Clinical Trial: Safety, Tolerability and Immunogenicity of Meningococcal B Recombinant Vaccine Administered With or Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules

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

Official Title: A Phase 2b, Open Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered With or

Brief Summary: Primary :1.To demonstrate a sufficient immune response of rMenB+OMV NZ, when given concomitantly with routine infant vaccines to healthy infants at 2, 4 and 6 and 2, 3 and 4 months of age, as measured by percentage of subjects with serum bactericidal activity (SBA) titer ≥1:5, at 1 month after the third vaccination Secondary :To demonstrate that immunogenicity of routine infant vaccines, when given concomitantly with rMenB+OMV NZ to healthy infants at 2, 3 and 4 months of age, was non-inferior to that of routine infant vaccines given without rMenB+OMV NZ. 2. To demonstrate that the immunogenicity of rMenB+OMV NZ when given concomitantly with routine infant vaccines was non-inferior to that of rMenB+OMV NZ given without routine infant vaccines at 2, 4 and 6 months of age. 3. To assess prevalence of meningococcal B antibodies over the study period by evaluation of SBA, at baseline and at 1 month after third vaccination, in subjects- received routine infant vaccine without rMenB+OMV NZ.

Detailed Summary:
Sponsor: Novartis Vaccines

Current Primary Outcome:

• Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine [ Time Frame: One month after third Men B vaccination ]

  The percentage of subjects with serum bactericidal activity(hSBA)titer ≥1:5 after receiving three doses of rMenB+OMV NZ vaccine were evaluated to demonstrate sufficient immune response following rMenB+OMV NZ vaccination, when given concomitantly with routine infant vaccines to healthy infants.

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

  The immune response was considered sufficient for groups B+R246 and B+R234 if the lower limit of the 2-sided 95% confidence interval was ≥ 70% for all three strains.

• Safety and Tolerability of 3 Doses of rMenB - Concomitantly With Routine Infant Vaccines at 2, 4 and 6 Months of Age - Concomitantly With Routine Vaccines at 2, 3 and 4 Months of Age - Alone at 2, 4 and 6 Months of Age [ Time Frame: 10 months (groups 1 and 2); 8 months (groups 3 and 4) ]
  Safety and Tolerability of 3 Doses of rMenB was assessed in terms of the number of subjects who reported solicited local and systemic adverse events when administered concomitantly with routine infant vaccines at 2,4,6 months of age (B+R246) to when rMenB+OMV NZ and routine vaccines were administered separately (group B246_R357).

Original Primary Outcome:

• Immunogenicity (percentage of subjects with serum bactericidal activity (SBA) titer ≥1:4) of rMenB, given with or without routine infant vaccines to healthy infants at 2, 4 and 6 and 2, 3 and 4 months of age, at 1 month after the third vaccination [ Time Frame: 5 months (groups 1 and 2); 3 months (groups 3 and 4) ]
• Safety and tolerability of 3 doses of rMenB given: - concomitantly with routine infant vaccines at 2, 4 and 6 months of age - concomitantly with routine vaccines at 2, 3 and 4 months of age - alone at 2, 4 and 6 months of age [ Time Frame: 10 months (groups 1 and 2); 8 months (groups 3 and 4) ]

Current Secondary Outcome:

• Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age [ Time Frame: One month after 3rd Men B vaccination ]
  The non-inferiority of immune response to rMenB+OMV NZ vaccination when administered concomitantly with routine infant vaccines at 2,4,6 months of age(B+R246) to when rMenB+OMV NZ and routine vaccines were administered separately (group B246_R357)was assessed in terms of percentage of subjects With hSBA≥ 1:5.
• Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine [ Time Frame: One month after 3rd vaccination ]
  Non-inferiority of immune response to routine vaccine antigens when routine vaccines were administered concomitantly with rMenB+OMV NZ vaccine [group B+R234] to when only routine vaccines were given [Group R234] were assessed in terms of percentage of subjects with antibody concentrations ≥0.1 IU/mL against Diphtheria and Tetanus antigens as measured by enzyme-linked immunosorbent assay.
• Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. [ Time Frame: One month after third Men B vaccination ]
  The hSBA antibody titers when rMenB+OMV NZ vaccine is administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately are reported in terms of vaccine-group-specific geometric mean titers.
• Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. [ Time Frame: one month after third Men B vaccination ]
  The geometric mean ratio(GMR) of GMTs at 1 month after 3rd rMenB+OMV NZ vaccination to prevaccination GMTs, when rMenB+OMV NZ was administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately.
• Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. [ Time Frame: One month after third Men B vaccination ]
  The percentage of subjects with hSBA titers ≥1:8, following rMenB+OMV NZ vaccination when given concomitantly with routine infant vaccines to when rMenB+OMV NZ and routine vaccines were given separately.
• Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. [ Time Frame: One month after third Men B vaccination ]
  The percentage of subjects with 4-fold rise in hSBA titers at 1 month after 3rd rMenB+OMV NZ vaccination from baseline, when rMenB+OMV NZ was administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately.
• Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. [ Time Frame: 1 month after 3rd vaccination ]

  Non-inferiority of immune response to routine vaccine antigens when routine vaccines were administered concomitantly with rMenB+OMV NZ vaccine [group B+R234] to when only routine vaccines were given [Group R234] were assessed in terms of percentage of subjects achieving seroconversion for pertussis antigens - Filamentous Hemagglutinin (FHA), Pertactin and Pertussis Toxoid (PT) at 1 month after 3rd vaccination versus baseline.

  Seroconversion was defined as a 4-fold increase for each pertussis antigen or in those initially seropositive, persistence of the pre-vaccination antibody concentration at least at the same antibody concentration as before vaccination, taking into account the decay of maternal antibodies.

Original Secondary Outcome:

• Non-inferiority of rMenB immunogenicity given concomitantly with routine infant vaccines at 2, 4 and 6 months versus that of rMenB without routine infant vaccines at the same time points [ Time Frame: 5 months (groups 1 and 2); 3 months (groups 3 and 4) ]
• Non-inferiority of routine infant vaccines immunogenicity when given concomitantly with rMenB to healthy infants at 2, 3 and 4 months of age versus that of routine infant vaccines given without rMenB at the same time points [ Time Frame: 5 months (groups 1 and 2); 3 months (groups 3 and 4) ]
• Prevalence of meningococcal B antibodies over the study period by evaluation of the serum bactericidal activity (SBA), at baseline and at 1 month after the third vaccination, in the subjects receiving routine infant vaccines alone [ Time Frame: 5 months (groups 1 and 2); 3 months (groups 3 and 4) ]

Dates:
Date Received: July 22, 2008
Date Started: August 2008
Date Completion:
Last Updated: March 17, 2015
Last Verified: March 2015