Clinical trial NCT06397768: Co-administration Study of an Investigational Live-Attenuated Respiratory Syncytial Virus Vaccine in Infants and Toddlers
Official title: Phase III, Randomized, Single-blind, Placebo-controlled, Multi-center Study to Evaluate Non-interference of Concomitant Administration of Routine Pediatric Vaccines on the Antibody Response of an Investigational Live-attenuated Respiratory Syncytial Virus (RSV) Vaccine in Healthy Infants and Toddlers (CORAL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: RSV Immunization
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-05-03
Enrollment: 2226
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a Phase III, randomized, single-blind, placebo-controlled, multi-center study to be conducted in healthy infants and toddlers which will be enrolled at approximately 6 months of age (Cohort 1) and approximately 12 months of age (Cohort 2). The primary objective of the study will be to assess non-inferiority of the RSV infant and toddler (RSVt) vaccine antibody response when administered concomitantly with routine pediatric vaccines at 6 months of age (Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus b Conjugate and Hepatitis B Vaccine \[Vaxelis® or Pentacel® and Recombivax HB®\] Prevnar 20®, and RotaTeq®), and 12 months of age (M-M-R II, VARIVAX, and Prevnar 20 or per local country recommendations) compared to when administered non-concomitantly.

Detailed description: The study duration is approximately 9 months for each participant.

* Cohort 1: Visits at 6, 7, and 8 and 9 months of age for both groups with visit at 10 months of age for Group 2 only
* Cohort 2: Visits at 12, 13, 14 and 15 months of age for both groups with visit at 16 months of age for Group 4 only
* Routine pediatric vaccines (authorized auxiliary medicinal products (AxMP) will be administered at 6 months in Cohort 1 and 12 months of age in Cohort 2, as per Advisory Committee on Immunization Practice (ACIP) or local country recommendations.

Eligibility criteria: Inclusion Criteria:

* Aged 6 months for Cohort 1 and 12 months for Cohort 2 on the day of inclusion ("6 months" means from the day of the 6-month birthday to the day before the 7-month birthday and "12 months" means from the day of the 12-month birthday to the day before the 13-month birthday)
* Participants who are healthy as determined by medical evaluation including medical history and physical examination
* For Cohort 1: Infant received doses of vaccines containing hepatitis B, diphtheria, tetanus, pertussis, Haemophilus influenzae type B (Hib), and inactivated poliovirus vaccine (IPV) antigens, with Advisory Committee on Immunization Practice (ACIP) recommended vaccines. The last dose(s) of these vaccines must be at least 28 days before the first study visit
* Infant received the recommended doses of a recommended pneumococcal conjugate vaccine (as per local schedule) at least 28 days before the first study visit.

Exclusion Criteria:

* 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)
* Known previous infection with diphtheria, tetanus, Hib, measles, mumps, rubella, rotavirus, pneumococcus, polio, hepatitis B virus
* Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention used in the study or to a product containing any of the same substances
* Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
* History of medically diagnosed wheezing
* Any acute febrile illness in the past 48 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.
* Probable or confirmed ongoing case of viral respiratory infection (including COVID 19, influenza, rhinovirus, etc.) at the time of enrollment. A prospective participant should not be included in the study until the respiratory infection has resolved.
* Member of a household that contains an immunocompromised individual, including, but not limited to:
* A person living with human immunodeficiency virus (HIV)
* A person who has received chemotherapy within the 12 months prior to study enrollment
* A person who has received (within the past 6 months) or is receiving (at the time of enrollment) immunosuppressant agents
* A person living with a solid organ or bone marrow transplant
* Potential close contact with other immunocompromised individual within 30 days after each vaccination as per investigator's discretion
* History of definitive contraindications to any of the concomitant vaccines that will be administered as part of the study protocol
* Participant's biological mother with previous receipt or planned administration of an investigational RSV vaccine during pregnancy and/or breastfeeding
* Receipt of any vaccine in the 4 weeks preceding RSVt vaccine administration or planned receipt of any vaccine outside of study protocol in the 4 weeks following RSVt vaccine administration, except for influenza and/or COVID-19 vaccination, which may be received at least 1 week before or 1 week after RSVt vaccine administration
* Previous receipt of an investigational RSV vaccine or receiving any anti RSV product (such as ribavirin or RSV immune globulin) at the time of enrollment
* Receipt of immune globulins, blood or blood-derived products in the past 3 months
* Receipt of intranasal and intra-ocular medications within 3 days prior to study enrollment
* Previous receipt of an RSV monoclonal antibody within 6 months prior to the first study vaccine administration or planned receipt for duration of the study
* For Cohort 1: Prior receipt of routine 6-month pediatric vaccine doses (as per local schedule)
* For Cohort 2: Prior receipt of routine 12-month pediatric vaccine doses (as per local schedule)
* Participation at the time of study enrollment (or in the 6 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure

Note: The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Primary outcomes:
measure: RSV A serum neutralizing antibody titers at 28 days post dose 2 (D85) Groups 1 and 3
timeFrame: Day 85
measure: RSV B serum neutralizing antibody titers at 28 days post dose 2 (D85) Groups 1 and 3
timeFrame: Day 85
measure: RSV A serum neutralizing antibody titers at Day 113 Groups 2 and 4
timeFrame: Day 113
measure: RSV B serum neutralizing antibody titers at Day 113 Groups 2 and 4
timeFrame: Day 113
Secondary outcomes:
measure: Anti- hepatitis B surface antigen (HBsAg) Immunoglobulin g (IgG) antibody (A)b concentrations ≥ 10 milli international units per milliliter (mIU/mL) Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Anti- polyribosylribitol phosphate (PRP) Ab concentrations ≥ 0.15 micrograms per milliliter (µg/mL) Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Anti-poliovirus types (1, 2, and 3) Ab titers ≥ 1:8 Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Anti-pertussis Ab concentrations pertussis toxin, filamentous hemagglutinin , pertactin, fimbriae (PT, FHA, PRN, FIM) Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Anti-diphtheria Ab concentrations ≥ 0.1 IU/mL Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Anti-tetanus Ab concentrations ≥ 0.1 IU/mL Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Anti-pneumococcal Ab concentrations measured by electrochemiluminescence (ECL) for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Anti-measles Ab concentrations ≥ 255 mIU/mL Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Anti-mumps Ab concentrations ≥ 10 antibody units (AbU/mL) Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Anti-rubella Ab concentrations ≥ 10 IU/mL Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Anti-varicella Ab concentrations ≥ 5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) units/mL Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Anti-pneumococcal Ab concentrations measured by ECL Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Descriptive: Anti-PRP Ab concentrations (µg/mL) Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-diphtheria Ab concentrations (IU/mL) Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-diphtheria Ab concentrations ≥ 0.01 IU/mL Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-tetanus Ab concentrations (IU/mL) Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-tetanus Ab concentrations ≥ 0.01 IU/mL Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-HBsAg Ab concentrations (mIU/mL) Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-HBsAg Ab concentrations ≥ 100 mIU/mL Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-poliovirus types (1, 2, and 3) Ab titers Cohort 1
timeFrame: 28 days after the 6 month routine vaccinations
measure: Descriptive: Anti-measles Ab concentrations (mIU/mL) Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Descriptive: Anti-mumps Ab concentrations (AbU/mL) Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Descriptive: Anti-rubella Ab concentrations (IU/mL) Cohort 2
timeFrame: 28 days after the 12 month routine vaccinations
measure: Descriptive: Anti-varicella Ab concentrations (gpELISA units/mL)
timeFrame: 28 days after the 12 month routine vaccinations
measure: RSV A serum neutralizing antibody titers by baseline serostatus at Day 1 Cohort 1 and Cohort 2
timeFrame: Day 1
measure: RSV B serum neutralizing antibody titers by baseline serostatus at Day 1 Cohort 1 and Cohort 2
timeFrame: Day 1
measure: RSV A serum neutralizing antibody titers by baseline serostatus 28 days post-dose 2 1 Cohort 1 and Cohort 2
timeFrame: 28 days post-dose 2
measure: RSV B serum neutralizing antibody titers by baseline serostatus 28 days post-dose 2 Cohort 1 and Cohort 2
timeFrame: 28 days post-dose 2
measure: Presence of solicited administration site reactions within 21 days after each investigational medicinal product (IMP) administration Cohort 1 and Cohort 2
timeFrame: 21 days after each IMP administration
measure: Presence of solicited systemic reactions within 21 days after each IMP administration Cohort 1 and Cohort 2
timeFrame: 21 days after each IMP administration
measure: Presence of unsolicited systemic adverse events (AEs) reported in the 30 minutes after each study intervention administration Cohort 1 and Cohort 2
timeFrame: Within 30 minutes after each study intervention administration
measure: Presence of unsolicited AEs within 28 days after each study intervention administration Cohort 1 and Cohort 2
timeFrame: Within 28 days after each study intervention administration
measure: Presence of medically attended adverse events (MAAEs) throughout the study Cohort 1 and Cohort 2
timeFrame: Throughout the study, approximately 9 months
measure: Presence of serious adverse events (SAEs) throughout the study Cohort 1 and Cohort 2
timeFrame: Throughout the study, approximately 9 months
measure: Presence of adverse events of special interest (AESIs) throughout the study Cohort 1 and Cohort 2
timeFrame: Throughout the study, approximately 9 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics - Birmingham - St. Vincent's Drive- Site Number : 8400007
state: Alabama
city: Grand Bay
country: United States
facility: South Alabama Medical Clinic- Site Number : 8400065
state: Alabama
city: Mobile
country: United States
facility: MedPharmics - Mobile - Dauphin Street- Site Number : 8400017
state: Alabama
city: Fayetteville
country: United States
facility: Northwest Arkansas Pediatric Clinic- Site Number : 8400002
state: Arkansas
city: Bell Gardens
country: United States
facility: Alliance Research Institute- Site Number : 8400040
state: California
city: Huntington Park
country: United States
facility: Matrix Clinical Research - Huntington Park- Site Number : 8400018
state: California
city: La Mesa
country: United States
facility: Paradigm Clinical Research Centers- Site Number : 8400059
state: California
city: Los Angeles
country: United States
facility: Matrix Clinical Research - Los Angeles- Site Number : 8400008
state: California
city: Oakland
country: United States
facility: Kaiser Permanente - Oakland Medical Center- Site Number : 8400047
state: California
city: Roseville
country: United States
facility: Kaiser Permanente - Sierra Gardens- Site Number : 8400063
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Point West Medical Offices- Site Number : 8400064
state: California
city: San Jose
country: United States
facility: Kaiser Permanente - San Jose Medical Center- Site Number : 8400060
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente - Santa Clara- Site Number : 8400061
state: California
city: Tarzana
country: United States
facility: Integrated Clinical Research- Site Number : 8400036
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente - Walnut Creek Medical Center- Site Number : 8400062
state: California
city: Washington
country: United States
facility: Velocity Clinical Research - Washington DC- Site Number : 8400050
state: District of Columbia
city: Hollywood
country: United States
facility: The Medici Medical Research- Site Number : 8400055
state: Florida
city: Miami
country: United States
facility: Dade Research Center- Site Number : 8400014
state: Florida
city: Miami
country: United States
facility: Riveldi Biomedical Research and Associates - Miami- Site Number : 8400015
state: Florida
city: Pensacola
country: United States
facility: SEC Clinical Research- Site Number : 8400034
state: Florida
city: Tampa
country: United States
facility: PAS Research- Site Number : 8400005
state: Florida
city: Idaho Falls
country: United States
facility: Leavitt Women's Healthcare- Site Number : 8400009
state: Idaho
city: Sioux City
country: United States
facility: Velocity Clinical Research - Sioux City- Site Number : 8400054
state: Iowa
city: El Dorado
country: United States
facility: Alliance for Multispeciality Research - El Dorado- Site Number : 8400019
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center- Site Number : 8400051
state: Kentucky
city: New Orleans
country: United States
facility: Velocity Clinical Researchâ€" New Orleans- Site Number : 8400058
state: Louisiana
city: New Orleans
country: United States
facility: NOLA Research Works- Site Number : 8400044
state: Louisiana
city: Biloxi
country: United States
facility: MedPharmics - Biloxi- Site Number : 8400011
state: Mississippi
city: Springfield
country: United States
facility: QPS Bio-Kinetic Clinical Applications- Site Number : 8400046
state: Missouri
city: Great Falls
country: United States
facility: Boeson Research - Great Falls- Site Number : 8400041
state: Montana
city: Missoula
country: United States
facility: Boeson Research - Missoula- Site Number : 8400006
state: Montana
city: Hastings
country: United States
facility: Velocity Clinical Research - Hastings- Site Number : 8400016
state: Nebraska
city: Lincoln
country: United States
facility: Midwest Childrens Health Research Institute- Site Number : 8400038
state: Nebraska
city: Omaha
country: United States
facility: Velocity Clinical Research - Omaha- Site Number : 8400001
state: Nebraska
city: Henderson
country: United States
facility: PAS Research- Site Number : 8400049
state: Nevada
city: Liverpool
country: United States
facility: Summerwood Pediatrics- Site Number : 8400021
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University - Syracuse- Site Number : 8400029
state: New York
city: Dayton
country: United States
facility: Dayton Clinical Research- Site Number : 8400030
state: Ohio
city: Dayton
country: United States
facility: Ohio Pediatrics - Dayton- Site Number : 8400033
state: Ohio
city: South Euclid
country: United States
facility: Senders Pediatrics- Site Number : 8400022
state: Ohio
city: Gresham
country: United States
facility: Cyn3rgy Research- Site Number : 8400053
state: Oregon
city: Erie
country: United States
facility: Square-1 Clinical Research- Site Number : 8400031
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pas Research - Pittsburgh- Site Number : 8400043
state: Pennsylvania
city: Greenville
country: United States
facility: Tribe Clinical Research - 525 Verdae Boulevard- Site Number : 8400012
state: South Carolina
city: Corpus Christi
country: United States
facility: South Texas Clinical Research- Site Number : 8400004
state: Texas
city: Dallas
country: United States
facility: Javara - Privia Medical Group North Texas - Dallas- Site Number : 8400003
state: Texas
city: Edinburg
country: United States
facility: PAS RESEARCH- Site Number : 8400035
state: Texas
city: Fort Worth
country: United States
facility: Ventavia Research Group - Fort Worth- Site Number : 8400020
state: Texas
city: Houston
country: United States
facility: Ventavia Research Group - Houston - North Loop West- Site Number : 8400010
state: Texas
city: Houston
country: United States
facility: UTHealth Houston- Site Number : 8400037
state: Texas
city: Houston
country: United States
facility: DM Clinical Research - Houston - Jones Road- Site Number : 8400052
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research - Houston - Savoy Drive- Site Number : 8400045
state: Texas
city: Houston
country: United States
facility: Chemidox Clinical Trials- Site Number : 8400039
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Associates- Site Number : 8400013
state: Texas
city: League City
country: United States
facility: University of Texas Medical Branch at Galveston- Site Number : 8400057
state: Texas
city: League City
country: United States
facility: Maximos Ob/Gyn- Site Number : 8400024
state: Texas
city: Plano
country: United States
facility: Research Your Health- Site Number : 8400066
state: Texas
city: Richmond
country: United States
facility: Pediatric Center - Richmond- Site Number : 8400032
state: Texas
city: Tomball
country: United States
facility: North Houston Internal Medicine and Pediatric Center- Site Number : 8400025
state: Texas
city: Orem
country: United States
facility: Utah Valley Pediatrics - Orem- Site Number : 8400067
state: Utah
city: Pleasant View
country: United States
facility: Ogden Clinic - Mountain View - CCT Research- Site Number : 8400056
state: Utah
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840001
state: Ciudad De Mexico
city: Temixco
country: Mexico
facility: Investigational Site Number : 4840002
state: Morelos
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840004
city: Caguas
country: Puerto Rico
facility: Investigational Site Number : 6300001
city: Ponce
country: Puerto Rico
facility: Investigational Site Number : 6300003
city: Trujillo Alto
country: Puerto Rico
facility: Investigational Site Number : 6300004
Study officials:
References: