Study on a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW Conjugate Vaccine) Compared to Two Meningococcal Reference Vaccines in European Toddlers

Study Overview
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Brief Summary
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Primary Objective: To demonstrate: the non-inferiority of the seroprotection rate (antibody titers greater than or equal to [>=] 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate or Nimenrix® as measured by serum bactericidal assay using human complement (hSBA). If this non-inferiority was demonstrated, then the non-inferiority of the antibody response (geometric mean titers [GMT]). If this non-inferiority was demonstrated, then the superiority of the antibody response (GMT). If this superiority was demonstrated, then the superiority of the seroprotection rate. Or to demonstrate: the non-inferiority of the seroprotection rate (antibody titers >= 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate or NeisVac-C® as measured by serum bactericidal assay using baby rabbit complement (rSBA). If this non-inferiority was demonstrated, then the non-inferiority of the antibody response (GMT). If this non-inferiority was demonstrated, then the superiority of the antibody response (GMT). Secondary Objective: To demonstrate: the non-inferiority of the seroprotection rate (antibody titers >= 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate vaccine or Nimenrix® as measured by rSBA. If this non-inferiority was demonstrated, then the non-inferiority of the antibody response (GMT). If this non-inferiority was demonstrated, then the superiority of the antibody response (GMT). Or to demonstrate: the non-inferiority of the seroprotection rate (antibody titers >= 1:8) to meningococcal serogroup C following the administration of MenACYW Conjugate vaccine or NeisVac-C® as measured by hSBA. If this non-inferiority was demonstrated, then the non-inferiority of the antibody response (GMT). If this non-inferiority was demonstrated, then the superiority of the antibody response (GMT) .

Detailed Description
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Study duration per participant was approximately 30 days including: 1 day of screening and vaccination, a phone call and a safety-follow up/end of study visit at Day 8 and Day 30 after vaccine administration, respectively. Safety assessment included solicited reactions within 7 days after vaccination, unsolicited adverse events up to 30 days after vaccination, serious adverse events and adverse event of special interest throughout the study.

Official Title
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Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix® or NeisVac-C® in Healthy Toddlers 12 to 23 Months of Age

Conditions
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Meningococcal Immunisation (Healthy Volunteers)

Intervention / Treatment
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* Biological: Meningococcal polysaccharide (serogroups A, C, Y, and W) tetanus toxoid Conjugate vaccine
* Biological: Meningococcal polysaccharide group A, C, W-135 and Y Conjugate vaccine
* Biological: Meningococcal group C polysaccharide Conjugate vaccine adsorbed


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Aged 12 to 23 months on the day of the first study visit (12 to 23 months means from the 12th month after birth to the day before the 24th month after birth). Informed consent form (ICF) had been signed and dated by the parent(s)/legally acceptable representative(s) and by an independent witness if required by local regulations. Participant and parent/legally acceptable representative were able to attend all scheduled visits and complied with all trial procedures. Exclusion criteria: Participation in the 4 weeks (28 days) preceding the study vaccination or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, which might be received at least 2 weeks before or after study vaccines. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines. Receipt of immune globulins, blood or blood-derived products in the past 3 months. Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, or Y; or meningococcal B vaccine). 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). History of meningococcal infection, confirmed either clinically, serologically, or microbiologically At high risk for meningococcal infection during the trial (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). Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances . Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine. Personal history of Guillain-Barré syndrome. Thrombocytopenia, as reported by the parent/ legally acceptable representative or suspected thrombocytopenia contraindicating intramuscular vaccination in the Investigator's opinion. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion. Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion. Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0 degree Celsius). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided. Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw. Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: MenACYW Conjugate Vaccine<br>Healthy, toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0. | Biological: Meningococcal polysaccharide (serogroups A, C, Y, and W) tetanus toxoid Conjugate vaccine<br>* Pharmaceutical form: Liquid solution for injection Route of administration: Intramuscular<br>* Other names: MenACYW Conjugate vaccine;|
| Active Comparator: Group 2: Nimenrix® Vaccine<br>Healthy, toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0. | Biological: Meningococcal polysaccharide group A, C, W-135 and Y Conjugate vaccine<br>* Pharmaceutical form: Powder and solvent for suspension for injection Route of administration: Intramuscular<br>* Other names: Nimenrix®;|
| Active Comparator: Group 3: NeisVac-C® Vaccine<br>Healthy, toddlers aged 12 to 23 months received a single dose of NeisVac-C® vaccine on Day 0. | Biological: Meningococcal group C polysaccharide Conjugate vaccine adsorbed<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>* Other names: NeisVac-C®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis) | Antibody titers against Meningococcal Serogroup C were measured by hSBA. | Day 30 (post-vaccination) | 
| Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by hSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) | 
| GMTs of Antibodies Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Superiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by hSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) | 
| Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Superiority Analysis) | Antibody titers against Meningococcal Serogroup C were measured by hSBA. | Day 30 (post-vaccination) | 
| Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by Serum Bactericidal Assay Using Baby Rabbit Complement (rSBA) Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis) | Antibody titers against Meningococcal Serogroup C were measured by rSBA. | Day 30 (post-vaccination) | 
| GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by rSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) | 
| GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Superiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by rSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis) | Antibody titers against Meningococcal Serogroup C were measured by rSBA. | Day 30 (post-vaccination) | 
| GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Non-inferiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by rSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) | 
| GMTs of Antibodies Against Meningococcal Serogroup C Measured by rSBA Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® (Superiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by rSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) | 
| Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis) | Antibody titers against Meningococcal Serogroup C were measured by hSBA. | Day 30 (post-vaccination) | 
| GMTs of Antibodies Against Meningococcal Serogroup C Measured by hSBA After Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Non-inferiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by hSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) | 
| GMTs of Antibodies Against Meningococcal Serogroup C Measured by hSBA Following Vaccination With MenACYW Conjugate Vaccine or NeisVac-C® (Superiority Analysis) | GMT titers against Meningococcal Serogroup C were measured by hSBA. Titers were expressed in terms of 1/dilution. | Day 30 (post-vaccination) |