Evaluation of Meningococcal Immune Response Among Children Who Previously Received MenACWY Conjugate Vaccine

Study Overview
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Brief Summary
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The primary objective was to evaluate the persistence of bactericidal antibodies in children 40 and 60 months of age previously enrolled in the V59P14 (NCT00474526) study who received Novartis MenACWY Conjugate Vaccine. The study also enrolled age-matched subjects who have never received any meningococcal vaccine (naïve subjects) to serve as a control group. In addition, the response of a booster dose at 60 months was evaluated.

Official Title
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A Phase IIIb, Open-Label, Controlled, Multi-Center Study to Evaluate the Persistence Of Antibody Responses Among Children Who Previously Received Novartis MenACWY Conjugate Vaccine

Conditions
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Meningococcal Meningitis

Intervention / Treatment
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* Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children eligible to be enrolled in the study are those whose parents provide written informed consent, and are in generally good health based on the clinical judgment of the investigators. Group 1 and 2 (Follow up) subjects must be 40 +/- 3 months of age at the time of enrollment and participated in the original V59P14 study (NCT00474526). Group 3 and 4 (Naïve) subjects must be healthy, meningococcal vaccine-naïve children ages 40 +/- 3 months (Group 3) or 60 +/-3 months (Group 4) at the time of enrollment, respectively. Exclusion Criteria: Serious, acute, or chronic illnesses are reasons for exclusion. Subjects who have received any vaccine (excluding influenza vaccines) 28 days preceding enrollment visit. Influenza vaccines (including FluMist®) are excluded for the 14 days prior to the enrollment visit. Subjects who have received any meningococcal vaccine since birth (Groups 3 & 4 -naive) or last study dose in V59P14 (NCT00474526) trial (Groups 1 & 2 - follow on).

Ages Eligible for Study
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Minimum Age: 37 Months
Maximum Age: 63 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACWY - 4<br>Subjects who had previously received 4 doses of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine in the parent study during their first year of life are administered one booster dose of the same vaccine at 60 months of age. | Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine<br> <br> |
| Experimental: ACWY - 2<br>Subjects who had previously received 1 or 2 doses of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine in the parent study during their second year of life, are administered one booster dose of the same vaccine at 60 months of age. | Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine<br> <br> |
| Other: Naïve - 40<br>Control subjects, age-matched with the intervention groups subjects (40 months of age), to receive 1 optional dose of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine. | Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine<br> <br> |
| Active Comparator: Naïve - 60<br>Control subjects, age-matched with the intervention groups subjects (60 months of age), are administered one dose of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine. | Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Human Serum Bactericidal Assay (hSBA) Titers ≥ 1:8 Directed Against N. Meningitidis Serogroups A, C, W-135, and Y | The persistence of the antibody response in subjects of 40 months of age, previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentage of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:8 directed against N. meningitidis serogroups A, C, W-135, and Y. | Visit 9 (continuation from the parent study), 40-month visit. | 
| Percentages of Subjects With Human Serum Bactericidal Assay (hSBA) Titers ≥ 1:8 Directed Against N. Meningitidis Serogroups A, C, W-135, and Y | The persistence of the antibody response in subjects of 60 months of age previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentages of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:8 directed against N. meningitidis serogroups A, C, W-135, and Y. | Visit 10, 60 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With hSBA Titers ≥ 1:4 Against N Meningitidis Serogroups A, C, W-135, and Y in Subjects of 40 Months of Age | The persistence of the antibody response in subjects of 40 months of age previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentage of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:4 directed against N. meningitidis serogroups A, C, W-135, and Y. | Visit 9, 40 months of age. | 
| Percentages of Subjects With hSBA Titers ≥ 1:4 Against N Meningitidis Serogroups A, C, W-135, and Y Subjects of 60 Months of Age | The persistence of the antibody response in subjects of 60 months of age previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentage of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:4 directed against N. meningitidis serogroups A, C, W-135, and Y. | Visit 10, 60 months of age. | 
| hSBA Geometric Mean Titers (GMTs) Directed Against N. Meningitidis Serogroups A, C, W-135, and Y in Subjects of 40 Months of Age | The persistence of the antibody response in children of 40 months of age previously vaccinated with MenACWY-CRM in study V59P14 (NCT00474526), and baseline antibody levels in age-matched naive subjects, is measured by the hSBA GMTs directed against N meningitidis serogroups A, C, W-135, and Y. | Visit 9 (continuation from the parent study), 40-months of age. | 
| hSBA GMTs Directed Against N Meningitidis Serogroups A, C, W-135, and Y in Subjects of 60 Months of Age | The persistence of the antibody response in children of 60 months of age previously vaccinated with MenACWY-CRM in study V59P14 (NCT00474526), and baseline antibody levels in age-matched naive subjects is measured by the hSBA GMTs directed against N meningitidis serogroups A, C, W-135, and Y. | Visit 10, 60 months of age. | 
| Percentages of Subjects With hSBA Titers ≥ 1:8, and ≥ 1:4 Directed Against N. Meningitidis Serogroups A, C, W-135, and Y, at 1 Month Post-vaccination | The antibody response to one booster dose of MenACWY-CRM in children of 60 months of age who had previously received at least one dose of MenACWY-CRM in the parent study compared to the antibody response to one dose of MenACWY-CRM in meningococcal vaccine-naïve subjects, is measured by the percentage of subjects with hSBA titers ≥ 1:8 and ≥1:4 directed against N. meningitidis serogroups A, C, W-135, and Y, at 1 month post-vaccination. | Visit 11, 1 month after vaccination. | 
| Percentage of Subjects With Seroresponse at 1 Month Post-vaccination | The antibody response to one booster dose of MenACWY-CRM in children of 60 months of age who had previously received at least one dose of MenACWY-CRM in the parent study, compared to the antibody response to one dose of MenACWY-CRM in meningococcal vaccine-naïve subjects, is measured by the percentage of subjects with seroresponse at 1 month post-vaccination. Seroresponse is defined as hSBA ≥ 1:8 for subjects with pre-vaccination hSBA titer ≤1:4, and as at least a four-fold rise in hSBA for subjects with pre-vaccination hSBA titer ≥ 1:4. | Visit 11, 1 month after vaccination. | 
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) and Other Indicators of Reactogenicity | Number of subjects reporting solicited local and systemic Adverse Events (AEs) and other indicators of reactogenicity after receiving study vaccination. Note: solicited AEs were not recorded for naive subjects at 40 months of age, but only SAEs and medically attended AEs. | From day 1 to 7 after vaccination. | 
| Number of Subjects Reporting Unsolicited AEs and SAEs | Number of subjects reporting unsolicited AEs, serious adverse events (SAEs) and medically attended AEs after receiving study vaccination. | Day 1 to 7 after vaccination for any unsolicited AEs, day 1 to study termination for SAEs and medically attended AEs (for the naive-40 group), day 8 to study termination for SAEs and medically attended AEs (for the other groups). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal, ACWY, Conjugate Vaccine, Meningitis, Children, Persistence, Booster dose