Phase 2, Observer Blinded, Controlled, Randomized Multi-Center Study in Adolescents and Young Adults to Evaluate Safety and Immunogenicity of Two Different rMenB With OMV + MenACWY Combination Vaccination Formulations
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Invasive Meningococcal Disease
- Sponsor
- Novartis Vaccines
- Enrollment
- 484
- Locations
- 13
- Primary Endpoint
- Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine.
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This study will evaluate the safety and immunogenicity of combination vaccines as compared to the reference vaccines
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adolescents aged 10 through 25 years of age inclusive at the time of enrollment.
Exclusion Criteria
- •History of any meningococcal vaccine administration;
- •Current or previous, confirmed or suspected disease caused by N. meningitidis;
- •Pregnant or nursing (breastfeeding) mothers;
- •Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study;
- •Any serious, chronic, or progressive disease;
- •Known or suspected impairment/alteration of the immune system;
- •Receipt of blood, blood products and/or plasma derivatives, or a parenteral immunoglobulin preparation within the previous 90 days;
- •History of severe allergic reactions after previous vaccinations or hypersensitivity to any vaccine component.
Outcomes
Primary Outcomes
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine.
Time Frame: One month after the second vaccination (Day 91)
Non-inferiority of immune response of two doses of two different formulations of MenABCWY vaccine to a single dose of MenACWY vaccine as measured by the percentage of subjects with hSBA seroresponse against N.meningitidis serogroups A,C,W and Y. Seroresponse is defined as: 1. For subjects with a pre-vaccination hSBA titer \< 1:4, a post-vaccination hSBA titer ≥ 1:8; 2. For subjects with a pre-vaccination hSBA titer ≥ 1:4, an increase in hSBA titer of at least four times the prevaccination titer. Functional bactericidal antibodies directed against serogroups A,C,W,Y meningococci were measured with a serum bactericidal activity assay using human serum as the source of exogenous complement (hSBA).
Desirability Index for Each Vaccine Group, Based on Immunogenicity and Reactogenicity Parameters.
Time Frame: One month after the second vaccination (Day 91)
The overall desirability index (DI) used to identify the optimal formulation of the combination vaccine was based on immunogenicity and reactogenicity parameters (on a scale of 0 to 1, with 0 for an undesirable response and 1 for a highly desirable response) as follows: Between-group ratios of hSBA GMTs were calculated, adjusted for prevaccination titer and center, against serogroups A, C, W, and Y (ABCWY+OMV group or ABCWY+qOMV group vs. Placebo/ACWY group) and against the 4 serogroup B test strains (ABCWY+OMV group or ABCWY+qOMV group vs. rMenB+OMV group). Reactogenicity was measured by the percentage of doses associated with severe local and systemic solicited AEs within 3 days following vaccination. Each immunogenicity and reactogenicity endpoint was assigned its own DI based on predefined desirability functions. The overall DI was calculated using the weighted geometric mean of the DI values of each of the ten parameters to derive an overall DI for each formulation.
Secondary Outcomes
- The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.(Day 1 and one month after the second vaccination (Day 91))
- Percentages of Subjects With hSBA Titers ≥ 1:5 and ≥ 1:8 Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.(Day 1 and one month after the second vaccination (Day 91))
- Percentages of Subjects With at Least 4-fold Increase in hSBA Titers Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.(One month after the second vaccination (Day 91))
- Percentages of Subjects With hSBA Titers ≥ 1:8 Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.(Day 1 and one month after second vaccination (Day 91))
- The hSBA GMTs Against N.Meningitidis Serogroups A,C,W-135 and Y, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.(Day 1 and one month after the second vaccination (Day 91))
- The Geometric Mean Ratio of Post vs Pre Vaccination GMTs Against N.Meningitidis Serogroup B, After Vaccination With Different Formulations of MenABCWY Combination Vaccine.(One month after the second vaccination/prevaccination (Day 91/day 1))
- The Number of Subjects Reporting Solicited Adverse Events After Receiving Any Vaccination in This Study.(Day 1 through day 7 after any vaccination)
- The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study.(Throughout the study ( Day 1 to Day 241))