Extension Study of V72P13 to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster or as a Two-dose Catch-up to Healthy Toddlers

Study Overview
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Brief Summary
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The proposed study is an Extension Study of V72P13 to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster at 12 Months of Age or as a Two-dose Catch-up to Healthy Toddlers

Official Title
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A Phase 3, Open Label, Multi-Center, Extension Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster at 12 Months of Age or as a Two-dose Catch-up to Healthy Toddlers Who Participated in Study V72P13

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: 1a - rMenB+OMV NZ and routine vaccines
* Biological: 1b - rMenB+OMV NZ and routine vaccines
* Biological: 2a - Routine and rMenB+OMV NZ vaccines
* Biological: 2b - rMenB+OMV NZ and routine vaccines
* Biological: 3a - rMenB+OMV NZ and routine vaccines
* Biological: 3b - 1 dose of rMenB+OMV NZ plus routine infant vaccinations
* Biological: 4a- rMenB+OMV NZ and routine vaccines
* Biological: 4b - rMenB+OMV NZ and routine vaccines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy 12-month-old toddlers (0/ +29 days) who completed Study V72P13 Exclusion Criteria: Previous ascertained or suspected disease caused by N. meningitidis; History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component; Any serious chronic or progressive disease Known or suspected impairment/ alteration of the immune system, Receipt of, or intent to immunize with another vaccine, within 30 days prior to enrollment.

Ages Eligible for Study
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Minimum Age: 365 Days
Maximum Age: 394 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: 12B12M (1a)<br>Previously in the parent study subjects had received three doses of rMenB+OMV NZ and routine vaccine at 2, 4 and 6 months of age,respectively. These subjects received a booster (fourth) dose at 12 months of age concomitantly with one dose of MMRV vaccine in the present study. | Biological: 1a - rMenB+OMV NZ and routine vaccines<br>* One dose of rMenB vaccine and routine vaccine at study month 12.<br>|
| Experimental: 12B13M (1b)<br>Previously in the parent study subjects had received three doses of rMenB+OMV NZ and routine vaccine at 2, 4 and 6 months of age, respectively. These subjects received a booster (fourth) dose at 12 months and one dose of MMRV vaccine at 13 months of age in the present study. | Biological: 1b - rMenB+OMV NZ and routine vaccines<br>* One dose of rMenB vaccine at study month 12 and routine vaccine at study month 13.<br>|
| Experimental: 12M13B15B (2a)<br>Previously in the present study subjects had received routine vaccine at 2, 4 and 6 months of age respectively. These subjects received MMRV vaccine at 12 months of age and two catch-up doses of rMenB+OMV NZ vaccine at 13 and 15 months of age in the present study. | Biological: 2a - Routine and rMenB+OMV NZ vaccines<br>* One dose of routine vaccine at study month 12 and two doses of rMenB vaccine at study months 13 and 15.<br>|
| Experimental: 12M12B14B (2b)<br>Previously in the parent study subjects ahd received three doses of routine vaccine at 2, 4 and 6 months of age, respectively. These subjects received two catch-up doses of rMenB+OMV NZ at 12 and 14 months of age and one dose of MMRV vaccine given concomitantly at 12 months of age in the present study. | Biological: 2b - rMenB+OMV NZ and routine vaccines<br>* Two doses of rMenB vaccine at study months 12 and 14 and one dose of routine vaccine at study month 12.<br>|
| Experimental: 12B12M (3a)<br>Previously in the parent study subjects had received three doses of rMenB+OMV NZ at 2, 4 and 6 months of age respectively. These subjects had received one booster (fourth) dose of rMenB+OMV NZ at 12 months of age concomitantly with one dose of MMRV vaccine in the present study. | Biological: 3a - rMenB+OMV NZ and routine vaccines<br>* One dose of rMenB vaccine and one dose of routine vaccine at study month 12.<br>|
| Experimental: 12B13M (3b)<br>Previously in the present study subjects had received three doses of rMenB+OMV NZ at 12 months of age respectively. These subjects one booster (fourth) dose of rMenB+OMV NZ at 12 months of age and one dose of MMRV vaccine at 13 months of age in the present study. | Biological: 3b - 1 dose of rMenB+OMV NZ plus routine infant vaccinations<br>* One dose of rMenB vaccine at study month 12 and one dose of routine vaccine study month 13.<br>|
| Experimental: 12B12M_C (4a)<br>Previously in the parent study subjects had received three doses of Meningococcal C vaccine and routine vaccine at 2, 4 and 6 months of age respectively. These subjects had received one single dose of rMenB+OMV NZ at 12 months of age concomitantly with one dose of MMRV vaccine in the present study. | Biological: 4a- rMenB+OMV NZ and routine vaccines<br>* One dose of rMenB vaccine and one dose of routine vaccine at study month 12.<br>|
| Experimental: 12B13M_C (4b)<br>Previously in the parent study subjects had received three doses of Meningococcal C vaccine and routine vaccine at 2, 4 and 6 months of age. These subjects received one single dose o rMenB+OMV NZ at 12 months of age and one dose of MMRV vaccine at 13 months of age in the present study. | Biological: 4b - rMenB+OMV NZ and routine vaccines<br>* One dose of rMenB vaccine and one dose of routine vaccine at study month 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Serum Bactericidal Antibody Titers ≥1:5 After Receiving the Booster Dose of rMenB+OMV NZ Vaccination | Immunogenicity was assessed in terms of the percentage of subjects as measured by serum bactericidal antibody titers ≥1:5 the lower limit of the two-sided 95% confidence interval (CI) was ≥75%, directed against N.meningitidis serogroup B reference strains H44/76-SL , NZ98/254, 5/99, one month after the booster (fourth) dose of meningococcal B vaccine with or without the concomitant Measles, Mumps, Rubella, Varicella (MMRV) vaccine in toddlers who were previously vaccinated with three doses of Meningococcal B vaccine. | one month after the booster (fourth) dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects With Antibody Response After Receiving the MMRV Vaccination | Immunogenicity was assessed to demonstrate non-inferiority in terms of percentages of subjects as measured by antibody responses against MMRV vaccine when given concomitantly with the booster (fourth) dose of rMenB+OMV NZ vaccine at 12 months of age when compared to MMRV vaccine when given alone. The specified cut-off levels for the vaccine antigens : for measles antigen is ≥255mIU/mL, Mumps antigen is ≥10 Enzyme Linked Immunosorbent Assay(ELISA) Antibody(Ab) units, Rubella antigen is ≥10 IU/mL, Varicella antigen is ≥1.25 glycoprotein (gp) ELISA units/ml (seroconversion) and varicella antigen is ≥5 gp ELISA units/ml (seroprotection. | one month after booster (fourth) dose | 
| The Geometric Mean Titers After Receiving the Booster Dose of rMenB+OMV NZ Vaccination | The human serum bactericidal antibody (hSBA) titer responses, one month after receiving booster dose or rMenB+OMV NZ vaccination, are reported as geometric mean titers (GMTs). | one month after booster (fourth) vaccination. | 
| Geometric Mean Titers at 12 Months of Age (Predose 4) After Previously Receiving the Three Doses of rMenB+OMV NZ (Persistence) | The immunogenicity was assessed as the persistence of bactericidal antibodies at 12 months of age (pre-dose 4) who previously received three doses of rMenB+OMV NZ in the parent study as measured by hSBA GMTs directed against N meningitidis serogroup B reference strains H44/76, NZ98/254 and 5/99. | one month after third vaccination and pre dose fourth (booster) vaccination | 
| Percentages of Subjects With Serum Bactericidal Antibody Titers ≥1:5 After Previously Receiving the Three Doses of rMenB+OMV NZ Vaccination (Persistence) | Immunogenicity was assessed to evaluate the persistence in terms of percentages of subjects with hSBA titers ≥ 1:5, previously received three doses of rMenB+OMV NZ directed against N meningitidis serogroup B reference strains H44/76, NZ98/254 and 5/99. | One month post vaccination and pe-booster (fourth) dose vaccination | 
| Geometric Mean Titers After Receiving the Booster Dose and Single Dose of rMen+OMV NZ Vaccination (Induction of Immunological Memory) | The immunogenicity was assessed to demonstrate the induction of immunological memory in subjects who were previously received three doses of rMenB+OMV NZ as measured by SBA GMT response in comparison to the fourth dose of rMenB+OMV NZ at 12 months of age ( 12B12M(1a) group) to the response in subjects (12M12B14B 0 who received a single dose of rMenB+OMV NZ vaccine. | one month after booster (fourth) dose vaccination and pre-fourth dose vaccination | 
| SBA GMTs After a Two-dose Catch-up Schedule or Two-dose Schedule | The immunogenicity of a two-dose catch-up schedule of rMenB+OMV NZ given at 13 and 15 months (12M13B15B) or 12 and 14 months (12M12B14B) to naïve toddlers was assessed by SBA GMTs one month after the second dose. | One month after the second dose. | 
| Percentages of Subjects With SBA Titers ≥1:5 After a Two-dose Catch-up Schedule or Two-dose Schedule | The immunogenicity of a two-dose catch-up schedule of rMenB+OMV NZ given at 13 and 15 months (12M13B15B) or 12 and 14 months (12M12B14B) to naïve toddlers was assessed as percentages of subjects with SBA titers ≥1:5 one month after the second dose. | One month after the second dose. | 
| ELISA Geometric Mean Concentration Against Vaccine Antigen 287-953 One Month After the Fourth (Booster) Dose Given at 12 Months | The immune response against vaccine antigen 287-953 was measured by ELISA, one month after the fourth (booster) dose given at 12 months of age (groups 12B12M (1a), 12B13M (1b). | One month after the fourth (booster) dose. | 
| ELISA Geometric Mean Concentration Against Vaccine Antigen 287-953 After Two-dose Catch-up in Toddlers | The immune response against vaccine antigen 287-953was measured by ELISA one month after the first dose and one month after the second dose of a two-dose catch-up regimens (12M13B15B and 12M12B14B) in toddlers. | One month after the first dose and one month after the second dose. | 
| Percentages of Subjects With Bactericidal Titers ≥ 1:5 (95% CI) Against Strain M10713 One Month After the Fourth (Booster) Dose Given at 12 Months | The immune response was measured as percentages of subjects with SBA ≥ 1:5 (95% CI) against strain M10713, one month after the fourth (booster) dose given at 12 months of age (groups 12B12M (1a), 12B13M (1b). | One month after the fourth (booster) dose. | 
| Number of Subjects Reporting Solicited Local and Systemic Reactions During the 7 Days Following rMenB+OMV NZ Vaccination at 12 Months of Age | Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 through day 7 after rMenB+OMV NZ vaccination administered at 12 months. For the safety analysis purpose, Groups 12B12M (1a) and 12B12M (3a) are combined as Group 12B12M and Groups 12B13M (1b) and 12B13M (3b) are combined as Group 12B13M. | From day 1 to day 7 after each rMenB+OMV NZ vaccination. | 
| Number of Subjects Reporting Solicited Local and Systemic Reactions During the 7 Days Following Two-dose Catch-up Schedules of rMenB+OMV NZ Vaccination | Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 through day 7 after rMenB+OMV NZ vaccination administered with a two-dose catch-up schedules (groups 12M13B15B and 12M12B14B). | From day 1 to day 7 after each rMenB+MV NZ vaccination. | 
| Number of Subjects Reporting Solicited Local Reactions During the 7 Days Following MMRV Vaccination at 12 Months of Age | Safety was assessed as the number of subjects who reported solicited local reactions from day 1 through day 7 after the MMRV vaccination concomitantly with rMenB+OMV NZ at 12 months of age (groups 12B12M, 12M12B14B, 12B12M_C) or after MMRV vaccination alone without rMenB+OMV NZ at 12 months (Group 12M13B15B). For the safety analysis purpose, Groups 12B12M (1a) and 12B12M (3a) are combined as Group 12B12M. | From day 1 to day 7 after MMRV vaccination. | 
| Number of Subjects Reporting Solicited Systemic Reactions During 8-28 Days Following MMRV Vaccination at 12 Months of Age | Safety was assessed as the number of subjects who reported solicited systemic reactions from day 8 through day 28 after the MMRV vaccination concomitantly with rMenB+OMV NZ at 12 months of age (groups 12B12M, 12M12B14B, 12B12M_C) or after MMRV vaccination alone without rMenB+OMV NZ at 12 months (Group 12M13B15B). For the safety analysis purpose, Groups 12B12M (1a) and 12B12M (3a) are combined as Group 12B12M. | From day 8 to day 28 after MMRV vaccination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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toddler, Meningococcal disease, prevention, vaccination