Clinical trial NCT05794230: 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
Official title: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in India and the Republic of South Africa
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Meningococcal Immunisation
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-04-03
Enrollment: 1528
Sex: ALL
Minimum age (years): 6
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cohort I: Infants and toddlers 6 months to 16 months of age. Eligible participants are randomized in a 1:1 ratio to receive 2 injections of either MenACYW conjugate vaccine (Groups 1 and 3) or Menactra vaccine (Groups 2 and 4), co-administered with routine pediatric vaccines.

Cohort II: Infants and toddlers 6 weeks to 15 months of age. Eligible participants are randomized in a 2:1 ratio to receive either 3 injections of MenACYW conjugate vaccine co-administered with routine pediatric vaccines (Groups 5 and 7), or routine pediatric vaccines only (Groups 6 and 8).
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 30 days after the second vaccination
measure: 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
timeFrame: 30 days after the booster vaccination
Secondary outcomes:
measure: 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
timeFrame: Baseline; 30 days after primary series of vaccination; Before and 30 days after booster vaccination
measure: 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
timeFrame: Baseline; 30 days after primary series of vaccination; Before and 30 days after booster vaccination
measure: 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
timeFrame: Baseline; Before and 30 days after each vaccination
measure: 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
timeFrame: Baseline; Before and 30 days after each vaccination
measure: 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
timeFrame: Baseline; 30 days after primary series of vaccination; Before and 30 days after booster vaccination
measure: 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 and toddlers 6 to 16 months of age
timeFrame: Baseline; Before and 30 days after each vaccination
measure: GMCs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age
timeFrame: Baseline
measure: GMCR of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age
timeFrame: Baseline
measure: GMCs/GMTs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age
timeFrame: -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
measure: GMCRs/GMTRs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 weeks to 15 months of age
timeFrame: -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
measure: Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 weeks to 15 months of age
timeFrame: - 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
measure: Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 weeks to 15 months of age
timeFrame: 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
measure: GMCs/GMTs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age
timeFrame: 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
measure: GMCRs/GMTRs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age
timeFrame: 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
measure: Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 months to 16 months of age
timeFrame: 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
measure: GMCs of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age
timeFrame: Pre-booster dose vaccination of DTwP-HepB-Hib-IPV
measure: GMCR of Ab against the antigens of age-recommended vaccines in infants and toddlers 6 months to 16 months of age
timeFrame: Pre-booster dose vaccination of DTwP-HepB-Hib-IPV
measure: Percentage of participants with Ab concentrations/titers met the predefined criteria in infants and toddlers 6 months to 16 months of age
timeFrame: 30 days after booster dose of DTwP-HepB-Hib-IPV
measure: Number of participants reporting immediate adverse events (AEs)
timeFrame: Within 30 minutes post-vaccination
measure: Percentage of participants reporting solicited injection site and systemic reactions
timeFrame: Within 7 days post-vaccination
measure: Number of participants reporting unsolicited AEs
timeFrame: Up to Day 31 post-vaccination
measure: Number of participants reporting serious adverse events (SAEs)
timeFrame: From Day 1 to Month 18
Other outcomes:
Locations:
city: Chennai
country: India
facility: Investigational Site Number : 3560006
city: Hyderabad
country: India
facility: Investigational Site Number : 3560007
city: Kanpur
country: India
facility: Investigational Site Number : 3560016
city: Kolkata
country: India
facility: Investigational Site Number : 3560009
city: Manipal
country: India
facility: Investigational Site Number : 3560011
city: Mysore
country: India
facility: Investigational Site Number : 3560013
city: Mysore
country: India
facility: Investigational Site Number : 3560004
city: New Delhi
country: India
facility: Investigational Site Number : 3560003
city: Pune
country: India
facility: Investigational Site Number : 3560002
city: Pune
country: India
facility: Investigational Site Number : 3560001
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100002
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100003
city: George
country: South Africa
facility: Investigational Site Number : 7100006
city: Johannesburg
country: South Africa
facility: Investigational Site Number : 7100005
city: Middelburg
country: South Africa
facility: Investigational Site Number : 7100001
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: