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

• Sponsor: Novartis Vaccines (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01027351
• Collaborator: (none)
• Enrollment: 163
• Location: 1
• Arms: 6
• Duration (Months): 28
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Meningococcal Disease	Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine.; Biological: Meningococcal (group B) multicomponent recombinant adsorbed vaccine, without Outer Membrane Vesicles (OMV)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 163 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5rMenB 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); Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB).
Experimental: 5rMenB+OMV NZ 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.; 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.
Experimental: 3rMenB 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); Subjects received either one or two booster doses of the same vaccine they had received in the parent trial (rMenB).
Experimental: 3rMenB+OMV NZ 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.; 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.
Experimental: Naive_4042 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.; 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.
Experimental: Naive_6062 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.; 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.

Outcome Measures

Primary Outcome Measures

1. Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received 4 Doses of Men B Vaccine), at 40 Months of Age. [28 months after last vaccination; Baseline for Naïve]

   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.

2. 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. [28 months after last vaccination; baseline for naïve]

   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).

3. 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. [Day 1-7 after booster vaccination]

   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.

Secondary Outcome Measures

1. Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received One Dose of Men B Vaccine), at 40 Months of Age. [28 months after vaccination; Baseline for Naïve]

   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.

2. 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. [28 months after vaccination; baseline for naïve]

   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.

3. 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. [1 month post- booster/ dose 1 for Naïve]

   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.

4. 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. [1 month post- booster/ dose 1 for Naïve]

   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 .

5. 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. [1 month post - booster/ -dose 1 for Naïve]

   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.

6. 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. [1 month post vaccination]

   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.

7. 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. [1 month post vaccination]

   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.

8. 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. [1 month post vaccination]

   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.

9. 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. [1 month post -vaccine dose two]

   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.

10. 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. [1 month post vaccine dose two]

    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.

11. 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. [1 month post vaccine dose 2]

    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.

12. Persisting Geometric Mean Antibody Titers Against N.Meningitidis B in Children at 60 Months of Age. [18-20 months after last Men B vaccine; baseline for naïve_6062]

    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.

13. Percentage of Subjects With Persisting Serum Bactericidal Antibodies ≥1:4 and ≥1:8 in Children at 60 Months of Age. [18-20 months after last Men B vaccine; baseline for naïve_6062]

    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.

14. 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. [28 months after last Men B vaccination; Baseline for Naïve_4042 group]

    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).

15. 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. [28 months after last Men B vaccination; baseline for naïve_4042 group]

    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.

16. 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. [1 month post booster; 1 month post dose for naïve_4042 group]

    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.

17. 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. [1 month after each booster/ vaccine dose]

    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 .

18. 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. [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.

19. Persisting Geometric Mean Concentrations Against Vaccine Antigen 287-953 in Children at 60 Months of Age. [18-20 months after last Men B vaccine; baseline for naïve_6062]

    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.

20. 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. [Day 1-7 after any vaccination]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Months to 62 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Novartis Vaccines

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT01027351
• Other Study ID Numbers: V72P6E1; EUDRACT 2009-013054-33
• First Posted: Dec 7, 2009
• Last Update Posted: Oct 9, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Novartis Vaccines: Children; Pre-school; Meningococcal disease; Prevention; Vaccination
• Additional relevant MeSH terms: Meningococcal Infections; Vaccines

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled from 1 center in the United Kingdom.
Pre-assignment Detail	All subjects were included in the trial.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.	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
Period Title: Overall Study
STARTED	29	19	14	8	43	50
COMPLETED	26	18	13	6	32	45
NOT COMPLETED	3	1	1	2	11	5

Baseline Characteristics

Arm/Group Title	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062	Total
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.	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	Total of all reporting groups
Overall Participants	29	19	14	8	43	50	163
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	41.4 (1.5)	41.8 (1.4)	41.4 (1.5)	40.4 (0.7)	41.8 (1.7)	61.3 (0.9)	47.6 (9.2)
Sex: Female, Male (Count of Participants)
Female	17 58.6%	9 47.4%	5 35.7%	3 37.5%	23 53.5%	27 54%	84 51.5%
Male	12 41.4%	10 52.6%	9 64.3%	5 62.5%	20 46.5%	23 46%	79 48.5%
Region of Enrollment (Subjects) [Number]
United Kingdom	29	19	14	8	43	50	163

Outcome Measures

1. Primary Outcome

Title	Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received 4 Doses of Men B Vaccine), at 40 Months of Age.
Description	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.
Time Frame	28 months after last vaccination; Baseline for Naïve

Outcome Measure Data

Analysis Population Description

The analysis was done on the Modified- Intended to treat (MITT), 40 months of age, antibody persistence population.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	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.
Measure Participants	29	17	40
H 44/76 strain	3.24	5.34	4.25
5/99 strain (N=28, 17, 40)	5.11	28	1.11
NZ 98/254 strain	1.09	2.77	1
M10713 strain (N=28, 15, 40)	9.15	5.34	8.75

2. Primary Outcome

Title	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.
Description	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).
Time Frame	28 months after last vaccination; baseline for naïve

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT , 40 months of age, antibody persistence population.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	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.
Measure Participants	29	17	40
hSBA ≥1:4 (H44/76 strain)	45	65	63
hSBA≥1:4 (5/99 strain; N=28, 17, 40)	43	76	3
hSBA≥1:4 (NZ 98/254 strain)	3	41	0
hSBA≥1:4 (M10713 strain; N=28, 15, 40)	68	67	68
hSBA ≥1:8 (H44/76 strain)	14	35	30
hSBA≥1:8 (5/99 strain; N=28, 17, 40)	43	76	3
hSBA≥1:8 (NZ 98/254 strain)	0	24	0
hSBA≥1:8 (M10713 strain; N=28, 15, 40)	61	40	45

3. Primary Outcome

Title	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.
Description	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.
Time Frame	Day 1-7 after booster vaccination

Outcome Measure Data

Analysis Population Description

Analysis was done on the safety population i.e all subjects who received at least one Men B vaccination and provided post-baseline safety data.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.
Measure Participants	29	19	14	8
Local	28 96.6%	19 100%	14 100%	8 100%
Injection-site pain	17 58.6%	14 73.7%	8 57.1%	8 100%
Injection-site erythema	28 96.6%	19 100%	14 100%	8 100%
Injection-site swelling	13 44.8%	5 26.3%	9 64.3%	4 50%
Injection-site induration	14 48.3%	9 47.4%	8 57.1%	6 75%
Systemic	19 65.5%	13 68.4%	11 78.6%	8 100%
Changes in eating habits	5 17.2%	10 52.6%	5 35.7%	4 50%
Sleepiness	13 44.8%	12 63.2%	8 57.1%	6 75%
Vomiting	1 3.4%	3 15.8%	3 21.4%	0 0%
Diarrhea	3 10.3%	1 5.3%	3 21.4%	1 12.5%
Irritability	14 48.3%	10 52.6%	9 64.3%	8 100%
Headache	1 3.4%	0 0%	2 14.3%	1 12.5%
Arthralgia	0 0%	6 31.6%	4 28.6%	4 50%
Rash	3 10.3%	0 0%	2 14.3%	1 12.5%
Fever (≥38°C)	1 3.4%	1 5.3%	4 28.6%	0 0%
Other	10 34.5%	12 63.2%	5 35.7%	7 87.5%
Antipyretic preventive medication used	10 34.5%	12 63.2%	3 21.4%	7 87.5%
Antipyretic treatment medication used	1 3.4%	2 10.5%	4 28.6%	0 0%
Medically attended fever	0 0%	0 0%	1 7.1%	0 0%

4. Secondary Outcome

Title	Persistence of Geometric Mean Antibody Titers in Children (Who Previously Received One Dose of Men B Vaccine), at 40 Months of Age.
Description	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.
Time Frame	28 months after vaccination; Baseline for Naïve

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 40 months of age, antibody persistence population.

Arm/Group Title	3rMenB	3rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) in the parent study, were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) in the parent study, were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.
Measure Participants	14	8	40
H44/76 strain	3.59	3.47	4.25
5/99 strain	9.57	1	1.11
NZ 98/254 strain	1.23	1	1
M10713 strain (N=13, 8, 40)	3.26	3	8.75

5. Secondary Outcome

Title	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.
Description	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.
Time Frame	28 months after vaccination; baseline for naïve

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 40 months of age, antibody persistence population.

Arm/Group Title	3rMenB	3rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.
Measure Participants	14	8	40
hSBA ≥1:4 (H44/76 strain)	57	38	63
hSBA≥1:4 (5/99 strain)	57	0	3
hSBA≥1:4 (NZ 98/254 strain)	7	0	0
hSBA≥1:4 (M10713 strain; N=13, 8, 40)	54	25	68
hSBA ≥1:8 (H44/76 strain)	7	13	30
hSBA≥1:8 (5/99 strain)	43	0	3
hSBA≥1:8 (NZ 98/254 strain)	0	0	0
hSBA≥1:8 (M10713 strain; N=13, 8, 40)	15	13	45

6. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post- booster/ dose 1 for Naïve

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, booster response.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	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.
Measure Participants	29	19	38
H44/76 strain	99	89	12
5/99 strain (N=28, 18, 38)	778	1708	22
NZ 98/254 strain	1.64	47	7.73
M10713 strain (N=28, 18, 38)	38	39	11

7. Secondary Outcome

Title	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.
Description	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 .
Time Frame	1 month post- booster/ dose 1 for Naïve

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, booster response.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	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.
Measure Participants	28	19	38
hSBA ≥1:4 (H44/76 strain)	100	100	89
hSBA≥1:4 (5/99 strain; N=28, 18, 38)	100	100	76
hSBA≥1:4 (NZ 98/254 strain)	14	89	66
hSBA≥1:4 (M10713 strain; N=28, 18, 38)	96	94	76
hSBA ≥1:8 ( H44/76 strain)	96	100	63
hSBA≥1:8 (5/99 strain; N=28, 18, 38)	100	100	71
hSBA≥1:8 (NZ 98/254 strain)	11	89	58
hSBA≥1:8 (M10713 strain; N=28, 18, 38)	89	94	61

8. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post - booster/ -dose 1 for Naïve

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, booster response.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	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.
Measure Participants	28	17	37
H44/76 strain	89	94	41
5/99 strain (N=27, 16, 37)	100	94	68
NZ 98/254 strain	11	82	57
M10713 strain (N=27, 15, 37)	41	67	14

9. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post vaccination

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, booster response.

Arm/Group Title	3rMenB	3rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.
Measure Participants	13	8	38
H44/76 strain (dose 1; N=13, 7, 38)	94	76	12
H44/76 strain (dose 2; N=13, 8, 36)	127	145	88
5/99 strain (dose 1; N=13, 7, 38)	2379	509	22
5/99 strain (dose 2; N=13, 8, 36)	5240	2413	1019
NZ 98/254 strain (dose 1; N=13, 7, 38)	1.73	148	7.73
NZ 98/254 strain (dose 2; N=13, 8, 36)	1.86	65	47
M10713 strain (dose 1; N=13, 7, 38)	35	30	11
M10713 strain (dose 2; N=12, 8, 36)	21	36	33

10. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post vaccination

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, booster response.

Arm/Group Title	3rMenB	3rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.
Measure Participants	13	8	38
H44/76 strain (≥1:4 - dose 1; N=13, 7, 38)	100	100	89
H44/76 strain (≥1:4 - dose 2; N=13, 8, 36)	100	100	100
H44/76 strain (≥1:8 - dose 1; N=13, 7, 38)	100	100	63
H44/76 strain (≥1:8 - dose 2; N=13, 8, 36)	100	100	100
5/99 strain (≥1:4 - dose 1; N=13, 7, 38)	100	100	76
5/99 strain (≥1:4 - dose 2; N=13, 8, 36)	100	100	100
5/99 strain (≥1:8 - dose 1; N=13, 7, 38)	100	100	71
5/99 strain (≥1:8 - dose 2; N=13, 8, 36)	100	100	100
NZ 98/254 strain (≥1:4 - dose 1; N=13, 7, 38)	15	100	66
NZ 98/254 strain (≥1:4 - dose 2; N=13, 8, 36)	15	100	94
NZ 98/254 strain (≥1:8 - dose 1; N=13, 7, 38)	15	100	58
NZ 98/254 strain (≥1:8 - dose 2; N=13, 8, 36)	15	100	94
M10713 strain (≥1:4 - dose 1; N=13, 7, 38)	100	86	76
M10713 strain (≥1:4 - dose 2; N=12, 8, 36)	83	100	89
M10713 strain (≥1:8 - dose 1; N=13, 7, 38)	85	86	61
M10713 strain (≥1:8 - dose 2; N=12, 8, 36)	75	100	86

11. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post vaccination

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, booster response.

Arm/Group Title	3rMenB	3rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.
Measure Participants	13	8	37
H44/76 strain (dose 1; N=13, 7, 37)	100	86	41
5/99 strain (dose 1; N=13, 7, 37)	100	100	68
NZ 98/254 strain (dose 1; N=13, 7, 37)	15	100	57
M10713 strain (dose 1; N=12, 7, 37)	58	57	14
H44/76 strain (dose 2; N=13, 8, 34)	100	88	97
5/99 strain (dose 2; N=13, 8, 34)	100	100	100
NZ 98/254 strain (dose 2; N=13, 8, 34)	15	100	94
M10713 strain (dose 2; N=11, 8, 34)	64	75	53

12. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post -vaccine dose two

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, 2-dose catch-up regimen.

Arm/Group Title	Naive_4042	Naive_6062
Arm/Group Description	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.	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
Measure Participants	36	42
hSBA ≥1:4 ( H44/76 strain)	100	93
hSBA ≥1:8 (H44/76 strain)	100	93
hSBA ≥1:4 (5/99 strain)	100	100
hSBA ≥1:8 (5/99 strain)	100	100
hSBA ≥1:4 (NZ 98/254 strain)	94	100
hSBA ≥1:8 (NZ 98/254 strain)	94	90
hSBA ≥1:4 (M10713 strain; N=36, 41)	89	100
hSBA ≥1:8 (M10713 strain; N=36, 41)	86	98

13. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post vaccine dose two

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, 2-dose catch-up regimen.

Arm/Group Title	Naive_4042	Naive_6062
Arm/Group Description	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.	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
Measure Participants	36	42
H44/76 strain	88	34
5/99 strain	1019	865
NZ 98/254 strain	47	29
M10713 strain (N=36, 41)	33	43

14. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post vaccine dose 2

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, 2-dose catch-up regimen.

Arm/Group Title	Naive_4042	Naive_6062
Arm/Group Description	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.	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
Measure Participants	34	38
H44/76 strain	97	71
5/99 strain	100	100
NZ 98/254 strain	94	89
M10713 strain	53	21

15. Secondary Outcome

Title	Persisting Geometric Mean Antibody Titers Against N.Meningitidis B in Children at 60 Months of Age.
Description	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.
Time Frame	18-20 months after last Men B vaccine; baseline for naïve_6062

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 60 months of age, antibody persistence population.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.	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
Measure Participants	24	16	13	5	29	46
H44/76 strain (N=24, 16, 13, 5, 28, 46)	3.13	4.68	18	13	12	2.98
5/99 strain (N=23, 16, 13, 5, 28, 46)	43	136	369	210	44	1.14
NZ 98/254 strain	1.05	4.95	1	11	2.42	1.04
M10713 strain (N=22, 16, 12, 5, 27, 46)	12	10	12	25	8.52	18

16. Secondary Outcome

Title	Percentage of Subjects With Persisting Serum Bactericidal Antibodies ≥1:4 and ≥1:8 in Children at 60 Months of Age.
Description	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.
Time Frame	18-20 months after last Men B vaccine; baseline for naïve_6062

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 60 months of age, antibody persistence population.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.	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
Measure Participants	24	16	13	5	29	46
hSBA ≥1:4 (H44/76 strain; N=24, 16, 13, 5, 28, 46)	46	44	85	80	71	33
hSBA ≥1:4 (5/99 strain; N=23, 16, 13, 5, 28, 46)	83	88	100	100	100	2
hSBA ≥1:4 (NZ 98/254 strain)	0	69	0	80	31	2
hSBA ≥1:4 (M10713 strain; N=22, 16, 12, 5, 27, 46)	77	88	92	100	81	83
hSBA ≥1:8 (H44/76 strain; N=24, 16, 13, 5, 28, 46)	25	31	77	60	61	26
hSBA ≥1:8 (5/99 strain; N=23, 16, 13, 5, 28, 46)	74	88	100	100	93	2
hSBA ≥1:8 (NZ 98/254 strain)	0	31	0	40	21	0
hSBA ≥1:8 (M10713 strain; N=22, 16, 12, 5, 27, 46)	59	63	67	80	48	70

17. Secondary Outcome

Title	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.
Description	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).
Time Frame	28 months after last Men B vaccination; Baseline for Naïve_4042 group

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 40 months of age, antibody persistence population.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	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.
Measure Participants	28	17	38
Geometric Mean (95% Confidence Interval) [AU/mL]	82	62	23

18. Secondary Outcome

Title	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.
Description	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.
Time Frame	28 months after last Men B vaccination; baseline for naïve_4042 group

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 40 months of age, antibody persistence population.

Arm/Group Title	3rMenB	3rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.
Measure Participants	14	8	40
Geometric Mean (95% Confidence Interval) [AU/mL]	32	28	23

19. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post booster; 1 month post dose for naïve_4042 group

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 40 months of age, antibody persistence population.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	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.
Measure Participants	28	19	38
Geometric Mean (95% Confidence Interval) [AU/mL]	5592	3934	64

20. Secondary Outcome

Title	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.
Description	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 .
Time Frame	1 month after each booster/ vaccine dose

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, booster response.

Arm/Group Title	3rMenB	3rMenB+OMV NZ	Naive_4042
Arm/Group Description	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.
Measure Participants	13	8	38
after 1st booster/vaccine dose (N=13, N=7, N=38)	2100	1764	64
after 2nd booster/vaccine dose (N=13, N=8, N=36)	3790	3660	3464

21. Secondary Outcome

Title	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.
Description	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.
Time Frame	1 month post vaccine dose two

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT population, Booster response.

Arm/Group Title	Naive_4042	Naive_6062
Arm/Group Description	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.	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
Measure Participants	36	42
Geometric Mean (95% Confidence Interval) [AU/mL]	3464	1744

22. Secondary Outcome

Title	Persisting Geometric Mean Concentrations Against Vaccine Antigen 287-953 in Children at 60 Months of Age.
Description	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.
Time Frame	18-20 months after last Men B vaccine; baseline for naïve_6062

Outcome Measure Data

Analysis Population Description

The analysis was done on the MITT, 60 months of age, antibody persistence population population.

Arm/Group Title	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.	Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.	Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.	Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.	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.	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
Measure Participants	24	16	13	5	28	47
Geometric Mean (95% Confidence Interval) [AU/mL]	670	320	280	250	121	25

23. Secondary Outcome

Title	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.
Description	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.
Time Frame	Day 1-7 after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was done on the MITT - Two Dose Catch Up Schedule population.

Arm/Group Title	Naive_4042	Naive_6062
Arm/Group Description	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.	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
Measure Participants	42	50
Local	42	49
Injection-site pain	41	46
Injection-site erythema	42	48
Injection-site induration	23	29
Injection-site swelling	31	27
Systemic	38	42
Changes in eating habits	21	23
Sleepiness	25	23
Vomiting	1	8
Diarrhea	7	7
Irritability	35	31
Headache	8	8
Arthralgia	16	16
Rash	2	4
Fever (≥38°C)	7	6
Other	31	33
Antipyretic preventive medication used	30	33
Antipyretic treatment medication used	7	7
Medically attended fever	0	1

Adverse Events

Time Frame	Day 1-7 after each vaccination for Solicited AEs; Unsolicited AEs were collected throughout the study period.
Adverse Event Reporting Description	The analyses for the data in this section are from the safety set. Non serious AEs are reported based on MedDRA version 17.0.
Arm/Group Title	5rMenB		5rMenB+OMV NZ		3rMenB		3rMenB+OMV NZ		Naive_4042		Naive_6062
Arm/Group Description	Subjects who had received four doses of rMenB vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB vaccine, at 40 months of age in the present study.		Subjects who had received four doses of rMenB +OMV NZ vaccine (at 2,4,6 and 12 months of age) in the parent study were administered a fifth dose of rMenB +OMV NZ vaccine, at 40 months of age in the present study.		Subjects who had previously received one dose of rMenB vaccine (at 12 months of age) were administered two doses of rMenB vaccine, at 40 and 42 months of age in the present study.		Subjects who had previously received one dose of rMenB +OMV NZ vaccine (at 12 months of age) were administered two doses of rMenB +OMV NZ vaccine, at 40 and 42 months of age in the present study.		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.		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
All Cause Mortality
	5rMenB		5rMenB+OMV NZ		3rMenB		3rMenB+OMV NZ		Naive_4042		Naive_6062
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Serious Adverse Events
	5rMenB		5rMenB+OMV NZ		3rMenB		3rMenB+OMV NZ		Naive_4042		Naive_6062
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		1/19 (5.3%)		0/14 (0%)		1/8 (12.5%)		2/42 (4.8%)		2/50 (4%)
Blood and lymphatic system disorders
lymphadenitis	0/29 (0%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		0/50 (0%)
Congenital, familial and genetic disorders
cystic lymphangioma	0/29 (0%)		0/19 (0%)		0/14 (0%)		1/8 (12.5%)		0/42 (0%)		0/50 (0%)
Gastrointestinal disorders
abdominal pain	0/29 (0%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		0/50 (0%)
Infections and infestations
bronchopneumonia	0/29 (0%)		1/19 (5.3%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
oral herpes	0/29 (0%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		1/50 (2%)
urinary tract infection	0/29 (0%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
haemangioma	1/29 (3.4%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Nervous system disorders
migraine	0/29 (0%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		0/50 (0%)
Respiratory, thoracic and mediastinal disorders
asthma	0/29 (0%)		0/19 (0%)		0/14 (0%)		1/8 (12.5%)		0/42 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	5rMenB		5rMenB+OMV NZ		3rMenB		3rMenB+OMV NZ		Naive_4042		Naive_6062
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/29 (100%)		19/19 (100%)		14/14 (100%)		8/8 (100%)		42/42 (100%)		50/50 (100%)
Blood and lymphatic system disorders
Lymphadenitis	0/29 (0%)		1/19 (5.3%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Ear and labyrinth disorders
Ear pain	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		1/50 (2%)
Gastrointestinal disorders
Abdominal pain upper	1/29 (3.4%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		1/50 (2%)
Constipation	2/29 (6.9%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Diarrhoea	3/29 (10.3%)		1/19 (5.3%)		3/14 (21.4%)		1/8 (12.5%)		8/42 (19%)		7/50 (14%)
Faeces discoloured	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Vomiting	1/29 (3.4%)		3/19 (15.8%)		3/14 (21.4%)		0/8 (0%)		1/42 (2.4%)		8/50 (16%)
General disorders
Hyperpyrexia	1/29 (3.4%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Injection site erythema	28/29 (96.6%)		19/19 (100%)		14/14 (100%)		8/8 (100%)		42/42 (100%)		48/50 (96%)
Injection site induration	14/29 (48.3%)		9/19 (47.4%)		8/14 (57.1%)		6/8 (75%)		23/42 (54.8%)		29/50 (58%)
Injection site pain	17/29 (58.6%)		14/19 (73.7%)		8/14 (57.1%)		8/8 (100%)		41/42 (97.6%)		46/50 (92%)
Injection site swelling	13/29 (44.8%)		5/19 (26.3%)		9/14 (64.3%)		4/8 (50%)		31/42 (73.8%)		27/50 (54%)
Irritability	14/29 (48.3%)		10/19 (52.6%)		9/14 (64.3%)		8/8 (100%)		35/42 (83.3%)		31/50 (62%)
Local swelling	0/29 (0%)		0/19 (0%)		0/14 (0%)		1/8 (12.5%)		0/42 (0%)		0/50 (0%)
Pain	0/29 (0%)		0/19 (0%)		0/14 (0%)		1/8 (12.5%)		0/42 (0%)		0/50 (0%)
Pyrexia	1/29 (3.4%)		1/19 (5.3%)		7/14 (50%)		0/8 (0%)		7/42 (16.7%)		6/50 (12%)
Infections and infestations
Ear infection	2/29 (6.9%)		1/19 (5.3%)		2/14 (14.3%)		1/8 (12.5%)		4/42 (9.5%)		1/50 (2%)
Eczema infected	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Fungal skin infection	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Impetigo	1/29 (3.4%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		1/42 (2.4%)		1/50 (2%)
Localised infection	1/29 (3.4%)		0/19 (0%)		0/14 (0%)		1/8 (12.5%)		0/42 (0%)		0/50 (0%)
Lower respiratory tract infection	3/29 (10.3%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		1/50 (2%)
Nasopharingitis	0/29 (0%)		1/19 (5.3%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		0/50 (0%)
Otitis media	0/29 (0%)		1/19 (5.3%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Rhinitis	0/29 (0%)		0/19 (0%)		2/14 (14.3%)		0/8 (0%)		4/42 (9.5%)		1/50 (2%)
Skin infection	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Tonsillitis	2/29 (6.9%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		2/50 (4%)
Urinary tract infection	0/29 (0%)		1/19 (5.3%)		0/14 (0%)		0/8 (0%)		2/42 (4.8%)		0/50 (0%)
Varicella	0/29 (0%)		1/19 (5.3%)		1/14 (7.1%)		0/8 (0%)		1/42 (2.4%)		0/50 (0%)
Injury, poisoning and procedural complications
Fall	0/29 (0%)		1/19 (5.3%)		0/14 (0%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Heat stroke	0/29 (0%)		0/19 (0%)		0/14 (0%)		1/8 (12.5%)		0/42 (0%)		0/50 (0%)
Overdose	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/29 (0%)		6/19 (31.6%)		4/14 (28.6%)		4/8 (50%)		16/42 (38.1%)		16/50 (32%)
Nervous system disorders
Headache	1/29 (3.4%)		0/19 (0%)		2/14 (14.3%)		1/8 (12.5%)		8/42 (19%)		8/50 (16%)
Lethargy	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Somnolence	13/29 (44.8%)		12/19 (63.2%)		8/14 (57.1%)		6/8 (75%)		25/42 (59.5%)		23/50 (46%)
Psychiatric disorders
Eating disorders	5/29 (17.2%)		10/19 (52.6%)		5/14 (35.7%)		4/8 (50%)		21/42 (50%)		23/50 (46%)
Respiratory, thoracic and mediastinal disorders
Cough	2/29 (6.9%)		0/19 (0%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		2/50 (4%)
Oropharyngeal pain	0/29 (0%)		1/19 (5.3%)		0/14 (0%)		0/8 (0%)		1/42 (2.4%)		1/50 (2%)
Skin and subcutaneous tissue disorders
Alopecia	0/29 (0%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		0/50 (0%)
Eczema	1/29 (3.4%)		0/19 (0%)		1/14 (7.1%)		0/8 (0%)		0/42 (0%)		1/50 (2%)
Rash	4/29 (13.8%)		0/19 (0%)		2/14 (14.3%)		1/8 (12.5%)		2/42 (4.8%)		4/50 (8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.