Respiratory Syncytial Virus Infection
Conditions
Brief summary
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
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).
Interventions
BIOLOGICALRSVt Vaccine
Pharmaceutical Form: Suspension of virus in a nasal spray Route of Administration: Intranasal
OTHERControl Group
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
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Observer-blind: * Blinding for vaccine group assignment: participants, parents or legally acceptable representative (LAR), 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 23 Months
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Placebo Receiving Pediatric Participants With Vaccine Virus Detected in Nasal Swabs After the First Vaccination | Pre-vaccination on Day 1 and post-vaccination on Days 4, 8, 11, 15, 18 and 22 | Nasal swabs were collected to assess the presence of vaccine virus after first vaccination. Vaccine virus transmission was defined as presence of detected vaccine virus confirmed by RSVt quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay (vaccine virus shedding \>=lower limit of detection \[LOD=2.80 log10 copies/mL\]) in pediatric participants receiving placebo. Percentages are rounded off to the tenth decimal place. |
| Titer of Vaccine Virus Shedding in All Pediatric Participants Detected in Nasal Swabs | Pre-vaccination on Day 1 and post-vaccination on Days 4, 8, 11, 15, 18, 22, 64 and 71 | Nasal swabs were collected to assess the shedding of the attenuated RSV vaccine strain and quantified by RSVt qRT PCR assay. Quantified virus shedding was defined as vaccine virus shedding \>=lower limit of quantification (LLOQ=3.37 log10 copies/mL). |
| Percentage of Placebo Receiving Pediatric Participants With Detected Shedding Who Showed Any Genetic Sequence Variation After Each Vaccination | Up to 21 days after each vaccination (Day 1 to Day 22 and Day 57 to Day 78) | Nasal swabs were collected to identify the difference in genetic sequence of mutated vaccine virus segments compared to the reference strain vaccine virus isolates in the vaccine virus positive swabs from pediatric participants receiving placebo after each vaccination. Detected virus shedding was defined as vaccine virus shedding \>=LOD (2.80 log10 copies/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of RSV A Serum Neutralizing Antibody (nAb) Titers | Pre-vaccination on Day 1 (first vaccination) and Day 57 (second vaccination) and up to 28 days after second vaccination, Day 85 | Serum samples were collected at specified timepoints for immunogenicity assessments. RSV A serum neutralizing antibody titers were evaluated by microneutralization (MN) assay. |
| Secondary: Geometric Mean Titers of RSV Serum Anti-F Immunoglobulin G (IgG) Enzyme-linked Immuno-adsorbant Assay (ELISA) Antibody | Pre-vaccination on Day 1 (first vaccination) and Day 57 (second vaccination) and up to 28 days after second vaccination, Day 85 | Serum samples were collected at specified timepoints for immunogenicity assessments. Antibodies to RSV F antigen were measured using the anti RSV F IgG ELISA method. |
| Number of Participants With Immediate Unsolicited Adverse Events (AEs) | Up to 30 minutes after each vaccination (Days 1 and 57) | An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, i.e., pre-listed in the case report form (CRF) in terms of diagnosis and onset window post-vaccination. All participants were observed for 30 minutes after each vaccination and any unsolicited AEs that occurred during that time were recorded as immediate unsolicited AEs. |
| Number of Participants With Solicited Administration Site Reactions and Systemic Reactions | Up to 21 days after each vaccination (Day 1 to Day 22 and Day 57 to Day 78) | A solicited reaction was an expected adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF and considered as related to the study vaccine administered. An administration site reaction was an AR at and around the administration/injection site and were commonly inflammatory reactions. Solicited systemic reactions were systemic AEs and those occurring during the specified collection period were always considered related to the vaccine even if there was evidence of alternative etiology. |
| Number of Participants With Unsolicited Adverse Events | Up to 28 days after each vaccination (Day 1 to Day 29 and Day 57 to Day 85) | An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that is, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination. |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi Pasteur, a Sanofi Company
Participant flow
Recruitment details
The study was conducted at 3 sites in Puerto Rico from 06-Feb-2023 to 27-Dec-2024.
Pre-assignment details
A total of 80 healthy infants/toddlers 6 to \<24 months of age were randomized in contact groups of 2-3 in a 1:1 ratio to receive 2 administrations 56 days apart of either live-attenuated respiratory syncytial virus delta (Δ) non-structural (NS)2/Δ1313/I1314L vaccine (RSVt vaccine) or placebo.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 80 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 15.1 months STANDARD_DEVIATION 5.55 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 56 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 39 |
| other Total, other adverse events | 11 / 39 | 14 / 39 |
| serious Total, serious adverse events | 2 / 39 | 4 / 39 |
Outcome results
None listed