred terms 
and according to occurrence of each event.  
4.6. 
Other Analyses 
4.6.1. 
Other analyses for adolescent maternal participants 
Sub-analyses to evaluate objectives and endpoints will be performed on the 15-17 Years 
of Age (YOA) sub-group. 
4.6.1.1. 
Safety 
Due to small number of adolescent maternal participants in this trial, a Bayesian approach 
will be applied to predict the probability of AEs in this population. It is assumed a 
specific AE in an adolescent maternal participant receiving the RSV-MAT vaccine is a 
binary outcome (yes/no) with p as a probability that the outcome is “yes”; it is further 
assumed that p is a random variable having beta distribution as a prior, which will be 
estimated from other data sources. The prior beta distribution will be developed based on 
data collected in RSV-MAT vaccine recipients above 17 YOA in this trial. With the data 
observed in RSV-MAT vaccine recipients 15-17 YOA, a Bayesian approach will be 
applied to estimate the posterior distribution of p. Similar procedures will be used for 
estimating the posterior distribution of p0 (the probability of having this AE for an 
adolescent maternal participant in placebo group). However, the prior distribution for p0 
will be assumed as a mixture of beta distributions based on both the data collected in 
participants above 17 YOA in the placebo group in this trial and the adolescents younger 


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than 17 YOA in EPI-RSV-015 study [EPI-RSV-015, 2020]. Lastly, the predictive 
probability of the occurrence of this AE in an adolescent maternal participant 15-17 YOA 
will be calculated separately in the RSV-MAT vaccine group and the placebo group. A 
predictive probability in an adolescent maternal participant in RSV-MAT vaccine group 
no worse than that in placebo group will provide reassurance that vaccination does not 
result in higher risk of AE.  
4.6.1.2. 
Immunogenicity 
The immunogenicity data collected in adolescent maternal participants 15 to 17 YOA in 
this trial will be descriptively summarized by treatment group. In addition, a Bayesian 
approach will be used for further extrapolation of the immune response. It is assumed that 
the log transformed immune response (for example neutralizing antibody titers) in 
adolescent maternal participants follows a normal distribution with the mean µ and SD of 
σ; it is further assumed that the mean µ is a random variable and has a normal distribution 
as a prior. The prior normal distribution for the mean µ will be developed based on data 
collected in maternal participants above 17 YOA in this trial. With the data observed in 
adolescent maternal participants 15-17 YOA in this trial, a Bayesian approach will be 
applied to estimate the posterior distribution of the mean µ and the predictive probability 
of observing a high immune response (for instance, 6 fold increase) for an adolescent 
maternal participant 15-17 YOA in the RSV-MAT vaccine group. A high predictive 
probability of having at least 6-fold increase 1 month post-study intervention from 
baseline in a pregnant adolescent RSV-MAT vaccine recipient will provide reassurance 
of immune response for an adolescent maternal participant 15-17 YOA receiving the 
RSV-MAT vaccine. 
4.6.2. 
Subgroup analyses 
Subgroup analyses of the primary endpoints will be made to assess consistency of the 
intervention effect across the following subgroups: 
• 
Age group (for maternal participants): < 18 vs ≥ 18 years  
• 
Gestational age at birth (for infant participants):  ≥ 37 weeks; < 37 weeks (as 
assessed by the GAIA gestational age definition*) 
* Additional statistical analyses may also be performed by using the Intergrowth-
21st (IG-21) standard definition [Villar, 2014]. 
• 
Pre-existing HIV infection status: present vs absent (for maternal participants ≥18 
YOA only) 
• 
Pre-existing obstetric complications: present vs absent (for maternal participants ≥18 
YOA only) 
Except for maternal age group, if the number of participants is too small (less than 10%) 
within above mentioned subgroup, then the subgroup categories may be redefined prior 
to final analysis.  


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To take a more practical approach, subgroup analysis of safety by age category at study 
intervention administration (< 18; ≥ 18 years) in maternal participants will include 
summaries of solicited administration site and systemic events, unsolicited AEs, MAEs, 
SAEs, RSV-associated MA-RTIs, (S)AEs leading to study withdrawal, worsening of pre-
existing medical conditions and/or obstetric complications, pregnancy outcomes and 
pregnancy-related AESIs. 
Subgroup analysis of safety by gestational age at birth (≥ 37 weeks; <37 weeks) in infant 
participants will include summaries of neonatal AESIs, MAEs, SAEs, (S)AEs leading to 
study withdrawal, and occurrence of RSV- associated LRTIs, any severity and severe 
LRTIs, RSV-associated hospitalization.  
Subgroup analysis on other safety summaries will be performed if deemed necessary. 
Subgroup analysis of immunogenicity by age category at study intervention 
administration (< 18; ≥ 18 years) for maternal participants and by gestational age at birth 
(≥ 37 weeks; < 37 weeks) for infant participants will include analysis of GMT(C) and 
GMR calculation at each time point and geometric mean of placental transfer. 
Subgroup analysis on other immunogenicity analysis will be performed if deemed 
necessary. 
4.7. 
Conduct of Analyses 
No analysis requiring statistical adjustment will be performed. 
4.7.1. 
Sequence of analyses 
The final analysis will be performed when all data up to study end are available. A CSR 
including all available data will be written and made available to the investigators at that 
time. 
If the data for tertiary endpoints become available at a later stage, (an) additional 
analysis/ analyses may be performed. These data will be documented in annex(es) to the 
study report and will be made available to the investigators at that time. 
4.8. 
Changes to Protocol Defined Analyses 
The distribution analysis for antibody titers/concentration and scatter plots for individual 
immunogenicity data, which were originally planned statistical analysis specified in the 
protocol Amendment 1 (Dated: 15-MARCH-2022), are removed from this SAP as the 
sufficient relevant information has been obtained from other RSV MAT Phase I/II 
studies. 


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5. 
SAMPLE SIZE DETERMINATION 
Approximately 378 maternal participants* will be randomized in a 2:1 ratio to achieve at 
least 340 evaluable maternal participants (including at least 16 evaluable adolescents 
from 15 to less than 18 YOA). 
Participants who withdraw from the study will not be replaced. 
* Due to the recent safety signal in RSV-MAT-009, there will be no further enrollment 
and vaccination of maternal participants. 
5.1. 
Safety 
A sample size of 252 participants in RSV-MAT vaccine group will provide a probability 
of 72%, 92% or 98% to observe at least one participant with AE, if the true AE rate is 
0.5%, 1% or 1.5%, respectively. 
Table 13 presents the precision one can get on the percentage of participants with AEs 
following dosing in study vaccine group. 
If no AE was observed in RSV-MAT vaccine group, the exact, two-sided 95% 
confidence interval (CI) would rule out an AE rate of 1.5% or more. The current sample 
size also provides the precision on estimating the probability of observing AEs following 
dosing in RSV-MAT vaccine group. If 5% of the participants experienced an AE among 
252 participants following vaccination with the RSV-MAT vaccine, an exact 95% CI 
would be (2.7%, 8.5%). 
Table 13 
Exact 95% confidence interval (CI) on the percentage of participants 
with adverse events (AEs) following dosing in RSV-MAT vaccine 
group 
252 participants in RSV-MAT vaccine group 
Number (%) of participants with an AE 
Exact 95% CI 
Lower Limit 
Upper Limit 
0 (0) 
0.0 
1.5 
3 (1) 
0.2 
3.2 
5 (2) 
0.7 
4.6 
8 (3) 
1.3 
5.9 
10 (4) 
1.9 
7.2 
13 (5) 
2.7 
8.5 
15 (6) 
3.4 
9.7 
18 (7) 
4.2 
10.9 
20 (8) 
5 
12.1 
23 (9) 
5.8 
13.2 
25 (10) 
6.6 
14.4 
38 (15) 
10.8 
20.0 
50 (20) 
15.2 
25.5 
63 (25) 
19.8 
30.8 
75 (30) 
24.4 
36.1 
Note: Precision estimation using PASS2019 19.0.1 (Confidence Interval [CI] for one proportion) [Hahn, 1991] 
Exact 95% CI computed based on Clopper/ Pearson formula [Newcombe, 1998] 


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5.2. 
Immunogenicity 
With at least 226 evaluable maternal participants for immunogenicity in the RSV-MAT 
vaccine group (assuming a 10% non-evaluable rate), the current sample size can provide 
an adequate precision for estimating the fold increase. 
Table 14 presents the precision estimation of the fold increase from Day 1 to delivery 
based on standard deviation (SD) of log10 transformed titer for neutralizing antibody 
RSV-A and half width of the fold increase. 
If at least a 9-12 fold increase from Day 1 to delivery in terms of RSV-A neutralizing 
antibody is anticipated, then assuming a log 10 SD of 0.4, a 95% CI for a 9-fold increase 
would be (7.6, 10.7), and a 95% CI for a 12-fold increase would be (10.1, 14.2). 
Table 14 
Precision estimation on fold increase and its 95% CI with 226 
participants in RSV-MAT vaccine group 
Standard 
Deviation1 
Fold Increase from Day 1 
to delivery 
No. of participants in RSV-MAT 
vaccine group 
Half 
Widt
h2 
95% 
LL 
95% 
UL 
Log
10 
Fol
d 
0.3 
5 
226 
0.05
6 
4.4 
5.7 
0.69
9 
0.3 
6 
226 
0.05
6 
5.3 
6.8 
0.77
8 
0.3 
7 
226 
0.05
6 
6.2 
8.0 
0.84
5 
0.3 
8 
226 
0.05
6 
7.0 
9.1 
0.90
3 
0.3 
9 
226 
0.05
6 
7.9 
10.2 
0.95
4 
0.3 
10 
226 
0.05
6 
8.8 
11.4 
1 
0.3 
11 
226 
0.05
6 
9.7 
12.5 
1.04
1 
0.3 
12 
226 
0.05
6 
10.5 
13.7 
1.07
9 
0.4 
5 
226 
0.07
4 
4.2 
5.9 
0.69
9 
0.4 
6 
226 
0.07
4 
5.1 
7.1 
0.77
8 
0.4 
7 
226 
0.07
4 
5.9 
8.3 
0.84
5 
0.4 
8 
226 
0.07
4 
6.7 
9.5 
0.90
3 
0.4 
9 
226 
0.07
4 
7.6 
10.7 
0.95
4 
0.4 
10 
226 
0.07
4 
8.4 
11.9 
1 
0.4 
11 
226 
0.07
4 
9.3 
13.0 
1.04
1 
0.4 
12 
226 
0.07
4 
10.1 
14.2 
1.07
9 
1 Standard deviation on log10 transformed RSV-A neutralizing antibody titer based on previous studies on PreF2 vaccine. 


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2 Precision estimation using PASS2019 19.0.1 (Confidence Interval [CI] for one mean) [Hahn, 1991] 
LL=10^(log10(fold increase)-half width); UL=10^(log10(fold increase)+half width) 


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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Study Population Analyses 
6.1.1. 
Participant Disposition 
Participant disposition will be summarized by group using descriptive statistics: 
• 
Number of maternal participants screened, randomised, exposed and withdrawn 
including withdrawal reasons in each group and overall will be tabulated. 
• 
Number of infant participants enrolled and withdrawn including withdrawal reasons 
will be tabulated by group, by sub-cohort within each group and overall.  
6.1.2. 
Demographic and Baseline Characteristics 
6.1.2.1. 
Analysis of demographics/baseline characteristics planned in the 
protocol 
These analyses will be performed on the Exposed set and on the Per protocol for 
immunogenicity. 
For all maternal participants, demographic characteristics (e.g., age at study intervention 
administration (<18 years; ≥ 18 years; overall), gestational age at study intervention 
administration (<28 0/7; ≥ 28 0/7 weeks), geographic ancestry) will be summarized by 
group using descriptive statistics. The interval in days between maternal study 
intervention and delivery will be calculated and summarized by group using descriptive 
statistics. 
For their infants, demographic characteristics (e.g., gestational age at time of delivery (≥ 
37 weeks; <37 weeks), sex, weight, length, head circumference, geographic ancestry, 
APGAR score), and lifestyle characteristics (e.g., living environment, household 
composition, breastfeeding, passive smoking and extent of contact with children less than 
6 YOA) will be summarized by group, and for each immunogenicity sub-cohort within 
each group, using descriptive statistics. 
• 
Frequency tables will be generated for categorical variable such as geographic 
ancestry. 
• 
Mean, median, SD and range will be provided for continuous data such as age. 
6.1.2.2. 
Additional considerations 
Demographic characteristics for maternal and infant participants will also be summarized 
on Enrolled Set for web public disclosure. 
Subgroup analysis for demographic characteristics by age category at study intervention 
administration (<18 years; ≥ 18 years; overall) for maternal participants and by 


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gestational age at birth (≥ 37 weeks; < 37 weeks) for infant participants will also be 
performed on Exposed Set and PPS. 
Subject disposition will be summarized by group using descriptive statistics: 
• 
Number of maternal participants screened, randomised, exposed and withdrawn 
including withdrawal reasons in each group and overall will be tabulated. 
• 
Number of infant participants enrolled and withdrawn including withdrawal reasons 
will be tabulated by group, by sub-cohort within each group and overall.  
Summary of past medical history and current medical conditions will be performed on 
Exposed Set by Medical Dictionary for Regulatory Activities (MedDRA) term. Un-coded 
medical conditions or medical history will be summarized under ‘Other’ category. 
Vaccination history will be coded using GSK Drug dictionaries. Summary of vaccination 
history will be performed on Exposed Set by group. 
6.1.3. 
Protocol Deviations 
Important protocol deviations will be summarized based on Exposed Set by group. 
Protocol deviations will be tracked by the study team throughout the conduct of the 
study. These protocol deviations will be reviewed to identify those considered as 
important as follows: 
• 
Data will be reviewed prior to unblinding and freezing the database to ensure all 
important deviations (where possible without knowing the study intervention details) 
are captured and categorised in the protocol deviations dataset.  
• 
This dataset will be the basis for the summaries of important protocol deviations. 
• 
The summary will include number and percentage of participants with important 
protocol deviations by deviation category for each study group. 
• 
An individual listing of protocol deviation will also be provided. 
Protocol deviations which result in exclusion from the analysis set will also be 
summarized based on Exposed Set by group.  
• 
Data will be reviewed prior to unblinding and freezing the database to ensure all 
deviations leading to analysis population exclusions are captured and categorised in 
the protocol deviations ADaM dataset (note these exclusions are not captured in the 
SDTM dataset). 
In addition to the overall summary of important protocol deviations, separate summaries 
may be produced for important protocol deviations related to COVID-19, and important 
protocol deviations not related to COVID-19 respectively if deemed necessary. 
Summary of important protocol deviations leading to elimination will be tabulated by 
group. An individual listing will also be provided. 


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6.1.4. 
Concomitant Medications and Vaccinations 
Concomitant medications and vaccinations will be coded using the GSK Drug dictionary.  
• 
The number and percentage of maternal participants taking concomitant medications 
/vaccinations within 7 days following vaccination, 30 days following study 
intervention administration, up to 42 days post-delivery and up to 180 days post-
delivery will be summarized by group. A listing will also be provided. 
• 
The number and percentage of infants taking concomitant medications from birth up 
to 42 days after birth, 180 days after birth and 365 days after birth will be 
summarized by group. A listing will also be provided. 
• 
The number and percentage of infants taking concomitant vaccinations from birth up 
to 42 days after birth and 180 days after birth will be summarized by group. A listing 
will also be provided. 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic 
Depending on how the Covid-19 situation evolves, the SAP might be amended to reflect 
the analysis corresponding to Covid-19. 
6.2. 
Appendix 2 Data Derivations Rule 
6.2.1. 
Study Day and Reference Dates 
The safety reference date is the study intervention start date and will be used to calculate 
study day for safety measures.  
The study day is calculated as below: 
• 
Assessment Date = Missing              → Study Day = Missing  
• 
Assessment Date < Reference Date → Study Day = Assessment Date – Ref Date 
• 
Assessment Data ≥ Reference Date → Study Day = Assessment Date – Ref Date + 1 
6.2.2. 
Attributing events to vaccine doses 
The dose relative to an event is the most recent study dose given to a participant prior to 
the start of a given event.  
If an event starts on the same day as a study dose, the relative dose will be derived from 
the additional information provided in the case report form (CRF) using the contents of 
the flag indicating if the event occurred before or after study dose. If ‘after study dose’ is 
selected, the relative dose for the event will be the one administered on the start day of 
the event. If ‘before study dose’ is selected, the relative dose for the event will be the 
dose prior to this one. 


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6.2.3. 
Handling of missing data 
6.2.3.1. 
Dates 
When partially completed dates (i.e. dates missing a day and/or month) are used in 
calculations, the following standard rules will be applied: 
• 
A missing day will be replaced by 15 
• 
A missing day and month will be replaced by June 30th. 
The following exceptions apply: 
• 
Adverse event start dates with missing day: 
− 
If the event starts in the same month as at least one of the study doses, the 
contents of AE.AESTRTPT (the flag indicating if the event occurred before or 
after study dose) will be used to complete the date. If ‘after study dose’ is 
selected, the imputed start date will match the first (or only) study dose given 
during that month. If ‘before study dose’ is selected, the imputed date will be 
one day before the first (or only) study dose given during that month. 
• 
Adverse event start dates with missing day and month: 
− 
If the event starts in the same year as at least one of the study doses, the contents 
of AE.AESTRTPT (the flag indicating if the event occurred before or after study 
dose) will be used to complete the date. If ‘after study dose’ is selected, the 
imputed start date will match the first (or only) study dose given during that 
year. If ‘before study dose’ is selected, the imputed date will be one day before 
the first (or only) study dose given during that year. 
All other cases of incomplete AE or concomitant medication/vaccination start date will 
follow the standard rules above. 
6.2.3.2. 
Laboratory data 
Missing laboratory results (including immunological data) will not be replaced. 
6.2.3.3. 
Daily recording of solicited events 
6.2.3.3.1. Studies with electronic diaries 
For studies using electronic diaries for the collection of solicited events, a solicited event 
will be considered present only when a daily recording of grade 1 or more is present. 


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6.2.3.4. 
Unsolicited adverse events 
Unsolicited AE summaries are including SAEs unless specified otherwise.  
Missing severity, relationship with study intervention, and outcome of unsolicited AEs 
will not be replaced and will appear as ‘UNKNOWN’ when displayed in a statistical 
output. 
6.2.4. 
Data derivation 
6.2.4.1. 
Age at first dose in years 
When age at first dose is to be displayed in years, it will be calculated as the number of 
complete calendar years between the date of birth and the date of first dose. For example: 
DOB = 10SEP1983, Date of first dose = 09SEP2018 -> Age = 34 years 
DOB = 10SEP1983, Date of first dose = 10SEP2018 -> Age = 35 years 
6.2.4.2. 
Weight 
Weight will be presented in kilograms. Weights reported in pounds will be converted as 
follows: 
Weight in kilograms = Weight in pounds / 2.2 
6.2.4.3. 
Height 
Height will be presented in centimeters. Heights reported in feet and inches will be 
converted as follows: 
Height in centimeters = Height in inches x 2.54 
6.2.4.4. 
Body mass index (BMI) 
BMI will be calculated as follows: 
BMI = (Weight in kilograms) / (Height in meters)2 
6.2.4.5. 
Temperature 
Temperatures will be presented in degrees Celsius (°C). Temperatures reported in degrees 
Fahrenheit (°F) will be converted as follows: 
Temperature (Celsius) = ((Temperature (Fahrenheit) - 32) x 5)/9 


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6.2.4.6. 
Numerical serology results 
Numerical serology results will be derived from the content of IS.ISORRES in the SDTM 
dataset. For assays with a specific cut-off, the following derivation rules apply: 
IS.ISORRES 
Derived value 
“NEG”, “-”, or “(-)” 
cut-off/2 
“POS”, “+”, or “(+)” 
cut-off 
“< value” and value is <= assay cut-off 
cut-off/2 
“< value” and value is > assay cut-off 
value 
“> value” and value is < assay cut-off 
cut-off/2 
“> value” and value is >= assay cut-off 
value 
“value” and value is < cut-off 
cut-off/2 
“value” and value is >= cut-off 
value 
All other cases 
missing 
The cut-off tests for immunogenicity evaluation will be as per following: 
System 
Component 
Method 
Unit 
Cut-off (LLOQ) 
Serum 
RSV-A Neutralising Antibody  
NEUTRALISATION 
ED60 
18 
Serum 
RSV-A Neutralising Antibody  
NEUTRALISATION 
IU/mL 
56 
Serum 
RSVPreF3 IgG antibody concentrations 
ELISA 
EU/mL 
25 
Serum 
RSV-B Neutralising Antibody  
NEUTRALISATION 
ED60 
30 
Serum 
RSV-B Neutralising Antibody  
NEUTRALISATION 
IU/mL 
44 
Note: the assay cut-off (LLOQ), ULOQ and units may be further adjusted at time of analysis when notified by the lab. 
6.2.4.7. 
Geometric mean titres (GMTs) and concentrations (GMCs) 
Geometric Mean Titre (GMT) or Concentration (GMC) calculations are performed by 
taking the inverse logarithm of the mean of the log titre or concentration transformations. 
Non quantifiable antibody titres or concentrations will be converted as described in 
section 6.2.4.6 for the purpose of GMT/GMC calculation. The cut-off value is defined by 
the laboratory before the analysis. 
6.2.4.8. 
Onset day 
The onset day for an event (e.g. AE, concomitant medication/vaccination) is the number 
of days between the last study dose and the start date of the event. This is 1 for an event 
occurring on the same day as a study dose (and reported as starting after study dose). 
6.2.4.9. 
Duration of events 
The duration of an event with a start and end date will be the difference between the start 
and end date plus one day, i.e. an event that starts on 03MAR2018 and ends on 
12MAR2018 has a duration of 10 days. 


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The duration of solicited events will be calculated as the sum of the individual days with 
the adverse event reported at grade 1 or higher during the solicited event period. 
6.2.4.10. 
Counting rules for combining solicited and unsolicited adverse events 
For output combining solicited and unsolicited AEs, all SAEs will be considered general 
events since the administration site flag is not included in the expedited adverse event 
CRF pages. 
Multiple events with the same preferred term which start on the same day are counted as 
only one occurrence. 
6.2.4.11. 
Counting rules for occurrences of solicited events 
When the occurrences of solicited events are summarized, each event recorded as having 
occurred during a specific period will be counted as only one occurrence regardless of the 
number of days on which it occurs. Also, in the case of co-administered study 
interventions, an administration site event recorded for a participant following multiple 
study interventions will be counted as only one occurrence. 
6.2.5. 
Display of decimals 
6.2.5.1. 
Percentages 
Percentages and their corresponding confidence limits will be displayed with one decimal 
except for 100% in which case no decimal will be displayed.  
6.2.5.2. 
Differences in percentages 
Differences in percentages and their corresponding confidence limits will be displayed 
with two decimals. 
6.2.5.3. 
Demographic/baseline characteristics statistics 
The mean, median, and SD for continuous baseline characteristics (height, weight, BMI, 
pre-dose body temperature) will be presented with one decimal. 
The minimum and maximum values and quartile values (if required) will be presented 
with the same number of decimals as the observed values.  
The minimum and maximum of transformed height variables will be displayed with no 
decimals. 
The minimum and maximum of transformed weight variables will be displayed with no 
decimals with the exception of values are below 10kg where one decimal will be 
displayed. 


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The maximum and minima of transformed body temperatures will be displayed with one 
decimal. 
6.2.5.4. 
Serological summary statistics 
The number of decimals used when displaying GMT or GMC and their confidence limits 
is assay specific based on the magnitude of the assay result post-dose and the clinically 
relevant assay threshold. The same number of decimals will be used for a given assay 
regardless of the timepoint presented. 
Lowest clinically 
relevant threshold 
Example 
Number of decimals to display 
<0.3 
Diphtheria, tetanus, anti-PRP 
3 
>=0.3 and <4 
Streptococcus pneumoniae, 
Meningococal bactericide 
2 
>=4 and <1000 
Measles, rubella, varicella, polio 
1 
>=1000 
CMI 
0 
GMT/GMC fold increase from pre-dose follows the same principle. Namely when the 
lowest clinically relevant threshold is 2-fold, 2 decimals are displayed while when the 
lowest clinically relevant threshold is 4-fold, 1 decimal is displayed. 
GMT or GMC group ratios and their confidence limits will be displayed with 2 decimals 
regardless of the actual values. 


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7. 
REFERENCES 
Clopper CJ, Pearson E. The Use of Confidence or Fiducial Limits Illustrated in the case 
of the Binomial. Biometrika. 1934;26:404-13. 
Miettinen, O. S. and Nurminen, M. Comparative analysis of two rates. Statistics in 
Medicine, 1985;4,213-226. 
Modjarrad K, Giersing B, Kaslow DC, Smith PG, Moorthy VS; WHO RSV Vaccine 
Consultation Expert Group. WHO consultation on Respiratory Syncytial Virus Vaccine 
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