Study on a Live-attenuated Respiratory Syncytial Virus Vaccine for Assessment of Safety, Transmissibility, and Genetic Stability of the Vaccine Virus Among Close Contacts in Infants and Toddlers 6 to < 24 Months of Age in Puerto Rico (USA)

Study Overview
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Brief Summary
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The primary purpose of the study is to assess the shedding, transmission, and genetic stability of the live-attenuated RSVt vaccine after each intranasal vaccination (56 days apart) in infants and toddlers 6 to < 24 months of age.

Detailed Description
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The duration of each participant's participation is up to 8 months, including the 6 months safety follow-up phone call after the second study intervention administration for the pediatric participants The treatment administration for the pediatric participants will be on D01 and D57 (1 intranasal administration each).

Official Title
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Phase II, Randomized, Observer-blind, Placebo-controlled, Multi-center Study of a Live Attenuated Respiratory Syncytial Virus Vaccine to Assess the Vaccine Virus' Transmissibility in Household or Daycare Center Settings, Shedding, and Genetic Stability, and to Describe the Immunogenicity and Safety of the Vaccine in Infants and Toddlers 6 to < 24 Months of Age in Puerto Rico (USA)

Conditions
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Respiratory Syncytial Virus Infection

Intervention / Treatment
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* Biological: RSVt Vaccine
* Other: Control Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 6 months to < 24 months on the day of inclusion (from the day of the 6 months after birth to the day before the 2nd birthday) Participants who are healthy as determined by medical evaluation including medical history. Born at full term of pregnancy (≥ 37 weeks) or born after a gestation period of 27 through 36 weeks and medically stable as assessed by the investigator, based on the following definition: Medically stable refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study intervention Attends a daycare facility at least 3 days per week and 4 hours per day at which the participant would be in a contact group/playroom of at least one other child 6 to < 24 months of age who will participate in this study or is a member of a household, which includes at least one other child 6 to < 24 months of age who will participate in this study Exclusion Criteria: 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) Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention used in the study or to a product containing any of the same substances Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion Any acute febrile illness in the past 48 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. Probable or confirmed ongoing case of COVID-19 at the time of enrollment 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 study enrollment a person who has received (within the past 6 months) or is receiving (at the time of enrollment) immunosuppressant agents a person living with a solid organ or bone marrow transplant Member of a household that includes, or will include, an infant who is less than 6 months of age at the time of enrollment Attends a daycare facility and shares a daycare room with infants less than 6 months of age, and parent/legally acceptable representative is unable or unwilling to suspend attendance at the daycare facility for 28 days following study intervention administration Any need of supplemental oxygen therapy in a home or hospital setting at the time of enrollment. Participant's mother previous receipt or planned administration of an investigational RSV vaccine or any monoclonal antibody (such as Infliximab) during pregnancy and/or breastfeeding. Receipt or planned receipt of any of the following vaccines prior to or after the first study intervention administration: any influenza vaccine within 7 days prior to and after, or any COVID-19 or inactivated vaccine or live-attenuated rotavirus vaccine within 14 days prior to and after, or any live vaccine, other than rotavirus vaccine, within 28 days prior to and after Previous receipt of an investigational RSV vaccine or receiving any anti-RSV product (such as ribavirin or RSV Immunoglobulin (IG) or RSV monoclonal antibody) at the time of enrollment. Receipt of immune globulins, blood or blood-derived products in the past 3 months Receipt of intranasal and intra-ocular medications within 3 days prior to study enrollment Receipt at the time of enrollment or previous receipt of salicylate (aspirin) or salicylate-containing products Participation at the time of study enrollment (or in the 6 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure Deprived of freedom in an emergency setting, or hospitalized involuntarily Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RSVt Vaccine Group<br>2 intranasal administrations (56 days apart) of the RSVt vaccine at D01 and D57 | Biological: RSVt Vaccine<br>* Pharmaceutical Form: Suspension of virus in a nasal spray Route of Administration: Intranasal<br>|
| Placebo Comparator: Control Group<br>2 intranasal administrations (56 days apart) of the placebo at D01 and D57 | Other: Control Group<br>* Pharmaceutical Form: Suspension of virus in a nasal spray Route of Administration: Intranasal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of vaccine virus | Proportion of vaccinees infected with vaccine virus in the placebo group, defined as vaccine virus shedding, detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) | Day 1 through Day 22 | 
| Change in the Geometric Mean Titers (GMTs) of vaccine virus shedding | Titer of vaccine virus shedding in nasal swabs, quantified by qRT-PCR Assay in all pediatric participants | Day 1 through Day 71 | 
| Number of differences detected in genetic sequence of NS2 segment | Number of differences detected in genetic sequence of NS2 segment of the vaccine virus compared to the reference strain vaccine virus isolates in the vaccine virus positive swabs from pediatric participants receiving placebo and ad hoc close contact participants | Approximately Day 1 through Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of RSV A serum neutralizing antibody (nAb) titers | RSV A serum Nab titers | Day 1, Day 57 and Day 85 | 
| GMTs of RSV serum anti-F Immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) antibody titers up to 28 days after the second administration (D01, D57, and D85) | RSV serum anti-F IgG ELISA antibody titers | Day 1, Day 57 and Day 85 | 
| Presence of immediate unsolicited systemic Adverse Events (AEs) | Number of participants experiencing immediate unsolicited systemic AEs | Within 30 minutes after each vaccination administration | 
| Presence of solicited injection site or systemic reactions | Number of participants reporting: injection site reactions: pain, erythema and swelling systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills | Within 21 days after each vaccination administration | 
| Presence of unsolicited AEs | Number of participants experiencing unsolicited AEs | Within 28 days after each vaccination administration | 
| Presence of adverse events of special interest (AESIs) | Number of participants experiencing AESIs | Within 28 days after each vaccination administration | 
| Presence of medically attended adverse events (MAAEs) | Number of participants experiencing MAAEs | Within 28 days after each vaccination administration | 
| Presence of serious adverse events (SAEs) | Number of participants experiencing SAEs | From Day 1 until the end of the study (approximately 8 months) | 
| Presence of vaccine virus at Day 64 through Day 71 | Proportion of vaccinees infected with vaccine virus in the placebo group, defined as vaccine virus shedding, detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) | Day 64 through Day 71 |