Clinical Trial Results:
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.

Due to a system error, the data reported in v1 is not correct and has been removed from public view.

Summary
EudraCT number	2009-013054-33
Trial protocol	GB
Global end of trial date	22 May 2012

Results information
Results version number	v2(current)
This version publication date	10 Jun 2016
First version publication date	01 Nov 2014
Other versions	v1 (removed from public view)
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

V72P6E1

ISRCTN number

US NCT number

NCT01027351

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Vaccines and Diagnostics SRL

Sponsor organisation address

Via Fiorentina 1, Siena, Italy, 53100

Public contact

Novartis Vaccines and Diagnostics SRL, Novartis Vaccines and Diagnostics SRL, RegistryContactVaccinesUS@novartis.com

Scientific contact

Novartis Vaccines and Diagnostics SRL, Novartis Vaccines and Diagnostics SRL, RegistryContactVaccinesUS@novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000139-PIP01-07

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

10 Jun 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 May 2012

Was the trial ended prematurely?

Main objective of the trial

The present study, V72P6E1, is an extension of V72P6. The primary objective of this extension study will be to explore antibody persistence at approximately 40 months of age in subjects who received rMenB or rMenB+OMV NZ at 2, 4, 6 and 12 months of age in parent study V72P6.

Protection of trial subjects

Study vaccines were not administered to individuals with known hypersensitivity to any component of the vaccines. An oral temperature ≥38.0°C (≥100.4°F) or serious active infection was a reason for delaying vaccination. Standard immunization practices were observed and care was taken to administer the injection intramuscularly. As with all injectable vaccines, appropriate medical treatment and supervision was readily available in case of rare anaphylactic reactions following administration of the study vaccine. Epinephrine 1:1000 and diphenhydramine was available in case of any anaphylactic reactions. Care was taken to ensure that the vaccine is not injected into a blood vessel.

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Jan 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 163

Worldwide total number of subjects

163

EEA total number of subjects

163

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

163

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Subjects were recruited from one centre in the United Kingdom.

Screening details

All subjects were included in the trial.

Number of subjects started

163

Number of subjects completed

163

Period 1 title

overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

5rMenB

Arm 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.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (group B) multicomponent recombinant adsorbed vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Subjects were administered 1 dose of 0.5 millilitres.

5rMenB+OMV NZ

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus Outer Membrane Vesicles New Zealand (OMV NZ)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Subjects were administered 1 dose of 0.5 millilitres.

3rMenB

Arm 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.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (group B) multicomponent recombinant adsorbed vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Subjects were administered 2 doses of 0.5 millilitres.

3rMenB+OMV NZ

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus Outer Membrane Vesicles New Zealand (OMV NZ)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Subjects were administered 2 doses of 0.5 millilitres.

Naive_4042

Arm 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.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus Outer Membrane Vesicles New Zealand (OMV NZ)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Subjects were administered 2 doses of 0.5 millilitres.

Naive_6062

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (group B) multicomponent recombinant adsorbed vaccine plus OMV NZ

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Subjects were administered 2 doses of 0.5 millilitres.

Number of subjects in period 1	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Started	29	19	14	8	43	50
Completed	26	18	13	6	32	45
Not completed	3	1	1	2	11	5
Consent withdrawn by subject	1	-	1	-	3	5
Lost to follow-up	1	1	-	1	6	-
inappropriate enrollment	-	-	-	-	1	-
Protocol deviation	1	-	-	1	1	-

Baseline characteristics

Top of page

Reporting group title

5rMenB

Reporting 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.

Reporting group title

5rMenB+OMV NZ

Reporting group description

Reporting group title

3rMenB

Reporting 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.

Reporting group title

3rMenB+OMV NZ

Reporting group description

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.

Reporting group title

Naive_4042

Reporting 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.

Reporting group title

Naive_6062

Reporting group description

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.

Reporting group values	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062	Total
Number of subjects	29	19	14	8	43	50	163
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	41.4 ( 1.5 )	41.8 ( 1.4 )	41.4 ( 1.5 )	40.4 ( 0.7 )	41.8 ( 1.7 )	61.3 ( 0.9 )	-
Gender categorical
Units: Subjects
Female	17	9	5	3	23	27	84
Male	12	10	9	5	20	23	79

Subject analysis set title

MITT – 40 months of age antibody persistence population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

MITT – 40 months of age antibody persistence population (groups 5rMenB, 5rMenB+OMV, 3rMenB, 3rMenB+OMV, Naive_4042). All subjects in the all enrolled population who: provided an evaluable serum sample at 40 months of age, (ie at visit 1 of V72P6E1 for groups 5rMenB, 5rMenB+OMV, 3rMenB, 3rMenB+OMV and Naive_4042).

Subject analysis set title

MITT – 60 Months of Age Antibody Persistence population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

MITT – 60 Months of Age Antibody Persistence population (5rMenB, 5rMenB+OMV NZ, 3rMenB, 3rMenB+OMV NZ, Naive_4042, Naive_6062). All subjects in the All Enrolled Set who provide an evaluable serum sample at 60 Months of Age (Visit 3 of V72P6E1 for groups 5rMenB and 5rMenB+OMV NZ, Visit 5 for Groups 3rMenB, 3rMenB+OMV NZ, Naive_4042, Visit 1 for Group Naive_6062).

Subject analysis set title

MITT – Booster Response population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

MITT – Booster Response population (Groups 5rMenB, 5rMenB+OMV, 3rMenB, 3rMenB+OMV, Naive_4042, Naive_6062). For Groups 5rMenB, 5rMenB+OMV, 3rMenB, 3rMenB+OMV, Naive_4042, all subjects in the All enrolled set who: ▫ receive a study vaccination in the present V72P6E1 study; and ▫ provide an evaluable serum sample either, at one month after the (first) (booster) dose (Visit 2) or at one month after the second (booster) dose (for Groups 3rMenB, 3rMenB+OMV, Naive_4042 Visit 4); For Group Naive_6062, all subjects in the All enrolled set who provide an evaluable serum sample at 60 Months of Age (Visit 1).

Subject analysis set title

Exposed set

Subject analysis set type

Safety analysis

Subject analysis set description

All enrolled subjects who actually receive a rMenB + OMV vaccination

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects in the exposed set who provided post-baseline safety data

Subject analysis set title

MITT – Two Dose Catch Up Schedule population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

MITT – Two Dose Catch Up Schedule population (Groups Naive_4042 and Naive_6062). All subjects in the All enrolled set who: ▫ received a study vaccination in the present V72P6E1 study; and ▫ provided an evaluable serum sample either, at one month after the first dose (Visit 2 for Naive_4042 only) or at one month after the second dose (Visit 4 for Group Naive_4042 and Visit 3 for Group Naive_6062).

Subject analysis sets values	MITT – 40 months of age antibody persistence population	MITT – 60 Months of Age Antibody Persistence population	MITT – Booster Response population	Exposed set	Safety Set	MITT – Two Dose Catch Up Schedule population
Number of subjects	108	134	160	162	162	152
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	41.5 ( 1.6 )	48.4 ( 9.6 )	47.7 ( 9.3 )	47.6 ( 9.3 )	47.6 ( 9.3 )	47 ( 9 )
Gender categorical
Units: Subjects
Female	54	68	83	84	84	80
Male	54	66	77	78	78	72

End points

Top of page

Reporting group title

5rMenB

Reporting 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.

Reporting group title

5rMenB+OMV NZ

Reporting group description

Reporting group title

3rMenB

Reporting 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.

Reporting group title

3rMenB+OMV NZ

Reporting group description

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.

Reporting group title

Naive_4042

Reporting 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.

Reporting group title

Naive_6062

Reporting group description

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.

Subject analysis set title

MITT – 40 months of age antibody persistence population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

MITT – 60 Months of Age Antibody Persistence population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

MITT – Booster Response population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

Exposed set

Subject analysis set type

Safety analysis

Subject analysis set description

All enrolled subjects who actually receive a rMenB + OMV vaccination

Subject analysis set title

Safety Set

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects in the exposed set who provided post-baseline safety data

Subject analysis set title

MITT – Two Dose Catch Up Schedule population

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Primary: 1) Persistence of geometric mean antibody titers in children (who previously received 4 doses of Men B vaccine), at 40 months of age

Top of page

End point title

1) Persistence of geometric mean antibody titers in children (who previously received 4 doses of Men B vaccine), at 40 months of age ^[1] ^[2]

End point 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. Analysis was done on the MITT – 40 months of age antibody persistence population.

End point type

Primary

End point timeframe

28 months after last vaccination; Baseline for Naïve

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	5rMenB	5rMenB+OMV NZ	Naive_4042
Number of subjects analysed	29	17	40
Units: Titers
geometric mean (confidence interval 95%)
H 44/76 strain	3.24 (2.33 to 4.52)	5.34 (3.47 to 8.23)	4.25 (3.22 to 5.6)
5/99 strain (N=28, 17, 40)	5.11 (2.33 to 11)	28 (10 to 77)	1.11 (0.9 to 1.36)
NZ 98/254 strain	1.09 (0.79 to 1.51)	2.77 (1.81 to 4.23)	1 (1 to 1)
M10713 strain (N=28, 15, 40)	9.15 (5.01 to 17)	5.34 (2.35 to 12)	8.75 (5.22 to 15)

No statistical analyses for this end point

Primary: 2) Percentage of subjects (who previously received 4 doses of Men B vaccine) with persisting serum bactericidal antibody titers ≥ 1: 4 and ≥ 1: 8 at 40 months of age

Top of page

End point title

2) Percentage of subjects (who previously received 4 doses of Men B vaccine) with persisting serum bactericidal antibody titers ≥ 1: 4 and ≥ 1: 8 at 40 months of age ^[3] ^[4]

End point description

The percentages of subjects with persisting 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). Analysis was done on the MITT – 40 months of age antibody persistence population.

End point type

Primary

End point timeframe

28 months after last vaccination; Baseline for Naïve

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	5rMenB	5rMenB+OMV NZ	Naive_4042
Number of subjects analysed	29	17	40
Units: percentages of subjects
number (confidence interval 95%)
hSBA ≥1:4 (H44/76 strain)	45 (26 to 64)	65 (38 to 86)	63 (46 to 77)
hSBA≥1:4 (5/99 strain)	43 (24 to 63)	76 (50 to 93)	3 (0.063 to 13)
hSBA≥1:4 (NZ 98/254 strain)	3 (0.087 to 18)	41 (18 to 67)	0 (0 to 9)
hSBA≥1:4 (M10713 strain)	68 (48 to 84)	67 (38 to 88)	68 (51 to 81)
hSBA ≥1:8 (H44/76 strain)	14 (4 to 32)	35 (14 to 62)	30 (17 to 47)
hSBA≥1:8 (5/99 strain)	43 (24 to 63)	76 (50 to 93)	3 (0.063 to 13)
hSBA≥1:8 (NZ 98/254 strain)	0 (0 to 12)	24 (7 to 50)	0 (0 to 9)
hSBA≥1:8 (M10713 strain)	61 (41 to 78)	40 (16 to 68)	45 (29 to 62)

No statistical analyses for this end point

Primary: 3) Number of subjects reporting solicited adverse events after receiving one or two booster doses of rMen B or rMenB+OMV NZ vaccine at 40 months of age.

Top of page

End point title

3) Number of subjects reporting solicited adverse events after receiving one or two booster doses of rMen B or rMenB+OMV NZ vaccine at 40 months of age. ^[5] ^[6]

End point 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. Analysis was done on the safety population, ie, all subjects in the exposed set who provide post-baseline safety data.

End point type

Primary

End point timeframe

Day 1-7 after booster vaccination

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: There was no statistical null hypothesis associated with this safety objective.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this safety objective.

End point values	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ
Number of subjects analysed	29	19	14	8
Units: Number of participants
Local	28	19	14	8
Injection-site pain	17	14	8	8
Injection-site erythema	28	19	14	8
Injection-site swelling	13	5	9	4
Injection-site induration	14	9	8	6
Systemic	19	13	11	8
Changes in eating habits	5	10	5	4
Sleepiness	13	12	8	6
Vomiting	1	3	3	0
Diarrhea	3	1	3	1
Irritability	14	10	9	8
Headache	1	0	2	1
Arthralgia	0	6	4	4
Rash	3	0	2	1
Fever (≥38°C)	1	1	4	0
Other	10	12	5	7
Antipyretic preventive medication used	10	12	3	7
Antipyretic treatment medication used	1	2	4	0
Medically attended fever	0	0	1	0

No statistical analyses for this end point

Secondary: 4) Persistence of geometric mean antibody titers in children (who previously received one dose of Men B vaccine), at 40 months of age

Top of page

End point title

4) Persistence of geometric mean antibody titers in children (who previously received one dose of Men B vaccine), at 40 months of age ^[7]

End point 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. Analysis was done on the MITT – 40 months of age antibody persistence population.

End point type

Secondary

End point timeframe

28 months after vaccination; baseline for Naïve

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	3rMenB	3rMenB+OMV NZ	Naive_4042
Number of subjects analysed	14	8	40
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain	3.59 (1.8 to 7.15)	3.47 (1.39 to 8.64)	4.25 (3.22 to 5.6)
5/99 strain	9.57 (3.88 to 24)	1 (0.3 to 3.3)	1.11 (0.9 to 1.36)
NZ 98/254 strain	1.23 (0.96 to 1.57)	1 (0.72 to 1.38)	1 (1 to 1)
M10713 strain (N=13, 8, 40)	3.26 (1.49 to 7.11)	3 (1.11 to 8.11)	8.75 (5.22 to 15)

No statistical analyses for this end point

Secondary: 5) 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

Top of page

End point title

5) 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 ^[8]

End point 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. Analysis was done on the MITT – 40 months of age antibody persistence population.

End point type

Secondary

End point timeframe

28 months after vaccination; baseline for naïve

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	3rMenB	3rMenB+OMV NZ	Naive_4042
Number of subjects analysed	14	8	40
Units: Percentages of subjects
number (confidence interval 95%)
hSBA ≥1:4 (H44/76 strain)	57 (29 to 82)	38 (9 to 76)	63 (46 to 77)
hSBA≥1:4 (5/99 strain)	57 (29 to 82)	0 (0 to 37)	3 (0.063 to 13)
hSBA≥1:4 (NZ 98/254 strain)	7 (0 to 34)	0 (0 to 37)	0 (0 to 9)
hSBA≥1:4 (M10713 strain; N=13, 8, 40)	54 (25 to 81)	25 (3 to 65)	68 (51 to 81)
hSBA ≥1:8 (H44/76 strain)	7 (0 to 34)	13 (0 to 53)	30 (17 to 47)
hSBA≥1:8 (5/99 strain)	43 (18 to 71)	0 (0 to 37)	3 (0.063 to 13)
hSBA≥1:8 (NZ 98/254 strain)	0 (0 to 23)	0 (0 to 37)	0 (0 to 9)
hSBA≥1:8 (M10713 strain; N=13, 8, 40)	15 (2 to 45)	13 (0 to 53)	45 (29 to 62)

No statistical analyses for this end point

Secondary: 6) 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

Top of page

End point title

6) 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 ^[9]

End point 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. Analysis was done on the MITT – Booster Response population.

End point type

Secondary

End point timeframe

1 month post- booster/ dose 1 for Naïve

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	5rMenB	5rMenB+OMV NZ	Naive_4042
Number of subjects analysed	29	19	38
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain	99 (67 to 145)	89 (56 to 141)	12 (7.96 to 19)
5/99 strain (N=28, 18, 38)	778 (448 to 1349)	1708 (859 to 3396)	22 (12 to 40)
NZ 98/254 strain	1.64 (0.95 to 2.85)	47 (24 to 91)	7.73 (4.62 to 13)
M10713 strain (N=28, 18, 38)	38 (24 to 59)	39 (22 to 67)	11 (6.7 to 19)

No statistical analyses for this end point

Secondary: 7) 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

Top of page

End point title

7) 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 ^[10]

End point 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. Analysis was done on the MITT – Booster Response population.

End point type

Secondary

End point timeframe

1 month post- booster/ dose 1 for Naïve

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	5rMenB	5rMenB+OMV NZ	Naive_4042
Number of subjects analysed	28	19	38
Units: Percentages of subjects
number (confidence interval 95%)
hSBA ≥1:4 (H44/76 strain)	100 (88 to 100)	100 (82 to 100)	89 (75 to 97)
hSBA≥1:4 (5/99 strain)	100 (88 to 100)	100 (81 to 100)	76 (60 to 89)
hSBA≥1:4 (NZ 98/254 strain)	14 (4 to 33)	89 (67 to 99)	66 (49 to 80)
hSBA≥1:4 (M10713 strain)	96 (82 to 100)	94 (73 to 100)	76 (60 to 89)
hSBA ≥1:8 ( H44/76 strain)	96 (82 to 100)	100 (82 to 100)	63 (46 to 78)
hSBA≥1:8 (5/99 strain)	100 (88 to 100)	100 (81 to 100)	71 (54 to 85)
hSBA≥1:8 (NZ 98/254 strain)	11 (2 to 28)	89 (67 to 99)	58 (41 to 74)
hSBA≥1:8 (M10713 strain)	89 (72 to 98)	94 (73 to 100)	61 (43 to 76)

No statistical analyses for this end point

Secondary: 8) 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

Top of page

End point title

8) 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 ^[11]

End point 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. Analysis was done on the MITT – Booster Response population.

End point type

Secondary

End point timeframe

1 month post- booster/ dose 1 for Naïve

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	5rMenB	5rMenB+OMV NZ	Naive_4042
Number of subjects analysed	28	17	37
Units: Percentages of subjects
number (confidence interval 95%)
H44/76 strain	89 (72 to 98)	94 (71 to 100)	41 (25 to 58)
5/99 strain (N=27, 16, 37)	100 (87 to 100)	94 (70 to 100)	68 (50 to 82)
NZ 98/254 strain	11 (2 to 28)	82 (57 to 96)	57 (39 to 73)
M10713 strain (N=27, 15, 37)	41 (22 to 61)	67 (38 to 88)	14 (5 to 29)

No statistical analyses for this end point

Secondary: 9) 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

Top of page

End point title

9) 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 ^[12]

End point 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. Analysis was done on the MITT – Booster Response population.

End point type

Secondary

End point timeframe

1 month post vaccination

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	3rMenB	3rMenB+OMV NZ	Naive_4042
Number of subjects analysed	13	8	38
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain (dose 1; N=13, 7, 38)	94 (48 to 185)	76 (30 to 190)	12 (7.96 to 19)
H44/76 strain (dose 2; N=13, 8, 36)	127 (81 to 198)	145 (82 to 255)	88 (66 to 117)
5/99 strain (dose 1; N=13, 7, 38)	2379 (1164 to 4859)	509 (192 to 1348)	22 (12 to 40)
5/99 strain (dose 2; N=13, 8, 36)	5240 (3082 to 8911)	2413 (1226 to 4747)	1019 (762 to 1362)
NZ 98/254 strain (dose 1; N=13, 7, 38)	1.73 (0.86 to 3.48)	148 (57 to 384)	7.73 (4.62 to 13)
NZ 98/254 strain (dose 2; N=13, 8, 36)	1.86 (0.89 to 3.88)	65 (25 to 165)	47 (31 to 72)
M10713 strain (dose 1; N=13, 7, 38)	35 (18 to 68)	30 (12 to 74)	11 (6.7 to 19)
M10713 strain (dose 2; N=12, 8, 36)	21 (9.25 to 47)	36 (13 to 98)	33 (22 to 51)

No statistical analyses for this end point

Secondary: 10) 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

Top of page

End point title

10) 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 ^[13]

End point 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 are reported. Analysis was done on the MITT – Booster Response population.

End point type

Secondary

End point timeframe

1 month post vaccination

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	3rMenB	3rMenB+OMV NZ	Naive_4042
Number of subjects analysed	13	8	38
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 strain (≥1:4 – booster dose 1)	100 (75 to 100)	100 (59 to 100)	89 (75 to 100)
H44/76 strain (≥1:4 – booster dose 2)	100 (75 to 100)	100 (63 to 100)	100 (90 to 100)
H44/76 strain (≥1:8 – booster dose 1)	100 (75 to 100)	100 (59 to 100)	63 (46 to 78)
H44/76 strain (≥1:8 – booster dose 2)	100 (75 to 100)	100 (63 to 100)	100 (90 to 100)
5/99 strain (≥1:4 – booster dose 1)	100 (75 to 100)	100 (59 to 100)	76 (60 to 89)
5/99 strain (≥1:4 – booster dose 2)	100 (75 to 100)	100 (63 to 100)	100 (90 to 100)
5/99 strain (≥1:8 – booster dose 1)	100 (75 to 100)	100 (59 to 100)	71 (54 to 85)
5/99 strain (≥1:8 – booster dose 2)	100 (75 to 100)	100 (63 to 100)	100 (90 to 100)
NZ 98/254 strain (≥1:4 – booster dose 1)	15 (2 to 45)	100 (59 to 100)	66 (49 to 80)
NZ 98/254 strain (≥1:4 – booster dose 2)	15 (2 to 45)	100 (63 to 100)	94 (81 to 99)
NZ 98/254 strain (≥1:8 – booster dose 1)	15 (2 to 45)	100 (59 to 100)	58 (41 to 74)
NZ 98/254 strain (≥1:8 – booster dose 2)	15 (2 to 45)	100 (63 to 100)	94 (81 to 99)
M10713 strain (≥1:4 – booster dose 1)	100 (75 to 100)	86 (42 to 100)	76 (60 to 89)
M10713 strain (≥1:4 – booster dose 2)	83 (52 to 98)	100 (63 to 100)	89 (74 to 97)
M10713 strain (≥1:8 – booster dose 1)	85 (55 to 98)	86 (42 to 100)	61 (43 to 76)
M10713 strain (≥1:8 – booster dose 2)	75 (43 to 95)	100 (63 to 100)	86 (71 to 95)

No statistical analyses for this end point

Secondary: 11) 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

Top of page

End point title

11) 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 ^[14]

End point 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 are reported. Analysis was done on the MITT – Booster Response population.

End point type

Secondary

End point timeframe

1 month post vaccination

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	3rMenB	3rMenB+OMV NZ	Naive_4042
Number of subjects analysed	13	8	37
Units: Percentage of subjects
geometric mean (confidence interval 95%)
H44/76 strain (dose 1; N=13, 7, 37)	100 (75 to 100)	86 (42 to 100)	41 (25 to 58)
5/99 strain (dose 1; N=13, 7, 37)	100 (75 to 100)	100 (59 to 100)	68 (50 to 82)
NZ 98/254 strain (dose 1; N=13, 7, 37)	15 (2 to 45)	100 (59 to 100)	57 (39 to 73)
M10713 strain (dose 1; N=12, 7, 37)	58 (28 to 85)	57 (18 to 90)	14 (5 to 29)
H44/76 strain (dose 2; N=13, 8, 34)	100 (75 to 100)	88 (47 to 100)	97 (85 to 100)
5/99 strain (dose 2; N=13, 8, 34)	100 (75 to 100)	100 (63 to 100)	100 (90 to 100)
NZ 98/254 strain (dose 2; N=13, 8, 34)	15 (2 to 45)	100 (63 to 100)	94 (80 to 99)
M10713 strain (dose 2; N=11, 8, 34)	64 (31 to 89)	75 (35 to 97)	53 (35 to 70)

No statistical analyses for this end point

Secondary: 12) Percentage of subjects with serum bactericidal antibody 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

Top of page

End point title

12) Percentage of subjects with serum bactericidal antibody 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 ^[15]

End point description

The percentages 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. Analysis was done on the MITT – Two Dose Catch Up Schedule population.

End point type

Secondary

End point timeframe

1 month post -vaccine dose two

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	Naive_4042	Naive_6062
Number of subjects analysed	36	42
Units: Percentages of subjects
number (confidence interval 95%)
H44/76 strain (hSBA ≥1:4)	100 (90 to 100)	93 (81 to 99)
H44/76 strain (hSBA ≥1:8)	100 (90 to 100)	93 (81 to 99)
5/99 strain (hSBA ≥1:4)	100 (90 to 100)	100 (92 to 100)
5/99 strain (hSBA ≥1:8)	100 (90 to 100)	100 (92 to 100)
NZ 98/254 strain (hSBA ≥1:4)	94 (81 to 99)	100 (92 to 100)
NZ 98/254 strain (hSBA ≥1:8)	94 (81 to 99)	90 (77 to 97)
M10713 strain (hSBA ≥1:4)	89 (74 to 97)	100 (91 to 100)
M10713 strain (hSBA ≥1:8)	86 (71 to 95)	98 (87 to 100)

No statistical analyses for this end point

Secondary: 13) 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.

Top of page

End point title

13) 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. ^[16]

End point 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. Analysis was done on the MITT – Two Dose Catch Up Schedule population.

End point type

Secondary

End point timeframe

1 month post vaccine dose two

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	Naive_4042	Naive_6062
Number of subjects analysed	36	42
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain	88 (63 to 123)	34 (25 to 47)
5/99 strain	1019 (688 to 1510)	865 (601 to 1244)
NZ 98/254 strain	47 (32 to 69)	29 (20 to 41)
M10713 strain (N=36, 41)	33 (24 to 47)	43 (31 to 59)

No statistical analyses for this end point

Secondary: 14) 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

Top of page

End point title

14) 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 ^[17]

End point 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 are reported. Analysis was done on the MITT – Two Dose Catch Up Schedule population.

End point type

Secondary

End point timeframe

1 month post vaccine dose 2

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	Naive_4042	Naive_6062
Number of subjects analysed	34	38
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 strain (% 4 fold increase)	97 (85 to 100)	71 (54 to 85)
5/99 strain (% 4 fold increase)	100 (90 to 100)	100 (91 to 100)
NZ 98/254 strain (% 4 fold increase)	94 (80 to 99)	89 (75 to 97)
M10713 strain (% 4 fold increase)	53 (35 to 70)	21 (10 to 37)

No statistical analyses for this end point

Secondary: 15) Persisting geometric mean antibody titers against N.meningitidis B in children at 60 months of age

Top of page

End point title

15) Persisting geometric mean antibody titers against N.meningitidis B in children at 60 months of age

End point 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. Analysis was done on the MITT – 60 Months of Age Antibody Persistence population.

End point type

Secondary

End point timeframe

18-20 months after last Men B vaccine; baseline for naïve_6062

End point values	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Number of subjects analysed	24	16	13	5	29	46
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain (N=24, 16, 13, 5, 28, 46)	3.13 (1.75 to 5.59)	4.68 (2.3 to 9.52)	18 (8.08 to 39)	13 (3.52 to 45)	12 (6.27 to 23)	2.98 (1.86 to 4.78)
5/99 strain (N=23, 16, 13, 5, 28, 46)	43 (19 to 99)	136 (51 to 365)	369 (123 to 1103)	210 (36 to 1227)	44 (29 to 67)	1.14 (0.88 to 1.47)
NZ 98/254 strain	1.05 (0.8 to 1.38)	4.95 (3.54 to 6.92)	1 (0.69 to 1.45)	11 (5.93 to 20)	2.42 (1.59 to 3.66)	1.04 (0.96 to 1.14)
M10713 strain (N=22, 16, 12, 5, 27, 46)	12 (7.22 to 20)	10 (5.67 to 19)	12 (5.85 to 24)	25 (8.47 to 74)	8.52 (5.09 to 14)	18 (12 to 28)

No statistical analyses for this end point

Secondary: 16) Percentage of subjects with persisting hSBA antibody titers ≥1:4 and ≥1:8 in children at 60 months of age

Top of page

End point title

16) Percentage of subjects with persisting hSBA antibody titers ≥1:4 and ≥1:8 in children at 60 months of age

End point 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 study are reported. Analysis was done on the MITT – 60 Months of Age Antibody Persistence population.

End point type

Secondary

End point timeframe

18-20 months after last Men B vaccine; baseline for naïve_6062

End point values	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Number of subjects analysed	24	16	13	5	29	46
Units: Percentages of subjects
number (confidence interval 95%)
hSBA ≥1:4 (H44/76 strain; N=24, 16, 13, 5, 28, 46)	46 (26 to 67)	44 (20 to 70)	85 (55 to 98)	80 (28 to 99)	71 (51 to 87)	33 (20 to 48)
hSBA ≥1:4 (5/99 strain; N=23, 16, 13, 5, 28, 46)	83 (61 to 95)	88 (62 to 98)	100 (75 to 100)	100 (48 to 100)	100 (88 to 100)	2 (0.055 to 12)
hSBA ≥1:4 (NZ 98/254 strain)	0 (0 to 14)	69 (41 to 89)	0 (0 to 25)	80 (28 to 99)	31 (15 to 51)	2 (0.055 to 12)
hSBA ≥1:4 (M10713 strain; N=22, 16, 12, 5, 27, 46)	77 (55 to 92)	88 (62 to 98)	92 (62 to 100)	100 (48 to 100)	81 (62 to 94)	83 (69 to 92)
hSBA ≥1:8 (H44/76 strain; N=24, 16, 13, 5, 28, 46)	25 (10 to 47)	31 (11 to 59)	77 (46 to 95)	60 (15 to 95)	61 (41 to 78)	26 (14 to 41)
hSBA ≥1:8 (5/99 strain; N=23, 16, 13, 5, 28, 46)	74 (52 to 90)	88 (62 to 98)	100 (75 to 100)	100 (48 to 100)	93 (76 to 99)	2 (0.055 to 12)
hSBA ≥1:8 (NZ 98/254 strain)	0 (0 to 14)	31 (11 to 59)	0 (0 to 25)	40 (5 to 85)	21 (8 to 40)	0 (0 to 8)
hSBA ≥1:8 (M10713 strain; N=22, 16, 12, 5, 27, 46)	59 (36 to 79)	63 (35 to 85)	67 (35 to 90)	80 (28 to 99)	48 (29 to 68)	70 (54 to 82)

No statistical analyses for this end point

Secondary: 17) 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

Top of page

End point title

17) 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 ^[18]

End point description

The persisting geometric mean antibody concentrations (GMCs) against vaccine antigen 287-953 in 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 measure using enzyme linked immunosorbent assay (ELISA). Analysis was done on the MITT – 40 Months of Age Antibody Persistence population.

End point type

Secondary

End point timeframe

28 months after last Men B vaccination; Bbseline for Naïve_4042 group

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	5rMenB	5rMenB+OMV NZ	Naive_4042
Number of subjects analysed	28	17	40
Units: AU/mL
geometric mean (confidence interval 95%)	82 (59 to 113)	62 (41 to 94)	23 (19 to 26)

No statistical analyses for this end point

Secondary: 18) 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

Top of page

End point title

18) 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 ^[19]

End point description

The persisting geometric mean antibody concentrations (GMCs) against vaccine antigen 287-953 in in children (at 40 months of age) who had previously received 1 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 measure using enzyme linked immunosorbent assay (ELISA). Analysis was done on the MITT – 40 Months of Age Antibody Persistence population.

End point type

Secondary

End point timeframe

28 months after last Men B vaccination; baseline for Naïve_4042 group

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	3rMenB	3rMenB+OMV NZ	Naive_4042
Number of subjects analysed	14	8	38
Units: AU/mL
geometric mean (confidence interval 95%)	32 (21 to 49)	28 (16 to 50)	23 (19 to 26)

No statistical analyses for this end point

Secondary: 19) Geometric Mean Antibody Concentrations against vaccine antigen 287-953 in Children (Who Had Previously Received 4doses of MenB Vaccine) After Receiving One Booster Dose of Either rMenB or rMenB+OMV NZ at 40 Months of Age

Top of page

End point title

19) Geometric Mean Antibody Concentrations against vaccine antigen 287-953 in Children (Who Had Previously Received 4doses of MenB Vaccine) After Receiving One Booster Dose of Either rMenB or rMenB+OMV NZ at 40 Months of Age ^[20]

End point 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. Analysis was done on the MITT – Booster Response population.

End point type

Secondary

End point timeframe

1 month post booster ; 1month post dose for naïve_4042 group

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	5rMenB	5rMenB+OMV NZ	Naive_4042
Number of subjects analysed	28	19	38
Units: AU/mL
geometric mean (confidence interval 95%)	5592 (3900 to 8017)	3934 (2540 to 6093)	64 (44 to 94)

No statistical analyses for this end point

Secondary: 20) 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

Top of page

End point title

20) 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 ^[21]

End point description

The GMCs against vaccine antigen 287-953 in 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 . Analysis was done on the MITT - Booster Response population.

End point type

Secondary

End point timeframe

1 month after each booster/ vaccine dose

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	3rMenB	3rMenB+OMV NZ	Naive_4042
Number of subjects analysed	13	8	38
Units: AU/mL
geometric mean (confidence interval 95%)
after 1st booster/vaccine dose (N=13, N=7, N=38)	2100 (1100 to 4007)	1764 (731 to 4256)	64 (44 to 94)
after 2nd booster/vaccine dose (N=13, N=8, N=36	3790 (2265 to 6342)	3660 (1899 to 7055)	3464 (2782 to 4313)

No statistical analyses for this end point

Secondary: 21) 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

Top of page

End point title

21) 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 ^[22]

End point 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. Analysis was done on the MITT - Booster Response population.

End point type

Secondary

End point timeframe

1 month post vaccine dose two

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this immunogenicity objective.

End point values	Naive_4042	Naive_6062
Number of subjects analysed	36	42
Units: AU/mL
geometric mean (confidence interval 95%)	3464 (2672 to 4489)	1744 (1372 to 2218)

No statistical analyses for this end point

Secondary: 22) Persisting geometric mean concentrations against vaccine antigen 287-953 in children at 60 months of age

Top of page

End point title

22) Persisting geometric mean concentrations against vaccine antigen 287-953 in children at 60 months of age

End point 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. Analysis was done on the MITT – 60 Months of Age Antibody Persistence population.

End point type

Secondary

End point timeframe

18-20 months after last Men B vaccine; baseline for naïve_6062

End point values	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Number of subjects analysed	24	16	13	5	28	47
Units: AU/mL
geometric mean (confidence interval 95%)	670 (475 to 945)	320 (210 to 487)	280 (175 to 447)	250 (118 to 532)	121 (88 to 166)	25 (20 to 32)

No statistical analyses for this end point

Secondary: 23) 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

Top of page

End point title

23) 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 ^[23]

End point 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. Analysis was done on the MITT – Two Dose Catch Up Schedule population.

End point type

Secondary

End point timeframe

Day 1-7 after any vaccination

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: There was no statistical null hypothesis associated with this safety objective.

End point values	Naive_4042	Naive_6062
Number of subjects analysed	42	50
Units: Number of subjects
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

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Day 1-7 after each vaccination for Solicited Adverse; Unsolicited AEs were collected throughout the study period.

Adverse event reporting additional description

The analyses for the data in this section are from the safety set.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

5rMenB

Reporting 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.

Reporting group title

5rMenB+OMV NZ

Reporting group description

Reporting group title

3rMenB

Reporting 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.

Reporting group title

3rMenB+OMV NZ

Reporting group description

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.

Reporting group title

Naive_4042

Reporting 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.

Reporting group title

Naive_6062

Reporting group description

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.

Serious adverse events	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 29 (3.45%)	1 / 19 (5.26%)	0 / 14 (0.00%)	1 / 8 (12.50%)	2 / 42 (4.76%)	2 / 50 (4.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
haemangioma
subjects affected / exposed	1 / 29 (3.45%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
cystic lymphangioma
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
migraine
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
limphadenitis
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
abdominal pain
alternative assessment type: Systematic
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
asthma
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
bronchopneumonia
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
oral herpes
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
urinary tract infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	5rMenB	5rMenB+OMV NZ	3rMenB	3rMenB+OMV NZ	Naive_4042	Naive_6062
Total subjects affected by non serious adverse events
subjects affected / exposed	29 / 29 (100.00%)	19 / 19 (100.00%)	14 / 14 (100.00%)	8 / 8 (100.00%)	42 / 42 (100.00%)	49 / 50 (98.00%)
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0
Heat stroke
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	1	0	0
Overdose
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	1 / 29 (3.45%)	0 / 19 (0.00%)	2 / 14 (14.29%)	1 / 8 (12.50%)	8 / 42 (19.05%)	8 / 50 (16.00%)
occurrences all number	1	0	2	1	9	10
Lethargy
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0
Somnolence
subjects affected / exposed	13 / 29 (44.83%)	12 / 19 (63.16%)	8 / 14 (57.14%)	6 / 8 (75.00%)	25 / 42 (59.52%)	23 / 50 (46.00%)
occurrences all number	13	15	11	7	37	35
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0
General disorders and administration site conditions
Injection site erythema
alternative assessment type: Systematic
subjects affected / exposed	28 / 29 (96.55%)	19 / 19 (100.00%)	14 / 14 (100.00%)	8 / 8 (100.00%)	42 / 42 (100.00%)	48 / 50 (96.00%)
occurrences all number	30	21	28	16	90	97
Hyperpyrexia
subjects affected / exposed	1 / 29 (3.45%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	1	0	0	0
Injection site induration
alternative assessment type: Systematic
subjects affected / exposed	14 / 29 (48.28%)	9 / 19 (47.37%)	8 / 14 (57.14%)	6 / 8 (75.00%)	23 / 42 (54.76%)	29 / 50 (58.00%)
occurrences all number	15	9	10	11	36	45
Injection site pain
subjects affected / exposed	17 / 29 (58.62%)	14 / 19 (73.68%)	8 / 14 (57.14%)	8 / 8 (100.00%)	41 / 42 (97.62%)	46 / 50 (92.00%)
occurrences all number	18	14	10	15	76	86
Injection site swelling
alternative assessment type: Systematic
subjects affected / exposed	13 / 29 (44.83%)	5 / 19 (26.32%)	9 / 14 (64.29%)	4 / 8 (50.00%)	31 / 42 (73.81%)	27 / 50 (54.00%)
occurrences all number	14	5	12	6	47	41
Pain
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	1	0	0
Pyrexia
subjects affected / exposed	1 / 29 (3.45%)	1 / 19 (5.26%)	7 / 14 (50.00%)	0 / 8 (0.00%)	7 / 42 (16.67%)	6 / 50 (12.00%)
occurrences all number	1	1	8	0	9	9
Local swelling
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	0	1	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	1 / 50 (2.00%)
occurrences all number	0	0	1	0	0	1
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 29 (3.45%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	0	2	0	0	1
Constipation
subjects affected / exposed	2 / 29 (6.90%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	2	0	0	0	0	0
Diarrhoea
subjects affected / exposed	3 / 29 (10.34%)	1 / 19 (5.26%)	3 / 14 (21.43%)	1 / 8 (12.50%)	8 / 42 (19.05%)	7 / 50 (14.00%)
occurrences all number	3	1	3	1	8	8
Faeces discoloured
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0
Vomiting
subjects affected / exposed	1 / 29 (3.45%)	3 / 19 (15.79%)	3 / 14 (21.43%)	0 / 8 (0.00%)	1 / 42 (2.38%)	8 / 50 (16.00%)
occurrences all number	1	3	3	0	1	9
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 29 (6.90%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	2 / 50 (4.00%)
occurrences all number	2	0	0	0	1	2
Oropharyngeal pain
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	1 / 50 (2.00%)
occurrences all number	0	2	0	0	1	1
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0
Eczema
subjects affected / exposed	1 / 29 (3.45%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	0	1	0	0	1
Rash
subjects affected / exposed	4 / 29 (13.79%)	0 / 19 (0.00%)	2 / 14 (14.29%)	1 / 8 (12.50%)	2 / 42 (4.76%)	4 / 50 (8.00%)
occurrences all number	4	0	3	1	3	5
Psychiatric disorders
Irritability
subjects affected / exposed	14 / 29 (48.28%)	10 / 19 (52.63%)	9 / 14 (64.29%)	8 / 8 (100.00%)	35 / 42 (83.33%)	31 / 50 (62.00%)
occurrences all number	16	12	11	10	62	48
Eating disorders
subjects affected / exposed	5 / 29 (17.24%)	10 / 19 (52.63%)	5 / 14 (35.71%)	4 / 8 (50.00%)	21 / 42 (50.00%)	23 / 50 (46.00%)
occurrences all number	5	15	7	4	32	37
Musculoskeletal and connective tissue disorders
Arthralgia
alternative assessment type: Systematic
subjects affected / exposed	0 / 29 (0.00%)	6 / 19 (31.58%)	4 / 14 (28.57%)	4 / 8 (50.00%)	16 / 42 (38.10%)	16 / 50 (32.00%)
occurrences all number	0	6	4	4	24	22
Infections and infestations
Ear infection
subjects affected / exposed	2 / 29 (6.90%)	1 / 19 (5.26%)	2 / 14 (14.29%)	1 / 8 (12.50%)	4 / 42 (9.52%)	1 / 50 (2.00%)
occurrences all number	3	1	2	1	4	1
Eczema infected
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0
Fungal skin infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0
Impetigo
subjects affected / exposed	1 / 29 (3.45%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	1 / 42 (2.38%)	1 / 50 (2.00%)
occurrences all number	2	0	1	0	1	1
Localised infection
subjects affected / exposed	1 / 29 (3.45%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 8 (12.50%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	1	0	0
Lower respiratory tract infection
subjects affected / exposed	3 / 29 (10.34%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	1 / 50 (2.00%)
occurrences all number	4	0	0	0	1	1
Nasopharingitis
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	1	0
Otitis media
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	2 / 14 (14.29%)	0 / 8 (0.00%)	4 / 42 (9.52%)	1 / 50 (2.00%)
occurrences all number	0	0	2	0	4	1
Skin infection
subjects affected / exposed	0 / 29 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 8 (0.00%)	0 / 42 (0.00%)	0 / 50 (0.00%)
occurrences all number	0	0	1	0	0	0
Tonsillitis
subjects affected / exposed	2 / 29 (6.90%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 8 (0.00%)	1 / 42 (2.38%)	2 / 50 (4.00%)
occurrences all number	2	0	0	0	1	3
Urinary tract infection
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 8 (0.00%)	2 / 42 (4.76%)	0 / 50 (0.00%)
occurrences all number	0	1	0	0	3	0
Varicella
subjects affected / exposed	0 / 29 (0.00%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 8 (0.00%)	1 / 42 (2.38%)	0 / 50 (0.00%)
occurrences all number	0	1	1	0	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1) Persistence of geometric mean antibody titers in children (who previously received 4 doses of Men B vaccine), at 40 months of age

Primary: 1) Persistence of geometric mean antibody titers in children (who previously received 4 doses of Men B vaccine), at 40 months of age

Primary: 2) Percentage of subjects (who previously received 4 doses of Men B vaccine) with persisting serum bactericidal antibody titers ≥ 1: 4 and ≥ 1: 8 at 40 months of age

Primary: 2) Percentage of subjects (who previously received 4 doses of Men B vaccine) with persisting serum bactericidal antibody titers ≥ 1: 4 and ≥ 1: 8 at 40 months of age

Primary: 3) Number of subjects reporting solicited adverse events after receiving one or two booster doses of rMen B or rMenB+OMV NZ vaccine at 40 months of age.

Primary: 3) Number of subjects reporting solicited adverse events after receiving one or two booster doses of rMen B or rMenB+OMV NZ vaccine at 40 months of age.

Secondary: 4) Persistence of geometric mean antibody titers in children (who previously received one dose of Men B vaccine), at 40 months of age

Secondary: 4) Persistence of geometric mean antibody titers in children (who previously received one dose of Men B vaccine), at 40 months of age

Secondary: 5) 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

Secondary: 5) 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

Secondary: 6) 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

Secondary: 6) 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

Secondary: 7) 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

Secondary: 7) 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

Secondary: 8) 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

Secondary: 8) 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

Secondary: 9) 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

Secondary: 9) 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

Secondary: 10) 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

Secondary: 10) 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

Secondary: 11) 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

Secondary: 11) 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

Secondary: 12) Percentage of subjects with serum bactericidal antibody 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

Secondary: 12) Percentage of subjects with serum bactericidal antibody 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

Secondary: 13) 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.

Secondary: 13) 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.

Secondary: 14) 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

Secondary: 14) 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

Secondary: 15) Persisting geometric mean antibody titers against N.meningitidis B in children at 60 months of age

Secondary: 15) Persisting geometric mean antibody titers against N.meningitidis B in children at 60 months of age

Secondary: 16) Percentage of subjects with persisting hSBA antibody titers ≥1:4 and ≥1:8 in children at 60 months of age

Secondary: 16) Percentage of subjects with persisting hSBA antibody titers ≥1:4 and ≥1:8 in children at 60 months of age

Secondary: 17) 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

Secondary: 17) 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

Secondary: 18) 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

Secondary: 18) 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

Secondary: 19) Geometric Mean Antibody Concentrations against vaccine antigen 287-953 in Children (Who Had Previously Received 4doses of MenB Vaccine) After Receiving One Booster Dose of Either rMenB or rMenB+OMV NZ at 40 Months of Age

Secondary: 19) Geometric Mean Antibody Concentrations against vaccine antigen 287-953 in Children (Who Had Previously Received 4doses of MenB Vaccine) After Receiving One Booster Dose of Either rMenB or rMenB+OMV NZ at 40 Months of Age

Secondary: 20) 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

Secondary: 20) 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

Secondary: 21) 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

Secondary: 21) 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

Secondary: 22) Persisting geometric mean concentrations against vaccine antigen 287-953 in children at 60 months of age

Secondary: 22) Persisting geometric mean concentrations against vaccine antigen 287-953 in children at 60 months of age

Secondary: 23) 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

Secondary: 23) 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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information