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 2
• Start date: September 17, 2020
• Est. completion date: April 13, 2023

Study information

• Verified date: September 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of the study are: - 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 are: - 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 is 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. ebrile 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 is 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 :3400002	Municipio Del Distrito Central
Honduras	Investigational Site Number :3400001	San Pedro Sula
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 reporting immediate adverse events	Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination.	Within 30 minutes after vaccination
Primary	Number of participants reporting solicited reactions	Solicited administrative site reaction: rhinorrhea. Solicited systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability.	Within 28 days after vaccination
Primary	Number of participants reporting unsolicited adverse events	Unsolicited adverse events are spontaneously reported adverse events.	Within 28 days after vaccination
Primary	Number of participants reporting adverse events of special interest	Adverse events of special interest pre-defined adverse event collected using the same process as for other adverse events.	Within 28 days after vaccination
Primary	Number of participants reporting medically attended adverse events	Medically attended adverse events are adverse events with a new onset or a worsening of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department.	Within 28 days after vaccination
Primary	Number of participants reporting serious adverse events	Serious adverse events are collected throughout the study, from Day 0 until the end of the study.	Day 0 to maximum Month 12
Primary	RSV A serum neutralizing antibody levels after first vaccine administration	RSV A serum neutralizing antibody levels assessed in RSV-naïve participants in Cohorts 1, 2, 3, and 4.	Day 56
Primary	RSV A serum neutralizing antibody levels after second vaccine administration	RSV A serum neutralizing antibody levels are assessed in RS-naïve participants in Cohorts 2 and 4.	Day 84
Secondary	Titer of vaccine virus shedding (polymerase chain reaction [RT-PCR])	Titers are assessed by PCR at Day 7 for Cohorts 1, 2, 3 and 4 and Day 63 for Cohorts 2 and 4.	7 days after vaccination
Secondary	Number of participants infected with the vaccine virus	Infection is defined as detection of vaccine in nasal wash by culture or PCR and / or a = 4-fold rise in serum neutralizing antibodies or in serum antibodies to RSV F. Infectivity is assessed on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4	Day 56 and Day 84
Secondary	RSV A serum neutralizing antibody levels	RSV serum neutralizing antibody levels assessed in RSV-experienced participants on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4.	Day 56 and Day 84
Secondary	RSV serum anti-F binding antibody levels	RSV serum anti-F binding antibody levels assessed on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4.	Day 56 and Day 84
Secondary	RSV A serum neutralizing and serum anti-RSV F IgG antibody titers after the RSV surveillance season or at least 5 months after the last vaccine administration	RSV A serum neutralizing and serum anti-RSV F IgG antibody titers are assessed after the end of the RSV season (on average end of March in the Northern Hemisphere and end of September in the Southern Hemisphere) or at least 5 months after the last vaccine administration.	Within 1 month after the end of the RSV season or at least 5 months after the last vaccine administration.