Efficacy, Immunogenicity, and Safety Study of a Respiratory Syncytial Virus Vaccine in Infants and Toddlers

Phase 3TerminatedNCT06252285

Sanofi Pasteur, a Sanofi Company6,300 enrolled

Overview

This study is a phase III, randomized, observer-blind, placebo-controlled, multinational, multi-center study to be conducted in approximately 6300 children 6 months to \< 22 months of age. The purpose of the study is to evaluate the efficacy, immunogenicity, and safety of Respiratory Syncytial Virus Toddler (RSVt) vaccine administered by intranasal route compared to placebo. Eligible participants will be randomized in a 1:1 ratio to receive 2 intranasal administrations of either the RSVt vaccine or placebo. Study duration will be 24 months for each participant. The safety follow-up will start after the first vaccination and up to the end of the study.

Study duration will be 24 months for each participant. The safety follow-up will start at inclusion and up to the end of the study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

6,300

Conditions

RSV Immunisation

Interventions

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 21 MonthsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: -Aged 6 months to \< 22 months on the day of inclusion (means the day of the 6-month birthday to the day before the 22-month birthday) * Participants who are healthy as determined by medical evaluation including medical history * Born at full term of pregnancy (≥ 37 weeks) Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: * 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 * History of medically diagnosed wheezing * 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 viral respiratory infection (including COVID-19, influenza, rhinovirus, etc.) at the time of enrollment. A prospective participant should not be included in the study until the respiratory infection has resolved. * 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 * Potential close contact with other immunocompromised individual within 30 days after each vaccination as per investigator's discretion * Participant's biological mother's previous receipt or planned administration of an investigational RSV vaccine during pregnancy and/or breastfeeding. * Receipt or planned receipt of any of the following vaccines prior to enrollment or after the first study intervention administration: * Any other intranasal live attenuated vaccine within the 28 days prior to and after Dose 1 study administration * Unless given on the day of Dose 1 study administration, any other injectable live attenuated vaccines within the 28 days prior to and after. Concomitant receipt on the day of Dose 1 study administration is allowed. * Previous receipt of an investigational RSV vaccine or receiving any anti-RSV product (such as ribavirin or RSV immune globulin) at the time of enrollment. Previous receipt of an RSV monoclonal antibody within 6 months prior to the first study vaccine administration. * 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 * Participation at the time of study enrollment or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Locations (130)

Central Research Associates - Flourish - PPDS- Site Number : 8400009

Birmingham, Alabama, United States

Lakeview Clinical Research- Site Number : 8400024

Guntersville, Alabama, United States

Novak Clinical Research- Site Number : 8400069

Tucson, Arizona, United States

Madera Family Medical Group- Site Number : 8400029

Madera, California, United States

Integrated Clinical Research- Site Number : 8400056

Tarzana, California, United States

Outcomes

Primary Outcomes

Occurrence of lower respiratory tract disease (LRTD) (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of LRTD associated with any RT PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Secondary Outcomes

Occurrence of upper respiratory tract disease (URTD) (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of URTD associated with any RT PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of LRTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain leading to hospitalization > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of LRTD associated with any RT PCR confirmed RSV strain leading to hospitalization, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of severe LRTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of severe LRTD associated with any RT PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of urgent care visits, associated with an episode of LRTD over RSV Season 1, associated with any RT-PCR confirmed RSV strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of urgent care visit associated with an episode of LRTD associated with any RT PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of acute respiratory disease (ARD) (during RSV Season 1) associated with any RT-PCR confirmed RSV strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of ARD associated with any RT PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of hospitalizations, associated with an episode of ARD over RSV Season 1, associated with any RT-PCR confirmed RSV strain > 21 days post dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of hospitalizations associated with an episode of ARD associated with any RT PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of urgent care visits, associated with an episode of ARD over RSV Season 1, associated with any RT-PCR confirmed RSV strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of urgent care visit associated with an episode of ARD associated with any RT PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1

Occurrence of LRTD (during RSV Season 1) associated with an RT-PCR confirmed RSV A or B strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of LRTD associated with an RT PCR confirmed RSV A or B, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of URTD (during RSV Season 1) associated with an RT-PCR confirmed RSV A or B strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of URTD associated with an RT-PCR confirmed RSV A or B, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of ARD (during RSV Season 1) associated with an RT PCR confirmed RSV A or B strain > 21 days post-dose 2

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of ARD associated with an RT-PCR confirmed RSV A or B, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of LRTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 1

Time frame: from 22 days post-dose 1 up to the start date of first occurrence of LRTD associated with any RT-PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of URTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 1

Time frame: from 22 days post-dose 1 up to the start date of first occurrence of URTD associated with any RT-PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of ARD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 1

Time frame: from 22 days post-dose 1 up to the start date of first occurrence of ARD associated with any RT-PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of LRTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2, in RSV-exposed participants

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of LRTD associated with any RT-PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1

Occurrence of URTD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2, by baseline serostatus

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of URTD associated with any RT-PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of ARD (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2, by baseline serostatus

Time frame: from 22 days post-dose 2 up to the start date of first occurrence of ARD associated with any RT-PCR confirmed RSV strain, assessed up to the end of RSV season 1 (ie. up to 12 months post-dose 1)

Occurrence of LRTD (during RSV Season 2), associated with any RT-PCR confirmed RSV strain

Time frame: from 12 months post-dose 1 up to the start date of first occurrence of LRTD associated with any RT-PCR confirmed RSV strain, assessed up to the end of the study (ie. up to 24 months post-dose 1)

Occurrence of URTD (during RSV Season 2), associated with any RT-PCR confirmed RSV strain

Time frame: from 12 months post-dose 1 up to the start date of first occurrence of URTD associated with any RT-PCR confirmed RSV strain, assessed up to the end of the study (ie. up to 24 months post-dose 1)

Occurrence of ARD (during RSV Season 2), associated with any RT PCR confirmed RSV strain

Time frame: from 12 months post-dose 1 up to the start date of first occurrence of ARD associated with any RT-PCR confirmed RSV strain, assessed up to the end of the study (ie. up to 24 months post-dose 1

Occurrence of LRTD (during RSV Season 2), associated with any RT PCR confirmed RSV strain, by baseline serostatus

Occurrence of URTD (during RSV Season 2), associated with any RT PCR confirmed RSV strain, by baseline serostatus

Occurrence of ARD (during RSV Season 2), associated with any RT PCR confirmed RSV strain, by baseline serostatus

Presence of solicited administration site reactions within 21 days after each vaccination

Number of participants experiencing solicited site reactions

Time frame: Within 21 days after each vaccination

Presence of solicited systemic reactions within 21 days after each vaccination

Number of participants experiencing solicited systemic reactions

Time frame: Within 21 days after each vaccination

Presence of unsolicited systemic adverse events (AEs) reported in the 30 minutes after each vaccination

Number of participants experiencing immediate unsolicited systemic AES

Time frame: Within 30 minutes after each vaccination

Presence of unsolicited AEs within 28 days after each vaccination

Number of participants experiencing unsolicited AES

Time frame: Within 28 days after each vaccination

Presence of medically attended adverse events MAAEs throughout the study

Number of participants experiencing MAAEs

Time frame: Throughout the study (approximately 24 months)

Presence of serious adverse events (SAEs) throughout the study

Number of participants experiencing SAEs

Time frame: Throughout the study (approximately 24 months)

Presence of adverse events of special interest (AESIs) throughout the study

Number of participants experiencing AESIs

Time frame: Throughout the study (approximately 24 months)

RSV A serum neutralizing antibody titers at D01

Antibody titers are expressed as GMTs at baseline

Time frame: Day 01

RSV B serum neutralizing antibody titers at D01

Antibody titers are expressed as GMTs at baseline

Time frame: Day 01

RSV A serum neutralizing antibody titers at 28 days post-dose 2

Antibody titers are expressed as GMTs at post-baseline

Time frame: 28 days post-dose 2

RSV B serum neutralizing antibody titers at 28 days post-dose 2

Antibody titers are expressed as GMTs post-baseline

Time frame: 28 days post-dose 2

RSV serum anti-F Immunoglobulin A (IgA) Electrochemiluminescence (ECL) antibody titers at D01

Antibody titers are expressed as GMTs at baseline

Time frame: Day 01

RSV serum anti-F IgG ECL antibody titers at D01

Antibody titers are expressed as GMTs at baseline

Time frame: Day 01

RSV serum anti-F Immunoglobulin A (IgA) ECL antibody titers at 28 days post-dose 2

Antibody titers are expressed as GMTs post-baseline

Time frame: 28 Days post-dose 2

RSV serum anti-F IgG ECL antibody titers at 28 days post-dose 2

Antibody titers are expressed as GMTs post-baseline

Time frame: 28 Days post-dose 2