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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
42
Pharmaceutical form: Liquid for nasal spray Route of administration: Intranasal
Pharmaceutical form:Liquid for nasal spray-Route of administration:Intranasal
Pharmaceutical form:Liquid for nasal spray-Route of administration:Intranasal
Pharmaceutical form:Liquid for nasal spray-Route of administration:Intranasal
Investigational Site Number : 3400002
San Pedro Sula, Honduras
Investigational Site Number : 3400001
Tegucigalpa, Honduras
Investigational Site Number : 3400003
Tegucigalpa, Honduras
Cohort 2: Geometric Mean Titers (GMT) of RSV A Serum Neutralizing Antibodies at Day 85 (Post-Dose 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).
Time frame: Day 85 (28 days post-vaccination 2)
Cohort 2: Geometric Mean Titers of RSV B Serum Neutralizing Antibodies at Day 85 (Post-Dose 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.
Time frame: Day 85 (28 days post-vaccination 2)
Cohorts 1 and 2: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)
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.
Time frame: Up to 30 minutes after each vaccination (post-dose on Day 1)
Cohorts 1 and 2: Number of Participants With Solicited Administration Site Reactions
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.
Time frame: Up to 21 days after each vaccination (post-dose on Day 1)
Cohorts 1 and 2: Number of Participants With Solicited Systemic Reactions
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.
Time frame: Up to 21 days after each vaccination (post-dose on Day 1)
Cohorts 1 and 2: Number of Participants With Unsolicited Adverse Events
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.
Time frame: Up to 28 days after each vaccination (post-dose on Day 1)
Cohorts 1 and 2: Number of Participants With Medically Attended Adverse Events (MAAEs)
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.
Time frame: From first dose of study vaccine administration (Day 1) to 198 days
Cohorts 1 and 2: Number of Participants With Serious Adverse Events (SAEs)
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.
Time frame: From first dose of study vaccine administration (Day 1) to 198 days
Cohorts 1 and 2: Number of Participants With Adverse Events of Special Interest (AESIs)
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.
Time frame: From first dose of study vaccine administration (Day 1) to 198 days
Cohort 1: Geometric Mean Titers of RSV A and B Serum Neutralizing Antibodies at 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.
Time frame: Baseline (Day 1) and Day 85
Cohorts 1 and 2: Mean Titers of RSV Serum Anti-F Immunoglobulin (Ig) A and IgG Antibodies at 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.
Time frame: Baseline (Day 1) and Day 85
Cohorts 1 and 2: Percentage of Participants With Quantified Shedding >=3.37 Lower Limit of Quantitation (LLOQ)
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.
Time frame: Day 8 and Day 64
Cohorts 1 and 2: Percentage of Participants With Detectable Shedding >=2.08 Limit of Detection
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.
Time frame: Day 8 and Day 64
Cohorts 1 and 2: Titer of Vaccine Virus Shedding in Participants Detected in Nasal Samples Quantified by Quantitative Real Time-Polymerase Chain Reaction
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).
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Time frame: Day 8 and Day 64