RSV Immunisation
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALRSVt Vaccine
Pharmaceutical form:Suspension of virus in a nasal spray-Route of administration:Intranasal
BIOLOGICALPlacebo
Pharmaceutical form:Suspension of virus in a nasal spray-Route of administration:Intranasal
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
* Blinding for vaccine group assignment: participants, parents or legally acceptable representatives (LARs), outcome assessors, investigators, laboratory personnel, Sponsor study staff * No blinding for study staff who prepare and administer the study interventions
Eligibility
Sex/Gender
ALL
Age
6 Months to 21 Months
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of lower respiratory tract disease (LRTD) (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2 | 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
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of upper respiratory tract disease (URTD) (during RSV Season 1) associated with any RT PCR confirmed RSV strain > 21 days post-dose 2 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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, by baseline serostatus | 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, by baseline serostatus | 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) | — |
| Presence of solicited administration site reactions within 21 days after each vaccination | Within 21 days after each vaccination | Number of participants experiencing solicited site reactions |
| Presence of solicited systemic reactions within 21 days after each vaccination | Within 21 days after each vaccination | Number of participants experiencing solicited systemic reactions |
| Presence of unsolicited systemic adverse events (AEs) reported in the 30 minutes after each vaccination | Within 30 minutes after each vaccination | Number of participants experiencing immediate unsolicited systemic AES |
| Presence of unsolicited AEs within 28 days after each vaccination | Within 28 days after each vaccination | Number of participants experiencing unsolicited AES |
| Presence of medically attended adverse events MAAEs throughout the study | Throughout the study (approximately 24 months) | Number of participants experiencing MAAEs |
| Presence of serious adverse events (SAEs) throughout the study | Throughout the study (approximately 24 months) | Number of participants experiencing SAEs |
| Presence of adverse events of special interest (AESIs) throughout the study | Throughout the study (approximately 24 months) | Number of participants experiencing AESIs |
| RSV A serum neutralizing antibody titers at D01 | Day 01 | Antibody titers are expressed as GMTs at baseline |
| RSV B serum neutralizing antibody titers at D01 | Day 01 | Antibody titers are expressed as GMTs at baseline |
| RSV A serum neutralizing antibody titers at 28 days post-dose 2 | 28 days post-dose 2 | Antibody titers are expressed as GMTs at post-baseline |
| RSV B serum neutralizing antibody titers at 28 days post-dose 2 | 28 days post-dose 2 | Antibody titers are expressed as GMTs post-baseline |
| RSV serum anti-F Immunoglobulin A (IgA) Electrochemiluminescence (ECL) antibody titers at D01 | Day 01 | Antibody titers are expressed as GMTs at baseline |
| RSV serum anti-F IgG ECL antibody titers at D01 | Day 01 | Antibody titers are expressed as GMTs at baseline |
| RSV serum anti-F Immunoglobulin A (IgA) ECL antibody titers at 28 days post-dose 2 | 28 Days post-dose 2 | Antibody titers are expressed as GMTs post-baseline |
| RSV serum anti-F IgG ECL antibody titers at 28 days post-dose 2 | 28 Days post-dose 2 | Antibody titers are expressed as GMTs post-baseline |
Countries
Argentina, Brazil, Chile, China, Colombia, Finland, Japan, Kenya, Mexico, Nepal, Puerto Rico, South Africa, Spain, Thailand, United Kingdom, United States
Outcome results
None listed