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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT01272180
First received: January 6, 2011
Last updated: September 19, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Invasive Meningococcal Disease
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.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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:
  • 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. [ Time Frame: Day 1 and one month after second vaccination (Day 91) ] [ Designated as safety issue: No ]
    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. [ Time Frame: Day 1 and one month after the second vaccination (Day 91) ] [ Designated as safety issue: No ]
    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.

  • 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. [ Time Frame: Day 1 and one month after the second vaccination (Day 91) ] [ Designated as safety issue: No ]
    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. [ Time Frame: One month after the second vaccination (Day 91) ] [ Designated as safety issue: No ]

    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.


  • The hSBA GMTs Against N.Meningitidis serogroupB, After Vaccination With Different Formulations of MenABCWY Combination Vaccine. [ Time Frame: Day 1 and one month after the second vaccination (Day 91) ] [ Designated as safety issue: No ]
    The hSBA GMTs against N.meningitidis serogroup B after two doses of ABCWY+OMV, ABCWY+qOMV or rMenB+OMV 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. [ Time Frame: One month after the second vaccination/prevaccination (Day 91/day 1) ] [ Designated as safety issue: No ]
    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. [ Time Frame: Day 1 through day 7 after any vaccination ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Throughout the study ( Day 1 to Day 241) ] [ Designated as safety issue: Yes ]
    The number of subjects reporting unsolicited AEs after vaccination with ABCWY+OMV, ABCWY+qOMV, rMenB+OMV or MenACWY.


Enrollment: 484
Study Start Date: August 2011
Study Completion Date: September 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABCWY+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.
Biological: Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + OMV.
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.
Experimental: ABCWY+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.
Biological: Meningococcal (groups A, C, W, Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant vaccine + qOMV.
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.
Active Comparator: rMenB+OMV
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.
Two injections of Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV.
Active Comparator: MenACWY
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.
One injection of saline solution placebo and one of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.

  Eligibility

Ages Eligible for Study:   10 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01272180

Locations
United States, Alabama
Alabama Clinical Therapeutics, 806 St. Vincent's Drive, Suite 615
Birmingham, Alabama, United States, 35205
United States, California
Madera Family Medical Group,1111 West 4th Street
Madera, California, United States, 93637
Center for Clinical Trials LLC, 16660 Paramount Blvd, Suite 301
Paramount, California, United States, 90723
United States, Kentucky
Kentucky Pediatric/Adult Research, 201 south 5th street
Bardstown, Kentucky, United States, 40004
Bluegrass Clinical Research Inc.5512 Bardstown Road, Suite 2
Louisville, Kentucky, United States, 40291
United States, Ohio
Ohio Pediatric Research Association, 7371 Brandt Pike, Suite C
Huber Heights, Ohio, United States, 45424
Ohio Pediatric Research Association, 1775 Delco Park Drive
Kettering, Ohio, United States, 45420
United States, Tennessee
Focus Research Group,201 Signature Place
Lebanon, Tennessee, United States, 37087
Poland
Specjalistyczna Przychodnia Lekarska Internistyczno-Pediatryczna,,Juniperus"s.c, ul.Kościuszki 41
Izabelin (Warszawa), Poland, 05-080
NZOZ HIPOKRATES II.sp.zo.o, ul.Pachonskiego 12
Kraków, Poland, 31-223
NZOZ PRAKTIMED Sp.zo.o, ul.Strzelców 15
Kraków, Poland, 31-422
Klinika Pediatrii Centrum Medycznego Kształcenia PodyplomowegoSzpital Bielański, ul. Cegłowska 80
Warszawa, Poland, 01-809
Katedra i Klinika Pediatrii i Chorób Infekcyjnych, ul.O.Bujwida 44
Wrocław, Poland, 50-354
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines Novartis Vaccines
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01272180     History of Changes
Other Study ID Numbers: V102_03, 2010-023523-23
Study First Received: January 6, 2011
Results First Received: January 31, 2014
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration
Polish: Ministry of Health

Keywords provided by Novartis:
Safety
Immunogenicity
Vaccine
Meningococcal
Seroresponse

Additional relevant MeSH terms:
Meningococcal Infections
Bacterial Infections
Gram-Negative Bacterial Infections
Neisseriaceae Infections

ClinicalTrials.gov processed this record on October 21, 2014