Safety and Immunogenicity of Meningococcal ACWY Conjugate Versus Polysaccharide Vaccine in Children 2 to 10 Years of Age

Study Overview
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Brief Summary
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Safety and immunogenicity of meningococcal ACWY conjugate versus polysaccharide vaccine in children 2 to 10 years of age

Official Title
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A Phase 3, Randomized, Observer-blind, Controlled, Multi-Center Study to Compare the Safety of One Dose of Novartis Meningococcal ACWY Conjugate Vaccine With That of a Licensed Meningococcal ACWY Polysaccharide Vaccine (Menomune®) Administered to Healthy Children 2 to 10 Years of Age

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: Meningococcal ACWY-CRM conjugate vaccine
* Biological: Meningococcal ACWY-PS polysaccharide vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children 2 to 10 years of age inclusive whose parents or legal guardians gave written informed consent at the time of enrollment; Available for all visits and telephone calls (parents or legal guardians) scheduled for the study; Good health as determined by the clinical judgment of the investigator. Exclusion Criteria: Individuals not eligible to be enrolled into the study were those: whose parent or legal guardian was unwilling or unable to give written informed consent to participate in the study; whose parent or legal guardian were perceived as unreliable or unavailable for the duration of the study period; who had a previous or suspected disease caused by N meningitidis; who had household contact with and/or intimate exposure to an individual with culture-proven N. meningitidis infection within 60 days prior to enrollment; who had previously been immunized with a meningococcal vaccine or vaccine containing meningococcal antigen(s) (licensed or investigational); who had received any investigational agents or vaccines within 90 days prior to enrollment or who expected to receive an investigational agent or vaccine prior to the completion of the study; who had received any licensed vaccines within one month prior to enrollment or for whom receipt of a licensed vaccine was anticipated within one month after vaccination (Exception: influenza vaccine could be administered up to 15 days prior to study vaccination and no less than 15 days after study vaccination); who had received a live viral vaccine within 60 days prior to enrollment; who had experienced, within the 7 days prior to enrollment, significant acute or chronic infection (for example requiring systemic antibiotic treatment or antiviral therapy) or had experienced fever (defined as axillary temperature ≥38°C) within 3 days prior to enrollment; who had any serious acute, chronic or progressive disease (e.g., any history of neoplasm, cancer, diabetes, cardiac disease, autoimmune disease, Human Immunodeficiency Virus (HIV) infection or Acquired Immune Deficiency Syndrome (AIDS), or blood dyscrasias, with signs of cardiac or renal failure or severe malnutrition). (Exception: subjects with mild asthma were eligible for enrollment; subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids were not eligible for enrollment); who had epilepsy or any progressive neurological disease; who had a history of any anaphylaxis, serious vaccine reactions, or allergy to any vaccine component; who had a known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from (for example): receipt of immunosuppressive therapy within 30 days prior to enrollment (any systemic corticosteroid administered for more than 5 days, or in a daily dose >1 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy); receipt of immunostimulants; receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 90 days prior to enrollment and for the full length of the study; common childhood exanthematous diseases (varicella, mumps, measles, rubella) occurring 6 weeks prior to vaccination; who were known to have a bleeding diathesis or any condition that could be associated with a prolonged bleeding time; who had Down syndrome or other known cytogenic disorders; whose families were planning to leave the area of the study site before the end of the study period; who had any condition that, in the opinion of the investigator, could interfere with the evaluation of the study objectives.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 10 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MenACWY-CRM<br>Subjects ≥2 to ≤10 years of age received one dose of a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) | Biological: Meningococcal ACWY-CRM conjugate vaccine<br>* MenACWY-CRM vaccine was obtained by extemporaneous mixing of the lyophilized MenA component to be resuspended with the liquid MenCWY component. One dose (0.5 mL) was administered by IM injection in the deltoid area of the arm without a BCG scar.<br>|
| Active Comparator: MenACWY-PS<br>Subjects ≥2 to ≤10 years of age received one dose of a quadrivalent meningococcal polysaccharide (PS) vaccine (MenACWY-PS) | Biological: Meningococcal ACWY-PS polysaccharide vaccine<br>* MenACWY-PS vaccine was supplied as a single dose (one vial of vaccine and one vial of diluent). One dose (0.5 mL) of MenACWY-PS vaccine was administered by SC injection in the deltoid area of the arm without a BCG scar.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With hSBA Seroresponse Against Serogroups A, C, W and Y One Month After Vaccination With MenACWY-CRM or MenACWY-PS | Immunogenicity was measured as the percentage of subjects with hSBA seroresponse, directed against each of meningococcal serogroups A, C, W and Y, evaluated by serum bactericidal assay using human complement (hSBA), one month after vaccination (day 29)with MenACWY-CRM or MenACWY-PS vaccine. Seroresponse was defined as: for subjects with a prevaccination hSBA titer <1:4, a postvaccination hSBA titer ≥1:8; for subjects with a prevaccination hSBA titer ≥1:4, an increase in hSBA titer of at least four times the prevaccination titer. | 1 month after vaccination (day 29) | 
| Number of Subjects With At Least One Severe Systemic Reaction to MenACWY-CRM or MenACWY-PS Within 7 Days Postvaccination | Safety was assessed in terms of the number of subjects who reported at least one severe systemic reaction after vaccination with MenACWY-CRM or MenACWY-PS from day 1 to day 7 after vaccination. | Day 1 to 7 postvaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With hSBA Titers ≥1:4 and ≥1:8 Against Serogroups A, C, W and Y One Month After Vaccination With MenACWY-CRM or MenACWY-PS | Immunogenicity was measured as the percentage of subjects who achieved hSBA titers ≥1:4 and ≥1:8 against each of four meningococcal serogroups A, C, W and Y at baseline (day 1) and one month (day 29)after one vaccination with MenACWY-CRM or MenACWY-PS. | Day 1 and 29 | 
| The hSBA Geometric Mean Titers Against Serogroups A, C, W and Y One Month After Vaccination With MenACWY-CRM or MenACWY-PS | The immune response was measured as the hSBA geometric mean titers (GMTs) directed against each of four meningococcal serogroups A, C, W and Y at baseline (day 1) and one month(day 29) after one vaccination with MenACWY-CRM or MenACWY-PS. | Day 1 and 29 | 
| Percentage of Subjects With Persisting hSBA Titers ≥1:4 and ≥1:8 Against Serogroups A, C, W and Y at Day 181 After Vaccination With MenACWY-CRM or MenACWY-PS | The persistence of immune response was measured as the percentage of subjects with hSBA titers ≥1:4 and ≥1:8 against each of four meningococcal serogroups A, C, W and Y at day 181 after vaccination with MenACWY-CRM or MenACWY-PS. | Day 181 | 
| The hSBA Geometric Mean Titers Persisting Against Meningococcal Serogroups A, C, W and Y at Day 181 After Vaccination With MenACWY-CRM or MenACWY-PS | The persistence of immune response was measured in terms of the hSBA GMTs persisting at day 181 against each of four meningococcal serogroups A, C, W and Y after vaccination with MenACWY-CRM or MenACWY-PS | Day 181 | 
| Number of Subjects Reporting Local and Systemic Reactions and Axillary Temperature During 7-Day Period After Vaccination With MenACWY-CRM or MenACWY-PS | Safety was assessed as the number of subjects who reported local and systemic reactions and axillary temperature during day 1 to day 7 after vaccination with MenACWY-CRM or MenACWY-PS. | Day 1 to 7 postvaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningitis, children, vaccine, safety, efficacy