Study of an Live-Attenuated Respiratory Syncytial Virus Vaccine in Infants and Toddlers (VAD00001)

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infection
• Intervention / Treatment: Biological: RSV vaccine formulation 1; Biological: Placebo; Biological: RSV vaccine formulation 2

Detailed Description

Study duration per participant was maximum 12 months

• Study Type: Interventional
• Enrollment (Actual): 259
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Chile
  • Reg Metropolitana de Santiago
    • Santiago, Reg Metropolitana de Santiago, Chile, 8380453
      • Investigational Site Number :1520001
    • Santiago, Reg Metropolitana de Santiago, Chile, 8420383
      • Investigational Site Number :1520004
• Honduras
  • San Pedro Sula, Honduras, 21104
    • Investigational Site Number :3400001
  • Tegucigalpa, Honduras, 11101
    • Investigational Site Number :3400002
• United States
  • California
    • Gardena, California, United States, 90247
      • Matrix Clinical Research-Site Number:8400012
    • La Mesa, California, United States, 91942
      • Paradigm Clinical Research-Site Number:8400026
    • Los Angeles, California, United States, 90057
      • Matrix Clinical Research-Site Number:8400032
    • San Diego, California, United States, 92123-1881
      • California Research Foundation-Site Number:8400016
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials, Inc.-Site Number:8400001
    • Idaho Falls, Idaho, United States, 83404
      • Leavitt Clinical Research-Site Number:8400036
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research-Site Number:8400022
  • Indiana
    • South Bend, Indiana, United States, 46617
      • The South Bend Clinic Center for Research-Site Number:8400024
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • Alliance for Multispeciality Research-Site Number:8400014
    • Newton, Kansas, United States, 67114
      • AMR - Newton-Site Number:8400002
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Michael W. Simon, MD, PSC-Site Number:8400013
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Benchmark Research-Site Number:8400006
    • New Orleans, Louisiana, United States, 70125
      • Nola Research Works-Site Number:8400017
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute-Site Number:8400053
  • Montana
    • Missoula, Montana, United States, 59804
      • Boeson Research-Site Number:8400011
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Be Well Clinical Studies-Site Number:8400054
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research - Norfolk-Site Number:8400005
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • MedPharmics Inc-Site Number:8400040
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University/Brody Medical Sciences Building-Site Number:8400043
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research-Site Number:8400031
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research-Site Number:8400027
  • Texas
    • Lampasas, Texas, United States, 76550-1820
      • FMC Science-Site Number:8400042
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research-Site Number:8400041
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Pediatric Associates of Charlottesville North-Site Number:8400007
    • Richmond, Virginia, United States, 23294
      • National Clinical Research Inc-Site Number:8400004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (RSV vaccine formulation 1); 1 administration of RSV vaccine formulation 1 on Day 0	Biological: RSV vaccine formulation 1; Pharmaceutical form: Suspension of virus Route of administration: Intranasal
Placebo Comparator: Cohort 1 (Placebo); 1 administration of placebo on Day 0	Biological: Placebo; Pharmaceutical form: Suspension Route of administration: Intranasal
Experimental: Cohort 2 (RSV vaccine formulation 1); 2 administrations of RSV vaccine formulation 1 on Day 0 and Day 56	Biological: RSV vaccine formulation 1; Pharmaceutical form: Suspension of virus Route of administration: Intranasal
Placebo Comparator: Cohort 2 (Placebo); 2 administrations of placebo on Day 0 and Day 56	Biological: Placebo; Pharmaceutical form: Suspension Route of administration: Intranasal
Experimental: Cohort 3 (RSV vaccine formulation 2); 1 administration of RSV vaccine formulation 2 on Day 0	Biological: RSV vaccine formulation 2; Pharmaceutical form: Suspension of virus Route of administration: Intranasal
Placebo Comparator: Cohort 3 (Placebo); 1 administration of placebo on Day 0	Biological: Placebo; Pharmaceutical form: Suspension Route of administration: Intranasal
Experimental: Cohort 4 (RSV vaccine formulation 1); 2 administrations of RSV vaccine formulation 1 on Day 0 and Day 56	Biological: RSV vaccine formulation 1; Pharmaceutical form: Suspension of virus Route of administration: Intranasal
Experimental: Cohort 4 (RSV vaccine formulation 2); 2 administrations of RSV vaccine formulation 2 on Day 0 and Day 56	Biological: RSV vaccine formulation 2; Pharmaceutical form: Suspension of virus Route of administration: Intranasal
Placebo Comparator: Cohort 4 (Placebo); 2 administrations of placebo on Day 0 and Day 56	Biological: Placebo; Pharmaceutical form: Suspension Route of administration: Intranasal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 ΔNS2 vaccine strain (RSV ΔNS2/Δ1313/I1314L) in human nasal swab samples.	Cohorts 1 and 3: Day 7; Cohorts 2 and 4: Days 7 and 63
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Idoko OT, Vargas SL, Bueso A, Rivera D, Edward H, Simon M, Banooni P, Berger S, Janicot S, Vercasson C, Pallardy S, Nteene R, Adhikarla H, Gerchman E, Gasparotto M, Gallichan S, Rivas E, Buchholz UJ, Collins PL, Sesay S, Gurunathan S, De Bruijn I, Dhingra MS. Live-Attenuated Intranasal RSV Vaccine in Infants and Toddlers. NEJM Evid. 2025 Sep;4(9):EVIDoa2500026. doi: 10.1056/EVIDoa2500026. Epub 2025 Aug 26.

Helpful Links

• VAD00001 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2020
• Primary Completion (Actual): April 13, 2023
• Study Completion (Actual): April 13, 2023

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Respiratory Syncytial Virus Infections; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: VAD00001; U1111-1238-1869 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No