Safety, Immunogenicity, Infectivity, and Dose-Finding Study of an Investigational Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Infants and Toddlers
Phase: PHASE1
Conditions: Respiratory Syncytial Virus Infection
Sponsor: Sanofi Pasteur, a Sanofi Company

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Safety, Immunogenicity, Infectivity, and Dose-Finding Study of an 
Investigational Live-Attenuated Respiratory Syncytial Virus (RSV) 
Vaccine in Infants and Toddlers 
Phase I/II, randomized, observer-blind, placebo-controlled, multi-center, dose-finding study to 
evaluate the safety, immunogenicity, infectivity, and vaccine virus shedding after 1 and 2 
administrations of the live-attenuated Respiratory Syncytial Virus (RSV) ∆NS2/∆1313/I1314L 
vaccine in infants and toddlers 6 to 18 months of age in the United States, Canada, Latin 
America, and South Africa 
Clinical Study Protocol, Amendment 5 
Health Authority File Number(s): 
BB-IND #: 
IND #22050 
WHO Universal Trial Number 
(UTN): 
U1111-1238-1869 
Study Code: 
VAD00001 
Development Phase: 
Phase I/II 
Sponsor: 
Sanofi Pasteur Inc. 
Discovery Drive, Swiftwater, PA 18370-0187, USA 
Investigational Product(s): 
Live-Attenuated Respiratory Syncytial Virus (RSV) ∆NS2/∆1313/I1314L 
vaccine 
Form / Route: 
Suspension of virus / Intranasal 
Indication For This Study: 
Active immunization of infants and toddlers 6 to 18 months of age for the 
prevention of medically attended lower respiratory tract illness 
Manufacturer: 
Same as Sponsor 
Coordinating Investigators 
Not Applicable 
This is a multi-center study with multiple investigators. Investigators and 
study sites are listed in the “List of Investigators and Centers Involved in 
the Trial” document. 
Sponsor’s Responsible Medical 
Officer: 
Local Medical Officer / Clinical 
Team Leader / Medical Team 
Leader  
NCT04491877

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Global Safety Officer: 
Clinical Study Manager: 
Version and Date of the Protocol: 
Version 9.0 dated 19 January 2023 
 

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Information contained in this publication is the property of Sanofi Pasteur and is confidential. This information may not be 
disclosed to third parties without written authorization from Sanofi Pasteur. This document may not be reproduced, stored in a 
retrieval system, or transmitted in any form or by any means–electronic, mechanical recording, or otherwise–without prior 
authorization from Sanofi Pasteur. This document must be returned to Sanofi Pasteur upon request. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents  
History of Protocol Versions ........................................................................................................... 9 
List of Tables .................................................................................................................................. 10 
List of Figures ................................................................................................................................ 11 
Synopsis .......................................................................................................................................... 12 
List of Abbreviations ..................................................................................................................... 36 
1 
Introduction ..................................................................................................................... 39 
1.1 
Background ..................................................................................................................... 39 
1.2 
Background of the Investigational Product ..................................................................... 40 
1.3 
Potential Benefits and Risks ........................................................................................... 40 
1.3.1 
Potential Benefits to Participants .................................................................................. 40 
1.3.2 
Potential Risks to Participants ...................................................................................... 40 
1.4 
Rationale for the Study ................................................................................................... 41 
2 
Study Objectives .............................................................................................................. 42 
2.1 
Primary Objectives .......................................................................................................... 42 
2.2 
Secondary Objectives ...................................................................................................... 42 
2.3 
Exploratory Objectives ................................................................................................... 43 
3 
Investigators and Study Organization ........................................................................... 44 
4 
Independent Ethics Committee / Institutional Review Board .................................... 44 
5 
Investigational Plan ......................................................................................................... 45 
5.1 
Description of the Overall Study Design and Plan ......................................................... 45 
5.1.1 
Study Design ................................................................................................................. 45 
5.1.2 
Justification of the Study Design .................................................................................. 49 
5.1.3 
Study Plan ..................................................................................................................... 51 
5.1.4 
Visit Procedures ............................................................................................................ 55 
5.1.4.1 
In-Person Visits .......................................................................................................... 56 
5.1.4.2 
Non-Visit Telephone Contacts ................................................................................... 63 
5.1.5 
Planned Study Calendar ................................................................................................ 65 
5.1.6 
Early Safety Data Review ............................................................................................. 65 
5.2 
Enrollment and Retention of Study Population .............................................................. 68 
5.2.1 
Recruitment Procedures ................................................................................................ 68 
5.2.2 
Informed Consent Procedures ...................................................................................... 69 
5.2.3 
Screening Criteria ......................................................................................................... 69 
5.2.4 
Inclusion Criteria .......................................................................................................... 70 
5.2.5 
Exclusion Criteria ......................................................................................................... 70 

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5.2.6 
Medical History ............................................................................................................ 72 
5.2.7 
Contraindications for Subsequent Vaccinations ........................................................... 72 
5.2.7.1 
Temporary Contraindications ..................................................................................... 72 
5.2.7.2 
Definitive Contraindications ...................................................................................... 73 
5.2.8 
Conditions for Withdrawal ........................................................................................... 73 
5.2.9 
Lost to Follow-up Procedures ....................................................................................... 74 
5.2.10 
Classification of Participants Who Discontinue the Study ........................................... 74 
5.2.11 
Follow-up of Discontinuations ..................................................................................... 75 
5.2.12 
Follow-up of participants with COVID-19 in the study ............................................... 75 
5.3 
Safety Emergency Call ................................................................................................... 75 
5.4 
Modification of the Study and Protocol .......................................................................... 76 
5.5 
Interruption of the Study ................................................................................................. 76 
6 
Products Administered ................................................................................................... 76 
6.1 
Identity of the Investigational Product(s) ....................................................................... 76 
6.1.1 
Identity of Study Product 1 ........................................................................................... 77 
6.1.1.1 
Composition ............................................................................................................... 77 
6.1.1.2 
Preparation and Administration ................................................................................. 77 
6.1.1.3 
Dose Selection and Timing ........................................................................................ 77 
6.1.1.4 
Vaccination Device .................................................................................................... 77 
6.1.2 
Identity of Study Product 2 ........................................................................................... 79 
6.1.2.1 
Composition ............................................................................................................... 79 
6.1.2.2 
Preparation and Administration ................................................................................. 79 
6.1.2.3 
Dose Selection and Timing ........................................................................................ 79 
6.1.2.4 
Vaccination Device .................................................................................................... 79 
6.1.3 
Identity of Control Product(s) ....................................................................................... 80 
6.1.3.1 
Composition ............................................................................................................... 80 
6.1.3.2 
Preparation and Administration ................................................................................. 80 
6.1.3.3 
Dose Selection and Timing ........................................................................................ 80 
6.1.3.4 
Vaccination Device .................................................................................................... 80 
6.2 
Identity of Other Product(s) ............................................................................................ 80 
6.3 
Product Logistics ............................................................................................................ 80 
6.3.1 
Labeling and Packaging ................................................................................................ 80 
6.3.2 
Product Shipment, Storage, and Accountability ........................................................... 80 
6.3.2.1 
Product Shipment ....................................................................................................... 80 
6.3.2.2 
Product Storage .......................................................................................................... 81 
6.3.2.3 
Product Accountability ............................................................................................... 81 
6.3.3 
Replacement Doses ....................................................................................................... 81 
6.3.4 
Disposal of Unused Products ........................................................................................ 81 
6.3.5 
Recall of Products ......................................................................................................... 82 

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6.4 
Blinding and Code-breaking Procedures ........................................................................ 82 
6.5 
Randomization and Allocation Procedures ..................................................................... 83 
6.6 
Treatment Compliance .................................................................................................... 83 
6.7 
Concomitant Medications and Other Therapies.............................................................. 84 
6.7.1 
Prohibited Concomitant Medications ........................................................................... 85 
6.7.2 
Precautionary Concomitant Medications ...................................................................... 85 
7 
Management of Samples ................................................................................................. 85 
7.1 
Sample Collection ........................................................................................................... 86 
7.2 
Sample Preparation ......................................................................................................... 86 
7.3 
Sample Storage and Shipment ........................................................................................ 87 
7.4 
Future Use of Stored Biological Samples for Research .................................................. 87 
8 
Clinical Supplies .............................................................................................................. 88 
9 
Endpoints and Assessment Methods ............................................................................. 88 
9.1 
Primary Endpoints and Assessment Methods ................................................................. 88 
9.1.1 
Safety ............................................................................................................................ 88 
9.1.1.1 
Safety Definitions ....................................................................................................... 88 
9.1.1.2 
Safety Endpoints ........................................................................................................ 92 
9.1.1.3 
Safety Assessment Methods ....................................................................................... 92 
9.1.1.3.1 
Immediate Post-vaccination Observation Period ..................................................... 92 
9.1.1.3.2 
Reactogenicity (Solicited Reactions from Day 0 to Day 28 After Each 
Vaccination) ............................................................................................................. 93 
9.1.1.3.3 
Unsolicited Adverse Events ..................................................................................... 96 
9.1.1.3.4 
Medically Attended Adverse Events ....................................................................... 97 
9.1.1.3.5 
Adverse Events of Special Interest (AESI) .............................................................. 97 
9.1.1.3.6 
Assessment of Causality ........................................................................................ 101 
9.1.2 
Infectivity .................................................................................................................... 101 
9.1.3 
Immunogenicity .......................................................................................................... 102 
9.1.3.1 
Immunogenicity Definition ...................................................................................... 102 
9.1.3.2 
Immunogenicity Endpoints ...................................................................................... 102 
9.1.3.3 
Immunogenicity Assessment Methods..................................................................... 102 
9.1.4 
Efficacy ....................................................................................................................... 103 
9.2 
Secondary Endpoints and Assessment Methods ........................................................... 103 
9.2.1 
Safety .......................................................................................................................... 103 
9.2.1.1 
Safety Definitions ..................................................................................................... 103 
9.2.1.2 
Safety Endpoints ...................................................................................................... 103 
9.2.1.3 
Safety Assessment Methods ..................................................................................... 103 
9.2.2 
Infectivity .................................................................................................................... 105 
9.2.2.1 
Infectivity Endpoint.................................................................................................. 105 

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9.2.2.2 
Infectivity Assessment Methods .............................................................................. 105 
9.2.3 
Immunogenicity .......................................................................................................... 105 
9.2.3.1 
Immunogenicity Endpoints ...................................................................................... 105 
9.2.3.2 
Immunogenicity Assessment Methods..................................................................... 105 
9.2.4 
Efficacy ....................................................................................................................... 106 
9.3 
Exploratory Endpoints and Assessment Methods ......................................................... 106 
9.3.1 
Safety .......................................................................................................................... 106 
9.3.1.1 
Safety Definitions ..................................................................................................... 106 
9.3.1.2 
Safety Endpoints ...................................................................................................... 106 
9.3.1.3 
Safety Assessment Methods ..................................................................................... 106 
9.3.2 
Infectivity .................................................................................................................... 106 
9.3.3 
Immunogenicity .......................................................................................................... 107 
9.3.3.1 
Immunogenicity Endpoints ...................................................................................... 107 
9.3.3.2 
Immunogenicity Assessment Methods..................................................................... 107 
9.3.4 
Efficacy ....................................................................................................................... 108 
9.3.4.1 
Efficacy Endpoints ................................................................................................... 108 
9.3.4.2 
Efficacy Assessment Methods ................................................................................. 108 
10 
Reporting of Serious Adverse Events .......................................................................... 110 
10.1 
Initial Reporting by the Investigator ............................................................................. 111 
10.2 
Follow-up Reporting by the Investigator ...................................................................... 111 
10.3 
Reporting of SAEs Occurring After a Participant Has Completed the Study .............. 112 
10.4 
Assessment of Causality ............................................................................................... 112 
10.5 
Reporting SAEs to Health Authorities and IECs / IRBs ............................................... 112 
10.6 
Using a Verbal Autopsy Questionnaire to Aid in Determining the Cause of Death .... 112 
11 
Data Collection and Management................................................................................ 113 
11.1 
Data Collection and CRB Completion .......................................................................... 113 
11.2 
Data Management ......................................................................................................... 114 
11.3 
Data Review .................................................................................................................. 114 
12 
Statistical Methods and Determination of Sample Size ............................................. 115 
12.1 
Statistical Methods ........................................................................................................ 115 
12.1.1 
Hypotheses and Statistical Methods for Primary Objectives ..................................... 115 
12.1.1.1 
Hypotheses ............................................................................................................... 115 
12.1.1.2 
Statistical Methods ................................................................................................... 115 
12.1.2 
Hypotheses and Statistical Methods for Secondary Objectives ................................. 116 
12.1.2.1 
Hypotheses ............................................................................................................... 116 
12.1.2.2 
Statistical Methods ................................................................................................... 116 
12.1.3 
Statistical Methods for Exploratory Objectives .......................................................... 117 

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12.2 
Analysis Sets ................................................................................................................. 118 
12.2.1 
Full Analysis Set ......................................................................................................... 118 
12.2.2 
Safety Analysis Set ..................................................................................................... 118 
12.2.3 
Per-Protocol Analysis Set ........................................................................................... 118 
12.2.4 
Other Analysis Set(s) .................................................................................................. 119 
12.2.5 
Populations Used in Analyses .................................................................................... 119 
12.3 
Handling of Missing Data and Outliers ........................................................................ 120 
12.3.1 
Safety .......................................................................................................................... 120 
12.3.2 
Immunogenicity .......................................................................................................... 120 
12.3.3 
Efficacy ....................................................................................................................... 120 
12.4 
Interim / Preliminary Analysis ...................................................................................... 120 
12.5 
Determination of Sample Size and Power Calculation ................................................. 121 
13 
Ethical and Legal Issues and Investigator / Sponsor Responsibilities ...................... 122 
13.1 
Ethical Conduct of the Study / Good Clinical Practice ................................................. 122 
13.2 
Source Data and Source Documents ............................................................................. 122 
13.3 
Confidentiality of Data, Data Protection, and Access to Participant Records .............. 123 
13.4 
Monitoring, Auditing, and Archiving ........................................................................... 123 
13.4.1 
Monitoring .................................................................................................................. 123 
13.4.2 
Audits and Inspections ................................................................................................ 124 
13.4.3 
Archiving .................................................................................................................... 124 
13.5 
Financial Contract and Insurance Coverage ................................................................. 125 
13.6 
Stipends for Participation .............................................................................................. 125 
13.7 
Publication Policy ......................................................................................................... 125 
14 
Reference List ................................................................................................................ 126 
15 
Appendix ........................................................................................................................ 129 
16 
Signature Page ............................................................................................................... 131 
 

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History of Protocol Versions  
Version 
Date 
Comments 
1.0 
24 February 2020 
Version not approved by the IEC/IRB 
2.0 
04 May 2020 
IEC/IRB-approved version not used in the study  
3.0 
27 July 2020 
Original study protocol (first version used in the study) 
4.0 
29 September 2020 
Amendment 1 
5.0 
06 November 2020 
Amendment 2 
6.0 
24 September 2021 
Amendment 3 
7.0 
08 December 2021 
Amendment 4 
8.0 
09 January 2023 
Version not used in the study 
* Versions in bold font have been approved by the Independent Ethics Committee(s) (IEC[s]) / Institutional Review 
Board(s) (IRB[s]) and used in the study. 
 

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List of Tables  
Table 5-1: Schedule of blood sample collection (volume in mL) – Cohorts 1 and 3 ...................... 55 
Table 5-2: Schedule of blood sample collection (volume in mL) – Cohorts 2 and 4 ...................... 55 
Table 5-3: Timelines for end of enrollment and vaccination per hemisphere ................................. 57 
Table 5-4: Illness visit timeframe .................................................................................................... 62 
Table 9-1: Solicited administration site reactions: terminology, definitions, and intensity scales . 94 
Table 9-2: Solicited systemic reactions: terminology, definitions, and intensity scales ................. 95 
Table 9-3: DAIDS severity scale for AESIs, except wheeze ........................................................ 100 
Table 9-4: Brighton Collaboration severity grading system for wheeze ....................................... 101 
Table 9-5 Targets Detected by the ePlex Respiratory Pathogen Panel 2 Assay ........................... 110 
Table 12-1: Number of Participants by Serostatus, in Total and by RSV Group, According to 
Varying Possible RSV-experienced Rates Ranging from 5% to 35%  ......................................... 122 
 
 
 

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List of Figures  
Figure 5.1: Study Design ................................................................................................................. 52 
Figure 5.2: Study Plan and Timeframe for Cohorts 1 and 3 ........................................................... 52 
Figure 5.3: Study Plan and Timeframe for Cohorts 2 and 4 ........................................................... 54 
 
 

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Synopsis  
Company: 
Sanofi Pasteur 
Investigational Product: 
Live-Attenuated Respiratory Syncytial Virus (RSV) ∆NS2/∆1313/I1314L 
vaccine 
Active Substance(s): 
Live-attenuated RSV with (i) a 523 nucleotide (nt) deletion of the NS2 gene 
(∆NS2), (ii) an amino acid deletion in the L protein (Δ1313; deletion of 
S1313), and (iii) genetically stabilizing mutation in the L gene (I1314L) 
(RSV∆ NS2/∆1313/I1314L)  
Title of the Study: 
Safety, Immunogenicity, Infectivity, and Dose-Finding Study of an 
Investigational Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine 
in Infants and Toddlers 
Development Phase: 
Phase I/II 
Coordinating Investigator: 
Not Applicable 
Study Sites: 
This will be a multi-center, multinational study including approximately 
30 sites in the United States (US), approximately 2 sites in Canada, 
approximately 6 sites in Latin America (Argentina, Chile, and Honduras), 
and approximately 2 sites in South Africa. Investigators and sites are listed 
in the “List of Investigators and Centers Involved in the Trial” document. 
Planned Study Period: 
Q3 2020 to Q2 2023 
Study Design, Schedule of Study 
Procedures, and Methodology: 
Phase I/II, randomized, observer-blind, placebo-controlled, multi-center, 
dose-finding study to evaluate the safety, immunogenicity, infectivity, and 
vaccine virus shedding after 1 or 2 administrations of a live-attenuated RSV 
∆NS2/∆1313/I1314L vaccine in infants and toddlers 6 months to 18 months 
(Cohorts 1 to 4) of age in the United States, Canada, Latin America 
(Argentina, Chile, and Honduras), and South Africa.  
Vaccination: 
A total of 300 infants and toddlers 6 to18 months of age will be enrolled into 
1 of 4 cohorts, sequentially, and within each cohort will be randomized to 
receive intranasal administration of their assigned study product as follows.  
• 
Cohort 1 – 40 infants and toddlers to receive 1 administration, 1:1 
ratio of RSV ∆NS2/∆1313/I1314L 
 (low-dose) or placebo 
(same formulation buffer as the RSV ∆NS2/∆1313/I1314L vaccine) 
• 
Cohort 2 – 40 infants and toddlers to receive 2 administrations, 1:1 
ratio of RSV ∆NS2/∆1313/I1314L 
 (low-dose) or placebo 
• 
Cohort 3 – 40 infants and toddlers to receive 1 administration, 
1:1 ratio of RSV ∆NS2/∆1313/I1314L 
 (high-dose) or 
placebo 
• 
Cohort 4 – 180 infants and toddlers to receive 2 administrations, 
1:1:1 ratio of RSV ∆NS2/∆1313/I1314L 
 
 (low-dose), 
RSV ∆NS2/∆1313/I1314L 
 (high-dose) or placebo.  
 
Cohort 1 (Northern Hemisphere): 
1:1 randomized, placebo-controlled, 1 dose of RSV ∆NS2/∆1313/I1314L 
(
), 1 administration (
 in total per administration) at Day (D) 
0, n=20 per vaccine group. Participant enrollment will be initiated at 

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approximately 15 sites in the US in August/September 2020. Vaccine 
administration will be completed at least 5 days before the beginning of 
RSV season (the average 5-month RSV season in the northern hemisphere is 
01 November to 31 March). If recruitment in Cohort 1 does not reach the 
goal of n=40, no attempt will be made to include more participants in 
subsequent cohorts.  
Cohort 2 (Southern Hemisphere): 
1:1 randomized, placebo-controlled, 1 dose of RSV ∆NS2/∆1313/I1314L 
(
 
), 2 administrations (
 in total per administration) at D0 and 
D56, n=20 per vaccine group. Participant enrollment will be initiated at 
approximately 4 sites in Latin America (Argentina and Chile) at the earliest 
in November/December 2020. The first and the second vaccine 
administrations (D0 and D56, respectively) will be completed at least 5 days 
before the beginning of the RSV season (the average 5-month RSV season 
in the southern hemisphere is 01 May to 30 September). If recruitment in 
Cohort 1 does not reach the goal of n=40, no attempt will be made to 
include more participants in subsequent cohorts.  
Cohort 3 (Northern Hemisphere): 
1:1 randomized, placebo-controlled, 1 dose of RSV ∆NS2/∆1313/I1314L 
(
), 1 administration (
 per administration in total) at D0, 
n=20 per vaccine group. Participant enrollment will be initiated at 
approximately 30 sites in the US in April 2021. Vaccine administrations will 
be completed before 31 May 2021 If recruitment in Cohort 1 does not reach 
the goal of n=40, no attempt will be made to include more participants in 
subsequent cohorts.  
Cohort 4 (Northern and Southern Hemisphere) 
1:1:1 randomized, placebo-controlled, 2 doses of RSV ∆NS2/∆1313/I1314L 
(
), 2 administrations (
 per administration in 
total) at D0 and D56, n=60 per vaccine group. 
Participant enrollment will be initiated at approximately 30 sites in the US at 
the earliest in June 2021, approximately 2 sites in Canada at the earliest in 
May 2022, approximately 2 sites in Chile at the earliest in November 2021, 
approximately 2 sites in Honduras, at the earliest in April 2022, and 
approximately 2 sites in South Africa, at the earliest in June 2022. The first 
and the second vaccine administrations (D0 and D56, respectively) will be 
completed at any time of the year, including during the winter RSV season, 
regardless if normal RSV seasonality is restored after the disruption due to 
COVID-19 nonpharmaceutical interventions.  
 
Blood Sampling: 
All participants screened for inclusion in Cohorts 1, 2, 3 and 4 will provide a 
blood sample at enrollment (Visit 01) for baseline RSV serum antibody 
testing. 
All participants in each vaccine group in Cohorts 1, 2, 3 and 4 will provide a 
blood sample at the D56 Visit (before the second vaccine administration for 
Cohorts 2 and 4), for the measurement of post-vaccination 1 serum antibody 
titers to RSV. 
All participants in each vaccine group in Cohorts 2 and 4 will provide a 
blood sample at the D84 visit (28 days post-vaccination 2) for the 
measurement of post-vaccination 2 serum antibody titers to RSV. 

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All participants in Cohorts 1, 2, 3 and 4 will provide a blood sample during 
the month following the end of RSV season or at least 5 months after the 
last vaccine administration for the measurement of post-season RSV 
antibody titers, to determine if a 4-fold or greater rise in RSV antibody titers 
has occurred during the RSV season, indicating infection with wild-type 
(wt) RSV that was not detected by surveillance. 
Nasal swab samples: 
Nasal swab samples will be collected in all participants at D7 for Cohorts 1, 
2, 3 and 4; and on D63 for Cohorts 2 and 4 for the following: 
• 
Quantification of vaccine virus shedding on D7 for Cohorts 1, 2, 3 and 
4 and D63 for Cohorts 2 and 4. 
• 
The same nasal swab specimens will be tested for respiratory pathogens 
if the child is ill at the same time points (D7 for Cohorts 1, 2, 3 and 4 
and D63 for Cohorts 2 and 4). 
• 
A nasal swab specimen for the detection of RSV and respiratory 
pathogens will be collected from participants during illness visits and 48 
h later at any other protocol specified time point in the study including 
the medically attended surveillance during the RSV season. 
Collection of Safety Data: 
The Acute Phase for the first vaccine administration begins on D0 post-
vaccination and ends at midnight on D28. The Acute Phase for the second 
vaccine administration begins on D56 post-vaccination and ends at midnight 
on D84. Any adverse reactions, AEs, AESIs, MAAEs, or SAEs that begin 
within the Acute Phase (i.e. within 28 days after a vaccination) but are 
diagnosed by a medical professional after 28 days will still be considered as 
occurring within the Acute Phase. 
The Post-Acute Phase for participants receiving 1 administration begins at 
12:01am on D29 and ends at midnight on D56. The first Post-Acute Phase 
for participants receiving 2 administrations begins at 12:01am on D29 and 
ends at midnight on D56, except if second administration is exactly on D56 
when it ends immediately before receipt of the second administration. The 
second Post-Acute Phase for participants receiving 2 administrations begins 
at 12:01am on D85 and ends at midnight on D112. 
All participants will be observed for 30 minutes after each vaccine 
administration and any unsolicited systemic adverse events (AEs) occurring 
at that time will be recorded as immediate unsolicited systemic AEs in the 
case report book (CRB). 
All participants will be followed for solicited administration site reactions 
and systemic reactions, unsolicited adverse events, adverse events of special 
interest (AESIs) and medically attended adverse events (MAAEs) within 
28 days after each and any vaccination, and from vaccination to the end of 
study participation for serious adverse events (SAEs). 
The participant’s parent / guardian / legally authorized representative will 
record information in a Diary Card (DC) / Electronic Diary Card (eDC) to 
capture solicited reactions, unsolicited AEs, AESIs and MAAEs from D0 to 
D28 for Cohorts 1, 2, 3 and 4 and D56 to D84 for Cohorts 2 and 4. Parents / 
guardians / legally authorized representatives should alert the study site 
regarding reactions, AEs and any symptoms suggestive of respiratory tract 
illness. The study sites will follow up via phone calls. The eDC allows daily 
safety monitoring of the study participant also. In certain cases, when an 

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eDC cannot be used, a paper diary card will be used for daily safety 
monitoring. All solicited reactions will be graded by the Sanofi Pasteur 
Intensity scale, except for runny nose/rhinorrhea and stuffy or blocked 
nose/nasal congestion which will be graded by the Division of AIDS 
(DAIDS) scale. Adverse events of special interest will be graded by the 
DAIDS scale, except for wheeze, which will be graded according to 
Brighton Collaboration specifications. 
Based on previous National Institutes of Health (NIH) clinical experience 
with live-attenuated RSV vaccine candidates and Sanofi Pasteur Safety 
Guideline Standard Practice for the Collection, Analysis, and Reporting of 
Safety Data, the following predefined solicited reactions will be assessed 
during the Acute Phase for each vaccine administration: 
• 
Administration site reactions 
- 
Runny nose 
- 
Stuffy or blocked nose / nasal congestion 
• 
Systemic reactions 
- 
Fever 
- 
Vomiting 
- 
Crying abnormally 
- 
Drowsiness 
- 
Appetite loss 
- 
Irritability 
The following AESIs will be assessed during the Acute Phases of the study: 
• 
Acute otitis media 
• 
Upper respiratory tract illness (URI) 
- 
Pharyngitis 
- 
Cough without LRI 
• 
Lower respiratory tract illness (LRI) 
- 
Stridor 
- 
Rales 
- 
Tachypnea 
- 
Acute wheeze 
- 
Pneumonia 
- 
Laryngotracheobronchitis 
• 
Immediate hypersensitivity reactions including urticaria, anaphylaxis, or 
other immunoglobulin (Ig) E-mediated responses are possible as with 
any vaccine. 
• 
MAAEs will be collected during the Acute Phase for either vaccination 
using the same process as other AEs. 
• 
SAEs will be recorded throughout the participant’s participation in the 
study. The participant’s parent / guardian / legally authorized 

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representative will be asked to notify the site immediately about any 
potential SAE at any time during the study. In addition, the participant’s 
parent / guardian / legally authorized representative will record 
information in a DC / eDC about SAEs from the D0 to D56 visits 
(Cohorts 1 and 3), and from D0 to D84 visits (Cohorts 2 and 4). 
Participant’s parent / guardian / legally authorized representative will 
receive a memory aid (MA) to record the SAEs from the D56 visit until 
the end of the study (Cohorts 1 and 3) and from the D84 visit until the 
end of the study (Cohorts 2 and 4). 
• 
The completed DC / eDC or MA will be reviewed with the participant’s 
parent / guardian / legally authorized representative at each visit. 
Early Safety Data Review 
(ESDR): 
The safety of the investigational product will be continuously monitored by 
the Sponsor. To allow for a cautious, stepwise approach to vaccine 
administration, early safety data review (ESDR) will be performed during 
scheduled Safety Management Team (SMT) meetings: 
• 
Cohort 1 
o 
D7 post-vaccination ESDR/SMT 
o 
D28 post-vaccination ESDR/SMT 
o 
D56 post-vaccination ESDR/SMT 
• 
Cohort 2 
o 
D7 post-vaccination ESDR/SMT 
o 
D28 post-vaccination ESDR/SMT 
o 
D84 post-vaccination ESDR/SMT 
• 
Cohort 3 
o 
D7 post-vaccination ESDR/SMT 
o 
D28 post-vaccination ESDR/SMT 
o 
D56 post-vaccination ESDR/SMT 
• 
Cohort 4  
o 
D7 post-vaccination ESDR/SMT 
o 
D28 post-vaccination ESDR/SMT 
o 
D84 post-vaccination ESDR/SMT 
The safety data collected will be entered into the CRBs and summarized by 
the Sponsor in a blinded manner for each ESDR. The ESDR will be 
performed by the Sponsor during the SMT meetings. Enrollment will not be 
paused during SMT reviews.  
It is understood that all reviews are based on preliminary data that have not 
been subjected to validation and database lock. The usual and ongoing 
process of monitoring safety signals outside of those specified in the 
protocol-defined early interim safety analysis will continue unchanged. 
If at any other time point in the study the predetermined alert threshold for a 
safety event as outlined in the SMT charter is reached, regardless of the 
study time point, the trial will be paused for enrollment in order for an ad-
hoc SMT to be convened. 
In cases where the review of data by the SMT does not result in the 
identification of a potential safety signal, SMT oversight proceeds as 
assigned in the SMT charter. When a safety signal(s) is identified, the SMT 

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investigates the event(s), completes the Safety Analysis and/or Evaluation 
Report and decides about the safety signal and further actions and/or 
recommendations including: 
• 
Extending or pausing the trial and escalate to the Vaccine 
Adjudication Committee (VAC) 
• 
Investigate and develops a report 
• 
Recommends continuing the trial 
Within the investigation, the team may consult with non-clinical safety 
experts and research team members on whether there is a possible 
underlying mechanism for the event and review of toxicology data or other 
internal experts depending on the need.  
In case of disagreement in the team, the core team seeks respective 
functional management advice from the VAC shortly after the SMT 
meeting. The Vaccine Pharmacovigilance Global Business Unit (PV GBU) 
Head or Vaccines GBU Clinical & Sciences Head may be also consulted, 
especially in instance where escalation of the signal for PSB review is in 
question. 
Once the SMT core team agrees that there is a safety signal that can 
potentially impact the participant’s safety, study conduct (pause, extended 
pause, or termination) or design (modifications needed), the SMT PM 
informs the Vaccine PV GBU Head who validates the signal and urgently 
contacts the Vaccines GBU Clinical & Sciences Head and the Chair of the 
PSB. The decision is made on whether to convene a PSB or not.   
Based on the outcomes and recommendations from the PSB, the SMT may 
carry out any of the following operational actions related to the conduct and 
oversight of the study including: 
• 
Continue the trial 
• 
Extend the pause to conduct a further evaluation e.g., an ad hoc 
independent data monitoring committee (IDMC) 
• 
Modify the trial design, or 
• 
Stop the trial. 
An ad-hoc IDMC, which ideally will include at least 2 pediatric respiratory 
virus vaccine experts, will review upon request of the SMT unblinded study 
data. The ad-hoc IDMC will upon request review the relevant safety 
information and available data, including magnitude of vaccine virus 
shedding. If an ad hoc IDMC meeting is required, the ad hoc IDMC will 
review the data on safety available at that time point to determine if 
attributable to an etiology, a cause, or a diagnosis unrelated to the study 
vaccine, and if the adverse event(s) are associated with shedding of vaccine 
virus at the time of the event (even if another is identified). If the ad-hoc 
IDMC decides there is no proven causal relationship between the adverse 
events and study vaccine, the study can continue unchanged. Based on 
evaluation of the ad-hoc IDMC, the Sanofi Pasteur SMT will decide if there 
is a causal relationship between the adverse event and the study vaccine, 
then SMT will decide whether to: 
• 
Conduct internal signal detection processes (SOP # RDWIN-
000390) 
• 
Escalate validated signals to PSB as needed 
• 
Continue the trial 

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• 
Modify the trial design (with PSB and ad-hoc IDMC input) or, 
• 
Stop the trial (with PSB and ad-hoc IDMC input).  
 
The following safety parameters will be assessed as part of the early safety 
review: 
• 
Immediate reactions 
• 
Solicited respiratory and systemic reactions 
• 
Unsolicited adverse reactions 
• 
SAEs, MAAEs and AESIs 
The data will be examined for the following thresholds: 
1. Any deaths, regardless of causality. 
2. Any vaccine related SAEs. 
3. Grade 3 fever reported in > 2 participants. 
4. Any Grade 3 or above solicited adverse reaction other than fever 
5. >1 participant experiencing lower respiratory tract illness of >Grade 2 
DAIDS scale (except for wheeze by Brighton Collaboration Severity 
Scale) during the acute phase (i.e., within 28 days post-vaccination). 
6. Any participant experiencing an AESI of Grade 3 or above by the 
DAIDS scale (except for wheeze by Brighton Collaboration Severity 
Scale), including lower respiratory tract illness during the acute phase 
(i.e., within 28 days post-vaccination). 
7. >1 participant with a Grade 3 unsolicited AE during the acute phase 
(i.e., within 28 days post-vaccination). 
8. Any other pattern of research laboratory values or clinical symptoms 
other than fever that is considered a significant safety issue by 
Investigator. 
If any of the above thresholds are met, the study will be paused for 
enrollment and an ad-hoc SMT convened to review the available safety data.  
Interruption of the Study 
The study may be discontinued if new data about the investigational product 
resulting from this study or any other studies become available; or for 
administrative reasons; or on advice of the Sponsor, the Investigators, the 
Independent Ethics Committees (IECs) / Institutional Review Boards 
(IRBs), or the governing regulatory authorities in the countries where the 
study is taking place. 
If the study is prematurely terminated or suspended, the Sponsor shall 
promptly inform the Investigators, the IECs/IRBs, the regulatory authorities, 
and any contract research organization(s) used in the study of the reason for 
termination or suspension, as specified by the applicable regulatory 
requirements. The Investigator shall promptly inform the study participants’ 
parents / guardians / legally authorized representatives and should assure 
appropriate participant therapy and / or follow-up. 
Primary Objectives: 
Primary Safety Objective: 
• 
To assess the safety profile of each dose of RSV ∆NS2/∆1313/I1314L 
after each and any administration in all infants and toddlers regardless 
of baseline serostatus. 
Primary Immunogenicity Objective: 
• 
To characterize the RSV A serum neutralizing antibody responses to the 
study product in each vaccine group after vaccination 1 (D56) for 

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Cohorts 1, 2, 3 and 4, and after vaccination 2 (D84) for Cohorts 2 and 4 
in RSV-naïve participants. 
Primary Endpoints: 
Primary Safety Endpoints: 
In all infants and toddlers regardless of baseline serostatus: 
• 
Occurrence of any unsolicited systemic AEs reported in the 30 minutes 
after each and any vaccination. 
• 
Occurrence of solicited (i.e., pre-listed in the participant’s DC / eDC 
and in the CRB) administration site and systemic reactions within 28 
days after each and any vaccination (i.e, Acute Phase). 
• 
Occurrence of any unsolicited (spontaneously reported) AEs within 
28 days after each and any vaccination. 
• 
Occurrence of any AESIs within 28 days after each and any 
vaccination. 
• 
Occurrence of any MAAEs within 28 days after each and any 
vaccination. 
• 
Occurrence of any SAEs throughout the study. 
• 
Other safety endpoints will be recorded or derived as described in the 
statistical analysis plan. Depending on the item, these could include: 
nature (Medical Dictionary for Regulatory Activity [MedDRA] 
preferred term), time of onset, duration, number of days of occurrence, 
intensity, relationship to vaccine, action taken, whether the AE led to 
early termination from the study, seriousness, or outcome. 
Primary Immunogenicity Endpoint: 
RSV A serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4 
and by D84 for Cohorts 2 and 4 in RSV-naïve participants. 
For this Sanofi Phase I/II trial, data will be analyzed according to baseline 
serostatus. Baseline serostatus will be retrospectively determined from 
serum samples collected at baseline (V01). Participants will be categorized 
into RSV-experienced or RSV-naïve based on the presence or absence of 
detectable RSV serum anti-F IgA antibodies. This biomarker has been 
chosen since it is produced only in response to RSV infection and not 
transferred trans placentally from mother to child 
Secondary Objectives: 
Secondary Safety Objectives: 
• 
To quantify the amount of vaccine virus shed by each participant on D7 
for Cohorts 1, 2, 3 and 4, and D63 for Cohorts 2 and 4, measured by 
 
by baseline serostatus. 
Secondary Infectivity Objective: 
• 
To determine the proportion of vaccinated infants and toddlers in each 
vaccine group infecteda with the vaccine virus at D56 (56 days after 
vaccination 1) for Cohorts 1, 2, 3 and 4, and at D84 (28 days after 
vaccination 2) for Cohorts 2 and 4, by baseline serostatus. 
 
a  Infection defined as detection of vaccine in nasal swab sample by 
 and / or a 
≥ 4-fold rise in RSV A serum neutralizing antibody titers, or RSV serum anti-F IgG antibody titers. 

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*Infection defined as detection of vaccine in nasal swab sample by 
 and / or a ≥ 4-fold rise in RSV A serum 
neutralizing antibody titers, or in RSV serum anti-F IgG antibody titers. 
 
Secondary Immunogenicity Objectives: 
• 
To characterize the RSV A serum neutralizing antibody responses to the 
study product in each vaccine group after vaccination 1 (D56) for 
Cohorts 1, 2, 3 and 4, and after vaccination 2 (D84) in Cohorts 2 and 4 
in RSV-experienced participants. 
• 
To characterize RSV serum anti-F IgG antibody responses to the study 
product in each vaccine group after vaccination 1 (D56) for Cohorts 1, 
2, 3 and 4, and after vaccination 2 (D84) for Cohorts 2 and 4, by 
baseline serostatus. 
• 
To characterize RSV serum antibody responses (RSV A-neutralizing 
and anti-RSV F IgG) to the study product in each vaccine group after 
the RSV surveillance season or at least 5 months after the last vaccine 
administration by baseline serostatus. 
Secondary Endpoints: 
Secondary Safety Endpoints: 
• 
Titer of vaccine virus shedding by D7 for Cohorts 1, 2, 3 and 4, and 
D63 for Cohorts 2 and 4 measured by 
 assay. 
Secondary Infectivity Endpoint: 
• 
Vaccinees infected with the vaccine virus. Infection defined as detection 
of vaccine in nasal swab by 
 and / or a ≥ 4-fold rise in serum 
RSV A neutralizing antibodies, or in RSV serum anti-F IgG antibody 
titers. 
Secondary Immunogenicity Endpoints: 
• 
RSV A serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 
and 4, and by D84 for Cohorts 2 and 4 in RSV-experienced participants. 
• 
RSV serum anti-F IgG antibody titers by D56 for Cohorts 1, 2, 3 and 4, 
and by D84 for Cohorts 2 and 4. 
• 
RSV A serum neutralizing and RSV serum anti-F IgG antibody titers 
after the RSV surveillance season or at least 5 months after the last 
vaccine administration. 
Exploratory Objectives: 
Exploratory Safety Objective 
• 
To assess the safety profile of each dose of RSV after each and any 
administration by baseline serostatus. 
Exploratory Immunogenicity Objectives: 
• 
To characterize the RSV A serum neutralizing antibody responses to the 
study product converted to IU/mL values in each vaccine group after 
vaccination 1 (D56) for Cohorts 1, 2, 3 and 4, and after vaccination 2 
(D84) for Cohorts 2 and 4 by baseline serostatus. 
• 
To characterize the RSV A serum neutralizing antibody responses to the 
study product converted to IU/mL values in each vaccine group after 
the RSV season or at least 5 months after the last vaccine administration 
by baseline serostatus. 
• 
To characterize the RSV B serum neutralizing antibody responses to the 
study product in each vaccine group after vaccination 1 (D56) for 

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Cohorts 1, 2, 3 and 4, and after vaccination 2 (D84) for Cohorts 2 and 4 
by baseline serostatus. 
• 
To characterize the RSV B serum neutralizing antibody responses to the 
study product converted to IU/mL values in each vaccine group after 
vaccination 1 (D56) for Cohorts 1, 2, 3 and 4, and after vaccination 2 
(D84) for Cohorts 2 and 4 by baseline serostatus. 
• 
To characterize the RSV B serum neutralizing antibody responses to the 
study product in each vaccine group after the RSV season or at least 
5 months after the last vaccine administration by baseline serostatus. 
• 
To characterize the RSV B serum neutralizing antibody responses to the 
study product converted to IU/mL values in each vaccine group after 
the RSV season or at least 5 months after the last vaccine administration 
by baseline serostatus. 
• 
To characterize RSV A and RSV B serum anti-RSV protein G central 
conserved (anti-Gcc) IgG antibody responses to the study product in 
each vaccine group after vaccination 1 (D56) for Cohorts 1, 2, 3 and 4, 
and after vaccination 2 (D84) for Cohorts 2 and 4 by baseline 
serostatus. 
• 
To characterize RSV A and RSV B serum anti-Gcc IgG antibody 
responses to the study product in each vaccine group after the RSV 
season or at least 5 months after the last vaccine administration by 
baseline serostatus. 
• 
To characterize the RSV serum anti-F IgA antibody responses after 
vaccination 1 (D56) for Cohorts 1, 2, 3 and 4 and after vaccination 2 
(D84) for Cohorts 2 and 4 by baseline serostatus. 
• 
To characterize the RSV serum anti-F IgA antibody responses after the 
RSV season or at least 5 months after the last vaccine administration by 
baseline serostatus. 
Exploratory Efficacy Objective 
• 
To describe the frequency and severity of RSV-associated, medically 
attended acute respiratory illness (RSV MAARI) and RSV-associated, 
medically attended acute lower respiratory illness (RSV MAALRI) in 
all infants and toddlers in each vaccine group during the RSV season or 
at least 5 months after the last vaccine administration. 

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Exploratory Endpoints: 
Exploratory Safety Endpoints 
• 
Occurrence of any unsolicited systemic AEs reported in the 30 minutes 
after each and any vaccination. 
• 
Occurrence of any unsolicited (spontaneously reported) AEs within 
28 days after each and any vaccination. 
• 
Occurrence of solicited (i.e., pre-listed in the participant’s DC / eDC 
and in the CRB) administration site and systemic reactions within 28 
days after each and any vaccination (i.e, Acute Phase). 
• 
Occurrence of any AESIs within 28 days after each and any 
vaccination. 
• 
Occurrence of any MAAEs within 28 days after each and any 
vaccination. 
• 
Occurrence of any SAEs throughout the study. 
Exploratory Immunogenicity Endpoints: 
• 
RSV A serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 
and 4, and by D84 for Cohorts 2 and 4 converted into international 
units* (IU)/mL. 
• 
RSV A serum neutralizing antibody titers converted into IU/mL, after 
the RSV season or at least 5 months after the last vaccine 
administration. 
*The RSV A serum neutralizing antibody titer values obtained are further 
calibrated and converted into IU/mL against the World Health Organization 
(WHO) 1st international reference standard NIBSC 16/284 (with an assigned 
value of 2000 IU/mL) or converted with a qualified internal reference with an 
assigned IU/mL value. The calibrator (reference standard) is included in the 
same assay run.  
• 
RSV◦B serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 
and 4, and by D84 for Cohorts 2 and 4. 
• 
RSV B serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 
and 4, and by D84 for Cohorts 2 and 4, converted into international 
units* (IU)/mL. 
• 
RSV◦B serum neutralizing antibody titers after the RSV season or at 
least 5 months after the last vaccine administration. 
• 
RSV B serum neutralizing antibody titers converted into IU/mL, after 
the RSV season or at least 5 months after the last vaccine 
administration. 
*The RSV B serum neutralizing antibody titer values obtained are further 
calibrated and converted into IU/mL against the World Health Organization 
(WHO) 1st international reference standard NIBSC 16/284 (with an assigned 
value of 2000 IU/mL) or converted with a qualified internal reference with 
an assigned IU/mL value. The calibrator (reference standard) is included in 
the same assay run., 
• 
RSV A and RSV B serum anti-Gcc IgG antibody titers by D56 for 
Cohorts 1, 2, 3 and 4, and by D84 for Cohorts 2 and 4. 
• 
RSV A and RSV B serum anti-Gcc IgG antibody titers after the RSV 
season or at least 5 months after the last vaccine administration. 

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• 
RSV serum anti-F IgA antibody titers by D56 for Cohorts 1, 2, 3 and 4, 
and by D84 for Cohorts 2 and 4. 
• 
RSV serum anti-F IgA antibody titers after the RSV season or at least 5 
months after the last vaccine administration. 
Exploratory Efficacy Endpoints 
The following exploratory efficacy endpoints will be assessed through the 
RSV season surveillance phase or for at least five months after the last 
vaccine administration: 
• 
RSV medically attended acute respiratory illness (RSV MAARI) 
• 
RSV medically attended acute lower respiratory illness (RSV 
MAALRI) 
• 
A diagnosis of RSV MAARI requires a respiratory sample positive for 
RSV by 
 AND documented physical exam findings of 
respiratory tract illness including any of the following: 
o 
Fever 
o 
Acute otitis media 
o 
URI: 
 
Runny nose/rhinorrhea 
 
Stuffy or blocked nose/nasal congestion 
 
Pharyngitis 
 
Cough without LRI 
o 
LRI (see MAALRI below) 
• 
A diagnosis of RSV MAALRI (a subset of MAARI) requires a 
respiratory sample positive for RSV by 
 AND documented 
physical exam findings of lower respiratory tract illness including any 
of the following: 
o 
Stridor 
o 
Rales 
o 
Tachypnea 
o 
Acute wheeze 
o 
Pneumonia 
o 
Laryngotracheobronchitis 

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5. Known or suspected congenital or acquired immunodeficiency; or 
receipt of immunosuppressive therapy, such as anti-cancer 
chemotherapy or radiation therapy, within the preceding 6 months; or 
long-term systemic corticosteroid therapy (prednisone or equivalent for 
more than 2 consecutive weeks within the past 3 months). 
6. Probable or confirmed case of Coronavirus Disease 2019 (COVID-19). 
7. Known systemic hypersensitivity to any of the vaccine components, or 
history of a life-threatening reaction to the vaccine used in the trial or to 
a vaccine containing any of the same substances. 
8. Any chronic illness. 
• 
Chronic illness may include, but is not limited to, cardiac disorders, 
lung disease (including any history of reactive airway disease, 
receipt of bronchodilator therapy, or medically diagnosed 
wheezing), renal disorders, auto-immune disorders, diabetes, 
psychomotor diseases, and known congenital or genetic diseases 
9. Any history of medically diagnosed wheezing. 
10. Any acute febrile, respiratory or gastrointestinal illness in the past 
24 hours that according to investigator judgment is significant enough 
to interfere with successful inoculation on the day of vaccination. A 
prospective participant should not be included in the study until the 
condition has resolved or the febrile event has subsided. 
11. Receipt of any of the following medications within 3 days prior to study 
enrollment: 
• systemic antibacterial, antiviral, antifungal, anti-parasitic, or anti-
tuberculous agents, whether for treatment or prophylaxis, or 
• intranasal medications, or 
• other prescription medication except as permitted concomitant 
medications (prescription or non-prescription) including nutritional 
supplements, medications for gastroesophageal reflux, eye drops, 
and topical medications, including (but not limited to) cutaneous 
(topical) steroids, topical antibiotics, and topical antifungal agents. 
12. Receipt of salicylate (aspirin) or salicylate-containing products within 
the 28 days prior to enrollment. 
13. Deprived of freedom in an emergency setting or hospitalized 
involuntarily. 
14. Identified as a natural or adopted child of the Investigator or employee 
with direct involvement in the proposed study. 
15. Any previous anaphylactic reaction. 
16. Any previous vaccine-associated adverse reaction that was Grade 3 or 
above. Note: if grading is not possible, determine if the reaction was 
considered severe or life-threatening; if so, it is exclusionary. 
17. Member of a household that contains, or will contain, an infant who is 
less than 6 months of age at the enrollment date (or in the 6 weeks 
preceding the first trial vaccination) through Day 28. 
18. Member of a household that contains another child/other children who 
is/are, or is/are scheduled to be, enrolled in this study in the same year 
AND the date of enrollment will not be concurrent with the other 

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participant(s) living in the household (i.e., all eligible children from the 
same household must be enrolled on the same date). 
19. Member of a household that contains an immunocompromised 
individual, including, but not limited to: 
• 
a person who is HIV infected 
• 
a person who has received chemotherapy within the 12 months 
prior to enrollment 
• 
a person receiving immunosuppressant agents 
• 
a person living with a solid organ or bone marrow transplant. 
20. Attends a daycare facility and shares a daycare room with infants less 
than 6 months of age, and parent/ guardian / legally authorized 
representative is unable or unwilling to suspend daycare for 28 days 
following inoculation. 
21. Scheduled administration of the following after planned inoculation: 
• any influenza vaccine within 7 days after, or 
• inactivated vaccine or live-attenuated rotavirus vaccine within the 
14 days after, or 
• any live vaccine other than rotavirus in the 28 days after, or 
• another investigational vaccine or investigational drug in the 56 days 
after. 
22. Born at less than 34 weeks gestation. 
23. Born at less than 37 weeks gestation and less than 1 year of age at the 
time of enrollment. 
24. Current suspected or documented developmental disorder, delay, or 
other developmental problem. 
25. Any previous receipt of supplemental oxygen therapy in a home or 
hospital setting, except the temporary receipt of supplemental oxygen 
for transient tachypnea in newborn. 
Statistical Methods: 
The analysis will be performed with a stepwise approach as follows: 
• 
Several blinded early safety data reviews will be performed on 
safety data collected in participants from each cohort at specific 
timepoints, as specified in ESDR section 
• 
An unblinded interim analysis for dose confirmation of RSV 
∆NS2/∆1313/I1314L vaccine is planned on participants from 
Cohorts 1, 2 and 3 and at least 90 participants enrolled in Cohort 4. 
The interim analysis will take place when participants have 
provided safety data up to the D84 timepoint and have D84 
immunogenicity results available. Based on the results of this 
analysis, the dose for future clinical studies (frozen product) will be 
confirmed. The acceptability of safety, infectivity, and 
immunogenicity results of the two doses tested to justify clinically 
the future dose range boundaries of the non-frozen liquid 
formulation for final commercialization will also be descriptively 
assessed. 
• 
An early unblinded analysis is planned on all participants when 
they have provided safety data up to the D84 timepoint and have 
D84 immunogenicity results available. Based on the results of this 
analysis, a dose will be confirmed for future studies. 

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• 
The final unblinded analysis will address the objectives on all 
participants (Cohorts 1, 2, 3 and 4) including the post season follow 
up. 
All analyses will be descriptive; no hypotheses will be tested. 
During a cohort's safety review and/or at the end of the study, a Bayesian 
approach based on posterior distribution of the difference in incidence 
between groups may be applied. 
The Safety Analysis Set will be used for safety analyses. Immunogenicity 
analyses will be performed on the Full Analysis Set and, on the Per-Protocol 
Analysis Set for main immunogenicity parameters. 
All endpoints will be summarized by vaccine group. For the main 
parameters, 95% confidence intervals (CIs) of point estimates will be 
calculated using the normal approximation for quantitative data, and the 
exact binomial distribution (Clopper-Pearson method) for proportions. 
Calculation of Sample Size: 
No sample size calculation was done as there are no statistical hypotheses in 
this study. 
A total of 300 participants are planned to be enrolled into 1 of the 4 cohorts 
sequentially:  
• 
Cohort 1 (1 administration): 40 participants, i.e., 20 per vaccine 
group (RSV low-dose or placebo) 
• 
Cohort 2 (2 administrations): 40 participants, i.e., 20 per vaccine 
group (RSV low-dose or placebo) 
• 
Cohort 3 (1 administration): 40 participants, i.e., 20 per vaccine 
group (RSV high-dose or placebo) 
• 
Cohort 4 (2 administrations): 180 participants, i.e., 60 per vaccine 
group (RSV high-dose or RSV low-dose or placebo).  

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Table of Study Procedures for Cohorts 1 and 3  
Phase I/II Study, 4 Planned Visits, 30 (32) non-visit telephone contacts, 1 Vaccination, 3 Planned Blood Samples, 1 Planned Nasal Swab, up to a Maximum of 12 Months of 
Participation per Participant 
Visit (V) / Contact 
Visit 01 
Phone 
contacts 
1 - 6 
Visit 02 
Phone 
contacts 
7 - 16 
Phone 
Contact 17 
Phone 
contact 18 
Visit 03 
Phone 
contacts 
19 -30 (32) ‡ ‡ 
Visit 04§§ 
Illness 
Visit(s) 
Visit 99*** 
Study timelines - Days(D) 
D0 
Daily (x6) 
D7 
Three times 
weekly (x10)  
D29 (+1) 
D42 (+1) 
D56 (+7) 
Every 2 
weeks  
1 – 30 Apr 
(NH) 
 
In-person visit  
X 
 
X 
 
 
 
X 
 
X 
X 
Non-visit contact* 
 
X 
 
X 
X 
X 
 
X 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Demography data  
X 
 
 
 
 
 
 
 
 
 
Inclusion / Exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
Medical history and physical 
examination 
X 
 
 
 
 
 
 
 
 
 
Vital signs† 
X 
 
X 
 
 
 
X 
 
 
X 
COVID-19 test 
X 
 
 
 
 
 
 
 
 
X 
Interim history 
 
 
X 
 
 
 
X 
 
 
X 
Focused clinical examination 
 
 
X 
 
 
 
X 
 
 
X 
Collection of reportable concomitant 
medications/vaccinations 
 
 
 
 
 
 
X 
 
 
X 
Allocation participant number 
X 
 
 
 
 
 
 
 
 
 
Randomization / Dose number 
X 
 
 
 
 
 
 
 
 
 
Blood samples 
BL0001 
 
 
 
 
 
BL0002 
 
BL00P2 
 
Nasal swab‡ 
 
 
NS0001 
 
 
 
 
 
 
NS0001 or 
UN0001 to 
UN000X 
Vaccination 
X 
 
 
 
 
 
 
 
 
 
Immediate surveillance (30 min) § 
X 
 
 
 
 
 
 
 
 
 

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Visit (V) / Contact 
Visit 01 
Phone 
contacts 
1 - 6 
Visit 02 
Phone 
contacts 
7 - 16 
Phone 
Contact 17 
Phone 
contact 18 
Visit 03 
Phone 
contacts 
19 -30 (32) ‡ ‡ 
Visit 04§§ 
Illness 
Visit(s) 
Visit 99*** 
Study timelines - Days(D) 
D0 
Daily (x6) 
D7 
Three times 
weekly (x10)  
D29 (+1) 
D42 (+1) 
D56 (+7) 
Every 2 
weeks  
1 – 30 Apr 
(NH) 
 
Diary Card (DC) electronic DC (eDC) 
provided 
DC1/eDC 
 
DC2 
 
 
 
 
 
 
 
DC / eDC reviewed 
 
DC1/eDC **  
DC1/eDC 
DC1 /eDC ** 
DC2/eDC ** 
DC2/eDC** 
DC2 
 
X 
X 
DC collected 
 
 
 
 
 
 
DC1/DC2 
 
 
 
Memory aid (MA) provided 
 
 
 
 
 
 
X 
 
 
 
MA reviewed 
 
 
 
 
 
 
 
 
X 
X 
Collection of solicited local respiratory 
and systemic reactions†† 
X 
X 
X 
X 
X 
 
 
 
 
 
Collection of unsolicited adverse 
events†† 
X 
X 
X 
X 
X 
 
 
 
 
 
Collection of adverse events of special 
interest†† 
X 
X 
X 
X 
X 
 
 
 
 
 
Collection of medical attended adverse 
events†† 
X 
X 
X 
X 
X 
 
 
 
 
 
Collection of serious adverse events 
X 
*Non-site visit contacts are to be made by phone at scheduled timepoints in the study. 
† Vital signs will be collected in the eCRF. 
‡All participants will provide a nasal swab sample for quantification of vaccine virus shedding at D7, i.e., 7 days after vaccination. The same nasal swab specimens may also be tested for respiratory pathogens 
(including COVID-19), if the participant is ill at the time of D7 visit. 
§Any unsolicited systemic adverse events occurring within the 30 minutes from vaccine administration will be recorded as immediate unsolicited systemic adverse events in the case report book. 
**Diary Card (DC) / Electronic Diary Card (eDC) will be reviewed by telephone contact. 
††The participant’s parent / guardian / legally authorized representative will record information in a DC / eDC about solicited reactions, unsolicited AEs, AESIs and MAAEs from D0 to D28 after vaccine 
administration. 
‡‡Phone contact during the RSV season every 2 weeks. 
§§Visit 04: Post-RSV season visit in the month after the cessation of the RSV season. 
***Illness Visits: Additional nasal swab specimens for the detection of RSV and respiratory pathogens” (including COVID-19) will also be collected from participants during illness visits and 48 hours later at any 
other protocol specified time point in the study (Table 5-4) including medically attended visits during RSV season. If a participant visits any other non-study doctor / hospital for a serious adverse event (SAE) at any 
time in the study, a nasal swab sample will be obtained at the study site once the participant is discharged, if deemed appropriate by the study investigator. All the nasal swab specimens will be collected in the 
recommended viral transport media tube and will be stored between -60°C and -80°C until ready to ship. The requirement for an onsite or at home illness visit will be evaluated first by video call to enable remote 
evaluation of severity and remote management of mild (Grade 1) illness, as deemed appropriate by the study investigator. 

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Table of Study Procedures for Cohorts 2 and 4 – Vaccination 1 (D0 to D55)  
Phase I/II Study, 6 Planned Visits, 40 (42) Non-visit Telephone Contacts, 2 Vaccinations, 4 Planned Blood Samples, 2 Planned Nasal Swabs, up to a Maximum of 12 Months of 
Participation per Participant 
Visit (V) / Contact 
Visit 01 
Phone contacts 1-6 
Visit 02 
Phone contacts 7-
16 
Phone contact 
17 
Phone contact 
18 
Illness Visit(s) ‡ 
Visit 99 
Study timelines – Days (D) 
D0 
Daily (x6) 
D7 
Three times 
weekly (x10) 
between D8 and 
D28 
D29 (+1) 
D42 (+1) 
Any time between 
Visit 01 and Visit 06 
In-person visit  
X 
 
X 
 
 
X 
Non-visit contact* 
 
X 
 
X 
X 
X 
 
Informed consent 
X 
 
 
 
 
 
 
Demography data  
X 
 
 
 
 
 
 
Inclusion / Exclusion criteria 
X 
 
 
 
 
 
 
Medical history and physical examination 
X 
 
 
 
 
 
 
Vital signs† 
X 
 
X 
 
 
 
X 
COVID-19 test 
X 
 
 
 
 
 
X 
Interim history 
 
 
X 
 
 
 
X 
Focused clinical examination 
 
 
X 
 
 
 
X 
Collection of reportable concomitant medications/ 
vaccinations 
 
 
 
 
 
 
X 
Allocation of participant number 
X 
 
 
 
 
 
 
Randomization / Dose number 
X 
 
 
 
 
 
 
Blood samples  
BL0001 
 
 
 
 
 
 
Nasal swabs‡ 
 
 
NS0001 
 
 
 
NS0001 or UN0001 to 
UN0000X  
Vaccination (1st administration) 
X 
 
 
 
 
 
 
Immediate surveillance (30 min) § 
X 
 
 
 
 
 
 

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Visit (V) / Contact 
Visit 01 
Phone contacts 1-6 
Visit 02 
Phone contacts 7-
16 
Phone contact 
17 
Phone contact 
18 
Illness Visit(s) ‡ 
Visit 99 
Study timelines – Days (D) 
D0 
Daily (x6) 
D7 
Three times 
weekly (x10) 
between D8 and 
D28 
D29 (+1) 
D42 (+1) 
Any time between 
Visit 01 and Visit 06 
Diary Card (DC) / electronic DC (eDC) provided 
DC1/eDC 
 
DC2 
 
 
 
 
DC / eDC reviewed 
 
DC1/eDC** 
DC1/eDC 
DC1/eDC ** 
DC2/eDC ** 
DC2/eDC ** 
X 
Collection of solicited local respiratory and 
systemic reactions** 
X 
X 
X 
X 
X 
 
 
Collection of unsolicited adverse events** 
X 
X 
X 
X 
X 
 
 
Collection of adverse events of special interest** 
X 
X 
X 
X 
X 
 
 
Collection of medical attended adverse events** 
X 
X 
X 
X 
X 
 
 
Collection of serious adverse events 
X 
*Non-site visit contacts are to be made by phone at scheduled timepoints in the study. 
† Vital signs will be collected in the eCRF. 
‡All participants will provide a nasal swab sample for quantification of vaccine virus shedding at D7, i.e., 7 days after vaccination 1. The same nasal swab specimen may also be tested for respiratory 
pathogens (including COVID-19), if the participant is ill at the time of D7 visit. 
§Any unsolicited systemic adverse events occurring within the 30 minutes from vaccine administration will be recorded as immediate unsolicited systemic adverse events in the case report book. 
**Diary Card / Electronic Diary Card (DC / eDC) will be reviewed by telephone contact. 
††The participant’s parent / guardian / legally authorized representative will record information in a DC / eDC about solicited reactions, unsolicited AEs, AESIs and MAAEs from D0 to D28 after vaccine 
administration 1 (Acute phase 1). 
‡‡Illness Visits (between V01 and V06): Additional nasal swab specimens for the detection of RSV and respiratory pathogens” (including COVID-19) will also be collected from participants during illness 
visits and 48 hours later at any other protocol specified time point in the study (Table 5-4) including medically attended visits during RSV season. If a participant visits any other non-study doctor / 
hospital for a serious adverse event (SAE) at any time in the study, a nasal swab sample will be obtained at the study site once the participant is discharged, if deemed appropriate by the study 
investigator. All the nasal swab specimens will be collected in the recommended viral transport media tube and will be stored between -60°C and -80°C until ready to ship. The requirement for an at 
home or onsite illness visit will be evaluated first by video call to enable remote evaluation of severity and remote management of mild (Grade 1) illness, as deemed appropriate by the study 
investigator. 
 

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Table of Study Procedures for Cohorts 2 and 4 – Vaccination 2 (D56 to End of Study)  
Phase I/II Study, 6 Planned Visits, 40 (42) Non-visit Telephone Contacts, 2 Vaccinations, 4 Planned Blood Samples, 2 Planned Nasal Swabs, up to a Maximum of 12 Months of 
Participation per Participant 
Visit (V) / Contact 
Visit 03 
Phone contacts 
19-24 
Visit 04 
Phone contacts 
25-30 
Visit 05††† 
Phone contact  
31 – 40 (42)‡‡ 
Visit 06‡‡ 
Illness 
Visit(s) *** 
Visit 99 
Study timelines – Days (D) 
D56+7 
Daily (x6) 
D63 (+7) 
Twice weekly (x6) 
between D64 and 
D83 
D84 (+8) 
Every 2 weeks 
between Visit 
05 and Visit 06 
1 – 31 Oct (SH) 
1 – 30 Apr (NH) 
 or > 5 months 
after last 
vaccine admin. 
Any time 
between Visit 
01 and Visit 
06 
In-person visit  
X 
 
X 
 
X 
 
X 
X 
Non-visit contact* 
 
X 
 
X 
 
X 
 
 
Vital signs† 
X 
 
X 
 
X 
 
 
X 
Interim history 
X 
 
X 
 
X 
 
 
X 
Focused clinical examination 
X 
 
X 
 
X 
 
 
X 
COVID-19 test 
X 
 
 
 
 
 
 
X 
Collection of reportable concomitant 
medications/ vaccinations 
X 
 
 
 
 
 
 
X 
Dose Number 
X 
 
 
 
 
 
 
 
Blood samples  
BL0002 
 
 
 
BL0003 
 
BL00P2 
 
Nasal swabs ‡ 
 
 
NS0002 
 
 
 
 
NS0002 or 
UN0001 to 
UN000X  
Vaccination (2nd administration) 
X 
 
 
 
 
 
 
 
Immediate surveillance (30 min) § 
X 
 
 
 
 
 
 
 
Diary Card (DC1)  
DC3 
 
 
 
 
 
 
 
DC / eDC reviewed** 
DC2/eDC 
DC3/eDC ** 
DC3/eDC 
DC3/eDC ** 
DC3/eDC 
 
X 
X 
DC collected  
DC1/DC2 
 
 
 
DC3 
 
 
 

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Visit (V) / Contact 
Visit 03 
Phone contacts 
19-24 
Visit 04 
Phone contacts 
25-30 
Visit 05††† 
Phone contact  
31 – 40 (42)‡‡ 
Visit 06‡‡ 
Illness 
Visit(s) *** 
Visit 99 
Study timelines – Days (D) 
D56+7 
Daily (x6) 
D63 (+7) 
Twice weekly (x6) 
between D64 and 
D83 
D84 (+8) 
Every 2 weeks 
between Visit 
05 and Visit 06 
1 – 31 Oct (SH) 
1 – 30 Apr (NH) 
 or > 5 months 
after last 
vaccine admin. 
Any time 
between Visit 
01 and Visit 
06 
Memory aid (MA) provided 
 
 
 
 
X 
 
 
 
MA reviewed 
 
 
 
 
 
 
X 
X 
Collection of solicited local respiratory 
and systemic reactions†† 
X 
X 
X 
X 
X 
 
 
 
Collection of unsolicited adverse events†† 
X 
X 
X 
X 
X 
 
 
 
Collection of adverse events of special 
interest†† 
X 
X 
X 
X 
X 
 
 
 
Collection of medical attended adverse 
events†† 
X 
X 
X 
X 
X 
 
 
 
Collection of serious adverse events 
X 
*Non-site visit contacts are to be made by phone at scheduled timepoints in the study. 
† Vital signs will be collected in the eCRF. 
‡All participants will provide a nasal swab sample for quantification of vaccine virus shedding at D63, i.e., 7 days after vaccination 2. The same nasal swab specimen will also be tested for respiratory 
pathogens (including COVID-19), if the participant is ill at the time of D63 visit. 
§Any unsolicited systemic adverse events occurring within the 30 minutes from vaccine administration will be recorded as immediate unsolicited systemic adverse events in the case report book. 
**Diary Card (DC) / Electronic Diary Card (eDC) will be reviewed by telephone contact. 
††The participant’s parent / guardian / legally authorized representative will record information in a DC / eDC about solicited reactions, unsolicited AEs, AESIs and MAAEs from D56 to D84 
(Acute phase 2). 
‡‡Phone contact during the RSV season, every 2 weeks. 
§§Visit 06: Post-RSV season visit – In the month after the cessation of the RSV season in sites with differing seasons or at least 5 months after last vaccine administration. Study participants enrolled 
during the routine RSV season (ie November to March for NH and May to September for SH) will be followed up for at least 5 months after the last vaccine administration. 
***Illness Visits (between V01 and V06): Additional nasal swab specimen for the detection of RSV and respiratory pathogens (including COVID-19) will also be collected from participants during illness 
visits and 48 hours later at any other protocol specified time point in the study (Table 5-4) including medically attended visits during the RSV season. If a participant visits any other non-study doctor / 
hospital for a serious adverse event (SAE) at any time in the study, a nasal swab sample will be obtained at the study site once the participant is discharged, if deemed appropriate by the study 
investigator. All the nasal swab specimens will be collected in the recommended viral transport media tube and will be stored between -60°C and -80°C until ready to ship. The requirement for an at home 
or onsite illness visit will be evaluated first by video call to enable remote evaluation of severity and remote management of mild (Grade 1) illness, as deemed appropriate by the study investigator. 
††† Visit 05 is to occur 84 days after the first vaccination at Visit 01 and 28 days after the second vaccination visit at Visit 03. 

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List of Abbreviations  
 
AE 
adverse event 
AESI 
adverse event of special interest 
AR 
adverse reaction 
CDC 
Centers for Disease Control 
CDM 
Clinical Data Management 
CI 
confidence interval 
COVID-19 
Coronavirus Disease 2019 
CQA 
Clinical Quality Assessment 
CRA 
Clinical Research Associate 
CRB 
(electronic) case report book [all the case report forms for a participant] 
CRF 
(electronic) case report form 
D 
Day 
DAIDS 
Division of AIDS 
DC 
diary card 
eDC  
Electronic Diary Card 
EDC 
electronic data capture 
EENT 
eye, ear, nose, throat 
 
 
ESDR 
early safety data review 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FVFP 
first visit, first participant 
FVLP 
Gcc 
first visit, last participant 
G (glycoprotein) central conserved region 
GCI 
Global Clinical Immunology 
GCP 
Good Clinical Practice 
GMTs 
geometric mean titers  
GMTRs 
geometric mean titers ratios  
GPV 
Global Pharmacovigilance 
HIV 
human immunodeficiency virus 
IATA 
International Air Transport Association 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IDMC 
Independent Data Monitoring Committee 

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IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IME 
important medical event 
IND 
investigational new drug (application) 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
LCLS 
last contact, last participant 
LID 
Laboratory of Infectious Diseases 
LLOQ 
lower limit of quantification 
LLT 
lowest level term 
LRI 
lower respiratory illness 
MA 
memory aid 
MAAE 
medically attended adverse event 
MAARI 
medically attended acute respiratory illness 
 
 
MAALRI 
medically attended acute lower respiratory illness 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
milliliter 
MN 
microneutralization 
nAb 
NC 
neutralizing antibody 
Negative Control 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
NS 
National Institutes of Health 
nasal swab 
NSAID 
non-steroidal anti-inflammatory drug 
PFU 
PC 
plaque forming units 
Positive Control 
 
 
PSB 
Product Safety Board 
POC 
Point of care 
PPAS 
per-protocol analysis set 
PT 
preferred term 
RCDCs 
Reverse cumulative distribution curves 
RSV 
Respiratory Syncytial Virus 
RSV 
ΔNS2/Δ1313/I1314L 
Live-Attenuated Respiratory Syncytial Virus (RSV) ΔNS2/Δ1313/I1314L 
Vaccine 
RSV-LRI 
RSV-associated lower respiratory illness 
RSV MAARI 
RSV-associated, medically attended acute respiratory illness 

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RSV MAALRI 
RSV-associated, medically attended acute lower respiratory illness 
RMO 
Responsible Medical Officer 
 
 
 
 
 
 
SAE 
serious adverse event 
SafAS 
safety analysis set 
SMT 
Safety Management Team 
SOC 
system organ class 
TBD 
to be determined 
TMF 
trial master file 
ULOQ 
upper limit of quantification 
URI 
upper respiratory tract illness 
US 
United States 
VAC 
VTM 
Vaccine Adjudication Committee 
viral transport medium 
WHO 
wt 
World Health Organization 
wild-type 
 
 
 

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increases in RSV-neutralizing serum antibodies in 16 of 20 (80%) vaccine recipients (23), 
warranting further evaluation of this candidate as a vaccine for RSV. 
1.2 
Background of the Investigational Product  
The RSV genome can be manipulated genetically to introduce predetermined mutations into 
infectious RSV via a cDNA intermediate (15).  
The investigational RSV ΔNS2/Δ1313/I1314L vaccine is based on an attenuation approach 
involving the deletion of the gene encoding the RSV interferon / apoptosis antagonist NS2 protein 
(∆NS2) in the RSV A2 wt strain (23). Deletion of NS2 gene attenuates the virus and may enhance 
immunogenicity. RSV ΔNS2/Δ1313/I1314L vaccine additionally contains a genetically stabilized 
attenuating and temperature sensitivity mutation in the L protein (codon deletion ∆1313, as well 
as a missense mutation I1314L that prevents a de-attenuating mutation that otherwise can occur at 
position 1314), and as a result RSV ΔNS2/Δ1313/I1314L is temperature sensitive, with a shut-off 
temperature for virus replication of 38ºC-39°C (100.4ºF-102.2ºF). 
1.3 
Potential Benefits and Risks  
1.3.1 
Potential Benefits to Participants  
Participants may not receive direct study product-related benefit from enrollment in this study. 
Placebo recipients will not receive any direct benefit from enrollment in this study. It is hoped that 
information gained in this study will contribute to the development of a safe and effective vaccine 
for the prevention of illness associated with RSV infection. 
1.3.2 
Potential Risks to Participants  
Venipuncture 
Risks occasionally associated with venipuncture include pain and bruising at the site of 
venipuncture, lightheadedness, infection, and syncope (rarely). 
Nasal Swab 
Risks occasionally associated with nasal swab include pain or discomfort and occasionally 
epistaxis. Nasal swabs are not standard care in well children, but pediatric mid-turbinate swabs are 
sometimes performed on children with respiratory tract illness. 
Topical Anesthetic Cream 
Risks occasionally associated with the use of topical anesthetic cream include temporary skin 
discoloration, skin irritation, rash, hives, and rarely, dizziness or drowsiness. 
Receipt of Study Product 
If a live-attenuated RSV vaccine is insufficiently attenuated, participants could experience upper 
or lower respiratory tract illness. Immediate hypersensitivity reactions, which could be 
life-threatening, including urticaria, anaphylaxis, or other Immunoglobulin (Ig) E-mediated 
responses are possible, as with any vaccine. There is a theoretical possibility, as with any 

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investigational vaccine, of risks about which there is no present knowledge. Parents / guardians / 
legally authorized representatives will be informed of any such risks should further data become 
available. 
1.4 
Rationale for the Study  
Prior to RSV ΔNS2/Δ1313/I1314L vaccine, 3 RSV vaccine viruses with the NS2 gene deletion 
(rA2cpΔNS2, rA2cp248/404ΔNS2, and rA2cp530/1009ΔNS2) had been evaluated in clinical 
studies (7). The rA2cpΔNS2 candidate was over-attenuated for adults but under-attenuated for use 
in young children, whereas both rA2cp248/404ΔNS2 and rA2cp530/1009ΔNS2 were over-
attenuated and insufficiently immunogenic in seronegative children. Based on these results RSV 
∆NS2/∆1313/I1314L was developed. In a recent Phase Ia study sponsored by the National 
Institutes of Health (NIH) in RSV seronegative children aged 6 to 24 months, (n=20) (23), at the 
 dose, RSV ∆NS2/∆1313/I1314L was safe, had good infectivity (100% of vaccinated 
participants infected) and immunogenicity (80% of participants with a >4-fold rise in neutralizing 
antibody titers) and primed for a strong anamnestic response to wt RSV infection in the post-RSV 
season surveillance.  
The NIH proceeded to age de-escalate in order to evaluate RSV ΔNS2/Δ1313/I1314L in younger 
infants, aged 4 to 6 months, who are the likely primary target population for a live-attenuated 
RSV vaccine since they are at highest risk for severe RSV-associated LRI. This study is currently 
ongoing, with 2:1 randomization to receive either 
 of RSV ΔNS2/ Δ1313 /I1314L or 
placebo, and a sample size of up to 30 infants (ClinicalTrials.gov Identifier: NCT01893554) (23). 
To date, data is available on 15 infants aged 4 to 6 months who have been enrolled up to date and 
have completed the post-vaccination Acute and Post-Acute Phase of follow-up. Based on this 
data, the vaccine was well tolerated at the 
 dose, infectivity was 100% and vaccine virus 
replication was limited. Immunogenicity data from this study is pending.  
RSV ∆NS2/∆1313/I1314L vaccine appears to be safe and immunogenic in RSV seronegative 
infants and toddlers aged 6 to 24 months; and appears to be safe with restricted shedding in infants 
aged 4 to 6 months. Based on NIH Phase I trial data, RSV ∆NS2/∆1313/I1314L will be evaluated 
by Sanofi Pasteur for further clinical development. 

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2 
Study Objectives  
2.1 
Primary Objectives  
Primary Safety Objective: 
• To assess the safety profile of each dose of RSV ∆NS2/∆1313/I1314L after each and any 
administration in all infants and toddlers regardless of baseline serostatus. 
Primary Immunogenicity Objective: 
• To characterize the RSV A serum neutralizing antibody responses to the study product in 
each vaccine group after vaccination 1 (D56) for Cohorts 1, 2, 3 and 4, and after 
vaccination 2 (D84) for Cohorts 2 and 4 in RSV-naive participants. 
The endpoints for the primary objectives are presented in Section 9.1. 
2.2 
Secondary Objectives  
Secondary Safety Objectives:  
• To quantify the amount of vaccine virus shed by each participant on D7 for Cohorts 1, 2, 3 
and 4, and D63 for Cohorts 2 and 4, measured by 
 
 by baseline serostatus. 
Secondary Infectivity Objective: 
• To determine the proportion of vaccinated infants and toddlers in each vaccine group 
infecteda with the vaccine virus at D56 (56 days after vaccination 1) for Cohorts 1, 2, 3 
and 4, and at D84 (28 days after vaccination 2) for Cohorts 2 and 4 by baseline serostatus. 
Secondary Immunogenicity Objectives:  
• To characterize the RSV A serum neutralizing antibody responses to the study product in 
each vaccine group after vaccination 1 (D56) for Cohorts 1, 2, 3 and 4, and after 
vaccination 2 (D84) in Cohorts 2 and 4 in RSV-experienced participants. 
• To characterize RSV serum anti-F IgG antibody responses to the study product in each 
vaccine group after vaccination 1 (D56) for Cohorts 1, 2, 3 and 4, and after vaccination 2 
(D84) for Cohorts 2 and 4 by baseline serostatus. 
• To characterize RSV serum antibody responses (RSV A-neutralizing and anti-RSV F IgG) 
to the study product in each vaccine group after the RSV surveillance season or at least 5 
months after the last vaccine administration by baseline serostatus. 
The endpoints for the secondary objectives are presented in Section 9.2. 
 
a  Infection defined as detection of vaccine in nasal swab sample by 
 and / or a 
≥ 4-fold rise in RSV A serum neutralizing antibody titers, or RSV serum anti-F IgG antibody titers. 

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2.3 
Exploratory Objectives  
Exploratory Safety Objective 
• To assess the safety profile of each dose of RSV after each and any administration by baseline 
serostatus. 
Exploratory Immunogenicity Objectives: 
• To characterize the RSV A serum neutralizing antibody responses to the study product 
converted to IU/mL values in each vaccine group after vaccination 1 (D56) for Cohorts 1, 2, 3 
and 4, and after vaccination 2 (D84) for Cohorts 2 and 4 by baseline serostatus. 
• To characterize the RSV A serum neutralizing antibody responses to the study product 
converted to IU/mL values in each vaccine group after the RSV season or at least 5 months 
after the last vaccine administration by baseline serostatus. 
• To characterize the RSV B serum neutralizing antibody responses to the study product in each 
vaccine group after vaccination 1 (D56) for Cohorts 1, 2, 3 and 4, and after vaccination 2 
(D84) for Cohorts 2 and 4 by baseline serostatus. 
• To characterize the RSV B serum neutralizing antibody responses to the study product 
converted to IU/mL values in each vaccine group after vaccination 1 (D56) for Cohorts 1, 2, 3 
and 4, and after vaccination 2 (D84) for Cohorts 2 and 4 by baseline serostatus. 
• To characterize the RSV B serum neutralizing antibody responses to the study product in each 
vaccine group after the RSV season or at least 5 months after the last vaccine administration 
by baseline serostatus. 
• To characterize the RSV B serum neutralizing antibody responses to the study product 
converted to IU/mL values in each vaccine group after the RSV season or at least 5 months 
after the last vaccine administration by baseline serostatus. 
• To characterize RSV A and RSV B serum anti-RSV protein G central conserved (anti-Gcc) 
IgG antibody responses to the study product in each vaccine group after vaccination 1 (D56) 
for Cohorts 1, 2, 3 and 4, and after vaccination 2 (D84) for Cohorts 2 and 4 by baseline 
serostatus. 
• To characterize RSV A and RSV B serum anti-Gcc IgG antibody responses to the study 
product in each vaccine group after the RSV season or at least 5 months after the last vaccine 
administration by baseline serostatus. 
• To characterize the RSV serum anti-F IgA antibody responses after vaccination 1 (D56) for 
Cohorts 1, 2, 3 and 4 and after vaccination 2 (D84) for Cohorts 2 and 4 by baseline serostatus. 
• To characterize the RSV serum anti-F IgA antibody responses after the RSV season or at least 
5 months after the last vaccine administration by baseline serostatus. 
Exploratory Efficacy Objective 
• To describe the frequency and severity of RSV-associated, medically attended acute 
respiratory illness (RSV MAARI) and RSV-associated, medically attended, acute lower 
respiratory illness (RSV MAALRI) in all infants and toddlers in each vaccine group during 
the RSV season or at least 5 months after last vaccine administration. 

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The endpoints for the exploratory objectives are presented in Section 9.3. 
3 
Investigators and Study Organization  
This study will be conducted in approximately 30 centers in the United States and approximately 
10 centers in Canada, Latin America, and South Africa. Details of the study centers and 
Investigators at each center, are provided in the “List of Investigators and Centers Involved in the 
Trial” document. 
An internal safety management team (SMT) will perform an analysis of safety data during the 
conduct of the study. 
If the predetermined alert threshold for a safety event as outlined in Section 5.1.6 and the SMT 
charter is reached, regardless of the study time point, the trial will be paused for enrollment in 
order for an ad hoc SMT to be convened to investigate and complete a study report, and the 
situation will be escalated to the Vaccine Adjudication Committee (VAC). The VAC decides 
whether to escalate the findings further up to the level of a Product Safety Board (PSB). Based on 
the recommendations of the PSB, an ad hoc Independent Data Monitoring Committee (IDMC) 
may be utilized to review upon request of the SMT unblinded study data and recommend to Sanofi 
Pasteur whether to continue, modify, or stop the study. The IDMC will make recommendations to 
the Sponsor on a medical and ethical basis. 
The Sponsor’s Responsible Medical Officer (the RMO, the person authorized to sign this protocol 
and any amendments on behalf of the Sponsor) is 
 
. 
4 
Independent Ethics Committee / Institutional Review Board  
Before the investigational product can be shipped to the investigational site and before the 
inclusion of the first participant, this protocol, the informed consent form (ICF), participant 
recruitment procedures, and any other written information to be provided to participants must be 
approved by, and / or receive favorable opinion from, the appropriate Independent Ethics 
Committee(s) (IEC[s]) or Institutional Review Board(s) (IRB[s]). 
In accordance with Good Clinical Practice (GCP) and local regulations, each Investigator and / or 
the Sponsor are responsible for obtaining this approval and / or favorable opinion before the start 
of the study. If the protocol is subsequently amended, approval must be re-obtained for each 
substantial amendment. Copies of these approvals, along with information on the type, version 
number, and date of document, and the date of approval, must be forwarded by the Investigator to 
the Sponsor together with the composition of the IEC / IRB (the names and qualifications of the 
members attending and voting at the meetings). 
The Investigator or Sponsor will submit written summaries of the status of the study to the IEC / 
IRB annually, or more frequently if requested. All serious adverse events (SAEs) occurring during 
the study that are related to the product administered will be reported by the Investigator to the 
IEC / IRB, according to the IEC / IRB policy. 

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5 
Investigational Plan  
5.1 
Description of the Overall Study Design and Plan  
5.1.1 
Study Design  
This is a Phase I/II, randomized, observer-blind, placebo-controlled, multi-center, dose-finding 
study to evaluate the safety, immunogenicity, infectivity, and vaccine virus shedding after 1 or 
2 administrations of a live-attenuated RSV ∆NS2/∆1313/I1314L vaccine in infants and toddlers 
6 months to 18 months (Cohorts 1 to 4) of age in the United States, Canada, Latin America 
(Argentina, Chile, and Honduras), and South Africa). 
Vaccination: 
A total of 300 infants and toddlers 6 to18 months of age will be enrolled into 1 of 4 cohorts, 
sequentially, and within each cohort will be randomized to receive intranasal administration of 
their assigned study product as follows: 
• Cohort 1 – 40 infants and toddlers to receive 1 administration, 1:1 ratio of 
RSV ∆NS2/∆1313/I1314L 
 (low-dose) or placebo (same formulation buffer as the 
RSV ∆NS2/∆1313/I1314L vaccine) 
• Cohort 2 – 40 infants and toddlers to receive 2 administrations, 1:1 ratio of 
RSV ∆NS2/∆1313/I1314L 
 (low-dose) or placebo 
• Cohort 3 – 40 infants and toddlers to receive 1 administration, 1:1 ratio of 
RSV ∆NS2/∆1313/I1314L 
 (high-dose) or placebo 
• Cohort 4 – 180 infants and toddlers to receive 2 administrations, 1:1:1 of RSV 
∆NS2/∆1313/I1314L 
 (low-dose), RSV ∆NS2/∆1313/I1314L 
 (high-dose) 
or placebo. 
Cohort 1 (Northern Hemisphere): 
1:1 randomized, placebo-controlled, 1 dose of RSV ∆NS2/∆1313/I1314L 
 
), 
1 administration (
 in total per administration) at Day (D) 0, n=20 per vaccine group. 
Participant enrollment will be initiated at approximately 15 sites in the US in August/September 
2020. Vaccine administration will be completed at least 5 days before the beginning of RSV 
season (the average 5-month RSV season in the northern hemisphere is 01 November to 
31 March). If recruitment in Cohort 1 does not reach the goal of n=40, no attempt will be made to 
include more participants receiving 1 administration in Cohort 2. 
Cohort 2 (Southern Hemisphere): 
1:1 randomized, placebo-controlled, 1 dose of RSV ∆NS2/∆1313/I1314L 
 
 
2 administrations (
 in total per administration) at D0 and D56, n=20 per vaccine group. 
Participant enrollment will be initiated at approximately 4 sites in Latin America ((Argentina and 
Chile) at the earliest in November/December 2020. The first and the second vaccine 
administrations (D0 and D56, respectively) will be completed at least 5 days before the beginning 

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of the RSV season (the average 5-month RSV season in the southern hemisphere is 01 May to 
30 September).  
Cohort 3 (Northern Hemisphere): 
1:1 randomized, placebo-controlled, 1 dose of RSV ∆NS2/∆1313/I1314L 
 
 
1 administration (
 per administration in total) at D0, n=20 per vaccine group. Participant 
enrollment will be initiated at approximately 30 sites in the US in April 2021. Vaccine 
administrations will be completed before 31 May 2021. If recruitment in Cohort 3 does not reach 
the goal of n=40, no attempt will be made to include more participants receiving 1 administration 
in Cohort 4. 
Cohort 4 (Northern and Southern Hemisphere): 
1:1:1 randomized, placebo-controlled, 2 doses of RSV ∆NS2/∆1313/I1314L (
 
), 2 administrations (
 per administration in total) at D0 and D56, n=60 per vaccine 
group. Participant enrollment will be initiated at approximately 30 sites in the US at the earliest in 
June 2021, approximately 2 sites in Canada at the earliest in May 2022, approximately 2 sites in 
Chile at the earliest in November 2021, approximately 2 sites in Honduras at the earliest in April 
2022, and approximately 2 sites in South Africa at the earliest in June 2022.  
The first and the second vaccine administrations will be completed at any time of the year, 
including the winter RSV season, regardless if normal RSV seasonality is restored after the 
disruption due to COVID-19 non-pharmaceutical interventions.    
Blood Sampling: 
All participants screened for inclusion in Cohorts 1, 2, 3 and 4 will provide a blood sample at 
enrollment (Visit 01), for baseline RSV serum antibody testing. 
All participants in each vaccine group in Cohorts 1, 2, 3 and 4 will provide a blood sample at the 
D56 Visit (before vaccination 2 for Cohorts 2 and 4), for the measurement of post-vaccination 
serum antibody titers to RSV. 
All participants in each vaccine group in Cohorts 2 and 4 will provide a blood sample at the D84 
visit (28 days post-vaccination 2) for the measurement of post-vaccination 2 serum antibodies to 
RSV. 
All participants in Cohorts 1, 2, 3 and 4 will provide a blood sample during the month following 
the RSV season or at least 5 months after the last vaccine administration for the measurement of 
post-season RSV antibody titers, to determine if a 4-fold or greater rise in RSV antibody titers has 
occurred during the RSV season, indicating infection with wt RSV that was not detected by 
surveillance. 
Nasal swab samples: 
Nasal swab samples will be collected in all participants at D7 for Cohorts 1, 2, 3 and 4; and on 
D63 for Cohorts 2 and 4 for the following: 
• Quantification of vaccine virus shedding on D7 for Cohorts 1, 2, 3 and 4, and D63 for 
Cohorts 2 and 4. 
• The same nasal swab specimens will be tested for respiratory pathogens if the child is ill at 
the same time points (D7 for Cohorts 1, 2, 3 and 4, and D63 for Cohorts 2 and 4). 

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• A nasal swab specimen for the detection of RSV and respiratory pathogens will be 
collected from participants during illness visits and 48 hours later at any other protocol-
specified time point in the study (see Table 5-4) including the medically attended 
surveillance during the RSV season. 
Collection of Safety Data: 
The Acute Phase for the first vaccine administration begins on D0 post-vaccination and ends at 
midnight on D28. The Acute Phase for the second vaccine administration begins on D56 post-
vaccination and ends at midnight on D84. Any adverse reactions, AEs, AESIs, MAAEs, or SAEs 
that begin within the Acute Phase (i.e., within 28 days after a vaccination) but are diagnosed by a 
medical professional after 28 days will still be considered as occurring within the Acute Phase. 
The Post-Acute Phase for participants receiving 1 administration begins at 12:01 am on D29 and 
ends at midnight on D56. The first Post-Acute Phase for participants receiving 2 administrations 
begins at 12:01am on D29 and ends at midnight on D56, except if second administration is exactly 
on D56 when it ends immediately before receipt of the second administration. The second Post-
Acute Phase for participants receiving 2 administrations begins at 12:01 am on D85 and ends at 
midnight on D112. 
• All participants will be observed for 30 minutes after each vaccine administration and any 
unsolicited systemic adverse events (AEs) occurring at that time will be recorded as 
immediate unsolicited systemic AEs in the case report book (CRB). 
• All participants will be followed for solicited administration site reactions and systemic 
reactions, unsolicited adverse events, adverse events of special interest (AESIs), medically 
attended adverse events (MAAEs) within 28 days after each and any vaccination, and from 
vaccination to the end of study participation for serious adverse events (SAEs). 
• The participant’s parent / guardian / legally authorized representative will record 
information in a Diary Card (DC) / Electronic Diary Card (eDC) to capture solicited 
reactions, unsolicited AEs, AESIs and MAAEs from D0 to D28 for Cohorts 1, 2, 3 and 4, 
and D56 to D84 for Cohorts 2 and 4. Parents / guardians / legally authorized 
representatives should alert the study site regarding reactions, AEs and any symptoms 
suggestive of respiratory tract illness. The study sites will follow up via phone calls. The 
eDC allows daily safety monitoring of the study participant also. In certain cases, when an 
eDC cannot be used, a paper diary card will be used for daily safety monitoring. All 
solicited reactions will be graded by the Sanofi Pasteur Intensity scale, except for runny 
nose/rhinorrhea and stuffy of blocked nose/nasal congestion which will be graded by the 
Division of AIDS (DAIDS) scale. Adverse events of special interest will be graded by the 
DAIDS scale, except for wheeze which will be graded according to Brighton 
Collaboration specifications. 
• Based on previous NIH clinical experience with live-attenuated RSV vaccine candidates 
and Sanofi Pasteur Safety Guideline Standard Practice for the Collection, Analysis, and 
Reporting of Safety Data, the following predefined solicited reactions will be assessed 
during the Acute Phase for each vaccine administration: 
- 
Administration site reactions 
• Runny nose 

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• Stuffy or blocked nose /nasal congestion 
- 
Systemic reactions 
• Fever 
• Vomiting 
• Crying abnormally 
• Drowsiness 
• Appetite loss 
• Irritability 
The following AESIs will be assessed during the Acute Phase of the study: 
- 
Acute otitis media 
- 
Upper respiratory tract illness (URI) 
• Pharyngitis 
• Cough without LRI 
- 
Lower respiratory tract illness (LRI) 
• Stridor 
• Rales 
• Tachypnea 
• Acute wheeze 
• Pneumonia 
• Laryngotracheobronchitis 
• Immediate hypersensitivity reactions including urticaria, anaphylaxis, or other IgE-
mediated responses are possible as with any vaccine. 
• MAAEs will be collected during the Acute Phase for either vaccination using the same 
process as other AEs. 
• SAEs will be recorded throughout the participant’s participation in the study. The 
participant’s parent / guardian / legally authorized representative will be asked to notify the 
site immediately about any potential SAE at any time during the study. In addition, the 
participant’s parent / guardian / legally authorized representative will record information in 
a DC / eDC about SAEs from the D0 to D56 visits (Cohorts 1 and 3), and from D0 to D84 
visits (Cohorts 2 and 4). Participant’s parent / guardian / legally authorized representative 
receives a memory aid (MA) to record the SAEs from the D56 visit until the end of the 
study (Cohorts 1 and 3) and from the D84 visit until the end of the study (Cohorts 2 and 
4). 
• The completed DC / eDC or MA will be reviewed with the participant’s parent / guardian/ 
legally authorized representative at each visit. 

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5.1.2 
Justification of the Study Design  
For this Sanofi Phase I/II trial, data will be analyzed according to serostatus. Baseline serostatus 
will be retrospectively determined from serum samples collected at baseline. Participants will be 
categorized into RSV-experienced or RSV-naïve based on the presence or absence of detectable 
serum RSV anti-F IgA antibodies. This biomarker has been chosen since it is produced only in 
response to RSV infection and not transferred trans-placentally from mother to child. 
Evaluation of post-vaccination immunogenicity on Day 56 for Cohorts 1, 2, 3 and 4 and Day 84 
for Cohorts 2 and 4: 
To date, all studies with live-attenuated RSV candidate vaccines have used Day 56 as the time 
point to assess serum antibody response post-vaccination with a single dose administration. This 
time point is used for two reasons: 1) since this is a primary response (rather than an anamnestic 
[memory] response), serum antibody response may not have reached maximal levels by Day 28 
and 2) maximal replication of these highly attenuated vaccine viruses does not typically occur 
until Day 7, which may also delay induction of the immune response. In participants receiving 2 
administrations of vaccine, this is no longer likely to be a primary response and rather an 
anamnestic (memory) response and serum antibody response is likely to be maximal by Day 28 
after the second vaccination. 
RSV season or post-vaccination RSV surveillance for Cohort 4: 
Based on previous data regarding the seasonality of RSV in the US, Canada, Chile, Honduras, and 
South Africa, surveillance for RSV-associated disease will be largely conducted during the NH 
(1st November to 31st March) and SH (1st May to 30 September) RSV seasons respectively, 
adjusted for local site RSV seasonality. Due to the disruption of the seasonal pattern of RSV 
globally (24) (25), it is unclear when the normal seasonal transmission will resume though there is 
some suggestion of a rebound in the winter of 2021–2022 in the NH (26). Because of the 
unpredictability of the RSV season due to the impact of COVID-19 nonpharmaceutical 
interventions, study participant enrollment and vaccination will continue regardless of RSV 
activity. Study participants enrolled before the routine winter RSV season for that locality will be 
followed up until the consequent month after the end of the routine season (i.e. April for NH and 
October for SH). Study participants enrolled during the routine RSV season (i.e. November to 
March for NH and May to September for SH) will be followed up for at least 5 months after the 
last vaccine administration. During the RSV season or post-vaccination RSV surveillance, study 
participants will be monitored for symptomatic medically attended respiratory illness. Note, this 
surveillance may overlap with the Acute and Post-Acute phases. In this case, evaluations required 
for each of the relevant phases of the study will be conducted. 
Evaluation of two vaccine doses
: 
Previous Phase Ia studies done by the NIH have demonstrated that the 
 dose of RSV 
∆NS2/∆1313/I1314L vaccine resulted in better infectivity and neutralizing antibody seroresponse 
than the 
 dose, with no evidence of an excess of respiratory tract illness associated with 
receipt of the higher dose (
). However, in these studies, the vaccine was administered 
intranasally using a sterile, needle-less 1 mL oral syringe, at a volume of 0.5 mL as nasal drops 
(approximately 0.25 mL per nostril). In VAD00001 study, the vaccine would be administered at a 
total volume of 
 
 
 

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with adverse events that become apparent only when analyzed in a larger number of participants 
than the numbers enrolled in Laboratory of Infectious Disease (LID)/ National Institute of Allergy 
and Infectious Diseases (NIAID)/NIH Phase Ia studies, where each study assessed 10 to 
40 vaccinees. Additionally, the rate, magnitude and durability of antibody responses may differ 
according to dose, as well as the magnitude of the memory (anamnestic) seroresponse observed 
following naturally occurring RSV infection. The intranasal 
 device used in this study 
may also impact the safety and immunogenicity of the vaccine. Dose selection will be based on a 
descriptive comparison of the safety, infectivity and immunogenicity of 1 or 2 administrations of 
either dose category.  
5.1.3 
Study Plan  
See Table of Study Procedures and Section 5.1.4 Visit Procedures for the plan of activities for the 
study period. Figure 5.1 shows an overview of the study design. Figure 5.2 and Figure 5.3 provide 
overviews of the study plan and the timeframes for Cohorts 1 and 3, and Cohorts 2 and 4, 
respectively.

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Figure 5.2: Study Plan and Timeframe for Cohorts 1 and 3  

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Table 5-1: Schedule of blood sample collection (volume in mL) – Cohorts 1 and 3  
Visit Number 
Visit 01 
Visit 02 
Visit 03 
Visit 04 
Study Timelines 
D0 
D7 
D56+7 
Post-RSV 
season* 
Time Windows (Days) 
 
 
 
 
Vaccination 
X 
 
 
 
Blood Samples (mL) 
5† 
- 
5 
5* 
Total volume of blood collected 
(mL) 
5 
- 
5 
5 
† All participants screened will provide a blood sample up to 5 mL at enrollment (Visit 01) prior to receipt of the 
first administration of assigned study product, for baseline RSV serum antibody testing. 
*All participants will provide a blood sample up to 5 mL during the month following the RSV season or at least 
five months after the last vaccine administration for the measurement of post-season RSV antibody titers, 
respectively, to determine if a 4-fold or greater rise in RSV antibody titers has occurred during the RSV season. 
Table 5-2: Schedule of blood sample collection (volume in mL) – Cohorts 2 and 4  
Visit Number 
Visit 01 
Visit 02 
Visit 03 
Visit 04 
Visit 05 
Visit 06 
Study Timelines 
D0 
D7 
D56+7 
D63+7 
D84+8 
Post-RSV 
season‡ 
Time Windows 
(Days) 
 
 
 
 
 
 
Vaccination 
X 
 
X 
 
 
 
Blood samples (mL) 
5† 
- 
5* 
- 
5* 
5‡ 
Total volume of blood 
collected (mL) 
5 
- 
5 
- 
5 
5 
† All participants screened will provide a blood sample up to 5 mL at enrollment (Visit 01) prior to receipt of the first 
administration of assigned study product, for baseline RSV serum antibody testing. 
*All the participants will provide a blood sample up to 5 mL at the D56 Visit (before vaccination 2), and then at D84 
Visit for the measurement of post-vaccination serum antibodies to RSV. 
‡All participants will provide a blood sample up to 5 mL during the month following the RSV season or at least five 
months after the last vaccine administration for the measurement of post-season RSV antibody titers, to determine if a 
4-fold or greater rise in RSV antibody titers has occurred during the RSV season. 
5.1.4 
Visit Procedures  
See Table of Study Procedures for Cohorts 1, 2, 3 and 4. 

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5.1.4.1 
In-Person Visits  
Visit 01 (Day 0) for Cohorts 1, 2, 3 and 4  
Timelines for the end of enrollment (Visit 01), vaccination and RSV surveillance per hemisphere 
are shown in Table 5-3. 

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Table 5-3: Timelines for end of enrollment and vaccination per hemisphere  
 
Infants and Toddlers 6 to 18 Months of Age 
Northern Hemisphere 
(USA) 
Cohort 1 (1 administration) 
Southern Hemisphere (Latin 
America) 
Cohort 2 (2 administrations) 
Northern Hemisphere 
(USA) 
Cohort 3 (1 administration) 
Northern and Southern Hemispheres 
(USA and Latin America) 
Cohort 4 (2 administrations) 
Earliest day for 
enrollment (Visit 01)  
01 August 2020 
01 November 2020 
01 April 2021 
USA - 01 June 2021 
Canada – May 2022 
Chile - November 2021 
Honduras - April 2022 
South Africa - June 2022 
Last day for 
enrollment (Visit 01) 
5 days before the start of the 
RSV season 
61 days before the start of the 
RSV season 
31 May 2021 
Not applicable 
 
Last day for Visit 03 
(D56) Vaccination 2 
- 
5 days before the start of the RSV 
season 
- 
Not applicable 
  

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Visit 01 (Day 0): Enrollment, Randomization, and Vaccination Procedures for Cohorts 1, 2, 3 
and 4 (All Participants) 
1) Give the participant’s parent / guardian / legally authorized representative information about 
the study, obtain written informed consent, and give him / her a signed copy. 
2) Collect demographic data (including date of birth, sex, race, and ethnicity). 
3) Check inclusion and exclusion criteria for eligibility. 
4) Obtain verbal medical history about the participant, including past and ongoing medication, 
any signs and symptoms, and developmental delays. 
5) Review any past medical records including the immunization record to ensure participant will 
not meet exclusion criteria 2, 3 and 21. 
6) Prior to randomization conduct a full physical examination including body temperature, heart 
rate, respiratory rate, weight, length and assessment of HEENT [head, ears, eyes, nose, and 
throat], lungs, heart, and abdomen, musculoskeletal, age-appropriate neurological and skin 
exam. 
7) Perform Coronavirus Disease 2019 (COVID-19) point of care diagnostic test (POC). 
8) Contact the IRT for participant number, randomization and dose number based on age sub-
group. Additional information regarding randomization is in the Operating Guidelines. 
9) Obtain the first blood sample, to test the baseline RSV antibody serostatus, i.e., serum RSV-
nAb titer (Section 7.1 for detailed instructions regarding the handling of blood samples and 
Operating Guidelines for further details). 
10) Administer the appropriate study product, follow the instructions provided for the intranasal 
administration of study vaccine using the 
 in the Study Operating 
Guideline. 
11) Keep the participant under observation for 30 minutes and record any adverse reaction in the 
source document. 
12) Give or download the parent / guardian / legally authorized representative a diary card (DC1) 
/ eDC and a thermometer and go over the instructions for their use, as detailed in the Study 
Operating Guideline, and remind to complete the Day 0–7 pages of DC1 / eDC. The parent / 
guardian / legally acceptable representative will record the child’s temperature and signs of 
illness (solicited reactions and unsolicited AEs, including AESIs, MAAEs and SAEs) on the 
DC1 / eDC. 
13) Remind the parent / guardian / legally authorized representative to expect a telephone call 
from the study site nurse daily after this immunization Visit 01 to review what they have 
entered daily in the DC1 / eDC; and to complete the remaining entries of DC1 / eDC and 
bring to Visit 02 at the specified date. 
14) Remind the parent / guardian / legally authorized representative to notify the site in case of an 
SAE or any illness. The site staff, upon evaluation, will schedule an Illness Visit within the 
stipulated time frame of site notification, if required. 
15) Complete the relevant case report forms (CRFs) for this visit. 
 

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Visit 02: Day 07 Post-Vaccination 1 Visit Procedures for Cohorts 1, 2, 3 and 4 (All 
Participants) 
1) Review medical history, including past and ongoing medication since the last visit. 
2) Perform a focused clinical examination including temperature, pulse, and respirations, ears, 
eyes, nose, throat (EENT), respiratory, cardiac and lymphatic system. 
3) Obtain a nasal swab sample for viral quantification of vaccine virus shedding. If the 
participant meets criteria for an Illness Visit at Day 7, the same nasal swab specimens may 
also be tested for respiratory pathogens. 
4) Review the solicited reactions and unsolicited AEs, AESIs, MAAEs and SAEs in the 
completed DC1 / eDC with the participant’s parent / guardian / legally authorized 
representative. Provide instruction to complete DC2. 
5) If an SAE occurred, follow the instructions in Section 10 for reporting it. Remind to notify 
the site in case of an SAE. 
6) Complete the relevant CRFs for this visit. 
7) Remind the parent / guardian / legally acceptable representative of the following visit. 
 
 
Visit 03: Day 56+7 Post-Vaccination 1 Visit Procedures for Cohort 1 and 3 
1) Review medical history, including past and ongoing medication since the last visit. Check for 
contraindications. 
2) Perform a focused clinical examination including temperature, pulse, and respirations, EENT, 
respiratory, cardiac and lymphatic system. 
3) Obtain a blood sample for serum antibodies to RSV (see Section 7.1 for detailed instructions 
regarding the handling of blood samples). 
4) Collect and review SAEs in the completed DC1 and DC2 / eDC with the participant’s parent 
/ guardian / legally authorized representative. Provide MA. 
5) If an SAE had occurred, follow the instructions in Section 10 for reporting it. Remind to 
notify the site in case of an SAE. 
6) Complete the relevant CRFs for this visit. 
7) Remind the parent / guardian / legally authorized representative of the following visit. 
 
Visit 03: Day 56+7 Post-Vaccination 1 Visit Procedures for Cohorts 2 and 4 
1) Obtain verbal medical history about the participant, including past and ongoing medication 
and immunizations. 
2) Check for contraindications for receipt of second vaccination. 
3) Prior to vaccination, conduct a focused clinical examination including temperature, pulse, 
and respirations, EENT, respiratory, cardiac and lymphatic system. 
4) Perform COVID-19 POC diagnostic test. 
5) Collect reportable concomitant medications / vaccinations. 

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6) Contact the IRT for dose number. 
7) Obtain a blood sample for serum antibodies to RSV (see Section 7.1 for detailed instructions 
regarding the handling of blood samples). 
8) Administer the appropriate study product, follow the instructions provided for the intranasal 
administration of study vaccine using the 
 in the Study Operating 
Guideline. 
9) Keep the participant under observation for 30 minutes and record any adverse reaction in the 
source document. 
10) Collect and review solicited reactions and unsolicited AEs, including AESIs, MAAEs and 
SAEs in the completed DC1 and DC2 / eDC with the participant’s parent / guardian / legally 
authorized representative. 
11) Give or download the parent / guardian / legally authorized representative a diary card (DC3) 
/eDC and a thermometer and go over the instructions for their use, as detailed in the Study 
Operating Guideline, and remind to complete the Day 0–7 pages of DC3 / eDC. The parent / 
guardian / legally authorized representative will record the child’s temperature and signs of 
illness (solicited reactions and unsolicited AEs, including AESIs, MAAEs and SAEs) on the 
DC3 / eDC. 
12) Remind the parent / guardian / legally authorized representative to expect a telephone call 
from the study site nurse daily after this Visit 04 to review what they have entered daily in 
the DC3 / eDC, and to complete the entries of DC3 and bring to Visit 05 at the specified date 
and time. 
13) Remind the parent / guardian / legally authorized representative to notify the site in case of an 
SAE or any illness. The site staff, upon evaluation, will schedule an Illness Visit within the 
stipulated time frame of site notification, if required. 
14) Complete the relevant CRFs for this visit. 
 
Post-RSV Season or > 5 Months After Last Vaccine Administration Visit for All Cohorts (Visit 
04 for Cohorts 1 and 3 or Visit 06 for Cohorts 2 and 4) 
1) Obtain a blood sample for serum antibodies to RSV. 
2) Review the MA for SAEs with the participant’s parent / guardian / legally authorized 
representative. 
3) If an SAE had occurred, follow the instructions in Section 10 for reporting it. Remind to 
notify the site in case of an SAE. 
4) Complete the relevant CRFs for this visit and the End of Study CRF. 
 
Visit 04: D63+7 Post-Vaccination 1 (Day 07 Post-Vaccination 2) Visit Procedures for Cohorts 2 
and 4 
1) Review medical history, including past and ongoing medication since the last visit. 
2) Perform a focused clinical examination including temperature, pulse, and respirations, EENT, 
respiratory, cardiac and lymphatic system. 

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3) Obtain a nasal swab sample for quantification of vaccine virus shedding. If the participant 
meets criteria for an Illness Visit, the same nasal swab specimens may also be tested for 
respiratory pathogens. 
4) Review the solicited reactions and unsolicited AEs, AESIs, MAAEs and SAEs in the 
completed DC3 / eDC with the participant’s parent / guardian / legally authorized 
representative. 
5) If an SAE occurred, follow the instructions in Section 10 for reporting it. Remind to notify 
the site in case of an SAE. 
6) Complete the relevant CRFs for this visit. 
 
Visit 05: D84+8 Post-Vaccination 1 (Day 28+8 Post-Vaccination 2) Visit Procedures for 
Cohorts 2 and 4 
1) Review medical history, including past and ongoing medication and immunizations since the 
last visit. 
2) Perform a focused clinical examination including temperature, pulse, and respirations, EENT, 
respiratory, cardiac and lymphatic system. 
3) Obtain a blood sample for serum antibodies to RSV. 
4) Collect and review the solicited reactions and unsolicited AEs, AESIs, MAAEs and SAEs in 
the completed DC3 / eDC with the participant’s parent / guardian / legally authorized 
representative. Provide MA. 
5) If an SAE had occurred, follow the instructions in Section 10 for reporting it. Remind to 
notify the site in case of an SAE. 
6) Complete the relevant CRFs for this visit. 
 
Visit 99: Illness Visits 
Illness visits can be conducted remotely, as a home visit or an onsite visit depending on the 
judgment of the investigator. The requirement for an Illness Visit and which type of illness visit 
will be evaluated first by video call. The video call will be used to initially remotely evaluate the 
study participant’s clinical status and whether the illness can be managed remotely especially for 
mild (Grade 1) illness. This staged management of illness visits is required during the current 
COVID-19 pandemic situation to limit the number of contacts between the study participant and 
study site staff to only those that are absolutely required. Guidelines for remote evaluation are 
described in the Operating Guidelines.  
The timeframe after site notification in which the Illness Visit must occur, if deemed necessary by 
the Investigator, depends on grading of the fever and respiratory symptoms and the phase of the 
study. If the Illness Visit occurs on a day concurrent with a routine Study Visit when a nasal swab 
specimen is to be collected, the same nasal swab specimen would be used to test for respiratory 
pathogens. A second nasal swab should be collected 48 hours later. If the Illness Visits occurs on 
a day concurrent with a routine Study Visit when a nasal swab specimen is not collected, a nasal 

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swab specimen is required to test for respiratory pathogens. A second nasal swab should be 
collected 48 hours.  
If illnesses/safety events occur, the study participant should be managed according to the site/local 
standard of care, including the conduct of lab investigations required for diagnosis and/or 
management of the study participant. Following an Illness Visit, medical personnel should 
continue to follow participants until resolution.  
Illness visits may occur at any time during the study. The Illness visit timeframes are summarized 
in Table 5-4. 
Table 5-4: Illness visit timeframe  
Phase 
Symptom 
Grade 
Visit timeframe 
Acute (post-vaccination to 
midnight 28 days after each 
vaccination)* 
Fever, acute otitis media or URI 
1 
Within 3 days 
> 1 
Within 2 days 
LRI 
Any 
Within 2 days 
SAEs 
Any 
Within 2 days 
Post-acute (12:01am on 29th 
day after post-vaccination to 
midnight 56 days after each 
vaccination)* 
SAEs  
Any 
Within 2 days 
RSV surveillance season (on 
average, 01 November to 
31 March for NH and 01 May 
to 30 September for SH)* 
Medically attended fever, acute 
otitis media, URI or LRI 
>2 
Within 3 days 
SAEs 
Any 
Within 2 days 
Post-RSV season (on average, 
01 to 31 April for NH and 01 
to 31 October for SH) or at 
least 5 months after last 
vaccine administration 
SAEs 
Any 
Within 2 days 
LRI, lower respiratory tract illness; NH, Northern hemisphere; RSV, Respiratory Syncytial Virus; SAE, serious 
adverse event; SH, Southern hemisphere; URI, upper respiratory tract illness 
*In some circumstances, acute phase or post-acute phase may overlap with the RSV surveillance season, in which 
case the more conservative visit timeframe should be considered. 
 
Illness Visit procedures are as follows: 
1) Obtain verbal medical history about the participant, including past and ongoing medication 
and immunizations. 
2) Determine whether the participant can be managed remotely or if an at home visit or an 
onsite illness visit is required. 
3) If an at home or onsite visit, perform a focused clinical examination including temperature, 
pulse, and respirations, EENT, respiratory, cardiac and lymphatic system. Instructions for 

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conducting a focused clinical examination remotely are described in the Operating 
Guidelines. 
4) Collect and review the solicited and unsolicited AEs, AESIs, MAAEs and SAEs in the 
completed DC / eDC or memory aid with the participant’s parent / guardian / legally 
authorized representative. 
5) If an SAE had occurred, follow the instructions in Section 10 for reporting it. Remember to 
notify the site in case of an SAE, if illness starts within the 28 days of vaccination. 
6) Obtain a nasal swab sample for RSV viral detection and 
 
 for respiratory pathogens. 
7) COVID-19 testing if required according to the opinion of the investigator and CDC COVID 
testing algorithm.a  
8) Complete the relevant CRFs for this visit. 
9) Schedule follow-up as appropriate, including a visit for the collection of a confirmation nasal 
swab 48 hour later. 
10) If illnesses/safety events occur, the participant should be managed according to the site/local 
standard of care, including the conduct of lab investigations required for diagnosis and/or 
management of the study participant. 
Specific guidance for illness visits, including use of personal protective equipment (PPE) for full 
contact and droplet precaution, are described in the Operating Guidelines. 
Follow-up of participants with solicited reactions or with AEs That Led to Study/Vaccination 
Discontinuation: 
Unless a participant or participant’s parent / guardian / legally authorized representative refuses 
further contact, each participant who experiences an AE (whether serious or non-serious) during 
the study must be followed until the condition resolves, becomes stable, or becomes chronic (even 
after the end of the participant’s participation in the study) if either of the following is true: 
1. The AE is considered by the Investigator to be related to the product administered. 
2. The AE caused the discontinuation of the participant from the study or from vaccination. 
5.1.4.2 
Non-Visit Telephone Contacts  
Acute Phase Telephone Contacts to Review the DCs up to D29+1 (Cohorts 1, 2, 3 and 4) and 
D84+8 (Cohorts 2 and 4) 
Note: If any of the Acute Phase non-visit contacts fall on a weekend or a holiday, the telephone 
call may be made on the following business day. All telephone contacts with the participant’s 
parent / guardian / legally authorized representative must be made by a qualified person, such as a 
physician or qualified study nurse. 
 
a For CDC COVID testing algorithm, see: https://www.cdc.gov/coronavirus/2019-
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1) Review the information entered in the DC for solicited reactions and unsolicited AEs, AESIs, 
MAAEs and SAEs. The site staff upon evaluation, if required, will schedule an Illness Visit 
within the appropriate time window of site notification (Table 5-4). 
2) Record relevant information concerning the participant’s health status including any changes 
in medications and immunizations on the telephone contact form, and in the CRF, if required. 
The site staff, upon evaluation, will schedule an Illness Visit within the stipulated time frame 
of site notification, if required. 
3) If an SAE had occurred, follow the instructions in Section 10 for reporting it. Also remind to 
notify the site in case of an SAE. 
4) Remind the parent / guardian / legally authorized representative to do the following: 
• Complete the remaining pages of the diary card / electronic diary card and bring them to 
next visit. 
• Notify the site in case of an SAE. 
Day 42+1 Telephone Contact (Cohorts 1, 2, 3 and 4) 
1) Record relevant information concerning the participant’s health status including any changes 
in medications and immunizations on the telephone contact form, and in the CRF, if required. 
The site staff, upon evaluation, will schedule an Illness Visit within the stipulated time frame 
of site notification, if required. 
2) If an SAE had occurred, follow the instructions in Section 10 for reporting it. Also remind to 
notify the site in case of an SAE. 
3) Remind the parent / guardian / legally authorized representative to do the following: 
• Complete the remaining pages of the diary card / electronic diary card and bring them to 
next visit. 
• Notify the site in case of an SAE. 
 
Telephone Contacts During the RSV Season or Post-vaccination RSV Surveillance 
During the RSV season (01 November to 31 March in the northern hemisphere and 01 May to 
30 September in the southern hemisphere) or post-vaccination RSV surveillance (at least 5 months 
after last vaccine administration), make phone contacts every 2 weeks with the parent / guardian / 
legally authorized representative. 
1) Record relevant information concerning the participant’s health status including any changes 
in medications and immunizations on the telephone contact form. 
2) Schedule an Illness Visit within the guidelines and stipulated time frame from the phone 
contact for a medically attended illness of the following types: fever, URI, LRI or otitis 
media. If this illness overlaps with the Acute or Post-Acute Phases, the time frames specified 
for the relevant Acute or Post-Acute phase should be used (see Table 5-4). 

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3) If a participant had visited any other non-study doctor / hospital for a serious adverse event 
(SAE) (at any time in the study), schedule a site visit once the participant is discharged to 
obtain a nasal swab sample for RSV viral detection and 
 for 
respiratory pathogens. 
4) If an SAE had occurred, follow the instructions in Section 10 for reporting it. Remind to 
notify the site in case of an SAE. 
5.1.5 
Planned Study Calendar  
The following dates are approximate. The actual dates may differ as, for example, the study will 
not start until all the appropriate regulatory and ethical approvals have been obtained. 
Estimated planned study period: 
Cohort 1 – 03 September 2020 (FVFP) to 30 April 2021 (LCLS) 
Cohort 2 – 11 December 2020 (FVFP) to 31 October 2021 (LCLS) 
Cohort 3 – 01 April 2021 (FVFP) to 30 April 2022 (LCLS) 
Cohort 4 – 01 June 2021 (FVFP) to 30 April 2023 (LCLS) 
 
Estimated enrollment / 1st vaccination period: 
Cohort 1 –03 September 2020 to 27 October 2020 
Cohort 2 –11 December 2020 to 01 March 2021 
Cohort 3 – 01 April 2021 to 31 May 2021 
Cohort 4 – From 01 June 2021 
 
Estimated 2nd vaccination period: 
Cohort 2 –05 February 2021 to 26 April 2021 
Cohort 4 – From 27 July 2021 
Planned date of final clinical study report: 
First Interim CSR (6- to 18-month-old participants, Cohorts 1, 2, 3 and at least 90 participants 
from Cohort 4) – Planned January 2023. 
Based on timelines for Cohort 4, assuming 4 months from Day 84 timepoint for the 90th 
participant (July 2022) to the generation of final key tables for interim data. 
Early analysis CSR (all participants) – June 2023 
Final CSR – December 2023. 
Assuming 4 months from LCLS (April 2023) and 3 months for final statistical analysis and 
completion of CSR. 
5.1.6 
Early Safety Data Review  
The safety of the investigational product will be continuously monitored by the Sponsor. To allow 
for a cautious, stepwise approach to vaccine administration, early safety data review (ESDR) will 
be performed during scheduled SMT meetings: 
• Cohort 1 
- 
D7 post-vaccination ESDR/SMT 
- 
D28 post-vaccination ESDR/SMT 
- 
D56 post-vaccination ESDR/SMT 

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• Cohort 2 
- 
D7 post-vaccination ESDR/SMT 
- 
D28 post-vaccination ESDR/SMT 
- 
D84 post-vaccination ESDR/SMT 
• Cohort 3 
- 
D7 post-vaccination ESDR/SMT 
- 
D28 post-vaccination ESDR/SMT 
- 
D56 post-vaccination ESDR/SMT 
• Cohort 4 
- 
D7 post-vaccination ESDR/SMT 
- 
D28 post-vaccination ESDR/SMT 
- 
D84 post-vaccination ESDR/SMT 
 
The safety data collected will be entered into the CRBs and summarized by the Sponsor in a 
blinded manner for each ESDR. The ESDR will be performed by the Sponsor during the SMT 
meetings. Enrollment will not be paused during SMT reviews.  
It is understood that all reviews are based on preliminary data that have not been subjected to 
validation and database lock. The usual and ongoing process of monitoring safety signals outside 
of those specified in the protocol-defined early interim safety analysis will continue unchanged. 
If at any other time point in the study the predetermined alert threshold for a safety event is 
reached, regardless of the study time point, the trial will be paused for enrollment in order for an 
ad-hoc SMT to be convened. 
During the safety evaluation, a Bayesian approach based on Posterior Distribution may be used to 
assess the difference between each RSV formulation and placebo on the following safety 
endpoints: 
• Any Grade 3 lower respiratory tract illness e.g., wheezing, pneumonia, sustained 
tachypnea, laryngotracheobronchitis (see Section 9.1.1.3.5) 
• Grade 3 fever 
The probability that the difference of percentages of events between one RSV formulation and 
Placebo is greater than a pre-specified margin (δ) can be calculated based on posterior 
distribution, using non-informative prior Beta (1,1) (33) and observed binomial data: 
Proba (%RSV - %Placebo > δ) 
If this probability is high (e.g., >=80%) then it may be recommended to drop the formulation. 
Thus, it can help decision making for safety evaluation by SMT and/or IDMC (if applicable) and 
can also be applied at the end of the study. 

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In cases where the review of data by the SMT does not result in the identification of a potential 
safety signal, SMT oversight proceeds as assigned in the SMT charter. When a safety signal is 
identified, the SMT investigates the event(s), completes the Safety Analysis and/or Evaluation 
Report and decides about the safety signal and further actions and/or recommendations including: 
• Extending or pausing the trial and escalate to the Vaccine Adjudication Committee (VAC) 
• Investigate and develops a report 
• Recommends continuing the trial 
Within the investigation, the team may consult with non-clinical safety experts and research team 
members on whether there is a possible underlying mechanism for the event and review of 
toxicology data or other internal experts depending on the need.  
In case of disagreement in the team, the core team seeks respective functional management advice 
from the VAC shortly after the SMT meeting. The Vaccine Pharmacovigilance Global Business 
Unit (PV GBU) Head or Vaccines GBU Clinical & Sciences Head may be also consulted, 
especially in instance where escalation of the signal for PSB review is in question. 
Once the SMT core team agrees that there is a safety signal that can potentially impact the 
participant’s safety, study conduct (pause, extended pause, or termination) or design 
(modifications needed), the SMT PM informs the Vaccine PV GBU Head who validates the signal 
and urgently contacts the Vaccines GBU Clinical & Sciences Head and the Chair of the PSB. The 
decision is made on whether to convene a PSB or not.   
Based on the outcomes and recommendations from the PSB, the SMT may carry out any of the 
following operational actions related to the conduct and oversight of the study including: 
• Continue the trial 
• Extend the pause to conduct a further evaluation e.g., an ad hoc IDMC 
• Modify the trial design, or 
• Stop the trial. 
An ad-hoc IDMC, which ideally will include at least 2 pediatric respiratory virus vaccine experts, 
will review upon request of the SMT unblinded study data. The ad-hoc IDMC will upon request 
review the relevant safety information and available data, including magnitude of vaccine virus 
shedding. If an ad hoc IDMC meeting is required, the ad hoc IDMC will review the data on safety 
available at that time point to determine if attributable to an etiology, a cause, or a diagnosis 
unrelated to the study vaccine, and if the adverse event(s) is associated with shedding of vaccine 
virus at the time of the event (even if another is identified). If the ad-hoc IDMC decides there is 
no proven causal relationship between the adverse events and study vaccine, the study can 
continue unchanged. Based on evaluation of the IDMC, the Sanofi Pasteur SMT will decide if 
there is a causal relationship between the adverse event and the study vaccine, then SMT will 
decide whether to: 
• Conduct internal signal detection processes (SOP # RDWIN-000390) 
• Escalate validated signals to PSB as needed 
• Continue the trial 
• Modify the trial design (with PSB and ad-hoc IDMC input) or, 
• Stop the trial (with PSB and ad-hoc IDMC input). 

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The following safety parameters will be assessed as part of the early safety review: 
• Immediate reactions 
• Solicited respiratory and systemic reactions 
• Unsolicited reactions i.e., AEs reported as related by the Investigator 
• SAEs, MAAEs and AESIs 
Enrollment will not be paused during the review. The data will be examined for the following: 
1) Any deaths, regardless of causality. 
2) Any vaccine related SAEs. 
3) Grade 3 fever reported in > 2 participants. 
4) Any Grade 3 or above solicited adverse events other than fever. 
5) >1 participant experiencing lower respiratory tract illness of >Grade 2 DAIDS scale (except 
for wheeze by Brighton Collaboration Severity Scale) during the acute phase (i.e., within 28 
days post-vaccination). 
6) Any participant experiencing an AESI of Grade 3 or above by DAIDS scale (except for 
wheeze by Brighton Collaboration Severity Scale), including lower respiratory tract illness 
during the acute phase (i.e., within 28 days post-vaccination). 
7) >1 participant with a Grade 3 unsolicited AE during the acute phase (i.e., within 28 days 
post-vaccination). 
8) Any other pattern of research laboratory values or clinical symptoms other than fever that is 
considered a significant safety issue by the Investigator. 
If any of the above criteria are met, a decision will be made as to whether enrollment in the study 
will be allowed to resume. 
Case unblinding may be performed, if necessary, as determined by the SMT. 
5.2 
Enrollment and Retention of Study Population  
5.2.1 
Recruitment Procedures  
Before the start of the study the Investigator and/or study staff will determine the recruitment 
strategy to be used at their site for this study (e.g., advertising, database, direct mailing, word of 
mouth referrals). Using the relevant methods, they will contact an appropriate pool of potential 
parents / guardians/ legally authorized representatives and invite them to participate in the study. 
The sites will ensure that any materials used to recruit participants (e.g., information brochures, 
letters, pamphlets, posters, other advertisements, etc.) are submitted to Sanofi Pasteur prior to 
submission to the IRB for approval. 
In addition, a parent / guardian / legally authorized representative who brings a child to the study 
site for routine visit will be invited to enroll the participant in the study, if eligible. Participants 
may also be recruited from the general population. 

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5.2.2 
Informed Consent Procedures  
Informed consent is the process by which a participant’s guardian or appropriate legally 
acceptable representative voluntarily confirms his or her willingness to participate in a particular 
study. Informed consent must be obtained before any study procedures are performed. The 
process is documented by means of a written, signed, and dated ICF. 
In accordance with GCP, prior to signing and dating the consent form, the participant’s guardian/ 
representative must be informed by appropriate study personnel about all aspects of the study that 
are relevant to making the decision to participate and must have sufficient time and opportunity to 
ask any questions. 
If the participant’s guardian /legally authorized representative is not able to read and sign the ICF, 
then it must be signed and dated by an impartial witness who is independent of the Investigator. A 
witness who signs and dates the consent form is certifying that the information in this form and 
any other written information had been accurately explained to and understood by the participant 
or his / her guardian / representative. 
The actual ICF used at each center may differ, depending on local regulations and IEC / IRB 
requirements. However, all versions must contain the standard information found in the sample 
ICF provided by the Sponsor. Any change to the content of the ICF must be approved by the 
Sponsor and the IEC / IRB prior to the form being used. 
If new information becomes available that may be relevant to the participant’s guardian / legally 
authorized representative willingness to continue participation in the study, this will be 
communicated to him / her in a timely manner. Such information will be provided via a revised 
ICF or an addendum to the original ICF. 
Informed consent forms will be provided in duplicate, or a photocopy of the signed consent will 
be made. The original will be kept by the Investigator, and the copy will be kept by the 
participant’s guardian / legally acceptable representative. 
Documentation of the consent process should be recorded in the source documents. 
Rationale for Including Participants Unable to Give Consent: 
See Section 1.4 for the rationale for conducting this study in pediatric population. 
5.2.3 
Screening Criteria  
There are no screening criteria other than the inclusion and exclusion criteria. The Investigator 
must review the inclusion and exclusion criteria at enrollment (Visit 01). 

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5.2.4 
Inclusion Criteria  
An individual must fulfill all of the following criteria to be eligible for study enrollment (Visit 
01): 
1) Aged 6 through 18 months at D0.a 
2) Informed consent form has been signed and dated by the parent(s) / guardian / or other 
legally authorized representative (and by independent witness if required by local 
regulations). 
3) Participant and parent / guardian / legally authorized representative are able to attend all 
scheduled visits and to comply with all trial procedures. 
5.2.5 
Exclusion Criteria  
An individual fulfilling any of the following criteria is to be excluded from trial enrollment: 
1) Participation at the time of study enrollment (or in the 6 weeks preceding the first trial 
vaccination) or planned participation during the present trial period in another clinical trial 
investigating a vaccine, drug, medical device, or medical procedure. 
2) Receipt of any of the following vaccines prior to enrollment: 
• any influenza vaccine within 7 days prior, or 
• any inactivated vaccine within the 14 days prior, or 
• live-attenuated rotavirus vaccine within the 14 days prior, or 
• any live vaccine, other than rotavirus vaccine, within the 28 days prior, or 
• another investigational vaccine or investigational drug within 28 days prior. 
3) Previous receipt of a licensed or investigational RSV vaccine or previous receipt or planned 
administration of any anti-RSV product (such as ribavirin or RSV immune globulin [IG] or 
RSV monoclonal antibody). 
4) Receipt of immune globulins, blood or blood-derived products in the past 6 months prior to 
enrollment. 
5) Known or suspected congenital or acquired immunodeficiency; or receipt of 
immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within 
the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or 
equivalent for more than 2 consecutive weeks within the past 3 months). 
6) Probable or confirmed case of Coronavirus Disease 2019 (COVID-19). 
7) Known systemic hypersensitivity to any of the vaccine components, or history of a life-
threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same 
substances.b 
 
a  6 through 18 months means from 6th month after birth to the day before the 19th month after birth. 
b  The components of the study vaccine are listed in Section 6.1 and in the Investigator's Brochure. 

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8) Any chronic illness. 
• Chronic illness may include, but is not limited to, cardiac disorders, lung disease 
(including any history of reactive airway disease, receipt of bronchodilator therapy, or 
medically diagnosed wheezing), renal disorders, auto-immune disorders, diabetes, 
psychomotor diseases, and known congenital or genetic diseases 
9) Any history of medically diagnosed wheezing. 
10) Any acute febrile, respiratory or gastrointestinal illness in the past 24 hours that according to 
investigator judgment is significant enough to interfere with successful inoculation on the day 
of vaccination. A prospective participant should not be included in the study until the 
condition has resolved or the febrile event has subsided. 
11) Receipt of any of the following medications within 3 days prior to study enrollment: 
• systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, 
whether for treatment or prophylaxis, or 
• intranasal medications, or 
• other prescription medication except as permitted concomitant medications (prescription 
or non-prescription) including nutritional supplements, medications for gastroesophageal 
reflux, eye drops, and topical medications, including (but not limited to) cutaneous 
(topical) steroids, topical antibiotics, and topical antifungal agents. 
12) Receipt of salicylate (aspirin) or salicylate-containing products within the 28 days prior to 
enrollment. 
13) Deprived of freedom in an emergency setting or hospitalized involuntarily. 
14) Identified as a natural or adopted child of the Investigator or employee with direct 
involvement in the proposed study. 
15) Any previous anaphylactic reaction. 
16) Any previous vaccine-associated adverse reaction that was Grade 3 or above. Note: if grading 
is not possible, determine if the reaction was considered severe or life-threatening; if so, it is 
exclusionary. 
17) Member of a household that contains, or will contain, an infant who is less than 6 months of 
age at the enrollment date (or in the 6 weeks preceding the first trial vaccination) through 
Day 28. 
18) Member of a household that contains another child/other children who is/are, or is/are 
scheduled to be, enrolled in this study in the same year AND the date of enrollment will not 
be concurrent with the other participant(s) living in the household (i.e., all eligible children 
from the same household must be enrolled on the same date). 
19) Member of a household that contains an immunocompromised individual, including, but not 
limited to: 
• a person who is HIV infected 
• a person who has received chemotherapy within the 12 months prior to enrollment 
• a person receiving immunosuppressant agents 
• a person living with a solid organ or bone marrow transplant. 

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20) Attends a daycare facility and shares a daycare room with infants less than 6 months of age, 
and parent/ guardian / legally authorized representative is unable or unwilling to suspend 
daycare for 28 days following inoculation. 
21) Scheduled administration of the following after planned inoculation: 
• any influenza vaccine within 7 days after, or 
• inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or 
• any live vaccine other than rotavirus in the 28 days after, or 
• another investigational vaccine or investigational drug in the 56 days after. 
22) Born at less than 34 weeks gestation. 
23) Born at less than 37 weeks gestation and less than 1 year of age at the time of enrollment. 
24) Current suspected or documented developmental disorder, delay, or other developmental 
problem. 
25) Any previous receipt of supplemental oxygen therapy in a home or hospital setting, except 
the temporary receipt of supplemental oxygen for transient tachypnea in newborn. 
5.2.6 
Medical History  
Prior to enrollment, participants will be assessed for pre-existing conditions and illnesses, both 
past and ongoing. Any such conditions will be documented in the source document. Significant 
(clinically relevant) medical history (reported as diagnosis) including conditions/illnesses for 
which the participant is or has been followed by a physician or conditions/illnesses that could 
resume during the course of the study or lead to an SAE or to a repetitive outpatient care will be 
collected in the CRB. The significant medical history section of the CRB contains a core list of 
body systems and disorders that could be used to prompt comprehensive reporting, as well as 
space for the reporting of specific conditions and illnesses. 
For each condition, the data collected will be limited to: 
• Diagnosis (this is preferable to reporting signs and symptoms) 
• Presence or absence of the condition at enrollment 
• The reporting of signs and symptoms in lieu of a diagnosis is strongly discouraged. 
Dates, medications, and body systems are not to be recorded, and the information collected will 
not be coded. The purpose of limited data is to assist in the later interpretation of safety data 
collected during the study. 
5.2.7 
Contraindications for Subsequent Vaccinations  
5.2.7.1 
Temporary Contraindications  
Should a participant experience one of the conditions listed below at Day 0 (Cohorts 1, 2, 3 and 4) 
or Day 56 (Cohorts 2 and 4), the Investigator will postpone further vaccination until the condition 
is resolved. Postponement must still be within the timeframe for vaccination i.e., within 5 days of 
randomization for Day 0 (Cohorts 1, 2, 3 and 4) and within 7 days of Day 56 (Cohorts 2 and 4). 

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1) Any acute febrile illness (rectal temperature ≥38.0°C [≥100.4°F]), acute otitis media, upper 
and lower respiratory signs or symptoms (including but not limited to rhinorrhea, cough, and 
pharyngitis), or nasal congestion in the past 24 hours that according to investigator’s 
judgment is significant enough to interfere with successful absorption of the study product. 
2) Receipt of any of the following before any study vaccination or scheduled administration 
after any study vaccination: 
• any influenza vaccine within 7 days prior, or 
• any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or 
• any live vaccine, other than rotavirus vaccine, within the 28 days prior, or 
• another investigational vaccine or investigational drug within 28 days prior. 
All eligible participants from the same household who are enrolled on the same date must receive 
the study product on the same date, and therefore if one child experiences illness as above, 
product administration should be deferred for both children. 
5.2.7.2 
Definitive Contraindications  
Should a participant experience one of the conditions listed below, the Investigator will 
discontinue vaccination: 
1) An anaphylactic or any other significant allergic reaction to the previous dose of vaccine. 
2) Any AE greater than Grade 2, LRI of any grade or SAE assessed by the investigator as 
related to the previous dose of vaccine. 
3) Diagnosis of COVID-19 
Participants with a definitive contraindication will continue to be followed up for the study-
defined safety and immunogenicity assessments, as applicable. 
In the event of a local or national immunization program with a pandemic vaccine e.g. influenza, 
participants who receive pandemic vaccine at any time during the study will not be withdrawn 
from the study. 
5.2.8 
Conditions for Withdrawal  
Parents / guardians / legally authorized representatives will be informed that they have the right to 
withdraw their child from the study at any time. Any participant who has received study product 
will be encouraged to remain in study follow-up for the duration of the study even if sample 
collection is refused. 
A participant may be withdrawn from the study: 
• At the request of the parent / guardian / legally authorized representative either verbally or 
in writing (i.e., withdrawal of consent/dropout). 
• At the discretion of the Investigator or Sponsor due to safety concern of significant non-
compliance with the protocol (based on the Investigator’s judgment), without the parent’s / 
guardian’s / legally authorized representative’s permission (i.e., non-compliant with the 
protocol/withdrawal). 

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The reason for a withdrawal or dropout should be clearly documented in the source documents 
and in the CRB. 
The Investigator must determine whether voluntary withdrawal is due to safety concerns (in which 
case, the reason for discontinuation will be noted as “Adverse Event”) or for another reason. 
Withdrawn participants will not be replaced. 
For any participant who withdraws or is terminated from the study prior to scheduled completion 
of follow-up, study staff will document the reason for the withdrawal or termination in detail and 
will make every effort to complete the following final evaluations: 
1) Obtain verbal medical history about the participant, including past and ongoing medication 
and immunizations. 
2) Obtain a blood sample for serum antibodies to RSV if possible (see Section 7.1 for detailed 
instructions regarding the handling of blood samples). 
3) Obtain a nasal swab sample for quantification of vaccine virus shedding (if in the Acute 
Phase), other respiratory pathogens including a COVID-19 POC test on the discretion of the 
investigator. 
4) Complete the relevant section of the CRF. 
5.2.9 
Lost to Follow-up Procedures  
In the case of participants who fail to return for a follow-up examination, documented reasonable 
effort (i.e., documented telephone calls and certified mail) should be undertaken to locate or recall 
them, or at least to determine their health status while fully respecting their rights. These efforts 
should be documented in the source documents. 
5.2.10 Classification of Participants Who Discontinue the Study  
For any participant who discontinues the study prior to completion, the most significant reason for 
early termination will be checked in the CRB. Reasons are listed below from the most significant 
to the least significant (refer to the CRF completion instructions for additional details and 
examples): 
Adverse Event 
To be used when the participant is permanently terminated from the study because of 
an AE (including an SAE), as defined in Section 9.1.1.1. 
This category also applies if the participant experiences a definitive contraindication 
that is an SAE or AE. 
IMPORTANT NOTE: in case participants are discontinued from the study due to 
COVID-19 infection related event, “Adverse Event” should be selected and an 
Adverse Event Form completed if within the protocol defined period for safety 
collection. 
Lost to Follow-up 
To be used when the participant cannot be found or contacted in spite of efforts to 
locate him/her before the date of his/her planned last visit, as outlined in Section 5.2.9. 
The certified letter was sent by the investigator and returned unsigned, and the 
participant or parent / guardian/ legally authorized representative did not give any other 
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Protocol Deviation 
To be used: 
In case of significant non-compliance with the protocol (e.g., deviation of the Inclusion 
/ Exclusion criteria, non-compliance with time windows, blood sampling or 
vaccination refusal, missed injection/treatment, or error in the vaccine/treatment 
administration or any issue leading to definitely discontinue the participant from the 
study due to COVID-19 pandemic like for e.g. quarantine, transportation restriction). 
If the participant experiences a definitive contraindication that is not an SAE or AE. 
The participant or the parent / guardian / legally authorized representative signed the 
certified letter sent by the investigator but did not give any other news and did not 
come to any following visit. 
Withdrawal by 
Participant or Parent / 
Guardian / Legally 
authorized 
Representative 
To be used: 
• 
When the participant or parent / guardian/ legally authorized representative 
indicated unwillingness to continue in the study 
• 
When the participant or parent / guardian/ legally authorized representative 
made the decision to discontinue participation in the study for any personal 
reason other than an SAE/AE (e.g., participant is relocating, inform consent 
withdrawal, including fear of exposure to COVID-19 during pandemic period, 
etc.) 
5.2.11 Follow-up of Discontinuations  
The site should complete all scheduled safety follow-ups and contact any participant who has 
prematurely terminated the study because of an AE or a protocol deviation. 
For participants where the reason for early termination was lost to follow-up or if the participant 
withdrew informed consent and specified that they do not want to be contacted again and it is 
documented in the source document, the site will not attempt to obtain further safety information. 
If the participant’s status at the end of the study is “Withdrawal by Participant or Parent / 
Guardian / Legally Authorized Representative”, the site will attempt to contact them for the post-
RSV season visit except if they specified that they do not want to be contacted again and it is 
documented in the source document. 
5.2.12 Follow-up of participants with COVID-19 in the study  
If a participant develops COVID-19 during the study, the patient will be followed up according to 
national/regional/local health authority guidelines for as long as possible. All attempts will be 
made to monitor the safety of the study participant and collect key samples whilst complying with 
national/regional/local health authority guidelines. 
5.3 
Safety Emergency Call  
If, as per the Investigator's judgment, a participant experiences a medical emergency, the 
Investigator may contact the Sponsor's RMO for advice on how to address any study-related 
medical question or problem. If the RMO is not available, then the Investigator may contact the 
Call Center—available 24 hours a day, 7 days a week—that will forward all safety emergency 
calls to the appropriate primary or back-up Sanofi Pasteur contact, as needed. The toll-free contact 
information for the Call Center is provided in the Operating Guidelines. 

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This process does not replace the need to report an SAE. The Investigator is still required to 
follow the protocol-defined process for reporting SAEs to the Global Pharmacovigilance (GPV) 
Department (please refer to Section 10). 
In case of emergency code-breaking, the Investigator is required to follow the code-breaking 
procedures described in Section 6.4. 
5.4 
Modification of the Study and Protocol  
Any amendments to this study plan and protocol must be discussed with and approved by the 
Sponsor. If agreement is reached concerning the need for an amendment, it will be produced in 
writing by the Sponsor, and the amended version of the protocol will replace the earlier version. 
All substantial amendments (e.g., those that affect the conduct of the study or the safety of 
participants) require IEC / IRB approval, and must also be forwarded to regulatory authorities. 
An administrative amendment to a protocol is one that modifies some administrative, logistical, or 
other aspect of the study but does not affect its scientific quality or have an impact on the 
participants’ safety. The IECs / IRBs should only be notified, no formal approval is required. 
The Investigator is responsible for ensuring that changes to an approved study, during the period 
for which IEC / IRB approval has already been given, are not initiated without IEC / IRB review 
and approval, except to eliminate apparent immediate hazards to participants. 
5.5 
Interruption of the Study  
The study may be discontinued if new data about the investigational product resulting from this or 
any other studies become available; or for administrative reasons; or on advice of the Sponsor, the 
Investigators, the IECs/IRBs, or the governing regulatory authorities in the countries where the 
study is taking place. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by applicable regulatory 
requirements. The Investigator shall promptly inform the participant’s parents / guardians / legally 
authorized representatives and should assure appropriate participant therapy and/or follow-up. 
6 
Products Administered  
6.1 
Identity of the Investigational Product(s)  
The identity of the investigational products is described in the sections below for Cohorts 1 
through 4. 

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6.1.3 
Identity of Control Product(s)  
Placebo 
6.1.3.1 
Composition  
Same formulation buffer as the RSV ∆NS2/∆1313/I1314L vaccine, to be delivered as 
approximately 
 
6.1.3.2 
Preparation and Administration  
The procedures for preparing and administering the control product are the same as those 
described for the study product in Section 6.1.1.2. 
6.1.3.3 
Dose Selection and Timing  
Participants in Cohort 1 and 3 will receive 1 administration of placebo on Day 0. 
Participants in Cohorts 2 and 4 will receive 2 administrations: 1 administration of placebo on Day 
0 and a subsequent administration on Day 56. 
6.1.3.4 
Vaccination Device  
The vaccination device is described in Section 6.1.1.4 . 
6.2 
Identity of Other Product(s)  
Not applicable 
6.3 
Product Logistics  
6.3.1 
Labeling and Packaging  
The investigational and placebo products in single-dose vials will be supplied with investigational 
labeling and packaging according to national regulations. Each single dose of investigational or 
placebo product will be identified by a unique number on the primary label and on the outer 
carton label. The carton label will also have a detachable label for the sites to attach to the source 
documents. See the Operating Guidelines for additional label detail. 
The investigational and placebo products are blinded at the level of the carton. 
6.3.2 
Product Shipment, Storage, and Accountability  
6.3.2.1 
Product Shipment  
The Clinical Study Manager or designee will contact the Investigator or a designee to determine the 
dates and times of delivery of products. 

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Each vaccine shipment will include a temperature-monitoring device to verify maintenance of the 
cold chain during transit. On delivery of the product to the site, the person in charge of product 
receipt will follow the instructions given in the Operating Guidelines, including checking that the 
cold chain was maintained during shipment (i.e., verification of the temperature recorders). If 
there is an indication that the cold chain was broken, this person should immediately quarantine 
the product, alert the Sanofi Pasteur representative, and request authorization from Sanofi Pasteur 
to use the product. 
6.3.2.2 
Product Storage  
The Investigator will be personally responsible for product management or will designate a staff 
member to assume this responsibility. 
At the site, products must be kept in a secure place with restricted access. Vaccines will be stored 
in a freezer at <-60°C (<-76ºF) and should be protected from light. The temperature must be 
monitored and documented (see the Operating Guidelines) for the entire time that the vaccine is at 
the study site. In case of accidental disruption of the cold chain, vaccines must not be 
administered and must be quarantined, and the Investigator or authorized designee should contact 
the Sanofi Pasteur representative for further instructions. 
6.3.2.3 
Product Accountability  
The person in charge of product management at the site will maintain records of product delivery 
to the study site, product inventory at the site, the dose(s) given to each participant, and the 
disposal of or return to the Sponsor of unused doses. Because the vaccine and placebo differ in 
appearance, an unblinded coordinator(s) will verify the product accountability and also dispense 
the vaccine. 
The necessary information on the product labels is to be entered into the source document and the 
CRB. If applicable, information may also be entered into the participant’s vaccination card. 
The Sponsor’s monitoring staff will verify the study site’s product accountability records against 
the record of administered doses in the CRBs and the communication from the IRT (if applicable). 
In case of any expected or potential shortage of product during the study, the Investigator or an 
authorized designee should alert the Sanofi Pasteur representative as soon as possible, so that a 
shipment of extra doses can be arranged. 
6.3.3 
Replacement Doses  
If a replacement dose is required (e.g., because the syringe broke or particulate matter was 
observed in the syringe), the site personnel must either contact the IRT to receive the new dose 
allocation, or follow the instructions given in the Operating Guidelines. 
6.3.4 
Disposal of Unused Products  
Unused or wasted products will be returned to the Sponsor in accordance with the instructions in 
the Operating Guidelines. Product accountability will be verified throughout the study period. 

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6.3.5 
Recall of Products  
If the Sponsor makes a decision to launch a retrieval procedure, the Investigator(s) will be 
informed of what needs to be done. 
6.4 
Blinding and Code-breaking Procedures  
The study will be performed in an observer-blind fashion: 
• Investigators and study staff who conduct the safety assessment and the participant will 
not know which vaccine is administered. 
• Only the study staff who prepare and administer the vaccine and are not involved with the 
safety evaluation will know which vaccine is administered. 
The parent / guardian / legally authorized representative, the Investigator and study staff members 
who collect safety data, and laboratory personnel who analyze the blood samples, will not know 
which product was administered. The vaccinator will be in charge of preparing and administering 
the products and will not be authorized to collect any safety data. In addition, the vaccinator or 
authorized designee will have to ensure that the documents on randomization are stored in a 
secure place where only she / he has access. 
The code may be broken in the event of an AE only when the identification of the vaccine 
received could influence the treatment of the participant. Code breaking should be limited to the 
participant(s) experiencing the AE. 
The blind can be broken by the Investigator or a delegate through the IRT system, as explained in 
the code-breaking procedures described in the Operating Guidelines. Once the emergency has 
been addressed by the site, the Investigator or a delegate must notify the Sanofi Pasteur RMO if a 
participant’s code was broken. All contact attempts with the Sponsor prior to unblinding are to be 
documented in the source documents, and the code breaking CRF is to be completed. 
A request for the code to be broken may also be made: 
• by the GPV Department through an internal system for reporting to Health authorities in 
the case of an SAE as described in International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) E2A. In this case, the code will 
be broken only for the participant(s) in question. The information resulting from code-
breaking (i.e., the participant’s vaccine or group assignment) will not be communicated to 
either the Investigator or the immediate team working on the study, except for the GPV 
representative. 
• by the ad hoc IDMC if needed to facilitate their assessment of safety. 
The IEC / IRB must be notified of the code breaking. All documentation pertaining to the event 
must be retained in the site’s study records and, in the Sanofi Pasteur files. Any intentional or 
unintentional code breaking must be reported, documented, and explained, and the name of the 
person who requested it must be provided to the Sponsor. 
An unblinded interim analysis for dose selection of RSV ∆NS2/∆1313/I1314L vaccine is planned 
on participants from Cohorts 1, 2 and 3, and at least 90 participants enrolled in Cohort 4. The 

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interim analysis will take place when participants have provided safety data up to the D84 
timepoint and have D84 immunogenicity results available. This unblinded interim analysis 
requires the unblinding of data; a specific process will be implemented to maintain the blind at the 
participant and Investigator levels. 
An early unblinded analysis is planned on all participants when they have provided safety data up 
to the D84 timepoint and have D84 immunogenicity results available. Based on the results of this 
analysis, a dose will be confirmed for future studies. 
Testing performed within Global Clinical Immunology (GCI) and GCI outsourced laboratories are 
blinded with respect to study treatment group assignment. The code(s) linking information on 
sample vials to study treatment group assignment are retained by the Clinical Department and 
cannot be accessed by GCI or contract laboratory testing personnel. 
6.5 
Randomization and Allocation Procedures  
An IRT will be implemented to assign the participant numbers and allocate vaccine groups with 
dose numbers to the participants at Visit 01. 
At Visit 01 visit, participants who meet the inclusion/exclusion criteria and whose parent / 
guardian/ legally authorized representative signs the ICF will be randomly assigned to one of the 
vaccine groups, according to the cohort: 
• Cohorts 1 and 2: RSV ∆NS2/∆1313/I1314L 
 (RSV low-dose) or Placebo in a 1:1 
ratio 
• Cohort 3: RSV ∆NS2/∆1313/I1314L 
 (RSV high-dose) or Placebo in a 1:1 ratio 
• Cohort 4: RSV ∆NS2/∆1313/I1314L 
 (RSV high-dose) or RSV 
∆NS2/∆1313/I1314L 
 (RSV low-dose) or Placebo in a 1:1:1 ratio 
At Visit 01, randomization will be stratified by cohort and by age sub-group (< 12 months / 
≥ 12 months). 
Site staff will connect to the IRT, enter the identification and security information, and confirm a 
minimal amount of data in response to IRT prompts. The IRT will then provide the dose number 
assignment and have the site staff confirm it. The full detailed procedures are described in the 
Operating Guidelines. If the participant is not eligible to participate in the study, then the 
information will only be recorded on the participant recruitment log. 
Participant numbers that are assigned by the IRT will consist of a 12-digit string (a 3-digit country 
identifier, a 4-digit study center identifier, and a 5-digit participant identifier). For example, 
Participant 840000100005 is the fifth participant enrolled in Center Number 1 in the US (840 
being the US country code). 
6.6 
Treatment Compliance  
The following measures will ensure that the vaccine doses administered comply with those planned, 
and that any non-compliance is documented so that it can be accounted for in the data analyses: 

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• All vaccinations will be administered by qualified study personnel 
• The person in charge of product management at the site will maintain accountability 
records of product delivery to the study site, product inventory at the site, dose(s) given to 
each participant, and the disposal of unused or wasted doses 
6.7 
Concomitant Medications and Other Therapies  
At the time of enrollment, ongoing medications and other therapies (e.g., blood products) should 
be recorded in the source document as well as new medications prescribed for new medical 
conditions / AEs during study participation. 
Documentation in the CRB of ongoing concomitant medication(s) will be limited to specific 
categories of medication(s) of interest beginning on the day of first vaccination. This may include 
medications of interest that were started prior to the day of vaccination. 
Reportable medications will be collected in the CRB from the day of each vaccination to the end 
of the solicited and unsolicited follow-up period. 
Reportable medications include medications that impact or may impact the consistency of the safety 
information collected after any vaccination and/or the immune response to vaccination. Three standard 
categories of reportable medications are defined: 
• Medications impacting or that may have an impact on the evaluation of the safety (e.g., 
antipyretics, analgesics, and non-steroidal anti-inflammatory drugs [NSAIDs], 
steroids/corticosteroids). 
• Medications impacting or that may have an impact on the immune response (e.g., other 
vaccines, blood products, antibiotic classes that may interfere with bioassays used by the 
GCI department, steroids/corticosteroids, immune-suppressors, immune-modulators with 
immunosuppressive properties, anti-proliferative drugs such as DNA synthesis inhibitors). 
• Medications impacting or that may have an impact on both the safety and the immune 
response (e.g., steroids/corticosteroids) 
The information reported in the CRB for each reported medication will be limited to: 
• Trade name 
• Origin of prescription: prophylaxis Yes/No. Medication(s) prescribed for AE prophylaxis 
will be recorded in the Action Taken of the AE collection tables. 
• Start and stop dates 
• Reason for treatment 
Dosage and administration route, homeopathic medication, topical and inhaled steroids, as well as 
topical, ophthalmic, and ear treatments will not be recorded. Topical analgesics should not be 
applied at the site of vaccination; however, if they are applied inadvertently to the vaccination site, 
they should be recorded as a Category 1 medication in this specific instance. 

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Medications given in response to an AE will be captured in the “Action Taken” section of the AE 
CRF only. No details will be recorded in the concomitant medication CRF unless the medication(s) 
received belongs to one of the pre-listed categories.  
Medications will be coded. 
6.7.1 
Prohibited Concomitant Medications  
The use of the following is prohibited: 
• Prophylactic antipyretics, decongestants, or antihistamines during the Acute Phase 
(28 days following study product administration) – note that use of these medications for 
treatment of symptoms is allowed. 
• An investigational drug or investigational vaccine other than the study product within 
56 days after receiving study product. 
6.7.2 
Precautionary Concomitant Medications  
Due to their potentially confounding effect on immunogenicity results, the following treatments 
should be avoided after study product administration unless clinically indicated: 
• Systemic corticosteroids for more than 14 days at a dosage equivalent to prednisone 
at >2 mg/kg or 20 mg daily or other immune-modifying drugs. 
• Immunoglobulins and/or any blood products. 
The following should be avoided after study product administration unless indicated in an 
outbreak setting: 
• Licensed inactivated vaccine or live-attenuated rotavirus vaccine within 14 days after 
receiving study product. 
• Licensed live virus vaccine, other than rotavirus vaccine, within 28 days after receiving 
study product 
7 
Management of Samples  
Blood samples for the assessment of antibody responses will be collected at Visits 01, 03, and 04 
for Cohorts 1 and 3 participants who receive 1 administration and Visits 01, 03, 05 and 06 for 
Cohorts 2 and 4 participants who receive 2 administrations. See the Table of Study Procedures 
and Section 5.1.3 for details of the sampling schedule. 
Nasal swab samples for confirmation of RSV will be collected at Visit 02 (Day 7) for Cohorts 1 
and 3 participants who receive 1 administration and at Visit 02 (Day 7) and Visit 04 (Day 63) for 
Cohorts 2 and 4 participants who receive 2 administrations. A nasal swab specimen for the 
detection of RSV and respiratory pathogens will be collected from participants during illness 
visits. 
All collection of samples in the US will adhere to the Centers for Disease Control (CDC) 
recommended Interim Infection Prevention and Control Recommendations for Patients with 
Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings (34). 

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Collection of samples in the sites outside the US will comply to local regulatory guidelines for 
COVID-19. 
See the Table of Study Procedures and Section 5.1.3 for details of the sampling schedule. 
7.1 
Sample Collection  
At the above-mentioned visits, up to 5 mL of blood will be collected in tubes provided by or 
recommended by the Sponsor. 
At the above-mentioned visits, nasal swab samples will be collected and transferred into tubes 
provided by or recommended by the Sponsor. Staff collecting the samples should use adequate 
infection prevention and control measures, as described in the Operating Guidelines. 
Immediately prior to the blood draw or nasal swab, the staff member performing the procedure 
will verify the participant’s identity as well as the assigned participant’s number and sampling 
stage on the pre-printed label and will attach the label to the tube. 
7.2 
Sample Preparation  
Serum Samples 
Detailed instructions on how to prepare blood samples for assessment of immune response are 
contained in the Operating Guidelines provided to the site. An overview of the procedures is 
provided here. 
Following the blood draw, the tubes are to be left undisturbed, positioned vertically and not 
shaken, for a minimum of 1 hour and a maximum of 24 hours to allow the blood to clot. Samples 
can be stored at room temperature for up to 2 hours; beyond 2 hours, they must be refrigerated at a 
temperature of +2°C to +8°C (+35.6°F to +46.4°F) after the period of clotting at room 
temperature and must be centrifuged within a maximum of 24 hours. 
The samples are then centrifuged, and the serum is transferred to the appropriate number of 
aliquoting tubes. These tubes are pre-labeled with adhesive labels that identify the study code, the 
participant’s number and the sampling stage or visit number. 
The participant’s number and the date of sampling, the number of aliquots obtained, the date and 
time of preparation, and the participant’s consent for future use of his / her samples are to be 
specified on a sample identification list and recorded in the source document. Space is provided 
on this list for comments on the quality of samples. 
Nasal Swab Samples 
Detailed instructions on how to collect nasal swab samples in appropriate viral transport media for 
viral shedding assay(s) are contained in the Operating Guidelines provided to the site. 
The participant’s identification number and any other required information, the date of sampling, 
and the date and time of preparation will be clearly documented. 

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7.3 
Sample Storage and Shipment  
Serum Samples 
During storage, serum tubes are to be kept in a freezer whose temperature is set and maintained at 
-20°C (-4°F) or below. The temperature will be monitored and documented on the appropriate 
form during the entire study. If it rises above -10°C (14°F) for any period of time, the Clinical 
Logistics Coordinator must be notified. See the Operating Guidelines for further details. 
Shipments to the laboratories will be made only after appropriate monitoring and following 
notification of the Clinical Logistics Coordinator. Sera will be shipped frozen, using dry ice to 
maintain them in a frozen state, in the packaging container provided by the carrier. Again, 
temperatures will be monitored. Shipments must be compliant with the United Nations (UN) 
Class 6.2 specifications and the International Air Transport Association (IATA) 602 packaging 
instructions. 
Samples will be shipped to Sample, Reagent, & Animal Services within R&D Global Operations 
at Sanofi Pasteur. The address is provided in the Operating Guidelines. 
Nasal Swab Samples 
Nasal swab samples will be shipped frozen, using dry ice to maintain them in a frozen state, in the 
packaging container provided by the carrier. Detailed instructions for the storage of nasal swab 
samples at study site and shipment of nasal swab samples to testing laboratory are contained in the 
Operating Guidelines provided to the site. 
7.4 
Future Use of Stored Biological Samples for Research  
Any unused part of the serum samples and nasal swab samples will be securely stored at SRAS 
within Global Research Office (GRO) at Sanofi Pasteur) for at least 25 years after the end of the 
study. These samples are being retained in long-term storage to support answers to regulatory 
questions related to the product’s licensure and the potential revalidation of the study results. In 
addition, these samples will also be used for assay development activities related to RSV or other 
respiratory pathogens. 
The other biological samples collected to qualify the participants for inclusion in the study or to 
monitor their health are dedicated for immediate use. In case they are not completely used up, 
they will be destroyed at the latest at the end of the study or after the time requested by local law. 
In addition, parents / guardians / legally authorized representatives will be asked to indicate in the 
ICF whether they will permit the future use of any unused stored serum samples for other tests. If 
they refuse permission, the samples will not be used for any testing other than that directly related 
to this study. If they agree to this use, they will not be paid for giving permission. Anonymity of 
samples will be ensured. The aim of any possible future research is unknown today and may not 
be related to this particular study. It may be to improve the knowledge of vaccines or infectious 
diseases, or to improve existing tests or develop new tests to assess vaccines. Human genetic tests 
will never be performed on these samples without specific individual informed consent. 

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8 
Clinical Supplies  
Sanofi Pasteur will supply the study sites with protocols, ICFs, CRBs, SAE reporting forms, diary 
cards, memory aids and other study documents, as well as with the following study materials: all 
study vaccines including the device for vaccine administration, blood collection tubes, cryotubes, 
cryotube storage boxes, cryotube labels, temperature recorders, shipping containers, and digital 
thermometers. 
The means for performing Electronic Data Capture (EDC) will be defined by Sanofi Pasteur. If a 
computer is provided by Sanofi Pasteur, it will be retrieved at the end of the study. 
The Investigator will supply all vaccination supplies, phlebotomy, and centrifugation equipment, 
including biohazard and / or safety supplies. The biohazard and safety supplies include needles 
and syringes, examination gloves, laboratory coats, sharps disposal containers, and absorbent 
countertop paper. The site will ensure that all biohazard wastes are autoclaved and disposed of in 
accordance with local practices. The Investigator will also supply appropriate space in a 
temperature-monitored refrigerator for the storage of the products and for the blood samples, and 
appropriate space in a temperature-monitored freezer for serum aliquots. 
In the event that additional supplies are required, study staff must contact Sanofi Pasteur, 
indicating the quantity required. Contact information is provided in the Operating Guidelines. 
9 
Endpoints and Assessment Methods  
9.1 
Primary Endpoints and Assessment Methods  
9.1.1 
Safety  
9.1.1.1 
Safety Definitions  
The following definitions are taken from the ICH E2A Guideline for Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting. 
Adverse Event (AE): 
An AE is any untoward medical occurrence in a patient or in a clinical investigation participant 
administered a medicinal product and which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom or disease temporally associated with the use 
of a medicinal product, whether or not considered related to the medicinal product. 
Therefore, an AE may be: 
• A new illness 
• The worsening of a pre-existing condition 
• An effect of the vaccination, including the comparator 
• A combination of the above 

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All AEs include serious and non-serious AEs. 
Surgical procedures are not AEs; they are the actions taken to treat a medical condition. It is the 
condition leading to the action taken that is the AE (if it occurs during the study period). 
Pre-existing medical conditions are not to be reported as AEs. However, if a pre-existing medical 
condition worsens following study interventions in frequency or intensity, or if according to the 
Investigator there is a change in its clinical significance, this change should be reported as an AE 
(exacerbation). This applies equally to recurring episodes of pre-existing conditions (e.g., asthma) 
if the frequency or intensity increases post-vaccination. 
Serious Adverse Event (SAE): 
Serious and severe are not synonymous. The term severe is often used to describe the intensity of 
a specific event as corresponding to Grade 3. This is not the same as serious, which is based on 
participant / event outcome or action criteria usually associated with events that pose a threat to a 
participant’s life or functioning. Seriousness, not severity, serves as a guide for defining 
regulatory reporting obligations. 
An SAE is any untoward medical occurrence that at any dose 
• Results in death 
• Is life-threateninga 
• Requires inpatient hospitalization or prolongation of existing hospitalizationb 
• Results in persistent or significant disability / incapacityc 
• Is a congenital anomaly / birth defect 
• Is an important medical event (IME) 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as IMEs that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the health of the participant or may require 
intervention to prevent one of the other outcomes listed in the definition above. These IMEs 
should also usually be considered serious. Examples of such events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse, new-onset diabetes, or auto-immune disease. 
 
a  The term “life-threatening” refers to an event in which the participant was at risk of death at the time of the event; 
it does not refer to an event which hypothetically might have caused death if it were more severe. 
b  All medical events leading to hospitalizations will be recorded and reported as SAEs, with the exception of: 
hospitalization planned before inclusion into the study or outpatient treatment with no hospitalization. 
c  “Persistent or significant disability or incapacity” means that there is a substantial disruption of a person’s ability 
to carry out normal life functions. 

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Adverse Reaction: 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered adverse reactions (AR). 
(The phrase “responses to a medicinal product” means that a causal relationship between a 
medicinal product and an AE is at least a reasonable possibility) 
The following additional definitions are used by Sanofi Pasteur: 
Immediate Event/Reaction: 
Immediate events are recorded to capture medically relevant unsolicited systemic AEs (including 
those related to the product administered) that occur within the first 30 minutes after vaccination. 
Solicited Reaction: 
A solicited reaction is an “expected” adverse reaction (sign or symptom) observed and reported 
under the conditions (nature and onset) pre-listed in the protocol and CRB (e.g., fever and runny 
nose occurring between D0 and D28 post-vaccination). 
By definition, solicited reactions are to be considered as being related to the product administered. 
For vaccines administered nasally, solicited reactions can either be solicited administration site 
reactions or solicited systemic reactions. 
Unsolicited AE / AR: 
An unsolicited AE is an observed AE that does not fulfill the conditions pre-listed in the CRB in 
terms of diagnosis and/or onset window post-vaccination. For example, if fever between D0 and 
D28 is a solicited reaction (i.e., pre-listed in the protocol and CRB), then a fever starting on D28 
is a solicited reaction, whereas fever starting on D29 post-vaccination is an unsolicited AE. 
Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. 
Medically Attended AE (MAAE): 
An MAAE is a new onset or a worsening of a condition that prompts the participant or 
participant’s parent / guardian/ legally authorized representative to seek unplanned medical advice 
at a physician’s office or Emergency Department. A physician contact made over the phone or by 
e-mail will be considered a physician office visit for the purpose of MAAE collection. This 
definition excludes pre-planned medical office visits for routine medical care, as well as pediatric 
check-ups or follow-up visits of chronic conditions with an onset prior to entry in the study. An 
AE discovered during a planned routine visit (e.g., upper respiratory tract infection, otitis) will be 
collected as an MAAE. 
Administration Site Reaction:  
An administration site reaction is an AR at and around the administration site i.e., the intranasal 
mucosa. They are considered related to the product administered. 
Systemic AE: 
Systemic AEs are all AEs that are not injection or administration site reactions. They therefore 
include systemic manifestations such as headache, fever, as well as localized or topical 

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manifestations that are not associated with the vaccination or administration site (e.g., 
conjunctivitis that is localized but that is not occurring at the administration site). 
Adverse Event of Special Interest (AESI): 
An adverse event of special interest is one of scientific and medical concern specific to the 
Sponsor’s product or program, for which ongoing monitoring and rapid communication by the 
investigator to the sponsor can be appropriate. Such an event might warrant further investigation 
in order to characterize and understand it. Depending on the nature of the event, rapid 
communication by the study Sponsor to other parties (e.g., regulators) might also be warranted. 
AESIs include both serious (SAEs) and non-serious unsolicited AEs. 
The following definitions are for the different phases of safety follow post-vaccine administration: 
Acute Phase: 
The Acute Phase begins with vaccine administration on D0 and ends at midnight on the 28th day 
after vaccine administration (D28). The Acute Phase for the second vaccine administration begins 
on D56 post-vaccination and ends at midnight on D84 
During the Acute Phase of the study, a study healthcare professional will be available by 
telephone 24 hours a day for consultation with parents / guardians / legally authorized 
representatives regarding any illnesses that may occur during this period. Study personnel will 
have daily contact with the parents / guardians / legally authorized representatives for the first 
7 days after each vaccine administration and then 3 times weekly after Day 07 up to 28 days after 
each vaccine administration. This 28-day Acute Phase of safety follow-up is consistent with the 
duration of shedding of live-attenuated RSV viruses in RSV seronegative infants and toddlers (5) 
(6). If the parent / guardian/ legally authorized representative reports an SAE, a safety event that 
meets the study pause or stop criteria (Section 5.1.6), or symptoms suggestive of a respiratory 
tract illness, then an illness visit should be scheduled (Section 5.1.4, Table 5-4). During the Acute 
Phase, the eDC allows daily safety monitoring of the study participant and will be programmed to 
send an alert to the parent / guardian / legally authorized representative and study site when there 
are symptoms suggestive of respiratory tract illness (Table 5-4). 
Post-Acute Phase: 
The Post-Acute Phase for participants receiving 1 administration begins at 12:01am on D29 and 
ends at midnight on D56. The first Post-Acute Phase for participants receiving 2 administrations 
begins at 12:01am on D29 and ends at midnight on D56, except if second administration is exactly 
on D56 when it ends immediately before receipt of the second administration. The second Post-
Acute Phase for participants receiving 2 administrations begins at 12:01am on D85 and ends at 
midnight on D112. 
During the Post-Acute Phase of the study, parents / guardians / legally authorized representatives 
will be instructed to monitor for and contact study staff if their child has had symptoms that are 
suggestive of a serious adverse event. If the parent /guardian / legally authorized representative 
reports an SAE or safety event that meets the study pause or stop criteria (Section 5.1.6), then an 
illness visit should be scheduled (Section 5.1.4, Table 5-4). 

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9.1.1.2 
Safety Endpoints  
The primary endpoints for the evaluation of safety are as follows (in all infants and toddlers 
regardless of baseline serostatus): 
• Occurrence of any unsolicited systemic AEs reported in the 30 minutes after each and any 
vaccination. 
• Occurrence of solicited (i.e., pre-listed in the participant’s DC / eDC and in the CRB) 
administration site and systemic reactions within 28 days after each and any vaccination 
(i.e, Acute Phase). 
• Occurrence of any unsolicited (spontaneously reported) AEs within 28 days after each and 
any vaccination (i.e, Acute Phase) 
• Occurrence of any AESIs within 28 days after each and any vaccination. 
• Occurrence of any MAAEs within 28 days after each and any vaccination. 
• Occurrence of any SAEs throughout the study period. 
• Other safety endpoints will be recorded or derived as described in the statistical analysis 
plan. Depending on the item, these could include nature (Medical Dictionary for 
Regulatory Activity [MedDRA] preferred term), time of onset, duration, number of days 
of occurrence, intensity, relationship to vaccine, action taken, whether the AE led to early 
termination from the study, seriousness, or outcome. 
9.1.1.3 
Safety Assessment Methods  
At each vaccination in-person or non-visit contact, the Investigator or a delegate will either 
perform a focused medical examination (in-person visit) or ask the parent / guardian / legally 
authorized representative about any solicited reactions and unsolicited AEs recorded in the diary 
card / electronic diary card, as well as about any other AEs that may have occurred since the 
previous visit. All relevant data will be transcribed into the CRB according to the instructions 
provided by the Sponsor. 
This study monitors safety, infectivity, replication, and immunogenicity of both doses of RSV 
∆NS2/∆1313/I1314L, with attention to vaccine virus infectivity and replication (i.e., percentage of 
participants shedding virus, vaccine virus titer in nasal swab) 7 days post-vaccination 1 and 2, 
which is the most quantifiable metric for the level of attenuation of the vaccine virus. 
9.1.1.3.1 
Immediate Post-vaccination Observation Period  
Participants will be kept under observation for 30 minutes after each vaccination to ensure their 
safety. The post-vaccination observation should be documented in the source document. Any AE 
that occurs during this period will be noted on the source document and recorded in the CRB, as 
follows: 
• Unsolicited systemic AEs will be recorded as immediate AEs in the CRB (presence 
marked as “yes”, and details collected). 

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• Solicited and unsolicited administration site reactions and solicited systemic reactions will 
be recorded in the CRB in the same way as any reactions starting on the day of 
vaccination.  
• SAEs will be recorded in the CRB and reported to the Sponsor in the same way as any 
other SAEs, according to the procedures described in Section 10. 
9.1.1.3.2 
Reactogenicity (Solicited Reactions from Day 0 to Day 28 After Each 
Vaccination)  
After each vaccination, the participant’s parents / guardians / legally authorized representatives 
will be provided with a DC / eDC, and a digital thermometer, and will be instructed how to use 
them. The following items will be recorded by the participants in the diary card / electronic diary 
card on the day of vaccination and for the next 28 days (i.e., Day 0 through Day 28) until 
resolution: 
• Daily temperature, with the route by which it was taken 
• Daily measurement and intensity grade of any solicited administration site reactions (e.g., 
runny nose) and systemic reactions (e.g., fever) 
• Action taken for each event (e.g., medication) 
The action(s) taken by the parent /guardian / legally authorized representative to treat and/or 
manage any solicited reactions will be classified in the CRB using the following list (all 
applicable items should be checked): 
• None 
• Medication 
• Health care provider contact 
• Hospitalized 
• Discontinuation of study vaccination 
Parents / guardians / legally authorized representatives of study participants will be contacted by 
telephone each day for the first 7 days after each vaccination and then 3 times weekly after the 
D07 visit to remind them to record all safety information in the diary card / electronic diary card. 
If the timing of the telephone call should fall on a weekend or a holiday, the call should be made 
on the next business day. If contact is not made on the designated day, study staff will continue 
calling until contact is made. Every telephone attempt and its outcome will be documented in the 
source document. 
Table 9-1 and Table 9-2 present, respectively, the administration site reaction that is pre-listed in 
the diary cards and CRB, together with the intensity scales. 

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Table 9-1: Solicited administration site reactions: terminology, definitions, and intensity scales  
CRB term 
(MedDRA lowest level term 
[LLT]) 
Rhinorrhea 
Nasal congestion 
Diary card term 
Runny nose 
Stuffy or blocked nose 
Definition 
Two or more consecutive days of clear, mucous or purulent 
discharge from the nose. 
Note: Not associated with crying, change of room temperature, 
or eating and drinking. 
Two or more consecutive days of stuffy or blocked nose. 
Note: Not associated with crying, change of room 
temperature, or eating or drinking. 
Intensity scale* 
Grade 1 (mild): No medical intervention required; may include 
use of over-the-counter medications managed by the caregiver 
for treatment of symptoms 
Grade 2 (moderate): Outpatient medical intervention by a health 
care provider required; may include use of over-the-counter 
and/or prescription medications 
Grade 3 (severe): Prolonged medical intervention and/or 
hospitalization required 
Grade 4 (life-threatening): Illness requiring hospitalization with 
intensive care 
Grade 5 (death): Event resulting in fatal outcome to the 
participant  
Grade 1 (mild): No medical intervention required; may 
include use of over-the-counter 
medications managed by the caregiver for treatment of 
symptoms 
Grade 2 (moderate): Outpatient medical intervention by a 
health care provider required; may include use of over-the-
counter and/or prescription medications 
Grade 3 (severe): Prolonged medical intervention and/or 
hospitalization required 
Grade 4 (life-threatening): Illness requiring hospitalization 
with intensive care 
Grade 5 (death): Event resulting in fatal outcome to the 
participant 
*  For the measurable reactions of rhinorrhea and nasal congestion, the parent / guardian / legally authorized representative will decide whether or not medical intervention was 
required and if so the type of intervention, and the classification as Grade 1 - 5 will be assigned at the time of review of the diary card. 
 
 

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Table 9-2: Solicited systemic reactions: terminology, definitions, and intensity scales  
CRB term 
(MedDRA lowest 
level term [LLT]) 
Fever 
Vomiting 
Crying abnormal  
Drowsiness 
Appetite lost 
Irritability 
Diary card term 
Temperature 
Vomiting 
Abnormal crying 
Drowsiness 
Loss of appetite 
Irritability 
Definition 
Elevation of 
temperature to ≥ 38.0°C 
(≥ 100.4°F) 
Vomiting does not 
include spitting up 
Inconsolable crying 
without a determined 
reason 
Reduced interest in 
surroundings, or 
increased sleeping 
See intensity scale 
An excessive 
response to 
stimuli: increased 
fussiness, 
whining, and 
fretfulness despite 
attempts to 
comfort the infant 
and despite 
caregiver 
responses that 
would normally 
be soothing 
Intensity scale* 
Grade 1:  
≥ 38.0°C to ≤ 38.5°C 
or ≥ 100.4°F to ≤ 101.3°F 
Grade 1: 1 episode per 
24 hours 
Grade 1: < 1 hour 
Grade 1: Sleepier than 
usual or less interested 
in surroundings 
Grade 1: Eating less 
than normal 
Grade 1: Easily 
consolable 
 
Grade 2: 
> 38.5°C to ≤ 39.5°C 
or > 101.3°F to ≤ 103.1°F 
Grade 2: 2–5 episodes 
per 24 hours 
Grade 2: 1–3 hours  
Grade 2: Not interested 
in surroundings or did 
not wake up for a feed / 
meal 
Grade 2: Missed 1 or 2 
feeds / meals 
completely 
Grade 2: 
Requiring 
increased 
attention 
 
Grade 3: > 39.5°C 
or > 103.1°F 
Grade 3: ≥ 6 episodes 
per 24 hours or 
requiring parenteral 
hydration 
Grade 3: > 3 hours 
Grade 3: Sleeping most 
of the time or difficult 
to wake up 
Grade 3: Refuses ≥ 3 
feeds / meals or refuses 
most feeds / meals 
Grade 3: 
Inconsolable 
*  For all reactions but fever, the parent / guardian / legally authorized representative will record the intensity level (Grade 1, 2, or 3) in the diary card. For fever, they will record the 
body temperature, and the classification as Grade 1, 2, or 3 will be assigned based on the information in the diary card. 

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Important notes for the accurate assessment of temperature: 
Parents / guardians / legally authorized representatives are to measure body temperature once per 
day, preferably always at the same time. The optimal time for measurement is the evening, when 
body temperature is the highest. Temperature is also to be measured at the time of any apparent 
fever. The observed daily temperature and the route of measurement are to be recorded in the 
diary card, and the highest temperature will be recorded by the site in the CRB. The preferred 
route for this study is rectal. Pre-vaccination temperature is also systematically collected by the 
investigator on the source document. Tympanic thermometers must not be used. 
9.1.1.3.3 
Unsolicited Adverse Events  
In addition to recording solicited reactions, parents / guardians / legally authorized representatives 
will be instructed to record any other medical events that may occur during the 28-day period after 
each vaccination. Space will be provided in the diary card for this purpose. 
Information on SAEs will be collected and assessed throughout the study, from the time of 
enrollment until up the last visit. Any SAE occurring at any time during the study will be reported 
by the Investigator in the CRB according to the completion instructions provided by the Sponsor; 
this includes checking the "Serious" box on the AE CRF and completing the appropriate Safety 
Complementary Information CRFs. All information concerning the SAE is to be reported either as 
part of the initial reporting or during follow-up reporting if relevant information became available 
later (e.g., outcome, medical history, results of investigations, copy of hospitalization reports and 
verbal autopsy questionnaire if used). In case a participant experiences febrile convulsion 
(neurological event associating fever and seizure), the assessment will be performed according to 
the “Guideline for definition and collection of cases of febrile convulsion”, and this event will be 
considered an SAE. See Section 10 for further details on SAE reporting. 
For each unsolicited AE (whether serious or non-serious), the following information is to be 
recorded: 
• Start and stop datesa 
• Intensity of the event: 
The temperature for fever will be collected and analyzed based on the corresponding 
scale used for solicited reactions (see Table 9-2). 
All other unsolicited AEs will be classified according to the following intensity scale: 
• Grade 1: A type of adverse event that is usually transient and may require only 
minimal treatment or therapeutic intervention. The event does not generally 
interfere with usual activities of daily living. 
 
a  The stop date of all related AEs will be actively solicited. For other events, the investigator will provide the stop 
date when it becomes available. AEs for which no stop date was obtained during the course of the study will be 
considered as ongoing at the end of the study. 

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• Grade 2: A type of adverse event that is usually alleviated with additional 
therapeutic intervention. The event interferes with usual activities of daily living, 
causing discomfort but poses no significant or permanent risk of harm to the 
research participant.  
• Grade 3: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic 
intervention. 
• Whether the AE was related to the investigational product (for unsolicited systemic AEs) 
The Investigator will assess the causal relationship between the AE and the 
investigational product as either “Not related” or “Related”, as described in 
Section 9.1.1.3.6. 
• Action taken for each AE (e.g., medication) 
The action(s) taken by the parents / guardians / legally authorized representatives to treat 
and/or manage any unsolicited AEs will be classified in the CRB using the following list 
(all applicable items should be checked): 
• None 
• Medication 
• Health care provider contact 
• Hospitalized 
• Discontinuation of study vaccination 
• Whether the AE was an AESI, MAAE and/or SAE. 
For each SAE, the investigator will complete all seriousness criteria that apply (outcome, elapsed 
time, and relationship to study procedures) 
• Whether the AE caused study discontinuation 
9.1.1.3.4 
Medically Attended Adverse Events  
Any MAAEs occurring within the first 28 days post-vaccination (D0 to D28 for all participants in 
Cohorts 1, 2, 3 and 4 and D56 to D84 for participants in Cohorts 2 and 4) will be collected using 
the same process as other AEs. Medically attended acute respiratory illness (MAARI) and 
medically attended acute lower respiratory illness (MAALRI) events occurring within this time 
frame and outside the RSV surveillance season will be classified as MAAEs. 
9.1.1.3.5 
Adverse Events of Special Interest (AESI)  
Any AESIs occurring within the first 28 days post-vaccination (D0 to D28 for all participants in 
Cohorts 1, 2, 3 and 4 and D56 to D84 for participants in Cohorts 2 and 4) will be collected using 
the same process as other AEs. 

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All adverse events of special interest in the study would be graded by the Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected 
Version 2.1 - July 2017; see Table 9-3) (35) except for acute wheeze, which would be graded by 
the Brighton Collaboration Wheeze severity grading system (see Table 9-4) (36). The following 
adverse events of special interest are derived from previous NIH research experience with similar 
candidates and will be assessed in this study: 
• Acute otitis media 
• URI 
- 
Pharyngitis 
- 
Cough without LRI 
• LRI 
- 
Stridor 
- 
Rales 
- 
Tachypnea 
- 
Acute wheeze 
- 
Pneumonia 
- 
Laryngotracheobronchitis 
Acute Otitis media: 
Loss of tympanic membrane landmarks accompanied by erythema and loss of mobility. May or 
may not be associated with fever or other respiratory symptoms. Confirmed with tympanometry if 
possible. This diagnosis must be made by a medical professional. 
Pharyngitis: 
Pharyngeal erythema accompanied by exudate or pharyngeal erythema with enlarged tender 
lymph nodes. Note: May be associated with sore throat, or painful or difficult swallowing. This 
diagnosis must be made by a medical professional. 
Cough without LRI: 
Two or more consecutive days of 3 or more episodes of cough during a 15-minute timed 
observation period, or cough awakens child from sleep. There should be no associated lower 
respiratory tract illness. This diagnosis must be made by a medical professional. Note: Not 
associated with eating, drinking or choking. 
Stridor: 
Harsh medium-pitched inspiratory sound associated with obstruction of the laryngeal area or the 
extra-thoracic trachea, often accompanied by croupy cough and hoarse voice. This diagnosis must 
be made by a medical professional. 

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Rales: 
Abnormal lung sound heard through a stethoscope. Rales may be sibilant (whistling), dry 
(crackling) or wet (more sloshy) depending on the amount and density of fluid refluxing back and 
forth in the air passages. Must be sustained over 20 minutes and assessed and diagnosed by a 
medical professional with confirmation by a second medical professional, if possible. 
Tachypnea: 
Increased respiratory rate >40 breaths per minute in infants aged 6-12 months and >30 breaths per 
minute in toddlers aged 1-3 years. This diagnosis must be made by a medical professional. 
Acute Wheeze (36): 
According to the Brighton Collaboration case definition, for all levels of diagnostic certainty, 
acute wheeze is a clinical sign defined by: 
• Sudden onset, occurred unexpectedly and without warning, leading to a marked change in 
a participant’s previously stable condition, AND 
• Breath sound audible on auscultation, AND 
• Audible during expiration, the sound is primarily expiratory though an inspiratory 
component is possible in severe forms different from stridor, AND 
Characterized by the following criteria defining the level of diagnostic certainty: 
Level 1 
- 
Classified as wheeze based on digital stethoscope recording as compared with 
reference audio file, OR 
- 
Classified as wheeze by 2 health care providers with specific training e.g., 
Pulmonologist or formal auscultation training based on standard wheeze training 
tool 
Level 2a (one health care provider with specific training) 
- 
Classified as wheeze by 1 health care provider with specific training e.g., 
Pulmonologist or formal auscultation training based on standard wheeze training 
tool, AND 
- 
Immediate response to bronchodilator treatment i.e., absence of wheeze following 
treatment or improvement of wheeze severity documented by a healthcare provider 
Level 2b (2 health care providers) 
- 
Classified as wheeze by 2 health care providers without specific training i.e., 
neither a pulmonologist nor someone with formal auscultation training based on 
standard wheeze training tool, AND 
- 
Immediate response to bronchodilator treatment i.e., absence of wheeze following 
treatment or improvement of wheeze severity documented by a healthcare provider, 
OR 
- 
Infant diagnosed with acute bronchiolitis 

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Level 3 (pre-existing diagnosis) 
- 
Classified as wheeze by 1 health care provider OR caretaker (e.g., parent / guardian 
/ legally authorized representative) without specific training, AND 
- 
Pre-existing physician diagnoses of a respiratory disease of which wheeze is a key 
symptom 
The full Brighton Collaboration case definition is listed here but Level 3 of diagnostic certainty 
will not be required in this study and children with a pre-existing diagnosis of wheeze would not 
be enrolled in this study. 
Pneumonia: 
Rales and crackles sustained over 20 minutes, originating in the lower respiratory tract, usually 
accompanied by tachypnea, which do not clear with cough. This may be confirmed by x-ray 
showing areas of consolidation. Clinical assessment and diagnosis must be made by a medical 
professional with confirmation by a second medical professional, if possible. 
Laryngotracheobronchitis (croup): 
Barking cough, hoarseness, and inspiratory stridor and sustained over 20 minutes assessed and 
diagnosed by a medical professional with confirmation by a second medical professional, if 
possible. 
Table 9-3 presents the DAIDS severity scale for AESIs, except wheeze, Grade 1 through 4. 
Table 9-3: DAIDS severity scale for AESIs, except wheeze  
Grade 1 Mild 
Grade 2 Moderate 
Grade 3 Severe 
Grade 4 Potentially Life-
Threatening 
Mild symptoms 
causing no or minimal 
interference with usual 
social & functional 
activities with 
intervention not 
indicated  
Moderate symptoms 
causing greater than 
minimal interference 
with usual social & 
functional activities with 
intervention indicated  
Severe symptoms 
causing inability to 
perform usual social & 
functional activities with 
intervention or 
hospitalization indicated  
Potentially life-threatening 
symptoms causing inability to 
perform basic self-care functions 
with intervention indicated to 
prevent permanent impairment, 
persistent disability, or death  
All deaths related to an AESI are to be classified as Grade 5. 
Table 9-4 presents the Brighton Collaboration severity grading system for wheeze. 

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Table 9-4: Brighton Collaboration severity grading system for wheeze  
Grade 1 (mild) 
Grade 2 (moderate) 
Grade 3 (severe) 
Wheeze only 
Wheeze with respiratory distress 
Wheeze with danger signs 
Wheeze*† 
Wheeze 
AND  
• 
Lower chest wall indrawing  
OR 
• 
prolonged expirium (i.e., I/E 
ratio > 1:3) 
Wheeze‡ 
AND 
• 
Oxygen saturation <92% 
OR 
• 
Central cyanosis 
OR 
• 
Confusion or drowsiness 
OR 
• 
Inability to speak or drink 
I/E, Inspiratory/Inspiratory 
* There may even be tachypnea without other signs of respiratory distress 
† There may be tachycardia without other signs of respiratory distress 
‡ or silent chest on auscultation in a patient with history of wheeze 
 
9.1.1.3.6 
Assessment of Causality  
The Investigator will assess the causal relationship between each unsolicited systemic AE and the 
product administered as either not related or related, based on the following definitions: 
• Not related – The AE is clearly / most probably caused by other etiologies such as an 
underlying condition, therapeutic intervention, or concomitant therapy; or the delay 
between vaccination and the onset of the AE is incompatible with a causal relationship; 
or the AE started before the first vaccination 
• Related – There is a “reasonable possibility” that the AE was caused by the product 
administered, meaning that there is evidence or arguments to suggest a causal 
relationship 
Note: By convention, all AEs reported at the administration site (whether solicited or unsolicited) 
and all solicited systemic AEs are considered to be related to the administered product and 
therefore are referred to as reactions and do not require the Investigator’s opinion on relatedness. 
Adverse events likely to be related to the product, whether serious or not, that persist at the end of 
the study will be followed up by the Investigator until their complete disappearance or the 
stabilization of the participant’s condition. The Investigator will inform the Sponsor of the date of 
final disappearance of the event or the date of “chronicity” establishment. 
9.1.2 
Infectivity  
There are no primary objectives for infectivity. 

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9.1.3 
Immunogenicity  
9.1.3.1 
Immunogenicity Definition  
RSV Serostatus 
For this Sanofi Phase I/II study, serum IgA detection was chosen as a biomarker for RSV 
encounter in infants and toddlers. IgA serostatus, ie RSV-naïve and RSV-experienced, will be 
defined as undetectable or detectable serum anti-RSV A IgA antibodies, respectively. 
RSV IgA Serostatus Assessment  
The RSV IgA 
 for serostatus determination will be performed at Sanofi HEXIM lab, 
Orlando, FL or at a qualified contract laboratory for Sanofi GCI, Swiftwater, Pennsylvania. 
The IgA serostatus method to be used is summarized below. 
RSV IgA Method Description  
IgA antibodies to RSV F antigen will be measured using the anti RSV F IgA 
. RSV F 
protein antigen is coated on the surface of microtiter plates. The plates are blocked, then 
unadsorbed coating antigen is washed from the wells and serially diluted human serum samples 
(test samples, reference, and quality controls) are incubated in the wells. Anti-RSV F protein 
specific antibodies in the serum samples bind to the immobilized RSV F protein antigen. Unbound 
antibodies are washed from the wells and horseradish peroxidase (HRP)-conjugated goat anti-
human IgA enzyme conjugate is added. The conjugate binds to the antigen-antibody complexes. 
Excess conjugate is washed away, and a colorimetric substrate is added. Bound enzyme catalyzes 
a hydrolytic reaction which causes color development. The intensity of the color generated is 
proportional to the amount of antigen specific IgA antibody bound to the wells. The results are 
read on a spectrophotometer. 
The concentration of IgA antibodies to RSV F antigen is calculated over 6 serial two-fold 
dilutions with an assigned value in 
 Units (EU)/mL.  
9.1.3.2 
Immunogenicity Endpoints  
The primary endpoint for the evaluation of immunogenicity is: 
• RSV A serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4 in RSV-naïve participants. 
RSV-experienced and RSV-naïve participants are defined in Section 9.1.3.1. 
9.1.3.3 
Immunogenicity Assessment Methods  
Immunogenicity of the vaccine candidate will be evaluated by determining RSV A serum 
neutralizing antibody titers (using the Microneutralization assay). 
RSV Neutralizing Antibody Assessment  
The RSV Microneutralization (MN) assay will be performed at Sanofi Pasteur GCI, Swiftwater, 
Pennsylvania or at a qualified contract laboratory for GCI. 

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The MN method to be used is summarized below. Development and qualification of this method 
is completed. The evaluation of an optimized MN assay (developed at Sanofi) and a micro plaque 
reduction neutralization test (being developed at CRO) are ongoing for Phase III studies (23) (28). 
RSV MN Method Description 
RSV neutralizing antibodies will be measured using a MN assay. Serial, two-fold dilutions of 
serum to be tested (previously heat-inactivated) are mixed with a constant concentration of the 
RSV-A2 strain (ATCC VR-1540). The mixtures are inoculated into wells of a 96-well microplate 
with permissive HEp-2 cells (ATCC CCL-23) and incubated for 2 days. A reduction in virus 
infectivity (viral antigen production) due to neutralization by antibody present in serum samples is 
detected by 
 After washing and fixation, RSV 
antigen production in cells is detected by successive incubations with an RSV-specific mAb, 
horse radish peroxidase anti-mouse IgG conjugate, and a chromogenic substrate. The resulting 
Optical Density is measured using a microplate reader. The reduction in RSV infectivity as 
compared to that in the virus control wells constitutes a positive neutralization reaction indicating 
the presence of neutralizing antibodies in the serum sample. 
9.1.4 
Efficacy  
There are no primary objectives for efficacy. 
9.2 
Secondary Endpoints and Assessment Methods  
9.2.1 
Safety  
9.2.1.1 
Safety Definitions  
The safety definitions are presented in Section 9.1.1.1. 
9.2.1.2 
Safety Endpoints  
The secondary endpoints for the evaluation of safety are: 
• Titer of vaccine virus shedding on D7 for Cohorts 1, 2, 3 and 4, and D63 for Cohorts 2 and 
4 measured by 
. 
9.2.1.3 
Safety Assessment Methods  
Shedding of the attenuated RSV vaccine strain in nasal swab samples will be evaluated by RSV 
quantitative Reverse Transcriptase Polymerase Chain Reaction 
, which can 
specifically detect and quantify RSVt ΔNS2 vaccine strain (RSV ΔNS2/Δ1313/I1314L) in human 
nasal swab samples. Based on the evaluation of precision (intra-assay and intermediate precision), 
dilutional accuracy, linearity, and specificity, RSVt 
 is suitable for clinical testing 
of human nasal swab samples in support of the development of RSV Vaccine candidates. 

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RSVt NS2 
 
The RSVtNS2 
 will be performed at Sanofi Pasteur GCI, Swiftwater, PA or at a 
qualified contract laboratory for GCI. 
The RSVtNS2 
 will be used to measure virus shedding from nasal swab 
samples from study participants. Development and qualification of this method is completed; this 
method will be validated prior to Phase III clinical testing. 
RSVt NS2 
 Description 
To quantify viral shedding in infants vaccinated with RSV ΔNS2/Δ1313/I1314L (RSVt) vaccine, 
a
 was developed that would specifically detect and quantify RSV ΔNS2 
candidate in nasal swab samples. Beyond the deletion of the NS2 gene, there are few sequence 
differences between RSV ΔNS2/Δ1313/I1314L vaccine and wt RSV A. 
RSVt 
 was designed using the Light Cycler Probe system from Sigma. This 
system consists of two hybridization probes that are designed so that they bind the target 1-5 
nucleotides apart. Probe 1 (donor) is labeled on the 3’ end with a donor reporter. Probe 2 
(acceptor) is labeled at the 5’ end with an acceptor reporter. During the annealing step, the 
 
primers and the LightCycler Probes hybridize to their specific target regions, bringing the probes 
in proximity. When this happens, the donor dye is excited by the LightCycler, and energy is 
transferred from the donor to the acceptor dye. The acceptor reporter’s emission is detected by the 
Light Cycler at 640 nm. 
If the probes bind, but are not in proximity, no signal is produced. The Light Cycler probes for the 
RSVt 
 target the deletion site of the NS2 gene in RSVt ΔNS2. Probe 1 binds 
before the deletion and Probe 2 binds across the deletion site. While the primers and probes may 
bind wild-type RSV A due to high sequence similarity, the two probes would not bind in close 
enough proximity to create signal as the NS2 gene is over 500 nucleotides long, making this 
method highly specific. 
Collection of nasal swab samples from infants can be difficult and sample quality cannot be visually 
verified. Therefore, an RNase P assay, based on one developed by the CDC will be used in 
conjunction with the RSVt 
 to evaluate sample quality.  
RNase P is a human housekeeping gene. Use of the RNase P assay will limit the impact of false 
negatives because of poor sample collection or handling. Amplification in the RNase P assay 
indicates the presence of human cells in a sample. An RNase P Cp of ≤ 37 indicates that the sample 
was appropriately collected, and that sample integrity was maintained. RNase P testing will be 
performed only when 
 (to detect and quantify RSVt ΔNS2 vaccine strain) yields negative 
results. 
 

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9.2.2 
Infectivity  
9.2.2.1 
Infectivity Endpoint  
The secondary endpoint for the evaluation of infectivity is vaccinee infection with the vaccine 
virus. Infection is defined as detection of vaccine virus in nasal swab by 
 and / or a ≥ 4-
fold rise in RSV A serum neutralizing antibody titers, or in RSV serum anti-F IgG antibody titers. 
9.2.2.2 
Infectivity Assessment Methods  
The infectivity assessment methods are presented in Section 9.2.1.3. 
9.2.3 
Immunogenicity  
9.2.3.1 
Immunogenicity Endpoints  
The secondary endpoints for the evaluation of immunogenicity are: 
• RSV serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4 in RSV-experienced participants. 
• RSV serum anti-F IgG antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4. 
• RSV A serum neutralizing and serum anti-RSV F IgG antibody titers after the RSV season 
or at least five months after last vaccine administration. 
9.2.3.2 
Immunogenicity Assessment Methods  
RSV-experienced and RSV-naïve participants are defined in Section 9.1.3.1. 
Immunogenicity of the vaccine candidate will also be evaluated by determining RSV F protein 
binding antibody levels (by 
). 
RSV Anti-F IgG 
  
The anti-RSV F IgG 
 will be performed at Sanofi Pasteur GCI, Swiftwater, Pennsylvania 
or at a qualified contract laboratory for GCI. 
The 
 method to be used is summarized below. The method is currently in development and 
a detailed procedure will be submitted prior to the start of clinical testing. The method will be 
qualified for Phase I and II studies and will be validated prior to Phase III clinical testing. 
RSV Anti-F IgG 
 Method Description 
Antibodies to RSV F antigen will be measured using the anti RSV F IgG 
. Briefly, the RSV 
F antigen (from strain RSV A2) is coated onto a microtiter plate and serial 2-fold dilutions of 
human serum samples are added and incubated to allow binding to the RSV F antigen. Then an 
HRP-conjugated anti-human IgG detection antibody is added followed by colorimetric substrate. 
The concentration of IgG antibodies to RSV F antigen is calculated over 6-serial dilutions relative 
to qualified internal reference calibrated against WHO International standard (1st International 

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Standard for antiserum for Respiratory Syncytial Virus) with an assigned value (International 
Units /mL). 
9.2.4 
Efficacy  
There are no secondary objectives for efficacy. 
9.3 
Exploratory Endpoints and Assessment Methods  
9.3.1 
Safety  
9.3.1.1 
Safety Definitions  
The safety definitions are presented in Section 9.1.1.1. 
9.3.1.2 
Safety Endpoints  
The exploratory endpoints for the evaluation of safety are: 
• Occurrence of any unsolicited systemic AEs reported in the 30 minutes after each and any 
vaccination. 
• Occurrence of solicited (i.e., pre-listed in the participant’s DC / eDC and in the CRB) 
administration site and systemic reactions within 28 days after each and any vaccination 
(i.e, Acute Phase). 
• Occurrence of any unsolicited (spontaneously reported) AEs within 28 days after each and 
any vaccination. 
• Occurrence of any AESIs within 28 days after each and any vaccination. 
• Occurrence of any MAAE within 28 days after each and any vaccination. 
• Occurrence of any SAEs throughout the study. 
9.3.1.3 
Safety Assessment Methods  
The safety assessment methods are presented in Section 9.1.1.3. 
9.3.2 
Infectivity  
There are no exploratory objectives for infectivity. 

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RSV Anti-F IgA 
 Method Description 
The method is described in Section 9.1.3.1. 
9.3.4 
Efficacy  
9.3.4.1 
Efficacy Endpoints  
The exploratory endpoints for the evaluation of efficacy assessed through the RSV season or post-
vaccination surveillance period are: 
• RSV medically attended acute respiratory illness (RSV MAARI) 
• RSV medically attended acute lower respiratory illness (RSV MAALRI) 
• A diagnosis of RSV MAARI requires a respiratory sample positive for RSV by 
 AND 
documented physical exam findings of respiratory tract illness including any of the following: 
o Fever 
o Acute otitis media 
o Upper respiratory tract illness: 
• Runny nose/rhinorrhea 
• Pharyngitis 
• Cough without LRI 
o Lower respiratory tract illness (see MAALRI below) 
• A diagnosis of RSV MAALRI (a subset of MAARI) requires a respiratory sample positive for 
RSV by 
 AND documented physical exam findings of lower respiratory tract illness 
including any of the following: 
o Stridor 
o Rales 
o Tachypnea 
o Acute wheeze 
o Pneumonia 
o Laryngotracheobronchitis 
9.3.4.2 
Efficacy Assessment Methods  
The method for the exploratory efficacy endpoints is the 
, an automated 
qualitative nucleic acid multiplex in vitro diagnostic test designed to simultaneously detect and 
identify multiple respiratory viral and bacterial nucleic acids in NS samples.  
 Method: 
The ePlex system which is used to run the 
 is a closed system that automates 
all aspects of nucleic acid testing including extraction, amplification, and detection. Electrowetting 
or digital microfluidics use electrical fields to manipulate droplets on the surface of a 

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hydrophobically coated printed circuit board (PCB). Samples and reagents are moved in a 
programmable fashion in the ePlex cartridge to complete all portions of the sample processing. 
Nucleic acid extraction from biological samples occurs within the cartridge via cell lysis, followed 
by nucleic acid capture onto magnetic beads and release for 
 amplification. Thereafter, 
exonuclease digestion creates single-stranded DNA in preparation for eSensor detection. eSensor 
technology is based on the principles of competitive DNA hybridization and electrochemical 
detection, which is highly specific and is not based on fluorescent or optical detection. Competitive 
DNA hybridization: the single-stranded target DNA binds to a complementary, single-stranded 
capture probe, immobilized on the working gold electrode surface. The single-stranded signal 
probes (labeled with electrochemically active ferrocenes) bind to a specific target sequence/region 
adjacent to the capture probe. Simultaneous hybridization of the target to signal probes and capture 
probe is detected by alternating current voltammetry (ACV). Each working electrode on the array 
contains specific capture probes, and the sequential analysis of each electrode allows for the 
detection of multiple analyte targets. 
The 
 is a qualitative assay. It will only indicate the presence or absence of a 
viral or bacterial target in a nasal swab sample collected in viral transport medium (VTM) and will 
not be used to calculate a viral titer. The 
 can detect and distinguish between 
sixteen respiratory viral targets and two respiratory bacterial targets as shown in Table below. 

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Each clinical sample (NS sample in VTM) will be tested in singleton in an individual cartridge. One 
Negative Control (NC) must be included within each batch of clinical samples being tested. When 
possible, the NC should be the last sample of the batch to be loaded in cartridge. One set of Positive 
Control (comprising of six PC(s) designated PC1-PC6)) must be run simultaneously as the first 
Batch on the day clinical samples are tested. 
10 Reporting of Serious Adverse Events 
To comply with current regulations on SAE reporting to health authorities, the Investigator must 
document all SAEs regardless of causal relationship and notify the Sponsor and the Clinical 
Research Associate (CRA) within the notification timelines stated in the following sections. The 
Investigator will give access and provide the Sponsor and the CRA with all necessary information 
to allow the Sponsor to conduct a detailed analysis of the safety of the investigational product(s). 
It is the responsibility of the Investigator to request all necessary documentation (e.g., medical 
records, discharge summary, and verbal autopsy in order to provide comprehensive safety 

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information). All relevant information must then be transcribed onto the AE CRF and the 
appropriate Safety Complementary Information CRFs. 
10.1 Initial Reporting by the Investigator  
Serious adverse events occurring during a participant’s participation in the study or experiment 
must be reported within 24 hours to the Sponsor’s GPV Department and to the CRA. Every SAE 
must be reported, even if the Investigator considers that it is not related to the vaccine. The 
investigator (licensed physician [M.D. or D.O.]) must validate the information entered on the AE 
CRF by completing the investigator validation form. 
The Investigator must indicate on the AE CRF that the event was serious and must complete the 
relevant SAE section of this form as well as the appropriate Safety Complementary Information 
CRFs. An e-mail alert will automatically be sent by the EDC system to the GPV mailbox, the 
CRA and the Clinical Team Leader with relevant SAE information details. 
If the EDC system is unavailable, the site must notify the Sponsor, using the paper version of the 
CRB, as described in the operating guidelines. 
The Investigator must complete the paper copies of the AE CRF and of the appropriate Safety 
Complementary Information CRFs and send them to the Sponsor by one of the following means: 
• By fax, to the following number: 570-957-2782 
• In PDF format to the following e-mail address, using a method of transmission that 
includes password protection: SanofiPasteurPharmaco@sanofi.com 
By express mail, to the following address: 
Sanofi Pasteur Inc. 
Reception and Triage – Case Management 
Global Pharmacovigilance 
Mail Drop: 45D38 
Discovery Drive 
Swiftwater, PA 18370 
When the EDC system becomes available, the Investigator must transcribe the information from 
the paper forms into the EDC system. 
If there is need for urgent consultation, the Investigator is to contact the RMO. If the RMO cannot 
be reached, the Investigator may contact the Call Center as described in Section 5.3. 
10.2 Follow-up Reporting by the Investigator  
The AE CRF completed initially must be updated within 24 hours after the Investigator has 
become aware of any new relevant information concerning the SAE (e.g., outcome, precise 
description of medical history, results of the investigation). All relevant information must be 
included directly in the AE CRF and the appropriate Safety Complementary Information CRFs. 
An e-mail alert will be sent automatically to the GPV Department and to the CRA. Copies of 
documents (e.g., medical records, discharge summary, autopsy) may be requested by the GPV 
Department. 

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The anonymity of the participant must always be respected when forwarding this information. 
10.3 Reporting of SAEs Occurring After a Participant Has Completed the Study  
Any SAE that occurs after a participant has completed the study but that is likely to be related to 
the investigational product(s), other products (e.g., a benefit vaccine), or to the experiment must 
also be reported as soon as possible. In such a case, the reporting procedure to be followed is 
identical to that described in Section 10.1. 
10.4 Assessment of Causality  
The causal relationship between the SAE and the product administered will be evaluated by the 
Investigator as described in Section 9.1.1.3.6. 
Following this, the Sponsor’s Global Safety Officer will also assess the causal relationship to the 
product, based on the available information and current medical knowledge. 
The causal relationship to study procedures will be also assessed in the CRB. 
The decision to modify or discontinue the study may be made after mutual agreement between the 
Sponsor and the Investigators. 
10.5 Reporting SAEs to Health Authorities and IECs / IRBs  
The Sponsor will inform the relevant health authorities of any reportable SAEs according to the 
local regulatory requirements. Reporting to the health authorities will be according to the 
Sponsor’s standard operating procedures. 
The Sponsor’s RMO will notify the Investigators in writing of the occurrence of any reportable 
SAEs. The Investigators / Sponsor will be responsible for informing the IECs or IRBs that 
reviewed the study protocol. 
10.6 Using a Verbal Autopsy Questionnaire to Aid in Determining the Cause of 
Death  
In case of the absence or inadequacy of health information that would allow a thorough evaluation 
of the causes of the death of a participant participating in the study, the verbal autopsy procedure 
may be triggered by either the Investigator or the Sponsor. Detailed instructions on the use of the 
verbal autopsy questionnaire, as well as the questionnaire itself, are provided in the Operating 
Guidelines. 

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11 Data Collection and Management  
11.1 Data Collection and CRB Completion  
Individual diary cards / electronic diary cards, specifically designed for this study by the Sponsor 
and provided to the study sites, will be given to study participants for the recording of daily safety 
information as described in Section 9.1.1.3. These diary cards / electronic diary cards will include 
pre-listed terms and intensity scales (see Table 9-1 and Table 9-2) as well as areas for free text to 
capture additional safety information or other relevant details. Parents / guardians / legally 
authorized representatives will also be provided with standard digital thermometers for measuring 
daily temperatures. To ensure consistency of reporting, the study sites will instruct parents / 
guardians / legally authorized representatives on how to correctly use these tools. 
During the period between the final vaccination and the final visit, follow-up will be done by 
interviewing participants either during a visit or over the telephone using a questionnaire to 
capture SAEs, MAAEs and AESIs, if applicable. A memory aid may be provided to the 
participants at the preceding study visit to help them record information on events occurring 
between this visit and the 6-month follow-up. 
Relevant information will be transcribed into the AE CRF. Any SAEs captured during this 6-
month follow-up period will be reported and followed-up as per the normal process for reporting 
SAEs. 
At specified intervals, the Investigator or an authorized designee will interview the parents / 
guardians / legally authorized representatives to collect the information recorded in the diary card 
/ electronic diary card and will attempt to clarify anything that is incomplete or unclear. All 
clinical study information gathered by the study site will be reported electronically by the 
Investigator or authorized designee using a web-based CRB. (Any information that was not 
documented in the diary card / electronic diary card will first be captured in the source document 
and then reported electronically.) The CRB has been designed specifically for this study under the 
responsibility of the Sponsor, using a validated Electronic Records / Electronic Signature-
compliant platform (21 CFR Part 11). 
To ensure the correct and consistent completion of the CRBs, the Sponsor or authorized 
representative will provide all necessary tools, instructions, and training to all site staff involved 
in data entry prior to study start. Additional instructional documents such as training manuals and 
completion instructions will be provided to assist with data entry during the course of the study. 
Upon completion of training, each user requiring access to the EDC system will be issued a 
unique username and password. In the event of a change in study personnel, each newly assigned 
individual will receive a unique username and password; the username and password of a 
previous user may not be reissued. If any study personnel leave the study, the Investigator is 
responsible for informing the Sponsor immediately so that their access is deactivated. An audit 
trail will be initiated in the EDC system at the time of the first data entry to track all modifications 
and ensure database integrity. 

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The Investigator is responsible for the timeliness, completeness, and accuracy of the information 
in the CRBs; must provide explanations for all missing information; and must sign the CRB using 
an e-signature. 
11.2 Data Management  
Management of SAE 
During the study, SAE data (reported on the AE, Death, and Safety Complementary Information 
CRFs) will be integrated into the Sponsor’s centralized GPV database upon receipt of these forms 
and after a duplicate check. Each case will be assigned a case identification number. Each case 
will be assessed by the case management platform or its delegate before being reported to the 
relevant authorities as necessary. The assessment of related cases will be done in collaboration 
with the Global Safety Officer and the RMO. Follow-up information concerning a completed case 
will be entered into the GPV database, and a new of the case will be created. 
The information from the GPV database cases will be reconciled with that in the clinical database. 
Management of Clinical and Laboratory Data 
Clinical data, defined as all data reported in the CRB, and laboratory data will be handled by the 
Sponsor’s Clinical Data Management (CDM) platform or authorized representative. 
During the study, clinical data reported in the CRBs will be integrated into the clinical database 
under the responsibility of the Sanofi Pasteur CDM platform. Data monitoring at the sites and 
quality control in the form of computerized logic and / or consistency checks will be 
systematically applied to detect errors or omissions. In addition, data reviews may be performed 
several times by the Sponsor’s staff in the course of the study. Any questions pertaining to the 
reported clinical data will be submitted to the investigator for resolution using the EDC system. 
Each step of this process will be monitored through the implementation of individual passwords to 
maintain appropriate database access and to ensure database integrity. 
The validation of the immunogenicity data will be performed at the laboratory level following the 
laboratory’s procedures. Information from the laboratory will be checked for consistency before 
integration into the clinical Datawarehouse. 
After integration of all corrections in the complete set of data, and after the SAE information 
available from CDM and the GPV Department has been reconciled, the database will be released for 
statistical analysis. 
11.3 Data Review  
A blind review of the data is anticipated through the data review process led by Data Management 
before database lock. 

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12 Statistical Methods and Determination of Sample Size  
12.1 Statistical Methods  
12.1.1 Hypotheses and Statistical Methods for Primary Objectives  
12.1.1.1 Hypotheses  
All analyses will be descriptive; no hypothesis will be tested. 
12.1.1.2 Statistical Methods  
The statistical methodology will be based on the use of two-sided 95% confidence intervals (CI). 
The 95% CIs of point estimates will be calculated using the exact binomial distribution (Clopper-
Pearson method (37) for proportions. 
For immunogenicity data, assuming that log10 transformation of the titers/titer ratio follows a 
normal distribution, first, the mean and 95% CIs will be calculated on log10 (titers/titers ratio) 
using the usual calculation for normal distribution. Then antilog transformations will be applied to 
the results of calculations, to compute geometric mean titers (GMTs) and geometric mean titers 
ratios (GMTRs) and their 95% CIs. 
Safety 
Solicited adverse reactions (ARs), unsolicited AEs (including SAEs), MAAEs and AESIs will be 
summarized. The main parameters will be described with 95% CI. At least the following 
parameters will be presented by vaccine group after each and any vaccination, in all participants 
regardless of baseline serostatus: 
• Unsolicited systemic AEs occurring within 30 minutes of administration (immediate 
unsolicited AEs) 
• Solicited administration site reactions and solicited systemic reactions within 28 days after 
each and any administration according to occurrence, time to onset, intensity, number of 
days of occurrence, action taken, and whether the reaction led to early termination from 
the study. When more than 1 intensity level is reported within a time period, the highest 
intensity will be used. 
• Unsolicited AEs occurring within 28 days after each and any administration by system 
organ class (SOC) and preferred term (PT), relationship, intensity, time to onset, duration 
and whether the AE led to early termination from the study. 
• All SAEs that occur throughout the study by SOC and PT, seriousness criteria, time to 
onset, outcome, relationship, and whether the SAE led to early termination throughout the 
study 
• All MAAEs and AESIs reported within 28 days after each and any vaccination by SOC 
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A Bayesian approach based on Posterior Distribution may be used to assess the difference 
between each RSV formulation and placebo on the following safety endpoints: 
• Any Grade 3 lower respiratory tract illness e.g., wheezing, pneumonia, sustained 
tachypnea, laryngotracheobronchitis 
• Grade 3 fever 
See Section 15 for further details. 
Immunogenicity  
The point estimates and their 95% CI of the following parameters will be presented for RSV A 
neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for Cohorts 2 and 4, for 
each vaccine group in RSV-naïve participants: 
• GMT 
• GMTR based on the baseline antibody titer 
• Seroresponse rates defined as percentage of participants with a ≥ 4-fold rise in RSV A 
serum neutralizing antibody titers based on the baseline value. 
• Reverse cumulative distribution curves (RCDCs) will be presented 
• Pairwise comparisons between vaccine groups may be conducted as exploratory analyses 
to compare seroresponse rates or GMTs for descriptive purpose. 
The 95% CIs of the difference of proportions between 2 groups would be computed using the 
Wilson Score method without continuity correction. CIs of ratio of GMTs between 2 groups will 
be computed from the difference in means of log10 transformed titers between 2 groups with 
normal approximation. 
12.1.2 Hypotheses and Statistical Methods for Secondary Objectives  
12.1.2.1 Hypotheses  
All analyses will be descriptive; no hypothesis will be tested. 
12.1.2.2 Statistical Methods  
Safety 
The point estimates and their 95% CI of the following parameter will be presented 7 days after 
each vaccination (D7 for Cohorts 1, 2, 3 and 4, and D63 for Cohorts 2 and 4) for each vaccine 
group by baseline serostatus: 
• GMT of vaccine virus shedding measured by 
 
Infectivity  
The point estimate and its 95% CI of the following parameters will be presented after vaccination 
1 (D56) for Cohorts 1, 2, 3 and 4, and after vaccination 2 (D84) for Cohorts 2 and 4 for each 
vaccine group by baseline serostatus: 

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• Proportion of vaccinees infected with the vaccine virus. Infection defined as detection of 
vaccine in nasal swab by 
 and / or a ≥ 4-fold rise in RSV A 
serum neutralizing antibody titers or RSV serum anti-F IgG antibody titers. 
Immunogenicity 
The point estimates of GMT and GMTR and their 95% CI will be presented by vaccine group for 
the following endpoints: 
• RSV A serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4, in RSV-experienced participants 
• RSV serum anti-F IgG antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4 by baseline serostatus. 
• RSV A serum neutralizing and anti-RSV F IgG antibody titers after RSV season or at least 5 
months after last vaccine administration by baseline serostatus. 
Seroresponse may also be presented, as applicable. 
12.1.3 Statistical Methods for Exploratory Objectives  
Safety 
Solicited ARs, unsolicited AEs (including SAEs), MAAEs and AESIs will be summarized. The 
main parameters will be described with 95% CI. Main parameters, as described in 
Section 12.1.1.2, will be presented by vaccine group after each and any vaccination by baseline 
serostatus. 
Immunogenicity 
The point estimates of GMT and GMTR and their 95% CI will be presented by vaccine group and 
by baseline serostatus for the following endpoints: 
• RSV A serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4, converted into international units (IU)/mL. 
• RSV A serum neutralizing antibody titers converted into IU/mL, after the RSV season or 
at least 5 months after last vaccine administration.  
• RSV B serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4. 
• RSV B serum neutralizing antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4, converted into IU/mL. 
• RSV B serum neutralizing antibody titers after the RSV season or at least 5 months after 
last vaccine administration. 
• RSV B serum neutralizing antibody titers converted into IU/mL, after the RSV season or 
at least 5 months after last vaccine administration. 
• RSV A and RSV B serum anti-Gcc IgG antibody titers by D56 for Cohorts 1, 2, 3 and 4, 
and by D84 for Cohorts 2 and 4. 

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• RSV A and RSV B serum anti-Gcc IgG antibody titers after the RSV season or at least 
5 months after last vaccine administration. 
• RSV serum anti-F IgA antibody titers by D56 for Cohorts 1, 2, 3 and 4, and by D84 for 
Cohorts 2 and 4. 
• RSV serum anti-F IgA antibody titers after the RSV season or at least 5 months after last 
vaccine administration. 
Seroresponse may also be presented, as applicable. 
Efficacy  
RSV Medically attended respiratory illness collected during the RSV season or at least 5 months 
after last vaccine administration will be summarized. The main parameters will be described with 
95% CI. At least the following parameters will be presented by vaccine group: 
• RSV medically attended acute respiratory illness (RSV MAARI) by SOC and PT, 
intensity, time to onset, and duration 
• RSV medically attended lower respiratory illness (RSV MAALRI) by SOC and PT, 
intensity, time to onset, and duration 
12.2 Analysis Sets  
12.2.1 Full Analysis Set  
The full analysis set (FAS) is defined as the subset of randomized participants who received at 
least 1 administration of the study vaccine. The data for any participant infected by laboratory 
confirmed wt RSV will be excluded from immunogenicity and viral shedding analyses from the 
date of wt RSV infection. 
12.2.2 Safety Analysis Set  
The safety analysis set (SafAS) is defined as those participants who have received at least 
1 administration of the study vaccine. All participants will have their safety analyzed after each 
administration according to the vaccine they actually received and after any vaccination according 
to the vaccine received at the first administration. 
Safety data recorded for a vaccine received out of the protocol design will be excluded from the 
analysis (and listed separately). 
12.2.3 Per-Protocol Analysis Set  
The per-protocol analysis set (PPAS) is a subset of the FAS. Two specific PPAS will be defined: 
PPAS1 after 1 administration (for participants in Cohorts 1, 2, 3 and 4) and PPAS2 after 2 
administrations (for participants in Cohorts 2 and 4). 
The participants presenting with at least one of the following relevant protocol deviations will be 
excluded from the PPAS: 
• Baseline serology blood sample was not collected at visit 01 (D0). 

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• Participant with temporary contraindication did not receive vaccination 1 in the proper 
time window from randomization. 
• Participant did not meet all protocol-specified inclusion criteria or met at least one of the 
protocol-specified exclusion criteria 
• Participant did not receive vaccine / did not complete the vaccination schedule 
• Participant received a vaccine other than the one that he / she was randomized 
• Preparation and / or administration of vaccine not done as per-protocol 
• Participant received a protocol-prohibited therapy before the post-vaccination serology 
blood sample (see Section 6.7.1) 
• Participant with confirmed diagnosis of wt RSV before the post-vaccination serology 
blood sample 
• Participant with an emergency unblinding performed by the Investigator 
The participants presenting with at least one of the following relevant protocol deviations will be 
excluded from the PPAS1 only: 
• Post-vaccination 1 serology blood sample not collected at visit 03  
• Post-vaccination 1 serology blood sample not collected at visit 03 in the proper time 
window 
The participants presenting with at least one of the following relevant protocol deviations will be 
excluded from the PPAS2 only (for participants in Cohorts 2 and 4): 
• Participant did not receive vaccination 2 at visit 03 in the proper time window 
• Post-vaccination 2 serology blood sample not collected at visit 05  
• Post-vaccination 2 serology blood sample not collected at visit 05 in the proper time 
window 
In addition to the reasons listed above, participants will also be excluded from the PPAS if their 
baseline serology sample or their post-vaccination serology sample did not produce a valid test 
result (i.e., result for RSV A serum neutralizing antibody titers is missing). 
Note: For PPAS1 (after 1 administration), timepoints to be considered are: D0 (visit 01) for 
vaccination and D56 (visit 03) for the post-vaccination serology sample. For PPAS2 (after 2 
administrations), timepoints to be considered are: both D0 (visit 01) and D56 (visit 03) for 
vaccinations and D84 (visit 05) for the post-vaccination serology sample. 
12.2.4 Other Analysis Set(s)  
Randomized participants 
A randomized participant is a participant for whom a vaccine group has been allocated. 
12.2.5 Populations Used in Analyses  
The safety analysis will be performed on the SafAS. Participants will be analyzed after each 
vaccination according to the vaccine they actually received, and after any vaccination according to 
the vaccine received at the first administration. 

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Immunogenicity analyses will be performed on the Full Analysis Set, and on the Per-Protocol 
Analysis Set for main immunogenicity parameters. In the FAS, participants will be analyzed by 
the vaccine group to which they were randomized. In the PPAS, participants will be analyzed 
according to the vaccine they actually received. 
12.3 Handling of Missing Data and Outliers  
12.3.1 Safety  
No replacement will be done. Nevertheless, missing relationship will be considered as related at 
the time of the statistical analysis. No search for outliers will be performed. In all participant 
listings, partial and missing data will be clearly indicated as missing. 
12.3.2 Immunogenicity  
Missing data will not be imputed. No test or search for outliers will be performed. 
For the calculation of GMT and proportion of participants with nAb titers above thresholds, any 
pre-vaccination or post-vaccination value reported as < lower limit of quantification (LLOQ) will 
be converted to a value of ½ LLOQ. 
For the calculation of GMTR, any pre-vaccination value reported as < LLOQ will be converted to 
LLOQ, and any post-vaccination value reported as < LLOQ will be converted to a value of ½ 
LLOQ when only either the numerator or the denominator is < LLOQ. If both numerator and 
denominator are < LLOQ, then both will be converted in the same way so that individual titer 
ratio = 1. 
Any value reported as > upper limit of quantification (ULOQ) will be converted to ULOQ. 
12.3.3 Efficacy  
Missing data will not be imputed. No test or search for outliers will be performed. 
12.4 Interim / Preliminary Analysis  
The analysis will be performed with a stepwise approach. 
Several blinded early safety data reviews will be performed on safety data collected in participants 
from each cohort at specific timepoints (see Section 5.1.6). 
An unblinded interim analysis is planned on participants from Cohorts 1, 2 and 3, and at least 90 
participants enrolled in Cohort 4. The interim analysis will take place when participants have 
provided safety data up to the D84 timepoint and have D84 immunogenicity results available. 
This unblinded interim analysis requires the unblinding of data; a specific process will be 
implemented to maintain the blind at the participant and Investigator levels. 
An unblinded early analysis is planned on participants from all Cohorts (Cohorts 1, 2, 3, and 4). 
The early analysis will take place when all participants have provided safety data up to the D84 
timepoint and have D84 immunogenicity results available. This early analysis requires unblinding 

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of data; a specific process will be implemented to maintain the blind at the participants and 
Investigator levels. Based on the results of this analysis, a dose will be confirmed for future 
studies. 
The final unblinded statistical analysis will address the objectives on all participants including 
post season data. 
No statistical adjustment is necessary because no hypotheses will be tested. 
12.5 Determination of Sample Size and Power Calculation  
No sample size calculation was done as there are no statistical hypotheses in this study. 
A total of 300 participants are planned to be enrolled into 1 of the 4 cohorts sequentially:  
• Cohort 1 (1 administration): 40 participants, i.e., 20 per vaccine group (RSV low-dose or 
placebo) 
• Cohort 2 (2 administrations): 40 participants, i.e., 20 per vaccine group (RSV low-dose or 
placebo) 
• Cohort 3 (1 administration): 40 participants, i.e., 20 per vaccine group (RSV high-dose or 
placebo) 
• Cohort 4 (2 administrations): 180 participants, i.e., 60 per vaccine group (RSV high-dose 
or RSV low-dose or placebo). 
Although there are no statistically powered hypotheses and no sample size computation in this 
study, the sample size of 100 participants in the RSV low-dose group (20 from Cohort 1, 20 from 
Cohort 2 and 60 from Cohort 4) will provide a probability of 95% to observe an event that has a 
true incidence of 3%. The sample size of 80 participants in the RSV high-dose group (20 from 
Cohort 3 and 60 from Cohort 4) will provide a probability of 95% to observe an event that has a 
true incidence of 3.75%. 
A total of 300 participants are planned to be enrolled in the study. This corresponds to 120 
participants in Placebo group, 100 participants in RSV low-dose group and 80 participants in RSV 
high-dose group. Table 12-1 below presents the number of participants by serostatus, in total and 
by RSV group, according to varying possible RSV-experienced rates ranging from 5% to 35% 
(derived from LID/NIH screening data) and provides a global overview of the proportion of RSV-
naïve/RSV-experienced participants that will be enrolled in the study. 

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Table 12-1: Number of Participants by Serostatus, in Total and by RSV Group, According 
to Varying Possible RSV-experienced Rates Ranging from 5% to 35%  
% RSV 
experienced 
Total (N=300) 
RSV low-dose group (N=100) 
RSV high-dose group (N=80) 
#RSV 
experienced 
#RSV-naïve  
#RSV 
experienced 
#RSV-naïve 
#RSV 
experienced 
#RSV -naïve 
5% 
15 
285 
5 
95 
4 
76 
10% 
30 
270 
10 
90 
8 
72 
15% 
45 
255 
15 
85 
12 
68 
20% 
60 
240 
20 
80 
16 
64 
25% 
75 
225 
25 
75 
20 
60 
30% 
90 
210 
30 
70 
24 
56 
35% 
105 
195 
35 
65 
28 
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13 Ethical and Legal Issues and Investigator / Sponsor Responsibilities  
13.1 Ethical Conduct of the Study / Good Clinical Practice  
The conduct of this study will be consistent with the standards established by the Declaration of 
Helsinki and compliant with the ICH guidelines for GCP as well as with all local and / or national 
regulations and directives. 
13.2 Source Data and Source Documents  
“Source data” are the data contained in source documents. Source documents are original 
documents or certified copies, and include, but are not limited to, diary cards / electronic diary 
cards, medical and hospital records, screening logs, informed consent / assent forms, telephone 
contact logs, and worksheets. The purpose of study source documents is to document the 
existence of participants and to substantiate the integrity of the study data collected. Investigators 
must maintain source documents so that they are accurate, complete, legible, and up to date. 
For missing or discrepant data on a diary card / electronic diary card, the study coordinator will 
obtain verbal clarification from the participant, enter the response into the “investigator’s 
comment” page of the diary card / electronic diary card, and transfer the information to the CRB. 
The participant pre-screening log should list all individuals contacted by the Investigators to 
participate in the study, regardless of the outcome. 
The Investigator must printa any electronic records on an ongoing basis, sign and date them 
immediately after creation, and keep the printouts on file as source documents that can be verified 
by the Sponsor or an inspector against the electronic records. Any subsequent changes of an 
electronic record require the record to be re-printed, dated (with an indication of the date of 
change), and signed. Such records must also be kept together with the original printed copy. 
 
a  Unless the electronic medical records are managed by validated computerized systems that are compliant with US 
21 CFR Part 11, in which case they are acceptable on their own. 

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Good Documentation Practice should be followed by the Investigator and the site staff managing 
source documents. 
13.3 Confidentiality of Data, Data Protection, and Access to Participant Records  
Prior to initiation of the study, the Investigator will sign a fully executed confidentiality agreement 
with Sanofi Pasteur. In the event a participant’s medical records are not at the investigational site, 
it is the responsibility of the investigator, to obtain those records if needed. 
All personal data collected related to participants, Investigators, or any person involved in the 
study, which may be included in the Sponsor’s databases, shall be treated in compliance with all 
applicable laws and regulations, including the GDPR (Global Data Protection Regulation). Data 
collected must be adequate, relevant and not excessive, in relation to the purposes for which they 
are collected. Each category of data must be properly justified and in line with the study objective. 
Participants’ race and ethnicity will be collected in this study because these data are required by 
regulatory agencies. 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names or 
any information that would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
When archiving or processing personal data pertaining to the Investigator and/or to the 
participants, the Sponsor shall take all appropriate measures to safeguard and prevent access to 
this data by any unauthorized third party. 
13.4 Monitoring, Auditing, and Archiving  
13.4.1 Monitoring  
Before the start of the study (i.e., before the inclusion of the first participant in the first center), the 
Investigators and the Sponsor’s staff or a representative will meet at the site-initiation visit to 
discuss the study protocol and the detailed study procedures. Emphasis will be placed on inclusion 
and exclusion criteria, visit timing, safety procedures, informed consent procedures, SAE 
reporting procedures, CRB completion, and the handling of samples and products. The Sponsor’s 
staff or a representative will ensure and document that all material to be used during the study has 
been received at the site; and that the study investigator team and local Sponsor/delegate staff 
have been properly informed about the study, GCP and regulatory requirements, and the 
Sponsor’s procedures. Specific training sessions for the study investigator team and the CRAs on 
these topics may be performed as necessary and should be documented. 

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The following instruction manuals will be provided: the CRF Completion Instructions for entering 
data into the CRB, and the Operating Guidelines for detailed study procedures such as the product 
management and sample-handling procedures. 
After the start of the study, the Sponsor’s staff or a representative will be in regular contact with 
the investigational team through telephone calls and regular follow-up visits. The Investigator or 
delegate must be available for these visits and must allow the Sponsor/delegate staff direct access 
to participant medical files and CRBs. During these visits, the Sponsor/delegate staff will: 
• Evaluate the quality of the study progress (adherence to protocol and any study-specific 
guidelines, quality of data collection and document completion, signature of consent 
forms, occurrence of SAEs, sample and product management, cold-chain monitoring, 
archiving) 
• Source-verify completed CRBs and any corresponding answered queries 
• Determine the number of complete or ongoing issues identified at monitoring visits (e.g., 
protocol deviations, SAEs). Any identified problems will be discussed with the 
Investigator, and corrective or preventive actions will be determined, as appropriate. 
• After all protocol procedures have been completed and the data have been entered into the 
CRB, the Investigator must still be available to answer any queries forwarded by the 
Sponsor. All data-related queries must be completed prior to database lock. 
At the end of the study, a close-out visit will be performed to ensure that: 
• The center has all the documents necessary for archiving 
• All samples have been shipped to the appropriate laboratories 
• All unused materials and products have been either destroyed or returned to the Sponsor 
13.4.2 Audits and Inspections  
A quality assurance audit may be performed at any time by the Sponsor’s Clinical Quality 
Assessment department (CQA) or by independent auditors to verify that the study has been 
conducted according to the protocol, GCP and ICH requirements, and other applicable 
regulations. An inspection may be conducted by regulatory authorities. The Investigator must 
allow direct access to study documents during these inspections and audits. 
13.4.3 Archiving  
The Investigator and the study site shall retain and preserve 1 copy of the study file containing the 
essential documents related to the study and records generated during the study (“Study File”) for 
the longer of the 2 following periods (“Retention Period”): 
• 25 years after the signature of the final study report or  
• such longer period as required by applicable regulatory requirements 
If during the Retention Period, the study site is no longer able to retain the Study File due to 
exceptional circumstances (such as bankruptcy), the study site shall contact the Sponsor to 

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organize the transfer of the Study File to the Sponsor’s designee at the Sponsor’s expense. 
Following the Retention Period, the Investigator and/or the study site are responsible to dispose of 
the Study File according to the applicable regulations. Patient medical records shall be retained in 
compliance with local regulations. 
Archived data may be held on electronic records, provided that a back-up exists and that a hard 
copy can be obtained if required. The protocol, documentation, approvals, and all other documents 
related to the study will be kept by the Sponsor in the Trial Master File (TMF). Data on AEs are 
included in the TMF. All data and documents will be made available if requested by relevant 
authorities. 
13.5 Financial Contract and Insurance Coverage  
A Clinical Trial Agreement will be signed by all the parties involved in the study’s performance, 
if relevant. The Sponsor has an insurance policy to cover any liabilities that may arise from use of 
the product and / or the study protocol. 
13.6 Stipends for Participation  
Participants’ parent / guardian / legally authorized representative may be provided with a stipend, 
according to local practice, to compensate for the time and travel required for study visits and 
procedures. 
13.7 Publication Policy  
Data derived from this study are the exclusive property of Sanofi Pasteur. Any publication or 
presentation related to the study must be submitted to Sanofi Pasteur for review before submission 
of the manuscript. After publication of the results of the study, any participating center may 
publish or otherwise use its own data provided that any publication of data from the study gives 
recognition to the study group. In addition, Sanofi Pasteur shall be offered an association with all 
such publications, it being understood that Sanofi Pasteur is entitled to refuse the association. 
Sanofi Pasteur must have the opportunity to review all proposed abstracts, manuscripts, or 
presentations regarding this study at least 90 days prior to submission for publication / 
presentation. Any information identified by Sanofi Pasteur as confidential must be deleted prior to 
submission, it being understood that the results of this study are not to be considered confidential. 
Sanofi Pasteur’s review can be expedited to meet publication guidelines. 

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15 Appendix  
Bayesian approach for safety signal detection 
At each safety evaluation, a Bayesian approach based on Posterior Distribution may be used to assess the 
difference between each RSV formulation and Placebo on the following safety endpoint: 
• 
Any Grade 3 lower respiratory tract illness e.g., wheezing, pneumonia, sustained tachypnea, 
laryngotracheobronchitis 
• 
Grade 3 fever 
The probability that the difference of percentages of events between one RSV formulation and Placebo is 
greater than a pre-specified margin (δ) can be calculated based on posterior distribution, using non-
informative prior Beta (1,1) (33) and observed binomial data: 
Proba (%RSV - %Placebo > δ) 
If this probability is high (e.g., >=80%) then it may be recommended to drop the formulation. Thus, it can 
help decision making for safety evaluation by SMT and/or IDMC (if applicable) and can also be applied at 
the end of the study. 
Example of application: SMT 
Consider δ = 5% the maximum difference of percentages of events tolerated between groups. 
Number of participants is planned to be 20 per group in Cohort 1, Cohort 2 and Cohort 3 for early safety 
data review.  
Probabilities P(%RSV - %Placebo > δ) are calculated according to each possible distribution of up to 6 
observed events between the 2 groups, as shown in the table below. 
 

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16 Signature Page