Healthy Volunteers, RSV Immunisation
Conditions
Keywords
RSV, RSVt (RSV toddler and Infant) Vaccine
Brief summary
This study was a Phase III, parallel group, randomized, observer blind, placebo controlled, multi-national, multi-center, multi-arm study conducted in 42 healthy children enrolled at 6 months to \<22 months of age. The purpose of the study was to evaluate the non-inferiority of the immune response of the lower dose (LD) when compared to the standard dose (SD) respiratory syncytial virus infant and toddler (RSVt) vaccine and the safety of the LD, SD and high dose (HD) vaccine in preterm born children and of the HD vaccine in full term born children administered by intranasal route and compared to placebo.
Detailed description
The study duration was approximately 8 months for each participant, including the 6 months safety follow-up phone call after the second study intervention administration.
Interventions
BIOLOGICALLow Dose (LD) RSVt vaccine
Pharmaceutical form: Liquid for nasal spray Route of administration: Intranasal
BIOLOGICALStandard Dose (SD) RSVt vaccine
Pharmaceutical form:Liquid for nasal spray-Route of administration:Intranasal
BIOLOGICALHigh Dose (HD) RSVt vaccine
Pharmaceutical form:Liquid for nasal spray-Route of administration:Intranasal
BIOLOGICALPlacebo
Pharmaceutical form:Liquid for 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 from the day of the 6-month birthday to the day before the 22-month birthday. The second vaccine administration was administered before the study participant has turned 24 months of age). * Participants who were healthy as determined by medical evaluation including medical history. * For Cohort 1 and Cohort 2 (contingent upon satisfactory safety profile of the RSVt vaccine in Cohort 1): --Participant born 28 through 36 weeks of gestation 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. * For Cohort 2: * Participant born at full term of pregnancy (≥ 37 weeks of gestation).
Exclusion criteria
Participants were 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. Children with a history of recurrent wheezing will be excluded. Children with a previous single episode of wheezing may be included if that episode of wheezing was not associated with hospitalization or if does not have a family history of 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 the first study intervention administration, any other injectable live attenuated vaccines within the 28 days prior to and after. Concomitant receipt on the day of the first study intervention administration is allowed * Planned receipt of any monoclonal antibody for RSV (such as Nirsevimab or Palivizumab) for the duration of the study. * 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 Note: 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 |
|---|---|---|
| Cohort 2: Geometric Mean Titers (GMT) of RSV A Serum Neutralizing Antibodies at Day 85 (Post-Dose 2) | Day 85 (28 days post-vaccination 2) | Serum samples were planned to be collected at specified timepoints for immunogenicity assessments. RSV A serum neutralizing antibody titers were planned to be determined using a validated plaque reduction neutralization test (PRNT). |
| Cohort 2: Geometric Mean Titers of RSV B Serum Neutralizing Antibodies at Day 85 (Post-Dose 2) | Day 85 (28 days post-vaccination 2) | Serum samples were planned to be collected at specified timepoints for immunogenicity assessments. RSV B serum neutralizing antibody titers were planned to be determined using a validated PRNT. |
| Cohorts 1 and 2: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs) | Up to 30 minutes after each vaccination (post-dose on Day 1) | 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. |
| Cohorts 1 and 2: Number of Participants With Solicited Administration Site Reactions | Up to 21 days after each vaccination (post-dose on Day 1) | A solicited injection/administration site reactions were adverse reactions (AR) at and around the injection/administration site of the study vaccine 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. |
| Cohorts 1 and 2: Number of Participants With Solicited Systemic Reactions | Up to 21 days after each vaccination (post-dose on Day 1) | A solicited reaction was an expected 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. |
| Cohorts 1 and 2: Number of Participants With Unsolicited Adverse Events | Up to 28 days after each vaccination (post-dose on Day 1) | 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. |
| Cohorts 1 and 2: Number of Participants With Medically Attended Adverse Events (MAAEs) | From first dose of study vaccine administration (Day 1) to 198 days | An MAAE was defined as a new onset or a worsening of a condition that prompted the participant or participant's parent/legally acceptable representative to seek unplanned medical advice at a physician's office or emergency department. |
| Cohorts 1 and 2: Number of Participants With Serious Adverse Events (SAEs) | From first dose of study vaccine administration (Day 1) to 198 days | An SAE was defined as any AE that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was other medically important event. |
| Cohorts 1 and 2: Number of Participants With Adverse Events of Special Interest (AESIs) | From first dose of study vaccine administration (Day 1) to 198 days | An AESI (serious or non-serious) was one of scientific and medical concern specific to the sponsor's study vaccine or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor was appropriate. Acute wheeze and anaphylaxis were collected as AESI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Geometric Mean Titers of RSV A and B Serum Neutralizing Antibodies at Baseline (Day 1) and Day 85 | Baseline (Day 1) and Day 85 | Serum samples were planned to be collected at specified timepoints for immunogenicity assessments. RSV A and RSV B serum neutralizing antibody titers were planned to be determined using a validated PRNT. |
| Cohorts 1 and 2: Mean Titers of RSV Serum Anti-F Immunoglobulin (Ig) A and IgG Antibodies at Baseline (Day 1) and Day 85 | Baseline (Day 1) and Day 85 | Serum samples were collected at specified timepoints for immunogenicity assessments. Antibodies to RSV F antigen were measured using the anti-RSV serum anti-F IgA and IgG using electrochemiluminescence method. Log10 titer values are reported. |
| Cohorts 1 and 2: Percentage of Participants With Quantified Shedding >=3.37 Lower Limit of Quantitation (LLOQ) | Day 8 and Day 64 | Nasal swabs were collected to assess shedding of the attenuated RSV vaccine strain at specified timepoints. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was developed to detect and quantify RSV ΔNS2 candidate in nasal swab samples. Percentages rounded off to tenth decimal place. |
| Cohorts 1 and 2: Percentage of Participants With Detectable Shedding >=2.08 Limit of Detection | Day 8 and Day 64 | Nasal swabs were collected to assess shedding of the attenuated RSV vaccine strain at specified timepoints. qRT-PCR assay was developed to detect and quantify RSV ΔNS2 candidate in nasal swab samples. Percentages rounded off to tenth decimal place. |
| Cohorts 1 and 2: Titer of Vaccine Virus Shedding in Participants Detected in Nasal Samples Quantified by Quantitative Real Time-Polymerase Chain Reaction | Day 8 and Day 64 | Nasal swabs were collected to assess shedding of the attenuated RSV vaccine strain at specified timepoints. qRT-PCR assay was developed to detect and quantify RSV ΔNS2 candidate in nasal swab samples. Quantified virus shedding was defined as vaccine virus shedding \>=lower limit of quantification (LLOQ=3.37 log10 copies/mL). |
Countries
Honduras
Participant flow
Recruitment details
Study was conducted at 1 center in a single country from 25 November 2024 to 13 December 2024. 42 healthy infants/toddlers aged 6 to\<22 months were randomized to 2 cohorts: preterm born children(Cohort1:randomized to receive either placebo or standard dose of live-attenuated respiratory syncytial virus delta\[Δ\] non-structural \[NS\]2/Δ1313/I1314L vaccine \[RSVt vaccine\]) and full term born children (Cohort2:randomized to receive either low dose, standard dose or high dose RSVt vaccine or placebo).
Pre-assignment details
Cohort 1: Groups 1 and 2 and Cohort 2 initiated enrollment at the same time. However, due to the early study termination (29 days following the first vaccination) as per sponsor's decision (no safety concerns), enrollment in Cohort 1 Groups 3 and 4 did not occur. No participants received the second vaccination.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 14.0 months STANDARD_DEVIATION 5.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 3 | 0 / 10 | 0 / 10 | 0 / 12 | 0 / 5 |
| other Total, other adverse events | 0 / 2 | 3 / 3 | 6 / 10 | 9 / 10 | 7 / 12 | 4 / 5 |
| serious Total, serious adverse events | 0 / 2 | 1 / 3 | 0 / 10 | 0 / 10 | 0 / 12 | 0 / 5 |
Outcome results
None listed