Study of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Given With Routine Pediatric Vaccines in Healthy Infants and Toddlers in India and the Republic of South Africa

Sanofi Pasteur, a Sanofi Company1,528 enrolled

Overview

This open label randomized study will be conducted to evaluate and/or describe the immunogenicity and describe the safety of MenACYW conjugate vaccine when administered in infants and toddlers. It will be conducted in India and the RSA in 2 cohorts: * Cohort I: Infants and toddlers 6 months to 16 months of age (Cohort I) * Cohort II: Infants and toddlers 6 weeks to 15 months of age (Cohort II) In Cohort I, eligible participants will be randomized in a 1:1 ratio to receive 2 intramuscular (IM) injections (1+1 vaccination schedule) of either MenACYW conjugate vaccine (Groups 1 and 3) or Menactra vaccine (Groups 2 and 4), co-administered with routine pediatric vaccines. In Cohort II, eligible participants will be randomized in a 2:1 ratio to receive either 3 IM injections (2+1 vaccination schedule) of MenACYW conjugate vaccine co-administered with routine pediatric vaccines (Groups 5 and 7) or routine pediatric vaccines only (Groups 6 and 8). The primary objectives of this study are: * To demonstrate the non-inferiority of immunogenicity of 2 doses of MenACYW conjugate vaccine compared to 2 doses of Menactra® vaccine in infants and toddlers 6 months to 16 months of age (Cohort I) in terms of serum bactericidal assay using human complement (hSBA) seroprotection (titers ≥ 1:8) in India and the Republic of South Africa (RSA) * To demonstrate the vaccine immune sufficiency of 3 doses of MenACYW conjugate vaccine in infants and toddlers 6 weeks to 15 months of age (Cohort II) in terms of hSBA seroprotection (titers ≥ 1:8) in India and the RSA The secondary objectives of this study are: * To describe the antibody titers to the meningococcal serogroups A, C, Y, and W: * before and 30 days post primary series of MenACYW conjugate vaccine and before and 30 days post booster dose of MenACYW conjugate vaccine in infants and toddlers 6 weeks to 15 months of age (Cohort II) in India and the RSA when administered concomitantly with other age-recommended vaccines. * before and after 30 days post each dose of MenACYW conjugate vaccine or Menactra vaccine in infants and toddlers 6 months to 16 months of age (Cohort I) in India and the RSA when administered concomitantly with other age-recommended vaccines. * To describe the antibody responses against the antigens of the other age-recommended vaccines when administered concomitantly with MenACYW conjugate vaccine: * in infants and toddlers 6 weeks to 15 months of age (Cohort II) in India and the RSA. * in infants and toddlers 6 months to 16 months of age (Cohort I) in India and the RSA. * To describe the safety profile of MenACYW conjugate vaccine and that of licensed Menactra vaccine in infants and toddlers 6 months to 16 months of age (Cohort I) in India and the RSA when administered concomitantly with other age-recommended vaccines. * To describe the safety profile of MenACYW conjugate vaccine in infants and toddlers 6 weeks to 15 months of age (Cohort II) in India and the RSA when administered concomitantly with other age-recommended vaccines. * To describe the safety profile of age-recommended vaccines: * in infants 6 weeks to 15 months of age (Cohort II) in India and the RSA when administered concomitantly with MenACYW conjugate vaccine. * in infants and toddlers 6 months to 16 months of age (Cohort I) in India and the RSA when administered concomitantly with MenACYW conjugate vaccine. The duration of each participant's active participation in the study will be approximately 10 to 11 months for Cohort I and 13,5 to 14,5 months for Cohort II.

Interventions

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate VaccineBIOLOGICAL

Liquid solution - intramuscular

Meningococcal (Groups A, C, Y and W 135) Polysaccharide Diphtheria Toxoid Conjugate VaccineBIOLOGICAL

Liquid solution - intramuscular

Oral bivalent types 1 and 3; Poliomyelitis Vaccine (OPV)BIOLOGICAL

Oral suspension - oral

Pneumoccocal VaccineBIOLOGICAL

Suspension for injection - intramuscular

Measles, Mumps, and Rubella Vaccine live (MMR)BIOLOGICAL

Lyophilized powder for injection - subcutaneous

DTwP-HepB-Hib-IPV vaccineBIOLOGICAL

Suspension - intramuscular

DTaP-IPV-Hib-HepB vaccineBIOLOGICAL

Liquid solution - intramuscular

Hepatitis A vaccineBIOLOGICAL

Lyophilized powder for injection - subcutaneous

Rotavirus vaccineBIOLOGICAL

Oral solution - oral

Typhoid conjugate vaccine (TCV)BIOLOGICAL

Suspension for injection - intramuscular

Measles vaccineBIOLOGICAL

Freeze-dried powder for reconstitution and injection - subcutaneous

Varicella vaccine liveBIOLOGICAL

Sterile powder and diluent for injection - subcutaneous

Varicella vaccine liveBIOLOGICAL

Lyophilized powder for injection - subcutaneous

Measles, Mumps, and Rubella Vaccine live (MMR)BIOLOGICAL

Lyophilized powder for injection - subcutaneous

Hepatitis A vaccineBIOLOGICAL

Suspension for injection - intramuscular

Eligibility

Sex: ALLMin age: 6 WeeksMax age: 6 MonthsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Cohort I: 6 months of age (180 to 209 days of age) on the day of the first study visit * Cohort II: 6-8 weeks of age (42 to 62 days of age) on the day of the first study visit * Healthy infants as determined by medical history, physical examination, and judgment of the Investigator * Participant and parent/ legally acceptable representative (LAR) are able to attend all scheduled visits and to comply with all study procedures * Cohort I: Z-score ≥ -2 SD on the Weight-for-age table of the WHO Child Growth Standards. * Cohort II: Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg. 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). \*Note: Participants with a history of HIV but without evident severe immunosuppression can be included. * Family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated. * Individuals with active tuberculosis. * History of meningococcal infection, confirmed either clinically, serologically, or microbiologically. * At high risk for meningococcal infection during the study (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling to countries with high endemic or epidemic disease). * History of intussusception. * History of any neurologic disorders, including any seizures and progressive neurologic disorders. * History of Guillain-Barré syndrome (GBS). * Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the study or to a vaccine containing any of the same substances, including neomycin, gelatin, and yeast. * Verbal report of thrombocytopenia, as reported by the parent/LAR, contraindicating IM vaccination in the Investigator's opinion. * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination in the Investigator's opinion. * Chronic illness (including, but not limited to, cardiac disorders, congenital heart disease, chronic lung disease, renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases) that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion. * Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided. * Receipt of any vaccine in the 4 weeks preceding the first study vaccination (except for Bacille Calmette-Guérin \[BCG\], birth dose OPV and birth dose of HepB vaccine) or planned receipt of any vaccine in the 4 weeks following each study vaccination except for the following vaccinations, which may be received at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines, multivalent influenza vaccines, any COVID-19 vaccines, and administration of OPV on National Immunization Day in India. * Previous vaccination against meningococcal disease with either the study vaccine or another vaccine (ie, mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B serogroup-containing vaccine). * For Cohort II: Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis (other than birth dose of OPV), Hepatitis A, measles, mumps, rubella, varicella; and of Hib, Streptococcus pneumoniae, and/or RV infection or disease. * For Cohort II: Previous vaccination with more than 1 dose of HepB vaccine. * Receipt of immune globulins, blood, or blood-derived products in the past 3 months. * Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw. * Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. * Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study.

Locations (15)

Investigational Site Number : 3560006

Chennai, India

Investigational Site Number : 3560007

Hyderabad, India

Investigational Site Number : 3560016

Kanpur, India

Investigational Site Number : 3560009

Kolkata, India

Investigational Site Number : 3560011

Manipal, India

Investigational Site Number : 3560013

Mysore, India

Investigational Site Number : 3560004

Mysore, India

Investigational Site Number : 3560003

New Delhi, India

Investigational Site Number : 3560002

Pune, India

Investigational Site Number : 3560001

Pune, India

...and 5 more locations

Outcomes

Primary Outcomes

Percentage of participants with anti-meningococcal serogroups A, C, Y, W antibody titers above predefined thresholds after 2 doses of MenACYW conjugate vaccine compared to 2 doses of Menactra® vaccine in infants and toddlers 6 months to 16 months of age

Antibody (Ab) titers against meningococcal serogroups A, C, Y, and W will be measured in infants and toddlers 6 months to 16 months of age (\[Group 1 + Group 3\] versus \[Group 2 + Group 4\]) The following threshold values will be considered: ≥ 1:8

Time frame: 30 days after the second vaccination

Percentage of participants with anti-meningococcal serogroups A, C, Y, W Ab titers above predefined thresholds after 3 doses of MenACYW conjugate vaccine in infants and toddlers 6 weeks to 15 months of age

Ab titers against meningococcal serogroups A, C, Y, and W will be measured in infants and toddlers 6 months to 15 months of age (Group 5 + Group 7) The following threshold values will be considered: ≥ 1:8

Time frame: 30 days after the booster vaccination

Secondary Outcomes

Geometric Mean Titers (GMTs) of Ab against meningococcal serogroups A, C, Y, and W when MenACYW conjugate vaccine administered concomitantly with other age-recommended vaccine in infants 6 weeks to 15 months of age

Ab titers against meningococcal serogroups A, C, Y, and W will be measured Group 5 versus Group 6 in India Group 7 versus Group 8 in RSA Group 5 + Group 7 versus Group 6 + Group 8

Time frame: Baseline; 30 days after primary series of vaccination; Before and 30 days after booster vaccination

Geometric Mean Titers Ratio (GMTR) of Ab against meningococcal serogroups A, C, Y, and W when MenACYW conjugate vaccine administered concomitantly with other age-recommended vaccine in infants 6 weeks to 15 months of age

Ab titers against meningococcal serogroups A, C, Y, and W will be measured Group 5 versus Group 6 in India Group 7 versus Group 8 in RSA Group 5 + Group 7 versus Group 6 + Group 8

Time frame: Baseline; 30 days after primary series of vaccination; Before and 30 days after booster vaccination

GMTs of Ab against meningococcal serogroups A, C, Y, and W when MenACYW conjugate vaccine or Menactra vaccine when administered concomitantly with other age-recommended vaccines in infants and toddlers 6 months to 16 months of age

Ab titers after vaccination with MenACYW conjugate vaccine or Menetra® will be measured Group 1 versus Group 2 in India Group 3 versus Group 4 in the RSA Group 1 + Group 3 versus Group 2 + Group 4

Time frame: Baseline; Before and 30 days after each vaccination

GMTR of Ab against meningococcal serogroups A, C, Y, and W when MenACYW conjugate vaccine or Menactra vaccine when administered concomitantly with other age-recommended vaccines in infants and toddlers 6 months to 16 months of age

Ab titers after vaccination with MenACYW conjugate vaccine or Menetra® will be measured Group 1 versus Group 2 in India Group 3 versus Group 4 in the RSA Group 1 + Group 3 versus Group 2 + Group 4

Time frame: Baseline; Before and 30 days after each vaccination

Percentage of participants with anti-meningococcal serogroups A, C, Y, and W Ab titers met the predefined criteria when MenACYW conjugate vaccine administered concomitantly with other age-recommended vaccine in infants 6 weeks to 15 months of age

Ab titers against meningococcal serogroups A, C, Y, and W will be measured * hSBA titer ≥ 1:4 and ≥ 1:8 * hSBA titer ≥ 4-fold rise from pre-vaccination to post-vaccination * hSBA vaccine seroresponse

Time frame: Baseline; 30 days after primary series of vaccination; Before and 30 days after booster vaccination

Ab titers after vaccination with MenACYW conjugate vaccine or Menetra® will be measured * hSBA titer ≥ 1:4 and ≥ 1:8 * hSBA titer ≥ 4-fold rise from pre-vaccination to post-vaccination * hSBA vaccine seroresponse

Time frame: Baseline; Before and 30 days after each vaccination

GMCs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age

The following Ab concentrations will be measured: \- Anti-pertussis Ab concentrations (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\]), fimbriae types 2, 3 \[FIM\], and pertactin \[PRN\])

Time frame: Baseline

GMCR of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age

The following Ab concentrations will be measured: \- Anti-pertussis Ab concentrations (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\], fimbriae types 2, 3 \[FIM\], and pertactin \[PRN\])

Time frame: Baseline

GMCs/GMTs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age

The following Ab concentrations/titers will be measured: * against the antigens of DTwP-HepB-Hib/DTaP-IPV-Hib-HepB * against the antigens of PCV13 * against the antigens of RV (serum RV immunoglobulin \[Ig\]A) * against the antigens of measles, mumps and rubella * against the antigens of varicella vaccine

Time frame: -30 days after:-Dose3 of DTwP-HepB-Hib-IPV/DTaP-IPV-Hib-HepB;-1ry series of PCV13;-measles,mumps & rubella: Dose1 in RSA;Dose2 in India;-1st dose of varicella vaccine -30 days at least after booster dose of PCV13 -Before & 30 days after 1ry series of RV

GMCRs/GMTRs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age

The following Ab concentrations/titers will be measured: * against the antigens of DTwP-HepB-Hib-IPV/DTaP-IPV-Hib-HepB * against the antigens of PCV13 * against the antigens of RV (serum RV immunoglobulin \[Ig\]A) * against the antigens of measles, mumps and rubella * against the antigens of varicella vaccine

Time frame: -30days after:-1ry series of DTwP-HepB-Hib-IPV/DTaP-IPV-Hib-HepB;-1ry series of PCV13;-measles,mumps & rubella:Dose1 in RSA;Dose2 in India;-1st dose of varicella vaccine -30days at least after booster dose of PCV13 -Before&30 days after 1ry series of RV

Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 weeks to 15 months of age

The following Ab concentrations/titers will be measured: * Anti-tetanus Ab ≥ 0.01 International Units (IU)/milliliter (mL), ≥ 0.1 IU/mL and \> 1.0 IU/mL * Anti-diphtheria Ab ≥ 0.01 IU/mL, ≥ 0.1 IU/mL and \> 1.0 IU/mL * Anti-polyribosyl-ribitol phosphate (PRP) Ab ≥ 0.15 micrograms (μg)/mL and ≥ 1.0 μg/mL * Pertussis vaccine seroresponse for anti-PT, and anti-PT, anti-FHA, anti-FIM, and anti-PRN * Anti-hepatitis B surface antigen (HBsAg) Ab ≥ 10 mIU/mL and ≥ 100 mIU/mL * Anti-poliovirus types 1, 2, and 3 Ab titers ≥ 1:8 * Anti-pneumococcal Ab ≥ 0.35 μg/mL and ≥ 1.0 μg/mL

Time frame: - 30 days after dose 3 of DTwP-HepB-Hib/DTaP-IPV-Hib-HepB - 30 days after primary series of PCV13 and 30 days after the booster dose of PCV13

Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 weeks to 15 months of age

The following Ab concentrations/titers will be measured: * Anti-RV seroresponse * Anti-measles Ab concentrations (serostatus cutoff: 255 mIU/mL) * Anti-mumps Ab concentrations (serostatus cutoff: 10 Mumps antibody units/mL) * Anti-rubella Ab concentrations (serostatus cutoff: 10 IU/mL) * Anti-varicella Ab concentrations (serostatus cutoff: 5gpELISA unit/mL)

Time frame: 30 days after: - Primary series of RV - Dose 1 of measles, mumps and rubella in RSA - Dose 2 of measles, mumps and rubella in India - first dose of varicella vaccine

GMCs/GMTs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age

The following Ab concentrations will be measured: * against the antigens of varicella * against the antigens of PCV13 * against the antigens of measles, mumps and rubella * against the antigens of DTwP-HepB-Hib-IPV

Time frame: 30 days after: - first dose of varicella vaccine - the booster dose of PCV13 - Dose 1 of measles, mumps and rubella in RSA - Dose 2 of measles, mumps and rubella in India - after booster dose of DTwP-HepB-Hib-IPV

GMCRs/GMTRs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age

The following Ab concentrations/titers will be measured: * against the antigen of varicella * against the antigens of PCV13 * against the antigens of measles, mumps and rubella * against the antigens of DTwP-HepB-Hib-IPV

Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 months to 16 months of age

The following Ab concentrations/titers will be measured: * anti-pneumococcal Ab concentrations ≥ 0.35 μg/mL and ≥ 1.0 μg/mL * anti-measles Ab concentrations (serostatus cutoff: 255 mIU/mL) * anti-mumps Ab concentrations (serostatus cutoff: 10 Mumps antibody units/mL) * anti-rubella Ab concentrations (serostatus cutoff: 10 IU/mL) * anti-varicella Ab concentrations (serostatus cutoff: 5gpELISA unit/mL)

Time frame: 30 days after: - the booster dose of PCV13 - Dose 1 of measles, mumps and rubella in RSA - Dose 2 of measles, mumps and rubella in India - first dose of varicella vaccine

GMCs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age

The following Ab concentrations will be measured: \- Anti-pertussis Ab concentrations (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\], fimbriae types 2, 3 \[FIM\], and pertactin \[PRN\])

Time frame: Pre-booster dose vaccination of DTwP-HepB-Hib-IPV

GMCR of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age

The following Ab concentrations will be measured: \- Anti-pertussis Ab concentrations (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\], fimbriae types 2, 3 \[FIM\], and pertactin \[PRN\])

Time frame: Pre-booster dose vaccination of DTwP-HepB-Hib-IPV

Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 months to 16 months of age

The following Ab concentrations/titers will be measured: * anti-tetanus Ab concentrations ≥ 0.01 IU/mL, ≥ 0.1 IU/mL and ≥ 1.0 IU/mL * anti-diphtheria Ab concentrations ≥ 0.01 IU/mL, and ≥ 0.1 IU/mL * anti-PRP Ab concentrations ≥ 0.15 µg)/mL and ≥ 1.0 μg/mL * pertussis vaccine seroresponse for anti-PT, anti-FHA, anti-FIM, and anti-PRN * anti-HBsAg Ab concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL * anti-poliovirus types 1, 2, and 3 Ab titers ≥ 1:8

Time frame: 30 days after booster dose of DTwP-HepB-Hib-IPV

Number of participants reporting immediate adverse events (AEs)

Unsolicited (spontaneously reported) systemic AEs

Time frame: Within 30 minutes post-vaccination

Percentage of participants reporting solicited injection site and systemic reactions

Solicited injection site reactions: \- tenderness, erythema, swelling Solicited systemic reactions: \- fever, vomiting, crying abnormal, drowsiness, appetite lost, irritability

Time frame: Within 7 days post-vaccination

Number of participants reporting unsolicited AEs

Unsolicited AEs

Time frame: Up to Day 31 post-vaccination

Number of participants reporting serious adverse events (SAEs)

SAEs

Time frame: From Day 1 to Month 18

Study of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Given With Routine Pediatric Vaccines in Healthy Infants and Toddlers in India and the Republic of South Africa

Overview

Conditions

Interventions

Eligibility

Locations (15)

Outcomes

Primary Outcomes

Secondary Outcomes