Immunogenicity, Safety and 1 Year Persistence of Antibodies After Either One or Two Doses of Meningococcal ACWY Conjugate Vaccine in Healthy Children 2 Through 10 Years of Age.

Study Overview
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Brief Summary
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This study was designed to conduct a comparative trial to further evaluate the safety, immunogenicity and antibody persistence of two doses of Novartis MenACWY conjugate vaccine, given 2 months apart, versus one dose of Novartis MenACWY conjugate vaccine in children 2 through 10 years of age.

Official Title
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A Phase 3b, Randomized, Observer-Blind, Placebo-Controlled Multi-Center Study Comparing Immunogenicity, Safety and 1 Year Persistence of Antibodies After Either One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine, Administered to Healthy Children 2 to 10 Years of Age.

Conditions
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Meningococcal Disease, Infections, Meningococcal

Intervention / Treatment
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* Biological: MenACWY-CRM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children, 2 to 10 years of age who have up to date routine childhood vaccination, according to U.S. ACIP recommendations Exclusion Criteria: Unwilling or unable to give written informed assent or consent to participate in the study. Perceived to be unreliable or unavailable for the duration of the study period. Previous confirmed or suspected disease caused by N. meningitidis. Previously immunized with a meningococcal vaccine (licensed or investigational). Receipt of any investigational or non-registered product within 30 days prior to enrolment or who expect to receive an investigational drug or vaccine prior to the completion of the study. Receipt or plan to receive any vaccines within 30 days before and after administration of each dose of the study vaccine. (certain exceptions influenza vaccines apply) Significant acute infection within the 7 days prior to enrolment or body temperature of 38°C or greater within 3 days prior to enrolment. Previous serious acute, chronic or progressive disease, epilepsy or any progressive neurological disease or history of Guillain-Barre syndrome. History of any anaphylaxis, serious vaccine reactions, or allergy to any vaccine components Impairment/alteration of immune function, either congenital or acquired or resulting from (for example): receipt of immunosuppressive therapy, receipt of immunostimulants, receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives. Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

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 |
| --- | --- |
| Placebo Comparator: 2 through 5 years (1 Vac) MenACWY-CRM 1<br>Subjects 2 through 5 years received one vaccination of MenACWY-CRM | Biological: MenACWY-CRM<br>* The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm<br>|
| Active Comparator: 2 through 5 years (2 Vac) MenACWY-CRM 2<br>Subjects 2 through 5 years received two vaccinations of MenACWY-CRM | Biological: MenACWY-CRM<br>* The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm<br>|
| Placebo Comparator: 6 through 10 years (1 Vac) MenACWY-CRM 3<br>Subjects 6 through 10 years received one vaccination of MenACWY-CRM | Biological: MenACWY-CRM<br>* The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm<br>|
| Active Comparator: 6 through 10 years (2 Vac) MenACWY-CRM 4<br>Subjects 6 through 10 years received two vaccinations of MenACWY-CRM | Biological: MenACWY-CRM<br>* The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination | Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 97.5% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y, by serum bactericidal assay using human complement (hSBA) at 1 month after one vaccination or two vaccinations of MenACWY-CRM given two months apart. Seroresponse is defined as: a. postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4; b. for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer. | One Month After Last Vaccination ( day 86) | 
| Superiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination | Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 95% CI, directed against N. meningitidis serogroups A, C, W and Y, by hSBA at 1 month after one vaccination or two vaccinations of MenACWY-CRM. Seroresponse -postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4 and for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer. | One Month After Last Vaccination (day 86) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM | Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 and associated 95% CI, at one month after one vaccination or two vaccinations of MenACWY-CRM. | One Month After Last Vaccination (day 86) | 
| Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM | Immunogenicity was measured as hSBA geometric mean titers (GMTs) and 95% CI against N. meningitidis serogroups A, C, W and Y, one month after one vaccination or two vaccinations of MenACWY-CRM. | One Month After Last Vaccination (day 86) | 
| Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM | Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI at one year after one vaccination or two vaccinations of MenACWY-CRM. | One year after one vaccination or two vaccinations (day 422). | 
| Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM | Immunogenicity was measured as hSBA GMTs and 95% CI against N. meningitidis serogroups A, C, W and Y at one year after one vaccination or two vaccinations of MenACWY-CRM. | One year after one vaccination or two vaccinations (day 422). | 
| Number of 2 to 5 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination | Safety was assessed as the number of 2 to 5 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM | From Days 1-7 after each vaccination | 
| Numbers of 6 to 10 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination | Safety was assessed as the number of 6 to 10 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM | From Days 1-7 after each vaccination | 
| Number of Subjects Who Reported Selected AEs After Any Vaccination | Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 86 after one or two vaccination(s) of MenACWY-CRM | Day 1 to Day 86 | 
| Number of Subjects Who Reported Selected AEs After Any Vaccination | Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 422 after one or two vaccination(s) of MenACWY-CRM | Day 1 to Day 422 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention of meningococcal disease, children, vaccine