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

Respiratory Syncytial Virus Infection Clinical Trial

— VAD00001  

Official title:

Safety, Immunogenicity, Infectivity, and Dose-Finding Study of an Investigational Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Infants and Toddlers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04491877
• Other study ID #: VAD00001
• Secondary ID: U1111-1238-1869
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 17, 2020
• Est. completion date: April 13, 2023

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study duration per participant was maximum 12 months

Recruitment information / eligibility

• Status: Completed
• Enrollment: 259
• Est. completion date: April 13, 2023
• Est. primary completion date: April 13, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 18 Months

Eligibility

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.

Related Conditions & MeSH terms

• Respiratory Syncytial Virus Infection
• Respiratory Syncytial Virus Infections

Intervention

Biological:
• RSV vaccine formulation 1
Pharmaceutical form: Suspension of virus Route of administration: Intranasal
• RSV vaccine formulation 2
Pharmaceutical form: Suspension of virus Route of administration: Intranasal
• Placebo
Pharmaceutical form: Suspension Route of administration: Intranasal

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Chile,  Honduras, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)	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.	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
Primary	Number of Participants With Solicited Administration Site and Systemic Reactions	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.	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
Primary	Number of Participants With Unsolicited Adverse Events	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.	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
Primary	Number of Participants With Adverse Events of Special Interest (AESIs)	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.	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
Primary	Number of Participants With Medically Attended Adverse Events (MAAEs)	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.	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
Primary	Number of Participants With Serious Adverse Events (SAEs)	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.	From the first study vaccine administration (Day 0) up to end of the study, maximum of 12 months
Primary	Geometric Mean Titers Against RSV A Neutralizing Antibody in RSV-Naïve Participants	RSV A neutralizing antibody measured by microneutralization. RSV-naïve participants are defined as undetectable serum anti-RSV A IgA antibodies.	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
Secondary	Titer of Vaccine Virus Shedding Measured by Reverse Transcription Polymerase Chain Reaction (RT-PCR)	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 ?NS2 vaccine strain (RSV ?NS2/?1313/I1314L) in human nasal swab samples.	Cohorts 1 and 3: Day 7; Cohorts 2 and 4: Days 7 and 63
Secondary	Percentage of Participants Infected With Vaccine Virus at 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.	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
Secondary	Geometric Mean Titers Against RSV A Neutralizing Antibody in RSV-Experienced Participants	RSV A neutralizing antibody measured by microneutralization. RSV-experienced participants are defined as detectable serum anti-RSV A IgA antibodies. CI= confidence interval.	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
Secondary	Geometric Mean Titers Against Serum Anti-F Immunoglobulin G (IgG) Antibody	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.	Cohorts 1 and 3: Day 56; Cohorts 2 and 4: Days 56 and 84
Secondary	Geometric Mean Titers Against RSV A Neutralizing Antibody After the RSV Surveillance Season	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.	Cohorts 1 and 3: Within 5 months after vaccination on Day 0; Cohorts 2 and 4: Within 5 months after vaccination on Day 56
Secondary	Geometric Mean Titers Against Serum Anti-F Immunoglobulin G Antibody After the RSV Surveillance Season	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.	Cohorts 1 and 3: Within 5 months after vaccination on Day 0; Cohorts 2 and 4: Within 5 months after vaccination on Day 56