Co-administration Study of an Investigational Live-Attenuated Respiratory Syncytial Virus Vaccine in Infants and Toddlers (CORAL)

Sanofi

Status and phase: Enrolling; Phase 3

Conditions: RSV Immunization

Treatments: Biological: Diphtheria, tetanus, pertussis, Haemophilus influenzae type b and poliomyelitis vaccine; Biological: Streptococcus pneumoniae vaccine; Biological: Measles, mumps, and rubella vaccine; Biological: Hepatitis B vaccine; Biological: Placebo; Biological: Rotavirus vaccine; Biological: RSVt vaccine; Biological: Diphtheria, tetanus, pertussis, poliomyelitis , Haemophilus influenzae type b, and hepatitis B vaccine; Biological: Varicella virus vaccine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06397768

VAD00016 (Other Identifier)

U1111-1290-7356 (Registry Identifier)

2024-000262-15 (EudraCT Number)

Details and patient eligibility

About

This study is a Phase III, randomized, single-blind, placebo-controlled, multi-center study to be conducted in healthy infants and toddlers aged 6 months + 2 weeks for Cohort 1 and 12 months ± 2 weeks for Cohort 2. The primary objective of the study will be to assess non-inferiority of the respiratory syncytial virus toddler and infant (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.

Full 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.

Enrollment: 2,226 estimated patients

Sex: All

Ages: 6 to 12 months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Aged 6 months + 2 weeks for Cohort 1 and 12 months ± 2 weeks for Cohort 2 on the day of inclusion (means the day of the 6-month birthday + 2 weeks and "12 months ± 2 weeks" means the day of the 12-month birthday ± 2 weeks)
• Participants who are healthy as determined by medical evaluation including medical history and physical examination
• Born at full term of pregnancy (≥ 37 weeks)
• For Cohort 1 (US/Puerto Rico participants only): Infant received the first dose of a hepatitis B vaccine at birth; first and second doses of routine vaccines containing diphtheria, tetanus, pertussis, Haemophilus influenzae type B (Hib), and inactivated poliovirus vaccine (IPV) antigens with either Vaxelis or Pentacel vaccine; and second or third doses of hepatitis B with either Vaxelis or RECOMBIVAX HB or other monovalent hepatitis B vaccine. The last dose of Vaxelis or Pentacel/RECOMBIVAX HB or alternate monovalent hepatitis B vaccine must be at least 28 days before the first study visit
• For Cohort 1 (US/Puerto Rico participants only): Infant received the first and second doses of RotaTeq vaccine at least 28 days before the first study visit
• For Cohort 1(US/Puerto Rico participants only): Infant received the first and second doses of an ACIP recommended pneumococcal conjugate vaccine at least 28 days before the first study visit
• For Cohort 2 (US/Puerto Rico participants only): Infant received the first 3 doses of an Advisory Committee on Immunization Practice (ACIP) recommended pneumococcal conjugate vaccine at least 28 days before the first study visit

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• 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
• History of RSV infection, confirmed either clinically, serologically, or microbiologically
• 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. Chronic illness may include, but is not limited to, cardiac disorders, lung disease (including any history of reactive airway disease, receipt of bronchodilator or inhaled steroid therapy), atopy, renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases
• History of medically diagnosed wheezing. Children with a history of recurrent wheezing will be excluded. Children with a previous single episode of wheezing may be included if that episode of wheezing was not associated with hospitalization or if the child does not have a family history of 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 or licensed RSV vaccine during pregnancy and/or breastfeeding
• Receipt of any vaccine in the 4 weeks preceding the first study intervention administration or planned receipt of any vaccine outside of study protocol in the 4 weeks following any study intervention administration, except for influenza and/or COVID-19 vaccination, which may be received at least 1 week before or 1 week after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines, as applicable per local recommendations.
• Previous receipt of a licensed or investigational RSV vaccine or receiving any anti RSV product (such as ribavirin or RSV immune globulin or RSV monoclonal antibody) 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
• Receipt of Beyfortus or other RSV antibodies Note: The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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2,226 participants in 4 patient groups

Cohort 1: Group 1- (RSVt vaccine concomitantly at 6 months)

Experimental group

Description:

Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 6 months. Vaccines administered at age 6 months: RSVt Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered non-concomitantly at 7 months of age

Treatment:

Biological: Diphtheria, tetanus, pertussis, poliomyelitis , Haemophilus influenzae type b, and hepatitis B vaccine

Biological: RSVt vaccine

Biological: Placebo

Biological: Rotavirus vaccine

Biological: Hepatitis B vaccine

Biological: Streptococcus pneumoniae vaccine

Biological: Diphtheria, tetanus, pertussis, Haemophilus influenzae type b and poliomyelitis vaccine

Cohort 1: Group 2- (RSVt vaccine non-concomitantly at 7 months)

Experimental group

Description:

Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 7 months. Vaccines administered at age 6 months: Vaxelis or Pentacel and Recombivax HB, Prevnar 20, and RotaTeq. Placebo will be administered concomitantly at 6 months of age

Treatment:

Biological: Diphtheria, tetanus, pertussis, poliomyelitis , Haemophilus influenzae type b, and hepatitis B vaccine

Biological: RSVt vaccine

Biological: Placebo

Biological: Rotavirus vaccine

Biological: Hepatitis B vaccine

Biological: Streptococcus pneumoniae vaccine

Biological: Diphtheria, tetanus, pertussis, Haemophilus influenzae type b and poliomyelitis vaccine

Cohort 2: Group 3- (RSVt vaccine concomitantly at 12 months)

Experimental group

Description:

Participants will be administered RSVt vaccine concomitantly with routine pediatric vaccines, 2 doses, at age 12 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered non-concomitantly at 13 months of age

Treatment:

Biological: Varicella virus vaccine

Biological: RSVt vaccine

Biological: Placebo

Biological: Measles, mumps, and rubella vaccine

Biological: Streptococcus pneumoniae vaccine

Cohort 2: Group 4- (RSVt vaccine non-concomitantly at 13 months)

Experimental group

Description:

Participants will be administered RSVt vaccine non-concomitantly with routine pediatric vaccines, 2 doses, at age 13 months. Vaccines administered at age 6 months: M-M-R II, VARIVAX, and Prevnar 20. Placebo will be administered concomitantly at 12 months of age

Treatment:

Biological: Varicella virus vaccine

Biological: RSVt vaccine

Biological: Placebo

Biological: Measles, mumps, and rubella vaccine

Biological: Streptococcus pneumoniae vaccine