Safety and Immunogenicity of an Investigational Pentavalent Meningococcal ABCYW Vaccine Against Meningococcal Disease in Children, Toddlers, and Infants

• Pentavalent Meningococcal ABCYW vaccine (Biological), also known as MenPenta: Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
• MenACYW conjugate vaccine (Biological), also known as MenQuadfi®: Pharmaceutical form: Solution for injection in vial Route of administration: Intramuscular (IM)
• MenACYW conjugate vaccine (Biological), also known as Nimenrix®: Pharmaceutical form: Powder and solvent for injectable solution in a pre-filled syringe Route of administration: Intramuscular (IM)
• Meningococcal group B vaccine (Biological), also known as Bexsero®: Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular (IM)
• Paracetamol (Drug): Pharmaceutical form:Suspension-Route of administration:oral
• DTap-HepB-IPV-Hib vaccine (Biological), also known as Hexyon®: Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular (IM)
• DTap-HepB-IPV-Hib vaccine (Biological), also known as Vaxelis®: Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular (IM)
• DTap-HepB-IPV-Hib vaccine (Biological), also known as Infanrix hexa®: Pharmaceutical form: Oral solution in tube Route of administration: oral
• Rotavirus vaccine (Biological), also known as RotaTeq® Rotarix®: Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular (IM)
• Pneumococcal 13-valent conjugate vaccine (Biological), also known as Prevnar 13®: Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: Intramuscular (IM)

Primary outcomes

• Number of participants with unsolicited immediate adverse events (AEs) [Within 30 minutes after each vaccination]: Unsolicited systemic AEs that occur within 30 minutes after vaccination
• Number of participants with solicited injection site reactions or systemic reactions [Within 7 days after each vaccination]: Pre-defined solicited injection site reactions and systemic reactions that are pre-listed in the diary cards and CRF
• Number of participants with unsolicited AEs [Within 30 days after each vaccination]: Unsolicited AEs other than solicited reactions
• Number of participants with serious adverse events (SAEs) [Throughout the study, from first visit until 180 days after the last vaccination]: SAEs (including adverse events of special interest \[AESIs\]) reported throughout the study
• hSBA meningococcal serogroups A, C, W, and Y antibody titers pre-dose and 30 days after the second and third dose in infant participants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]: hSBA titers ≥ 1:8 post-vaccination (post-second and third dose)
• hSBA meningococcal serogroups A, C, W, and Y vaccine seroresponse pre-dose and 1 month after the second and third dose in infant participants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]: Seroresponse defined as post-vaccination titers ≥ 1:16 for participants with pre-vaccination hSBA titers < 1:4 or or postvaccination titers ≥ 4 times the lower limit of quantification (LLOQ) for participants with a pre-vaccination titer ≤ LLOQ or a post-vaccination titer ≥ 4 times the pre-vaccination titer for participants with a pre-vaccination titer ≥ LLOQ
• Geometric mean titers (GMTs) of Antibodies against Meningococcal Serogroups A, C, W and Y pre-dose and 1 month after the second and third dose in infant participants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]: Geometric mean titers (pre-dose and post-second and third dose)
• Percentage of participants with hSBA titers more or equal to lower limit of quantification (LLOQ) against each of serogroups A, C, W, and Y pre-dose and 1 month after the second and third dose in infant participants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]
• Percentage of Participants With Meningococcal Antibody Titers against meningococcal serogroup B (reference MenB strains) ≥ 1:4 pre-dose and 1 month after second dose of vaccination against serogroup B, before and 30 days after third dose in infants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]: hSBA titers ≥ 1:4 for reference MenB strains
• Percentage of Participants With Meningococcal Antibody Titers against meningococcal serogroup B (reference MenB strains) ≥ 1:8 pre-dose and 1 month after the second dose of vaccination against serogroup B, before and 30 days after third dose in infants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]: hSBA titers ≥ 1:8 for reference MenB strains
• hSBA meningococcal serogroup B seroresponse pre-dose and 1 month after the second dose of vaccination against serogroup B, before and 30 days after third dose in infant participants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]: Seroresponse defined as a 4-fold increase in hSBA titers
• Geometric mean titers (GMTs) of Antibodies against Meningococcal Serogroup B (reference MenB strains) pre-dose and 1 month after the second dose of vaccination against serogroup B, before and 30 days after third dose in infant participants [Day 01, Day 91, Day 181 and Day 211 (for Stage 3)]: Geometric mean titers (pre-dose and post-second dose) for the reference MenB strains
• Percentage of participants with hSBA titers more or equal to lower limit of quantification (LLOQ) against each and all of serogroup B (ref. MenB strains) predose and 1 month after 2nd dose against serogroup B, before and 30 days after 3rd dose in infants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]
• Percentage of participants with hSBA titers less than LLOQ against all serogroup B (ref. MenB strains) pre-dose and 1 month after the 2nd dose of vaccination against serogroup B, before and 30 days after 3rd dose in infants [For Stage 3: Day 1, Day 91, Day 301-361, Day 331-391]
• hSBA meningococcal serogroups A, C, W, and Y antibody titers in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]: hSBA titers ≥ 1:8 for serogroups A, C, W, and Y
• hSBA meningococcal serogroups A, C, W, and Y vaccine seroresponse in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]: Seroresponse defined as post-vaccination titers ≥ 1:16 for participants with pre-vaccination hSBA titers < 1:4 or or postvaccination titers ≥ 4 times the lower limit of quantification (LLOQ) for participants with a pre-vaccination titer ≤ LLOQ or a post-vaccination titer ≥ 4 times the pre-vaccination titer for participants with a pre-vaccination titer ≥ LLOQ
• Geometric mean titers (GMTs) of Antibodies against Meningococcal Serogroups A, C, W and Y pre-dose and 1 month after the second dose children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]
• Percentage of participants with hSBA titers more or equal to lower limit of quantification (LLOQ) against each of serogroups A, C, W, and Y children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]
• Percentage of Participants With Meningococcal Antibody Titers against meningococcal serogroup B (reference MenB strains) ≥ 1:4 in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]
• Percentage of Participants With Meningococcal Antibody Titers against meningococcal serogroup B (reference MenB strains) ≥ 1:8 in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]
• hSBA meningococcal serogroup B (reference MenB strains) vaccine seroresponse in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]: Seroresponse defined as a 4-fold increase in hSBA titers
• Geometric mean titers (GMTs) of Antibodies against Meningococcal Serogroup B (reference MenB strains) in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]
• Percentage of participants with hSBA titers more or equal to lower limit of quantification (LLOQ) against each and all of serogroup B (reference MenB strains) in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]
• Percentage of participants with hSBA titers less than the lower limit of quantification (LLOQ) against all serogroup B (reference MenB strains) in children and toddlers [For Stage 1 and 2: Day 1, Day 31, Day 181, Day 211]

Secondary outcomes

• hSBA meningococcal serogroup B (additional MenB strains) vaccine seroresponse in children, toddler and infant participants [Stage 1 and 2: Day 1 and Day 211. Stage 3: Day 1, Day 331-391]
• Percentage of Participants With Meningococcal Antibody Titers against meningococcal serogroup B (additional MenB strains) ≥ 1:4 in children, toddler and infant participants [Stage 1 and 2: Day 1 and Day 211. Stage 3: Day 1, Day 331-391]: hSBA titers ≥ 1:4 for additional MenB strains
• Percentage of Participants With Meningococcal Antibody Titers against meningococcal serogroup B (additional MenB strains) ≥ 1:8 in children, toddler and infant participants [Stage 1 and 2: Day 1 and Day 211. Stage 3: Day 1, Day 331-391]: hSBA titers ≥ 1:8 for additional MenB strains
• Geometric mean titers (GMTs) of Antibodies against Meningococcal Serogroup B (additional MenB strains) in children, toddler and infant participants [Stage 1 and 2: Day 1 and Day 211. Stage 3: Day 1, Day 331-391]
• Percentage of participants with hSBA composite seroresponse titers more or equal to LLOQ each and all additional MenB strains in children, toddler and infant participants [Stage 1 and 2: Day 1 and Day 211. Stage 3: Day 1, Day 331-391]
• Percentage of participants with hSBA composite seroresponse titers less than LLOQ all additional MenB strains in children, toddler and infant participants [Stage 1 and 2: Day 1 and Day 211. Stage 3: Day 1, Day 331-391]

Sex: All, ages: 56 Days to 9 Years, accepts healthy volunteers

Inclusion Criteria:

* Aged 2 to 9 years (Stage 1) or 12 to 15 months (Stage 2) or 56 to 89 days (Stage 3) on the day of inclusion
* For infants and toddlers, born at full term of pregnancy (≥37 weeks) and with a birth weight ≥ 2.5 Kg or born after a gestation period of period above 28 (> 28 weeks) through 36 weeks with a birth weight ≥ 1.5 Kg and in both cases medically stable as assessed by the investigator, based on the following definition: "Medically stable" refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study intervention
* Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and judgement of the investigator

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 since birth for infants; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months or since birth for and infants)
* History of any meningitis infection, confirmed either clinically, serologically, or microbiologically
* At high risk of meningococcal infection during the study
* Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances
* Individual with active tuberculosis
* History of Guillain-Barré syndrome
* For Stage 3 infants: History of intussusception
* Previous vaccination against meningococcal serogroups A, B, C, W, and/or Y with an investigational or marketed vaccine
* For Stage 3 infants: receipt of the first dose of rotavirus vaccine less than 28 days before the first trial vaccination

NOTE: The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

NIH grants: 2023