Clinical Trial: Extension Study Evaluating Antibody Persistence and Safety, Tolerability and Immunogenicity of Booster Doses of Novartis rMenB±OMV NZ Vaccine in Healthy UK Children Who Previously Received One or Four Doses of the Same Vaccine

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2, Open-Label, Single-Center, Extension Study Evaluating Antibody Persistence Compared to Naïve Children and Safety, Tolerability and Immunogenicity of Booster Doses of Novartis rMenB

Brief Summary: The proposed study V72P6E1 is an Extension Study of V72P6 (NCT00381615). The objectives of this extension study will be to explore antibody persistence at approximately 40 months of age and to evaluate the safety, tolerability and immunogenicity of booster doses of rMenB±OMV NZ administered to subjects at approximately 40 months of age. Antibody persistence will be subsequently measured at 18-20 months after these booster doses when the subjects are 60 months of age. Two groups of naïve subjects, aged approximately 40 and 60 months, will be recruited in the study to serve as a baseline comparator for assessing antibody persistence at these ages. These subjects will receive a two-dose catch-up regimen with rMenB+OMV NZ. Subjects who are enrolled at 40 months of age are offered DTaP/IPV and MMR vaccinations, if they have not already received these vaccines prior to enrollment.

Detailed Summary:
Sponsor: Novartis Vaccines

Current Primary Outcome:

  • Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received 4 Doses of Men B Vaccine), at 40 Months of Age. [ Time Frame: 28 months after last vaccination; Baseline for Naïve ]
    Persistence of geometric mean titers (GMTs) against N.meningitidis B strains in children (at 40 months of age) who had previously received four doses of either rMenB or rMen+OMV NZ vaccines in parent study, are compared with the GMTs in vaccine-naïve children.
  • Percentage of Subjects (Who Previously Received 4 Doses of Men B Vaccine) With Persisting Human Complement Serum Bactericidal Antibody Titers ≥ 1:4 and ≥1:8 at 40 Months of Age. [ Time Frame: 28 months after last vaccination; baseline for naïve ]

    The percentages of subjects with persisting human serum bactericidal antibodies (hSBA) titers ≥ 1:4 and ≥ 1:8, against N.meningitidis B strains at 40 months of age; who had previously received four doses of either rMenB or rMen+OMV NZ vaccines in parent study are reported.

    The serum bactericidal antibodies directed against serogroup B meningococci, are measured by human complement Serum Bactericidal Assay (hSBA).

  • Number of Subjects Reporting Solicited Adverse Events After a Receiving One or Two Booster Doses of rMen B or rMenB+OMV NZ Vaccine at 40 Months of Age. [ Time Frame: Day 1-7 after booster vaccination ]
    The safety and tolerability of one or two booster doses of rMen B or rMenB+OMV NZ vaccine administered at 40 months of age in children who had previously received one or four doses of the

    Original Primary Outcome: Bactericidal antibody persistence in children at 40 months of age who received 4 doses of rMenB+/-OMV NZ. Safety and tolerability [ Time Frame: Individual subject participation either 3 months or 20 months ]

    Current Secondary Outcome:

    • Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received One Dose of Men B Vaccine), at 40 Months of Age. [ Time Frame: 28 months after vaccination; Baseline for Naïve ]
      Persisting GMTs against N.meningitidis B strains in children (at 40 months of age) who had previously received one dose of either rMenB or rMen+OMV NZ vaccines in parent study, are compared with the GMTs in vaccine-naïve children.
    • Percentage of Subjects (Who Had Previously Received One Dose of Men B Vaccine) With Persisting Serum Bactericidal Antibody Titers ≥ 1:4 and ≥1:8, at 40 Months of Age. [ Time Frame: 28 months after vaccination; baseline for naïve ]
      The percentages of subjects with persisting hSBA titers ≥ 1:4 and ≥1:8, against N.meningitidis B strains at 40 months of age; who had previously received one dose of either rMenB or rMen+OMV NZ vaccines in parent study are reported.
    • Geometric Mean Antibody Titers in Children (Who Previously Received 4 Doses of Men B Vaccine), After Receiving a Booster Dose of rMenB or rMenB+OMV NZ Vaccine at 40 Months of Age. [ Time Frame: 1 month post- booster/ dose 1 for Naïve ]
      The GMTs against N.meningitidis B strains in children (who had previously received four doses MenB vaccine in parent study) after a single booster dose of rMenB or rMenB+OMV NZ vaccine given at 40 months of age, are compared with the antibody titers following one catch-up dose rMenB+OMV NZ vaccine given at 40 months to vaccine-naive subjects.
    • Percentage of Subjects (Who Previously Received 4 Doses of Men B Vaccine) With Serum Bactericidal Antibody Titers ≥ 1:4 and ≥1:8 After Receiving a Booster Dose of Either rMenB or rMenB+OMV NZ Vaccine at 40 Months of Age. [ Time Frame: 1 month post- booster/ dose 1 for Naïve ]
      The percentages of subjects (who had previously received four doses MenB vaccine in parent study) with hSBA titers ≥ 1:4 and ≥ 1:8, against N.meningitidis B strains after receiving a single booster dose of either rMenB or rMen+OMV NZ vaccines at 40 months of age are compared with hSBA responses following one catch-up dose of rMenB+OMV NZ vaccine given at 40 months in vaccine-naive subjects .
    • Percentage of Subjects (Who Previously Received 4 Doses of Men B Vaccine) With 4-fold Increase in Serum Bactericidal Antibody Titers After Receiving a Booster Dose of Either rMenB or rMenB+OMV NZ Vaccine at 40 Months of Age. [ Time Frame: 1 month post - booster/ -dose 1 for Naïve ]

      The percentages of subjects (who had previously received four doses MenB vaccine in parent study) showing a 4-fold increase in hSBA titers over baseline against N.meningitidis B strains, after receiving a booster dose of either rMenB or rMen+OMV NZ vaccines at 40 months of age are compared with hSBA responses following one catch-up dose of rMenB+OMV NZ vaccine given at 40 months in vaccine-naive subjects.

      Baseline is defined as either the time that the (first) booster dose was given or the time of the first vaccination in this study.

    • Geometric Mean Antibody Titers in Children After Receiving Two Booster Doses of Either rMenB or rMenB+OMV NZ Vaccine at 40 & 42 Months of Age. [ Time Frame: 1 month post vaccination ]
      The GMTs against N.meningitidis B strains in children (who had previously received one dose MenB vaccine in parent study) after a two booster doses of either rMenB or rMenB+OMV NZ vaccine given at 40 & 42 months of age.
    • Percentage of Subjects With Serum Bactericidal Antibody Titers ≥ 1:4 and ≥ 1:8 After Receiving Two Booster Doses of Either rMenB or rMenB+OMV NZ Vaccine at 40 & 42 Months of Age. [ Time Frame: 1 month post vaccination ]
      The percentages of subjects (who had previously received one dose of MenB vaccine in parent study) with hSBA ≥ 1:4 and ≥ 1:8, against N.meningitidis B strains after receiving two booster doses of either rMenB or rMenB+OMV NZ vaccine at 40 & 42 months of age.
    • Percentage of Subjects With 4-fold Increase in Antibody Titers After Receiving Two Booster Doses of Either rMenB or rMenB+OMV NZ Vaccine at 40 & 42 Months of Age. [ Time Frame: 1 month post vaccination ]
      The percentages of subjects (who had previously received one dose of MenB vaccine in parent study) displaying 4-fold increase in antibody titers over baseline against N.meningitidis B strains, after receiving two booster doses of either rMenB or rMenB+OMV NZ vaccine at 40 & 42 months of age.
    • Percentage of Subjects With hSBA Titers ≥ 1:4 and ≥1:8 Following Two Catch up Doses of rMenB+OMV NZ Vaccine Given One Month Apart, Either at 40 or 60 Months of Age. [ Time Frame: 1 month post -vaccine dose two ]
      The percentage of subjects with hSBA ≥ 1:4 and ≥ 1:8 after two catch-up doses of rMenB+OMV NZ vaccine when given either at 40 & 42 months or 60 & 62 months of age are reported.