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 Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Meningococcal Infections

Intervention / Treatment
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* Biological: rMenB+OMV NZ
* Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine
* Biological: Pneumococcal vaccine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 55 Days
Maximum Age: 89 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B+R246<br>Subjects in this group received rMenB+OMV NZ vaccine at 2, 4, and 6 months of age, administered concomitantly with routine infant vaccinations. | Biological: rMenB+OMV NZ<br> <br> Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine<br> <br> * Other names: Infanrix Hexa;Biological: Pneumococcal vaccine<br> <br> * Other names: Prevenar;|
| Experimental: B246_R357<br>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. | Biological: rMenB+OMV NZ<br> <br> Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine<br> <br> * Other names: Infanrix Hexa;Biological: Pneumococcal vaccine<br> <br> * Other names: Prevenar;|
| Experimental: B+R234<br>Subjects in this group received rMenB+OMV NZ vaccine at 2, 3, 4 months of age, administered concomitantly with routine infant vaccinations. | Biological: rMenB+OMV NZ<br> <br> Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine<br> <br> * Other names: Infanrix Hexa;Biological: Pneumococcal vaccine<br> <br> * Other names: Prevenar;|
| Active Comparator: R234<br>Subjects in this group received routine infant vaccines administered at 2, 3 and 4 months of age. | Biological: combined diphtheria,tetanus,pertussis+polio+Hepatitis B+Haemophilus influenzae B vaccine<br> <br> * Other names: Infanrix Hexa;Biological: Pneumococcal vaccine<br> <br> * Other names: Prevenar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine | 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. | One month after third Men B vaccination | 
| 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 | 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). | 10 months (groups 1 and 2); 8 months (groups 3 and 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age | 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. | One month after 3rd Men B vaccination | 
| Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine | 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. | One month after 3rd vaccination | 
| Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 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. | One month after third Men B vaccination | 
| Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 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. | one month after third Men B vaccination | 
| Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine. | 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. | One month after third Men B vaccination | 
| Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines. | 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. | One month after third Men B vaccination | 
| Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine. | 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. | 1 month after 3rd vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meningococcal disease,, Neisseria meningitidis serogroup B,, Prevention,, Vaccination,, Infants