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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00721396
First received: July 22, 2008
Last updated: March 17, 2015
Last verified: March 2015

July 22, 2008
March 17, 2015
August 2008
July 2010   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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).
  • 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) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00721396 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.

  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety, Tolerability and Immunogenicity of Meningococcal B Recombinant Vaccine Administered With or Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules
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 Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules.

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Meningococcal Infections
  • Biological: rMenB+OMV NZ
  • Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine
    Other Name: Infanrix Hexa
  • Biological: Pneumococcal vaccine
    Other Name: Prevenar
  • Experimental: B+R246
    Subjects in this group received rMenB+OMV NZ vaccine at 2, 4, and 6 months of age, administered concomitantly with routine infant vaccinations.
    Interventions:
    • Biological: rMenB+OMV NZ
    • Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine
    • Biological: Pneumococcal vaccine
  • Experimental: B246_R357
    Subjects in this group received rMenB+OMV NZ vaccine at at 2, 4, and 6 months of age; routine infant vaccinations were administered at 3, 5 and 7 months of age.
    Interventions:
    • Biological: rMenB+OMV NZ
    • Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine
    • Biological: Pneumococcal vaccine
  • Experimental: B+R234
    Subjects in this group received rMenB+OMV NZ vaccine at 2, 3, 4 months of age, administered concomitantly with routine infant vaccinations.
    Interventions:
    • Biological: rMenB+OMV NZ
    • Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine
    • Biological: Pneumococcal vaccine
  • Active Comparator: R234
    Subjects in this group received routine infant vaccines administered at 2, 3 and 4 months of age.
    Interventions:
    • Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine
    • Biological: Pneumococcal vaccine
Gossger N, Snape MD, Yu LM, Finn A, Bona G, Esposito S, Principi N, Diez-Domingo J, Sokal E, Becker B, Kieninger D, Prymula R, Dull P, Ypma E, Toneatto D, Kimura A, Pollard AJ; European MenB Vaccine Study Group. Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial. JAMA. 2012 Feb 8;307(6):573-82. doi: 10.1001/jama.2012.85.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1885
July 2010
July 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy 2-month old infants (55-89 days, inclusive), who were born after full term pregnancy with an estimated gestational age ≥ 37 weeks and a birth weight ≥ 2.5 kg;
  • For whom a parent/legal guardian has given written informed consent after the nature of the study has been explained.

Exclusion Criteria:

  • History of any meningococcal B or C vaccine administration;
  • prior vaccination with routine infant vaccines (Diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenzae type b (Hib), and Pneumococcal antigens);
  • Previous ascertained or suspected disease caused by N. meningitidis;
  • History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;
  • Significant acute or chronic infection within the previous 7 days or axillary temperature major or equal to38 degrees within the previous day;
  • Antibiotics within 6 days prior to enrollment;
  • Any serious chronic or progressive disease;
  • Known or suspected impairment or alteration of the immune system;
  • Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation.
Both
55 Days to 89 Days
Yes
Contact information is only displayed when the study is recruiting subjects
Belgium,   Czech Republic,   Germany,   Italy,   Spain,   United Kingdom
 
NCT00721396
V72P12
Yes
Novartis ( Novartis Vaccines )
Novartis Vaccines
Not Provided
Study Chair: Novartis Vaccines Novartis Vaccines
Novartis
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP