Safety and Immunogenicity of Different Meningitis Vaccine Formulations in Adolescents and Young Adults

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity of combination vaccines as compared to the reference vaccines

Official Title
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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

Conditions
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Invasive Meningococcal Disease

Intervention / Treatment
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* Biological: Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + OMV.
* Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.
* Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.
* Biological: Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + qOMV.


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 25 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: ABCWY+OMV<br>Subjects in this group received two doses of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine plus Outer Membrane Vesicles (OMV) administered two months apart. | Biological: Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + OMV.<br>* Two injections of a combined vaccine formulation, Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine plus OMV.<br>|
| Experimental: ABCWY+qOMV<br>Subjects in this group received two doses of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine plus one quarter dose of Outer Membrane Vesicles (qOMV) administered two months apart. | Biological: Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + qOMV.<br>* Two injections of a combined vaccine formulation, Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine plus a quarter dose of OMV.<br>|
| Active Comparator: rMenB+OMV<br>Subjects in this group received two doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine,administered two months apart. | Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.<br>* Two injections of Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.<br>|
| Active Comparator: MenACWY<br>Subjects in this group received a dose of placebo followed by one dose of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine administered two months later. | Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.<br>* One injection of saline solution placebo and one of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine. | 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: For subjects with a pre-vaccination hSBA titer < 1:4, a post-vaccination hSBA titer ≥ 1:8; 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). | One month after the second vaccination (Day 91) | 
| Desirability Index for Each Vaccine Group, Based on Immunogenicity and Reactogenicity Parameters. | 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. | One month after the second vaccination (Day 91) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Percentages of subjects with hSBA titers ≥ 1:8 against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine or one dose of MenACWY 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. | The hSBA GMTs against N.meningitidis serogroups A,C,W-135 and Y, after two doses of either ABCWY+OMV or ABCWY+qOMV combination vaccine, or one dose of MenACWY 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. | The percentages of subjects with hSBA titers ≥ 1:5 and ≥ 1:8 against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV 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. | The percentages of subjects with at least 4-fold increase in hSBA titers against four different strains of N.meningitidis serogroup B, after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine. 4-fold increase is defined as follows; for subjects with a prevaccination hSBA < 1:2, a postvaccination hSBA ≥ 1:8, for subjects with a prevaccination hSBA ≥ 1:2, at least a 4-fold increase. | One month after the second vaccination (Day 91) | 
| The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. | The hSBA GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV 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. | The geometric mean ratio (GMR) of post vaccination versus pre vaccination GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV 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. | The number of subjects reporting solicited local and systemic adverse events and other indicators of reactogenicity after vaccination with ABCWY+OMV, ABCWY+qOMV or rMenB+OMV or MenACWY. | Day 1 through day 7 after any vaccination | 
| The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study. | The number of subjects reporting unsolicited AEs after vaccination with ABCWY+OMV, ABCWY+qOMV, rMenB+OMV or MenACWY. | Throughout the study ( Day 1 to Day 241) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Immunogenicity, Vaccine, Meningococcal, Seroresponse