Clinical trial NCT04491877: Study of an Live-Attenuated Respiratory Syncytial Virus Vaccine in Infants and Toddlers
Official title: Safety, Immunogenicity, Infectivity, and Dose-Finding Study of an Investigational Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Infants and Toddlers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Syncytial Virus Infection
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-07-29
Enrollment: 259
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The primary objectives of the study were:

* To assess the safety profile of each dose of the study product after each and any administration in all infants and toddlers regardless of baseline serostatus.
* To characterize the Respiratory Syncytial Virus (RSV) A serum neutralizing antibody responses to the study product in each vaccine group after vaccination in RSV-naïve participants.

The secondary objectives of the study were:

* To quantify the amount of vaccine virus shed by each participant by baseline serostatus.
* To determine the proportion of vaccinated infants and toddlers in each vaccine group infected with the vaccine virus at D56 (56 days after vaccination 1) for Cohorts 1, 2, 3 and 4, and at Day 84 (28 days after vaccination 2) for Cohorts 2 and 4 by baseline serostatus.
* To characterize the RSV A serum neutralizing antibody responses to the study product in each vaccine group after vaccination in RSV-experienced participants.
* To characterize serum RSV anti-F immunoglobulin G (IgG) antibody responses to the study product in each vaccine group after vaccination by baseline serostatus.
* To characterize serum RSV antibody responses (RSV A-neutralizing and anti-RSV F IgG) to the study product in each vaccine group after the RSV surveillance season or at least 5 months after the last vaccine administration by baseline serostatus.

Detailed description: Study duration per participant was maximum 12 months

Eligibility criteria: Inclusion Criteria:

Inclusion criteria :

* Aged 6 through 18 months at Day 0.
* Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by independent witness if required by local regulations).
* Participant and parent / guardian / legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures

Exclusion Criteria:

* Born at less than 34 weeks gestation
* Born at less than 37 weeks gestation and less than 1 year of age at the time
* 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).
* Probable or confirmed case of Coronavirus Disease 2019 (COVID-19).
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
* Any chronic illness

  • Chronic illness may include, but is not limited to, cardiac disorders, lung disease (including any history of reactive airway disease, receipt of bronchodilator therapy, or medically diagnosed wheezing), renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases
* Any history of medically diagnosed wheezing
* Any acute febrile, respiratory or gastrointestinal illness in the past 24 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
* Any previous anaphylactic reaction
* Current suspected or documented developmental disorder, delay, or other developmental problem
* Receipt of any of the following vaccines prior to enrollment:

  * any influenza vaccine within 7 days prior, or
  * any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
  * any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
  * another investigational vaccine or investigational drug within 28 days prior
* Previous receipt of a licensed or investigational RSV vaccine or previous receipt or planned administration of any anti-RSV product (such as ribavirin or RSV immune immune globulins \[IG\] or RSV monoclonal antibody)
* Receipt of immune globulins, blood or blood-derived products in the past 6 months prior to enrolment
* Receipt of any of the following medications within 3 days prior to study enrollment (Day 0):

  * systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
  * intranasal medications, or
  * other prescription medication except as permitted concomitant medications (prescription or non-prescription) including nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents
* Receipt of salicylate (aspirin) or salicylate-containing products within the 28 days prior to enrollment (Day 0)
* Any previous vaccine-associated adverse reaction that was Grade 3 or above. Note: if grading is not possible, determine if the reaction was considered severe or life threatening; if so, it is exclusionary.
* Scheduled administration of the following after planned inoculation:

  * any influenza vaccine within 7 days after, or
  * inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
  * any live vaccine other than rotavirus in the 28 days after, or
  * another investigational vaccine or investigational drug in the 56 days after.
* Any previous receipt of supplemental oxygen therapy in a home or hospital setting, except the temporary receipt of supplemental oxygen for transient tachypnea in newborn
* 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 enrollment
  * a person receiving immunosuppressant agents
  * a person living with a solid organ or bone marrow transplant
* Participation at the time of study enrollment (or in the 6 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
* Member of a household that contains, or will contain, an infant who is less than 6 months of age at the enrollment date (or in the 6 weeks preceding the first trial vaccination) through Day 28
* Member of a household that contains another child/other children who is/are, or is/are scheduled to be, enrolled in this study in the same year AND the date of enrollment will not be concurrent with the other participant(s) living in the household (i.e., all eligible children from the same household must be enrolled on the same date)
* Attends a daycare facility and shares a daycare room with infants less than 6 months of age, and parent/guardian is unable or unwilling to suspend daycare for 28 days following inoculation
* 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 was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)
timeFrame: Cohorts 1 and 3: Within 30 minutes after vaccination on Day 0; Cohorts 2 and 4: Within 30 minutes after vaccination on Days 0 and 56
measure: Number of Participants With Solicited Administration Site and Systemic Reactions
timeFrame: Cohorts 1 and 3: Within 28 days after vaccination on Day 0; Cohorts 2 and 4: Within 28 days after vaccination on Days 0 and 56
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Cohorts 1 and 3: Within 28 days after vaccination on Day 0; Cohorts 2 and 4: Within 28 days after vaccination on Days 0 and 56
measure: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Cohorts 1 and 3: Within 28 days after vaccination on Day 0; Cohorts 2 and 4: Within 28 days after vaccination on Days 0 and 56
measure: Number of Participants With Medically Attended Adverse Events (MAAEs)
timeFrame: Cohorts 1 and 3: Within 28 days after vaccination on Day 0; Cohorts 2 and 4: Within 28 days after vaccination on Days 0 and 56
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From the first study vaccine administration (Day 0) up to end of the study, maximum of 12 months
measure: Geometric Mean Titers Against RSV A Neutralizing Antibody in RSV-Naïve Participants
timeFrame: Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
Secondary outcomes:
measure: Titer of Vaccine Virus Shedding Measured by Reverse Transcription Polymerase Chain Reaction (RT-PCR)
timeFrame: Cohorts 1 and 3: Day 7; Cohorts 2 and 4: Days 7 and 63
measure: Percentage of Participants Infected With Vaccine Virus at Days 56 and 84
timeFrame: Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
measure: Geometric Mean Titers Against RSV A Neutralizing Antibody in RSV-Experienced Participants
timeFrame: Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
measure: Geometric Mean Titers Against Serum Anti-F Immunoglobulin G (IgG) Antibody
timeFrame: Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
measure: Geometric Mean Titers Against RSV A Neutralizing Antibody After the RSV Surveillance Season
timeFrame: Cohorts 1 and 3: Within 5 months after vaccination on Day 0; Cohorts 2 and 4: Within 5 months after vaccination on Day 56
measure: Geometric Mean Titers Against Serum Anti-F Immunoglobulin G Antibody After the RSV Surveillance Season
timeFrame: Cohorts 1 and 3: Within 5 months after vaccination on Day 0; Cohorts 2 and 4: Within 5 months after vaccination on Day 56
Other outcomes:
Locations:
city: Gardena
country: United States
facility: Matrix Clinical Research-Site Number:8400012
state: California
city: La Mesa
country: United States
facility: Paradigm Clinical Research-Site Number:8400026
state: California
city: Los Angeles
country: United States
facility: Matrix Clinical Research-Site Number:8400032
state: California
city: San Diego
country: United States
facility: California Research Foundation-Site Number:8400016
state: California
city: Blackfoot
country: United States
facility: Elite Clinical Trials, Inc.-Site Number:8400001
state: Idaho
city: Idaho Falls
country: United States
facility: Leavitt Clinical Research-Site Number:8400036
state: Idaho
city: Idaho Falls
country: United States
facility: Snake River Research-Site Number:8400022
state: Idaho
city: South Bend
country: United States
facility: The South Bend Clinic Center for Research-Site Number:8400024
state: Indiana
city: El Dorado
country: United States
facility: Alliance for Multispeciality Research-Site Number:8400014
state: Kansas
city: Newton
country: United States
facility: AMR - Newton-Site Number:8400002
state: Kansas
city: Lexington
country: United States
facility: Michael W. Simon, MD, PSC-Site Number:8400013
state: Kentucky
city: Covington
country: United States
facility: Benchmark Research-Site Number:8400006
state: Louisiana
city: New Orleans
country: United States
facility: Nola Research Works-Site Number:8400017
state: Louisiana
city: Minneapolis
country: United States
facility: Clinical Research Institute-Site Number:8400053
state: Minnesota
city: Missoula
country: United States
facility: Boeson Research-Site Number:8400011
state: Montana
city: Lincoln
country: United States
facility: Be Well Clinical Studies-Site Number:8400054
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research - Norfolk-Site Number:8400005
state: Nebraska
city: Albuquerque
country: United States
facility: MedPharmics Inc-Site Number:8400040
state: New Mexico
city: Greenville
country: United States
facility: East Carolina University/Brody Medical Sciences Building-Site Number:8400043
state: North Carolina
city: Charleston
country: United States
facility: Coastal Pediatric Research-Site Number:8400031
state: South Carolina
city: Greenville
country: United States
facility: Tribe Clinical Research-Site Number:8400027
state: South Carolina
city: Lampasas
country: United States
facility: FMC Science-Site Number:8400042
state: Texas
city: Salt Lake City
country: United States
facility: JBR Clinical Research-Site Number:8400041
state: Utah
city: Charlottesville
country: United States
facility: Pediatric Associates of Charlottesville North-Site Number:8400007
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research Inc-Site Number:8400004
state: Virginia
city: Santiago
country: Chile
facility: Investigational Site Number :1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number :1520004
state: Reg Metropolitana De Santiago
city: San Pedro Sula
country: Honduras
facility: Investigational Site Number :3400001
city: Tegucigalpa
country: Honduras
facility: Investigational Site Number :3400002
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: