Extension Study Evaluating Antibody Persistence and Safety, Tolerability and Immunogenicity of a Booster Dose of Novartis rMenB±OMV NZ Vaccine in Healthy UK Children Who Previously Received Three Doses of the Same Vaccine

Phase 2

Completed

Conditions: Meningococcal Disease

Interventions: Biological: rMenB
Biological: rMenB+OMV NZ

Registration Number: NCT01026974

Lead Sponsor: Novartis Vaccines

Brief Summary: The proposed study V72P9E1 is an Extension Study of V72P9. The objectives of this extension study will be to explore antibody persistence in children at approximately 40 months of age and to evaluate the safety, tolerability and immunogenicity of a booster dose 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 120

Inclusion Criteria

Healthy 40 to 44-months-old children, who participated and completed the study V72P9 (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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4rMenB	rMenB	Subjects received three primary doses of rMenB vaccine (at the age of 6-8 months; 2 months after and at 12 months) in parent study (NCT00433914) and one booster dose of rMenB vaccine at 40 months of age in the present study.
Naive_4042	rMenB+OMV NZ	Vaccine-naive subjects who received two catch -up doses of rMenB+OMV NZ vaccine at 40 and 42 months of age in the present study.
4rMenB+OMV NZ	rMenB+OMV NZ	Subjects received three primary doses of rMenB+OMV NZ vaccine (at the age of 6-8months; 2 months after and at 12 months) in parent study (NCT00433914) and one booster dose of rMenB+OMV NZ vaccine at 40 months of age in the present study.
Naive_6062	rMenB+OMV NZ	Vaccine-naive subjects who received two catch-up doses of rMenB+OMV NZ vaccine at 60 and 62 months of age in the present study.

Primary Outcome Measures

Name	Time	Method
Persistence of Serum Bactericidal Antibody Titers in Children (at 40 Months of Age), Twenty-eight Months After Completing Primary Vaccination.	28 months after primary vaccination; Baseline for Naïve	The geometric mean antibody titers (GMTs) against Neisseria meningitidis serogroup B in children (at 40 months of age); twenty-eight months after completion of primary vaccination with either rMenB or rMenB+OMV NZ vaccines, are compared with the GMTs in vaccine-naïve children.
Percentage of Subjects With Persisting Serum Bactericidal Antibodies Titers ≥4, Twenty-eight Months After Completing Primary Vaccination.	28 months after primary vaccination; Baseline for Naïve	The percentages of subjects with persisting serum bactericidal antibodies (hSBA) titers ≥4, against N meningitidis serogroup B at 40 months of age; twenty-eight months after completion of primary vaccination with either rMenB or rMenB+OMV NZ as compared to the vaccine-naïve children are reported. The serum bactericidal antibodies directed against serogroup B meningococci, are measured by human complement Serum Bactericidal Assay (hSBA).
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After a Booster Dose of rMenB or rMenB+OMV NZ Vaccine at Forty Months of Age.	Day 1 to Day 7 [after booster vaccination /post dose 1 for naive]	The safety and tolerability of a single booster dose of rMenB or rMenB+OMV NZ vaccine in 40 month old children who had previously received three primary doses of the same vaccine as infants in parent study was assessed in terms of number of subjects with solicited local and systemic reactions following vaccination and compared to tolerability in vaccine-naive children who received 1st catch-up dose of rMenB+OMV NZ at 40 months of age.

Secondary Outcome Measures

Name	Time	Method
Serum Bactericidal Antibody Titers in Children After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age	1 month post booster /1 month post dose 1 for Naïve	The serum bactericidal antibody response one month after a booster dose of rMenB or rMenB+OMV NZ vaccine was given to children at 40 months of age is compared with the antibody titers following one catch-up dose rMenB+OMV NZ vaccine given at 40 months to vaccine-naive subjects and reported as GMTs.
Percentage of Subjects With Persisting Serum Bactericidal Antibody Titers ≥4, Twenty Months After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine	20 months post booster/ Baseline for Naïve	The percentage of subjects (60 months of age) with persisting hSBA titers ≥4, twenty months after receiving a booster dose of either rMenB or rMenB+OMV NZ vaccine (at 40 months of age) are compared with hSBA response in vaccine-naïve subjects of the same age.
Persistence of Serum Bactericidal Antibody Titers in Children (at 60 Months), Eighteen Months After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine.	18 months post vaccine dose 2	The serum bactericidal antibody response in children at 60 months of age who had received two catch-up doses of rMenB+OMV NZ vaccine at- 40 \& 42 months age is reported as GMTs.
Geometric Mean Antibody Concentrations in Children, After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age.	1 month post booster /1 month post dose 1 for Naïve	The GMCs against vaccine antigen 287-953, in children one month after receiving a single booster dose of either rMenB or rMen+OMV NZ vaccine , is compared with GMCs following one catch-up dose of rMenB+ OMV NZ in children at 40 months.
Number of Children Reporting Solicited Local and Systemic Adverse Events After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine One Month Apart, Either at 40 or 60 Months of Age	Day 1-7 after each vaccination	The safety and tolerability of a two doses of rMenB+OMV NZ vaccine in children when given either at 40 \& 42 months or 60 \& 62 months of age is assessed in terms of number of subjects with solicited local and systemic reactions following vaccination.
Percentage of Subjects With Serum Bactericidal Antibody Titers ≥4 Following Two Doses of rMenB+OMV NZ Vaccine Given One Month Apart, Either at 40 or 60 Months of Age	1 month post -vaccine dose two	The percentage of subjects with hSBA titers ≥4 after two catch-up doses of rMenB+OMV NZ vaccine when given either at- 40 \& 42 months or 60 \& 62 months of age is reported.
Percentage of Subjects With Serum Bactericidal Antibody Titers ≥4, Eighteen Months After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine.	18 months post vaccine dose two	Persisting hSBA titers ≥4 in children at 60 months of age, who had received two catch-up doses of rMenB+OMV NZ vaccine at 40 \& 42 months age is reported.
Geometric Mean Antibody Concentrations in Children (at 60 Months), Eighteen Months After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine.	18 months post vaccine dose 2	Persistence of GMCs against vaccine antigen 287-953 in children (60 months of age), eighteen months after two catch-up doses of rMenB+OMV NZ vaccine given at 40 months of age.
Percentage of Subjects With Four Fold Increase in Geometric Mean Antibody Concentrations , After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age	1 month post booster / 1 month post dose 1	The percentage of subjects with four fold increase in GMCs over baseline against vaccine antigen 287-953 one month after receiving a single booster dose of either rMenB or rMen+OMV NZ vaccine, is compared with responses following one catch-up dose of rMenB+OMV NZ in children at 40 months.
Percentage of Subjects With Serum Bactericidal Antibody Titers ≥4 After Receiving a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine at 40 Months of Age	1 month post-booster/ 1 month post-dose 1 for Naïve	The percentages of subjects with hSBA titers ≥4 against N meningitidis serogroup B one month after receiving a single booster dose of rMenB or rMenB+OMV NZ vaccine at 40 months of age, is compared with hSBA response following one catch-up dose of rMenB+OMV NZ vaccine given at 40 months in vaccine-naive subjects.
Percentage of Subjects With a 4-fold Increase in Antibody Titers After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age	1 month post booster / 1 month post dose 1 for Naïve	The percentages of subjects with four-fold increase in hSBA titers over baseline against N meningitidis serogroup B, one month after receiving a single booster dose of rMenB or rMenB+OMV NZ vaccine at 40 months of age, and compared with 4-fold increase in hSBA titers following one catch-up dose of rMenB+OMV NZ vaccine given at 40 months to vaccine-naive subjects. Baseline was defined as either the time that the (first) booster dose was given (i.e. at 40 months of age) or the time of the first vaccination (i.e. at 40 months of age for Naive_4042 group.
Persistence of Serum Bactericidal Antibody Titers in Children (at 60 Months of Age), Twenty Months After Receiving a Booster Dose of rMenB or rMenB+OMV NZ Vaccine	20 months post booster/ Baseline for Naïve	The persisting serum bactericidal antibody titers in children (at 60 months of age), twenty months after receiving a booster dose of either rMenB or rMenB+OMV NZ vaccine (at 40 months of age) is compared with the antibody titers in vaccine -naïve subjects of the same age and reported as GMTs.
Serum Bactericidal Antibody Titers in Children Following Two Doses of rMenB+OMV NZ Vaccine Given One Month Apart, Either at 40 or 60 Months of Age.	1 month post vaccine dose two	The serum bactericidal antibody response 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 as GMTs.
Percentage of Subjects With a 4-fold Increase in Antibody Titers After Two Catch up Doses of rMenB+OMV NZ Vaccine Given One Month Apart Either at 40 or 60 Months of Age	1 month post vaccine dose 2	The percentages of subjects with four-fold increase in hSBA titers over baseline against N meningitidis serogroup 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.
Geometric Mean Antibody Concentrations in Children (at 40 Months of Age), Twenty Eight Months After Completing Primary Vaccination.	28 months after primary vaccination/ Baseline for Naïve	The persisting geometric mean antibody concentrations (GMCs) against vaccine antigen 287-953 in children (at 40 months of age), twenty-eight months after completion of primary vaccination with either rMenB or rMen+OMV NZ vaccines, are compared with the GMCs in vaccine-naïve children. GMCs against vaccine antigen 287-953 were measured using enzyme linked immunosorbent assay (ELISA).
Geometric Mean Antibody Concentrations in Children (at 60 Months of Age), Twenty Months After Receiving a Booster Dose of rMenB or rMenB+OMV NZ Vaccine	20 months post booster/ Baseline for Naïve	The persisting GMCs against vaccine antigen 287-953 in children (at 60 months of age), twenty months after receiving a booster dose of either rMenB or rMenB+OMV NZ vaccine (at 40 months), are compared with GMCs in vaccine-naïve children of same age.
Geometric Mean Antibody Concentrations in Children After Two Doses of rMenB+OMV NZ Vaccine Given One Month Apart, Either at 40 Months or 60 Months of Age.	1 month post vaccine dose two	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.
Percentage of Subjects With 4-fold Increase in Geometric Mean Antibody Concentrations, After Two Catch-up Doses of rMenB+OMV NZ Vaccine Given One Month Apart Either at 40 or 60 Months of Age	1 month post dose 2	The percentages of subjects with four-fold increase in GMCs over baseline against vaccine antigen 287-953, 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.