Study of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered in Children Aged 2 to 9 Years

Study Overview
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Brief Summary
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The purpose of the study was to evaluate the immunogenicity and describe the safety of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine compared to the licensed Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 (MENVEO®) vaccine in children 2 to 9 years of age in the United States (US) and Puerto Rico. Primary objective: - To demonstrate the non-inferiority of the vaccine seroresponse to meningococcal serogroups A, C, Y, and W following the administration of a single dose of MenACYW Conjugate vaccine compared to that observed following the administration of a single dose of MENVEO® in children aged 2 to 9 years. Secondary objectives: To compare the serum bactericidal assay using human complement (hSBA) antibody geometric mean titers (GMTs) of meningococcal serogroups A, C, Y, and W following the administration of MenACYW Conjugate vaccine to those observed following the administration of MENVEO® in children 2 to 9 years of age. To evaluate the hSBA antibody GMTs of meningococcal serogroups A, C, Y, and W following the administration of MenACYW Conjugate vaccine and those observed following the administration of MENVEO® in children 2 to 5 years of age, and in children 6 to 9 years of age, respectively. To evaluate the hSBA vaccine seroresponse to meningococcal serogroups A, C, Y, and W before and 30 days (+14 days) post-vaccination in children 2 to 5 years of age, and in children 6 to 9 years of age, respectively. Observational objective: - To describe the safety profile of MenACYW Conjugate vaccine and that of the licensed MENVEO®.

Detailed Description
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Healthy children were randomized and received a single dose of either MenACYW Conjugate vaccine or MENVEO®. They were assessed for immunogenicity at baseline (pre-vaccination) and at 30-44 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

Official Title
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Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered in Healthy Children 2 to 9 Years of Age

Conditions
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Meningitis, Meningococcal Meningitis, Meningococcal Infections

Intervention / Treatment
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* Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate
* Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 2 to 9 years on the day of inclusion. Assent form had been signed and dated by the participant (as required by local regulations) and informed consent form had been signed and dated by parent(s) or guardian. Participant and parent/guardian were able to attend all scheduled visits and complied with all trial procedures. Exclusion Criteria: Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche. Participation in the 4 weeks preceding the trial vaccination or planned participation during the present trial period in another clinical trial 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 the study investigational vaccines. This exception included monovalent, multivalent, live, and attenuated influenza vaccines. Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (ie., mono- or polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, Y, W; or meningococcal B serogroup containing vaccine). Receipt of immune globulins, blood or blood-derived products in the past 3 months. 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 traveling 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 trial or to a vaccine containing any of the same substances. Verbal report of thrombocytopenia, contraindicating intramuscular vaccination by the Investigator's judgment. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion. Personal history of Guillain-Barré syndrome. Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine. 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's judgment) on the day of vaccination or febrile illness (temperature ≥100.4°F). 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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 9 Years

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, meningococcal-vaccine naïve participants aged 2 to 9 years received a single dose of MenACYW Conjugate vaccine on Day 0. | Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate<br>* 0.5 milliliter (mL), Intramuscular<br>* Other names: MenACYW Conjugate vaccine;|
| Active Comparator: Group 2: MENVEO® Vaccine<br>Healthy, meningococcal-vaccine naïve participants aged 2 to 9 years received a single dose of MENVEO® Conjugate vaccine on Day 0. | Biological: Meningococcal (Groups A, C, Y and W 135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine<br>* 0.5 mL, Intramuscular<br>* Other names: MENVEO®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Seroresponse Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine | Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. The hSBA vaccine seroresponse against serogroups A, C, Y, and W was defined as post-vaccination hSBA titers greater than or equal to (>=) 1:16 for participants with pre-vaccination hSBA titers less than (<) 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >=1:8. | Day 30 (post-vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 2 to 9 Years of Age | Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. | Day 30 (post-vaccination) | 
| Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 2 to 5 Years of Age | Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. | Day 30 (post-vaccination) | 
| Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Measured by hSBA Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 6 to 9 Years of Age | Antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA. | Day 30 (post-vaccination) | 
| Percentage of Participants Achieving Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 2 to 5 Years of Age | Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >=1:16 for participants with pre-vaccination hSBA titers <1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >=1:8. | Day 30 (post-vaccination) | 
| Percentage of Participants Achieving Vaccine Seroresponse Measured by hSBA Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or MENVEO® Vaccine in Children 6 to 9 Years Age | Antibody titers against meningococcal serogroups A, C, Y, and W were measured by hSBA. The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >=1:16 for participants with pre-vaccination hSBA titers <1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >=1:8. | Day 30 (post-vaccination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningitis, Meningococcal Meningitis, MenACYW Conjugate vaccine, MENVEO®