Study of an Live-Attenuated Respiratory Syncytial Virus Vaccine in Infants and Toddlers

Phase 1

Completed

Conditions: Respiratory Syncytial Virus Infection

Interventions: Biological: RSV vaccine formulation 1
Biological: RSV vaccine formulation 2
Biological: Placebo

Registration Number: NCT04491877

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 259

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2 (RSV vaccine formulation 1)	RSV vaccine formulation 1	2 administrations of RSV vaccine formulation 1 on Day 0 and Day 56
Cohort 3 (RSV vaccine formulation 2)	RSV vaccine formulation 2	1 administration of RSV vaccine formulation 2 on Day 0
Cohort 3 (Placebo)	Placebo	1 administration of placebo on Day 0
Cohort 4 (RSV vaccine formulation 1)	RSV vaccine formulation 1	2 administrations of RSV vaccine formulation 1 on Day 0 and Day 56
Cohort 1 (RSV vaccine formulation 1)	RSV vaccine formulation 1	1 administration of RSV vaccine formulation 1 on Day 0
Cohort 1 (Placebo)	Placebo	1 administration of placebo on Day 0
Cohort 4 (RSV vaccine formulation 2)	RSV vaccine formulation 2	2 administrations of RSV vaccine formulation 2 on Day 0 and Day 56
Cohort 2 (Placebo)	Placebo	2 administrations of placebo on Day 0 and Day 56
Cohort 4 (Placebo)	Placebo	2 administrations of placebo on Day 0 and Day 56

Primary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Administration Site and Systemic Reactions	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	All noxious and unintended responses to a medicinal product related to any dose are considered adverse reactions (AR). A solicited reaction is an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB. An administration site reaction is an AR at and around the administration site. Systemic ARs are all ARs that are not injection or administration site reactions.
Number of Participants With Unsolicited Adverse Events	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	An AE is any untoward medical occurrence in a participant or in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An unsolicited AE is an observed AE that does not fulfill the conditions pre-listed in the CRB in terms of diagnosis and/or onset window post-vaccination.
Number of Participants With Adverse Events of Special Interest (AESIs)	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	An AESI is one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate.
Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)	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	An AE is any untoward medical occurrence in a participant or in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An unsolicited AE is an observed AE that does not fulfill the conditions pre-listed in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Systemic AEs are all AEs that were not injection or administration site reactions. Immediate events are recorded to capture medically relevant unsolicited systemic AEs (including those related to the product administered) that occur within the first 30 minutes after vaccination.
Number of Participants With Serious Adverse Events (SAEs)	From the first study vaccine administration (Day 0) up to end of the study, maximum of 12 months	An SAE is any untoward medical occurrence that at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event.
Number of Participants With Medically Attended Adverse Events (MAAEs)	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	An MAAE is a new onset or a worsening of a condition that prompts the participant or participant's parent/guardian/legally authorized representative to seek unplanned medical advice at a physician's office or Emergency Department.
Geometric Mean Titers Against RSV A Neutralizing Antibody in RSV-Naïve Participants	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84	RSV A neutralizing antibody measured by microneutralization. RSV-naïve participants are defined as undetectable serum anti-RSV A IgA antibodies.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Infected With Vaccine Virus at Days 56 and 84	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84	Infection is defined as detection of vaccine virus in nasal swab by RT-PCR and/or a \>= 4-fold rise in RSV A serum neutralizing antibody titers, or in RSV serum anti-F immunoglobulin G (IgG) antibody titers.
Titer of Vaccine Virus Shedding Measured by Reverse Transcription Polymerase Chain Reaction (RT-PCR)	Cohorts 1 and 3: Day 7; Cohorts 2 and 4: Days 7 and 63	Shedding of the attenuated RSV vaccine strain in nasal swab samples was evaluated by RSV quantitative RT-PCR (qRT-PCR) assay, which specifically detected and quantified RSVt ΔNS2 vaccine strain (RSV ΔNS2/Δ1313/I1314L) in human nasal swab samples.
Geometric Mean Titers Against RSV A Neutralizing Antibody in RSV-Experienced Participants	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84	RSV A neutralizing antibody measured by microneutralization. RSV-experienced participants are defined as detectable serum anti-RSV A IgA antibodies. CI= confidence interval.
Geometric Mean Titers Against Serum Anti-F Immunoglobulin G (IgG) Antibody	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84	The IgG antibodies to RSV F antigen was measured using the anti RSV F IgG ELISA. RSV-naïve and RSV-experienced participants are defined as undetectable or detectable serum anti-RSV A IgA antibodies, respectively.
Geometric Mean Titers Against Serum Anti-F Immunoglobulin G Antibody After the RSV Surveillance Season	Cohorts 1 and 3: Within 5 months after vaccination on Day 0; Cohorts 2 and 4: Within 5 months after vaccination on Day 56	The IgG antibodies to RSV F antigen was measured using the anti RSV F IgG ELISA. RSV-naïve and RSV-experienced participants are defined as undetectable or detectable serum anti-RSV A IgA antibodies, respectively.
Geometric Mean Titers Against RSV A Neutralizing Antibody After the RSV Surveillance Season	Cohorts 1 and 3: Within 5 months after vaccination on Day 0; Cohorts 2 and 4: Within 5 months after vaccination on Day 56	RSV A neutralizing antibody measured by microneutralization. RSV-naïve and RSV-experienced participants are defined as undetectable or detectable serum anti-RSV A IgA antibodies, respectively.

Trial Locations

Locations (29): Pediatric Associates of Charlottesville North-Site Number:8400007
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Charlottesville, Virginia, United States
Matrix Clinical Research-Site Number:8400032
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Los Angeles, California, United States
The South Bend Clinic Center for Research-Site Number:8400024
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South Bend, Indiana, United States
East Carolina University/Brody Medical Sciences Building-Site Number:8400043
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Greenville, North Carolina, United States
Nola Research Works-Site Number:8400017
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New Orleans, Louisiana, United States
Investigational Site Number :3400001
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San Pedro Sula, Honduras
Leavitt Clinical Research-Site Number:8400036
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Idaho Falls, Idaho, United States
Tribe Clinical Research-Site Number:8400027
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Greenville, South Carolina, United States
Meridian Clinical Research - Norfolk-Site Number:8400005
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Norfolk, Nebraska, United States
Snake River Research-Site Number:8400022
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Idaho Falls, Idaho, United States
Be Well Clinical Studies-Site Number:8400054
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Lincoln, Nebraska, United States
Investigational Site Number :1520001
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Santiago, Reg Metropolitana De Santiago, Chile
Boeson Research-Site Number:8400011
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Missoula, Montana, United States
Elite Clinical Trials, Inc.-Site Number:8400001
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Blackfoot, Idaho, United States
Benchmark Research-Site Number:8400006
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Covington, Louisiana, United States
Coastal Pediatric Research-Site Number:8400031
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Charleston, South Carolina, United States
Investigational Site Number :1520004
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Santiago, Reg Metropolitana De Santiago, Chile
Matrix Clinical Research-Site Number:8400012
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Gardena, California, United States
California Research Foundation-Site Number:8400016
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San Diego, California, United States
Paradigm Clinical Research-Site Number:8400026
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La Mesa, California, United States
AMR - Newton-Site Number:8400002
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Newton, Kansas, United States
Alliance for Multispeciality Research-Site Number:8400014
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El Dorado, Kansas, United States
Michael W. Simon, MD, PSC-Site Number:8400013
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Lexington, Kentucky, United States
Clinical Research Institute-Site Number:8400053
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Minneapolis, Minnesota, United States
MedPharmics Inc-Site Number:8400040
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Albuquerque, New Mexico, United States
JBR Clinical Research-Site Number:8400041
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Salt Lake City, Utah, United States
FMC Science-Site Number:8400042
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Lampasas, Texas, United States
National Clinical Research Inc-Site Number:8400004
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Richmond, Virginia, United States
Investigational Site Number :3400002
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Tegucigalpa, Honduras