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

Phase 2

Completed

Conditions: Invasive Meningococcal Disease

Interventions: 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 + OMV.
Biological: Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + qOMV.

Registration Number: NCT01272180

Lead Sponsor: Novartis Vaccines

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 484

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rMenB+OMV	Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.	Subjects in this group received two doses of "Meningococcal (group B) multicomponent recombinant adsorbed vaccine",administered two months apart.
MenACWY	Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.	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.
ABCWY+OMV	Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + OMV.	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.
ABCWY+qOMV	Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + qOMV.	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.

Primary Outcome Measures

Name	Time	Method
Percentages of Subjects With a Seroresponse Against N.Meningitidis Serogroups A,C,W-135,Y, After Receiving Different Formulations of MenABCWY Combination Vaccine.	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.	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 Outcome Measures

Name	Time	Method
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)	The hSBA GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV vaccine.
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)	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.
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)	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.
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)	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.
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 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.
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 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.
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 solicited local and systemic adverse events and other indicators of reactogenicity after vaccination with ABCWY+OMV, ABCWY+qOMV or rMenB+OMV or MenACWY.
The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Any Vaccination in This Study.	Throughout the study ( Day 1 to Day 241)	The number of subjects reporting unsolicited AEs after vaccination with ABCWY+OMV, ABCWY+qOMV, rMenB+OMV or MenACWY.

Trial Locations

Locations (13): NZOZ HIPOKRATES II.sp.zo.o, ul.Pachonskiego 12
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Kraków, Poland
Klinika Pediatrii Centrum Medycznego Kształcenia PodyplomowegoSzpital Bielański, ul. Cegłowska 80
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Warszawa, Poland
Bluegrass Clinical Research Inc.5512 Bardstown Road, Suite 2
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Louisville, Kentucky, United States
Alabama Clinical Therapeutics, 806 St. Vincent's Drive, Suite 615
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Birmingham, Alabama, United States
Center for Clinical Trials LLC, 16660 Paramount Blvd, Suite 301
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Paramount, California, United States
Madera Family Medical Group,1111 West 4th Street
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Madera, California, United States
Specjalistyczna Przychodnia Lekarska Internistyczno-Pediatryczna,,Juniperus"s.c, ul.Kościuszki 41
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Izabelin (Warszawa), Poland
NZOZ PRAKTIMED Sp.zo.o, ul.Strzelców 15
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Kraków, Poland
Katedra i Klinika Pediatrii i Chorób Infekcyjnych, ul.O.Bujwida 44
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Wrocław, Poland
Ohio Pediatric Research Association, 7371 Brandt Pike, Suite C
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Huber Heights, Ohio, United States
Kentucky Pediatric/Adult Research, 201 south 5th street
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Bardstown, Kentucky, United States
Ohio Pediatric Research Association, 1775 Delco Park Drive
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Kettering, Ohio, United States
Focus Research Group,201 Signature Place
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Lebanon, Tennessee, United States