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 Overview
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Brief Summary
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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.

Official Title
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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±OMV NZ Vaccine in Healthy UK Children Who Previously Received One or Four Doses of the Novartis Vaccine as Infants in Study V72P6

Conditions
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Meningococcal Disease

Intervention / Treatment
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* Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine.
* Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine, without Outer Membrane Vesicles (OMV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy 40 to 44-months-old children, who participated and completed the study V72P6 (NCT00381615; follow-on subjects) Healthy 40 to 44-months or 60 to 62-months-old children (naïve subjects) 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 and after vaccination with the investigational vaccines (within 14 days for licensed flu vaccines)

Ages Eligible for Study
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Minimum Age: 40 Months
Maximum Age: 62 Months

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5rMenB<br>Subjects who had received four doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, without Outer Membrane Vesicles (OMV) (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of the same vaccine, at 40 months of age in the present study. | Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine, without Outer Membrane Vesicles (OMV)<br>* Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB).<br>|
| Experimental: 5rMenB+OMV NZ<br>Subjects who had received four doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of the same vaccine, at 40 months of age in the present study. | Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine.<br>* Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB+OMV NZ) or two catch-up doses.<br>|
| Experimental: 3rMenB<br>Subjects who had previously received one dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine without OMV (at 12 months of age) were administered two doses of the same vaccine, at 40 and 42 months of age in the present study. | Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine, without Outer Membrane Vesicles (OMV)<br>* Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB).<br>|
| Experimental: 3rMenB+OMV NZ<br>Subjects who had previously received one dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine (at 12 months of age) were administered two doses of the same vaccine, at 40 and 42 months of age in the present study. | Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine.<br>* Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB+OMV NZ) or two catch-up doses.<br>|
| Experimental: Naive_4042<br>Vaccine-naive subjects who received two catch-up doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 40 and 42 months of age in the present study. | Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine.<br>* Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB+OMV NZ) or two catch-up doses.<br>|
| Experimental: Naive_6062<br>Vaccine-naive subjects who received two catch-up doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 60 and 62 months of age in the present study. | Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine.<br>* Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB+OMV NZ) or two catch-up doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received 4 Doses of Men B Vaccine), at 40 Months of Age. | 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. | 28 months after last vaccination; Baseline for Naïve | 
| 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. | 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). | 28 months after last vaccination; baseline for naïve | 
| 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. | 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 same vaccine as infants in parent study is assessed in terms of number of subjects with solicited local and systemic reactions following vaccination. | Day 1-7 after booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received One Dose of Men B Vaccine), at 40 Months of Age. | 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. | 28 months after vaccination; Baseline for Naïve | 
| 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. | 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. | 28 months after vaccination; baseline for naïve | 
| 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. | 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. | 1 month post- booster/ dose 1 for Naïve | 
| 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. | 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 . | 1 month post- booster/ dose 1 for Naïve | 
| 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. | 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. | 1 month post - booster/ -dose 1 for Naïve | 
| 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. | 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. | 1 month post vaccination | 
| 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. | 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. | 1 month post vaccination | 
| 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. | 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. | 1 month post vaccination | 
| 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. | 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. | 1 month post -vaccine dose two | 
| Geometric Mean Antibody Titers in Children After Two Catch up Doses of rMenB+OMV NZ Vaccine Given, Either at 40 or 60 Months of Age. | The geometric mean antibody titers in children 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. | 1 month post vaccine dose two | 
| Percentage of Subjects With a 4-fold Increase in Antibody Titers After Receiving Two Catch up Doses of rMenB+OMV NZ Vaccine, Either at 40 or 60 Months of Age. | The percentages of subjects with four-fold increase in hSBA titers over baseline against N.meningitidis B one month after receiving a two catch-up doses of rMenB+OMV NZ vaccine either at 40 & 42 months or 60 & 62 months of age. | 1 month post vaccine dose 2 | 
| Persisting Geometric Mean Antibody Titers Against N.Meningitidis B in Children at 60 Months of Age. | The persisting GMTs against N.meningitidis B strains in children at 60 months of age who had received one or two booster doses of either rMenB or rMenB+ OMV NZ vaccine or had received two catch-up doses of rMenB+ OMV NZ vaccine at 40 months of age in the present study are compared with GMTs in vaccine-naïve subjects. | 18-20 months after last Men B vaccine; baseline for naïve_6062 | 
| Percentage of Subjects With Persisting Serum Bactericidal Antibodies ≥1:4 and ≥1:8 in Children at 60 Months of Age. | The percentage of subjects with persisting hSBA titers ≥1:4 and ≥1:8 at 60 months of age against N.meningitidis B strains after having received one or two booster doses of either rMenB or rMenB+ OMV NZ vaccine or had received two catch-up doses of rMenB+ OMV NZ vaccine at 40 months of age in the present are reported. | 18-20 months after last Men B vaccine; baseline for naïve_6062 | 
| Persisting Geometric Mean Antibody Concentrations Against Vaccine Antigen 287-953 in Children (Who Had Previously Received 4 Doses of MenB Vaccine in Parent Study) at 40 Months of Age. | The persisting geometric mean antibody concentrations (GMCs) against vaccine antigen 287-953 in children (at 40 months of age) who had previously received 4 doses of either rMenB or rMen+OMV NZ vaccines in parent study , are compared with the the GMCs in vaccine-naïve children. GMCs against vaccine antigen 287-953 were measured using enzyme linked immunosorbent assay (ELISA). | 28 months after last Men B vaccination; Baseline for Naïve_4042 group | 
| Persisting Geometric Mean Antibody Concentrations Against Vaccine Antigen 287-953 in Children (Who Had Previously Received 1dose of MenB Vaccine in Parent Study) at 40 Months of Age. | The persisting GMCs against vaccine antigen 287-953 in children (at 40 months of age) who had previously received 1 dose of either rMenB or rMen+OMV NZ vaccines in parent study , are compared with the the GMCs in vaccine-naïve children. GMCs against vaccine antigen 287-953 were measure using ELISA. | 28 months after last Men B vaccination; baseline for naïve_4042 group | 
| Geometric Mean Antibody Concentrations Against Vaccine Antigen 287-953 in Children (Who Had Previously Received 4 Doses of MenB Vaccine) After Receiving One Booster Dose of Either rMenB or rMenB+OMV NZ at 40 Months of Age. | The GMCs against vaccine antigen 287-953 in children (who had previously received four doses MenB vaccine in parent study) after a single booster dose of either rMenB or rMenB+OMV NZ vaccine given at 40 months of age, are compared with the GMCs following one catch-up dose rMenB+OMV NZ vaccine given at 40 months to vaccine-naive subjects. | 1 month post booster; 1 month post dose for naïve_4042 group | 
| Geometric Mean Antibody Concentrations Against Vaccine Antigen 287-953 in Children After Receiving Two Booster Doses of Either rMenB or rMenB+OMV NZ at 40 & 42 Months of Age. | The GMCs against vaccine antigen 287-953 in children (who had previously received 1 dose of either rMenB or rMen+OMV NZ vaccines in parent study) , are compared with the GMCs in children who received to catch-up doses of rMenB+OMV NZ at 40 & 42 months . | 1 month after each booster/ vaccine dose | 
| Geometric Mean Concentrations Against Vaccine Antigen 287-953 in Children After Two Catch up Doses of rMenB+OMV NZ Vaccine Given Either at 40 or 60 Months of Age. | The GMCs against vaccine antigen 287-953 in children 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. | 1 month post vaccine dose two | 
| Persisting Geometric Mean Concentrations Against Vaccine Antigen 287-953 in Children at 60 Months of Age. | The persisting GMCs against vaccine antigen 287-953 in children at 60 months of age who had either received one or two booster doses of either rMenB or rMenB+OMV NZ vaccine or had received two catch-up doses of rMenB+OMV NZ vaccine at 40 months of age in the present are compared with GMCs in vaccine-naïve subjects. | 18-20 months after last Men B vaccine; baseline for naïve_6062 | 
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events After a Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine Either at 40 Months or 60 Months of Age. | The safety and tolerability of two catch-up doses of rMenB+OMV NZ vaccine when administered either at 40 & 42 months or 60 & 62 months of age in children is assessed in terms of number of subjects with solicited local and systemic reactions following vaccination. | Day 1-7 after any vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Pre-school, Meningococcal disease, Prevention, Vaccination