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Clinical Trial Results:
A Phase 3b, Open Label, Controlled, Multi-Center, Extension Study to Assess the Persistence of Bactericidal Activity at 4 to 7.5 Years After Two Dose Primary Series of GlaxoSmithKline Biologicals Meningococcal B Recombinant Vaccine and the Response to a Third Dose in Adolescents and Young Adult Subjects who Previously Participated in Parent Studies V72_41 and V72P10, Compared to Naïve Healthy Controls

Summary
EudraCT number	2017-000093-11
Trial protocol	Outside EU/EEA
Global end of trial date	23 Sep 2016

Results information
Results version number	v2
This version publication date	30 Nov 2017
First version publication date	14 Oct 2017
Other versions	v1 , v3 , v4
Version creation reason

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

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Trial information

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Sponsor protocol code

205218

ISRCTN number

US NCT number

NCT02446743

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l’Institut 89, Rixensart, Belgium, B-1330

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

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

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

22 Jun 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

22 Sep 2016

Global end of trial reached?

Yes

Global end of trial date

23 Sep 2016

Was the trial ended prematurely?

Main objective of the trial

•To assess and compare the safety and tolerability of a single dose (booster) of rMenB+OMV NZ administered to follow-on subjects approximately 4 to 7.5 years after a 2 dose primary series, with that of two doses of rMenB+OMV NZ administered to naïve subjects according to a 0, 1-month schedule. •To assess serum bactericidal activity at approximately 4 to 7.5 years following a 2 dose primary series (persistence) compared to serum bactericidal activity at baseline in vaccination-naïve subjects.

Protection of trial subjects

The subjects were observed closely for at least 30 minutes following the administration of vaccine(s), with appropriate medical treatment readily available in case of a rare anaphylactic reaction.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Nov 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 63

Country: Number of subjects enrolled

Canada: 187

Country: Number of subjects enrolled

Chile: 281

Worldwide total number of subjects

531

EEA total number of subjects

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)

Adolescents (12-17 years)

122

Adults (18-64 years)

409

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects were recruited from 4 sites in Australia, 6 sites in Canada and 2 sites in Chile.

Screening details

All enrolled subjects were included in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

The study was an open- label study. Therefore, no blinding procedures were utilized.

Are arms mutually exclusive

Yes

Group 3B

Arm description

Subjects who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during studies V72P10 (NCT00661713) or V72_41(NCT0142384), and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster.

Arm type

Experimental

Investigational medicinal product name

GlaxoSmithKline Meningococcal group B multicomponent recombinant adsorbed vaccine

Investigational medicinal product code

Other name

rMenB+OMV NZ

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

One dose (0.5 mL) vaccine administered by intramuscular (IM) injection in the deltoid area of the nondominant arm

Group B_0_1

Arm description

Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

Arm type

Active comparator

Investigational medicinal product name

GlaxoSmithKline Meningococcal group B multicomponent recombinant adsorbed vaccine

Investigational medicinal product code

Other name

rMenB+OMV NZ

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

One dose (0.5 mL) vaccine administered by intramuscular (IM) injection in the deltoid area of the nondominant arm

Number of subjects in period 1	Group 3B	Group B_0_1
Started	276	255
Completed	271	250
Not completed	5	5
Consent withdrawn by subject	1	1
Adverse event, non-fatal	1	1
Unspecified	2	3
Lost to follow-up	1	-

Baseline characteristics

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Reporting group title

Group 3B

Reporting group description

Reporting group title

Group B_0_1

Reporting group description

Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

Reporting group values	Group 3B	Group B_0_1	Total
Number of subjects	276	255	531
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age<37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	65	57	122
Adults (18-64 years)	211	198	409
From 65-84 years	0	0	0
85 years and over	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	19.5 ± 2.42	20.0 ± 2.69	-
Gender categorical
Units: Subjects
Female	133	128	261
Male	143	127	270
Race/Ethnicity, Customized
Units: Subjects
Race/Ethinicity American Indian or Alaska Native	11	1	12
Race/Ethinicity Asian	22	18	40
Race/Ethinicity Black or African American	3	2	5
Race/Ethinicity NativeHawaiian/pacific Islander	3	8	11
Race/Ethinicity White	98	74	172
Race/Ethinicity Other	139	152	291

End points

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Reporting group title

Group 3B

Reporting group description

Reporting group title

Group B_0_1

Reporting group description

Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

Primary: Percentage of subjects with human serum bactericidal activity (hSBA) ≥1:5

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End point title

Percentage of subjects with human serum bactericidal activity (hSBA) ≥1:5

End point description

Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 a nd M10713.

End point type

Primary

End point timeframe

Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

End point values	Group 3B	Group B_0_1
Number of subjects analysed	275	255
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	33 (27.9 to 39.4)	9 (5.5 to 12.8)
5/99	84 (78.7 to 88.2)	15 (10.4 to 19.8)
NZ98/254	18 (13.3 to 22.6)	8 (5.2 to 12.4)
M10713	74 (68.9 to 79.5)	70 (64.2 to 75.7)

Statistical analysis 1

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis group B indicator strain H44/76and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen.

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[1]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

18.2

upper limit

31.4

Notes
[1] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 2

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis group B indicator strain 5/99 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[2]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

62.3

upper limit

Notes
[2] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 3

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis group B indicator strain NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[3]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.6

upper limit

15.1

Notes
[3] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 4

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis group B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[4]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

11.9

Notes
[4] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Primary: Percentage of subjects with hSBA≥1:8

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End point title

Percentage of subjects with hSBA≥1:8

End point description

Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713

End point type

Primary

End point timeframe

Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

End point values	Group 3B	Group B_0_1
Number of subjects analysed	275	255
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	28 (23.1 to 34.1)	6 (3.3 to 9.5)
5/99	81 (75.3 to 85.4)	13 (9.0 to 17.9)
NZ98/254	14 (10.4 to 19.0)	6 (3.1 to 9.1)
M10713	68 (62.0 to 73.4)	63 (56.9 to 69.1)

Statistical analysis 1

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis group B indicator strain H44/76 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[5]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

16.5

upper limit

28.6

Notes
[5] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 2

Statistical analysis description

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[6]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

60.8

upper limit

73.7

Notes
[6] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 3

Statistical analysis description

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[7]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.7

upper limit

Notes
[7] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 4

Statistical analysis description

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[8]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

12.8

Notes
[8] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Primary: Percentage of subjects with hSBA≥1:16

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End point title

Percentage of subjects with hSBA≥1:16

End point description

Bactericidal activity was measured against each of the N. meningitidis group B Indicator strains H44/76,5/99,NZ98/254 and M10713

End point type

Primary

End point timeframe

Group 3B: Day 1 (prior to booster dose); Group B_0_1: Day 1 (prior to first dose).

End point values	Group 3B	Group B_0_1
Number of subjects analysed	275	255
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	20 (15.1 to 24.8)	4 (2.2 to 7.6)
5/99	75 (69.0 to 80.0)	8 (5.2 to 12.6)
NZ98/254	11 (7.8 to 15.7)	2 (0.9 to 5.1)
M10713	57 (51.2 to 63.2)	56 (49.4 to 61.9)

Statistical analysis 1

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[9]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

10.1

upper limit

20.9

Notes
[9] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 2

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[10]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

59.6

upper limit

72.4

Notes
[10] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 3

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[11]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.9

upper limit

13.6

Notes
[11] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 4

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[12]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

Notes
[12] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Primary: hSBA Geometric Mean Titers (GMTs) after the last dose of rMenB+OMV NZ vaccination in the parent study.

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End point title

hSBA Geometric Mean Titers (GMTs) after the last dose of rMenB+OMV NZ vaccination in the parent study.

End point description

Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76, 5/99, NZ98/254 a nd M10713.

End point type

Primary

End point timeframe

Group 3B: 1 month after the last rMenB+OMV NZ vaccination in parent study and Day 1(prior to booster dose); Group B_0_1: Day 1(prior to first dose)

End point values	Group 3B	Group B_0_1
Number of subjects analysed	275	255
Units: Titers
geometric mean (confidence interval 95%)
H44/76(1 month post last vacc in parent study)	124 (108 to 143)	0 (0 to 0)
H44/76( Day 1)	3.05 (2.61 to 3.56)	1.20 (1.02 to 1.42)
5/99(1 month post last vacc in parent study)	270 (234 to 311)	0 (0 to 0)
5/99 (Day 1)	26 (21 to 31)	1.57 (1.26 to 1.95)
NZ98/254(1 month post last vacc in parent study)	22 (19 to 27)	0 (0 to 0)
NZ98/254( Day 1)	1.66 (1.46 to 1.89)	1.11 (0.97 to 1.27)
M10713(1 month post last vacc in parent study)	19 (16 to 24)	0 (0 to 0)
M10713(Day 1)	16 (13 to 20)	12 (9.86 to 16)

Statistical analysis 1

Statistical analysis description

Adjusted geometric mean titers for H44/76 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[13]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

2.54

Confidence interval

level

95%

sides

2-sided

lower limit

2.07

upper limit

3.12

Notes
[13] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 2

Statistical analysis description

Adjusted geometric mean titers for 5/99 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[14]

Method

ANOVA

Parameter type

Vaccine group ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[14] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 3

Statistical analysis description

Adjusted geometric mean titers for NZ98/254 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[15]

Method

ANOVA

Parameter type

Vaccine group ratio of GMTs

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

1.78

Notes
[15] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 4

Statistical analysis description

Adjusted geometric mean titers for M10713 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

530

Analysis specification

Pre-specified

Analysis type

other ^[16]

Method

ANOVA

Parameter type

Vaccine group ratio of GMTs

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.68

Notes
[16] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 (Group 3B vs. Group B_0_1)

Primary: Geometric Mean Ratios (GMRs) of GMTs after the last dose of rMenB+OMV NZ Vaccination in the Parent Study.

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End point title

Geometric Mean Ratios (GMRs) of GMTs after the last dose of rMenB+OMV NZ Vaccination in the Parent Study. ^[17] ^[18]

End point description

The GMRs of GMTs at Day 1 versus one month after the last dose of rMenB+OMV NZ vaccination in the parent study were calculated. Bactericidal activity was measured against each of the N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713.

End point type

Primary

End point timeframe

Group 3B: 1 month after the last vaccination in parent study and Day1 (prior to booster dose)

Notes
[17] - 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: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.
[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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	Group 3B
Number of subjects analysed	275
Units: Ratio
geometric mean (confidence interval 95%)
H44/76	0.025 (0.020 to 0.030)
5/99	0.098 (0.079 to 0.12)
NZ98/254	0.073 (0.059 to 0.089)
M10713	0.81 (0.65 to 1.01)

No statistical analyses for this end point

Primary: Number of subjects with solicited local and systemic AEs.

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End point title

Number of subjects with solicited local and systemic AEs. ^[19]

End point description

Solicited adverse events are signs and symptoms derived from organized data collection systems, such as Subject Diaries or interview. The percentage and frequencies of subjects reporting solicited local and systemic AEs were tabulated. Threshold for any Erythema, Swelling and Induration: >= 25 mm Note:Vaccination 2 was performed only on group B_0_1 subjects.

End point type

Primary

End point timeframe

7 days (including the day of vaccination) after each vaccination

Notes
[19] - 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: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	266	254
Units: Subjects
Any	263	251
Any Local (vaccination 1)	258	247
Injection site pain (vaccination 1)	258	247
Erythema (vaccination 1)	54	18
Swelling (vaccination 1)	60	34
Induration (vaccination 1)	54	26
Any systemic (vaccination 1)	203	163
Fever (≥ 38.0°C) (vaccination 1)	16	4
High fever (≥ 39.5°C) (vaccination 1)	0	0
Nausea (vaccination 1)	56	30
Fatigue (vaccination 1)	155	110
Myalgia (vaccination 1)	120	71
Arthralgia (vaccination 1)	84	47
Headache (vaccination 1)	146	94
Any Local (vaccination 2)	0	226
Injection site pain (vaccination 2)	0	226
Erythema (vaccination 2)	0	21
Swelling (vaccination 2)	0	32
Induration (vaccination 2)	0	31
Any systemic (vaccination 2)	0	140
Fever (≥ 38.0°C) (vaccination 2)	0	5
High fever (≥ 39.5°C) (vaccination 2)	0	0
Nausea (vaccination 2)	0	33
Fatigue (vaccination 2)	0	92
Myalgia (vaccination 2)	0	64
Arthralgia (vaccination 2)	0	36
Headache (vaccination 2)	0	84

No statistical analyses for this end point

Primary: Number of subjects with any unsolicited adverse events (AEs).

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End point title

Number of subjects with any unsolicited adverse events (AEs). ^[20]

End point description

An unsolicited adverse event is an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject and/or parent(s)/legal guardian(s) who has signed the informed consent. Note : Vaccination 2 was performed only on group B_0_1 subjects.

End point type

Primary

End point timeframe

30 days (including the day of vaccination) after each vaccination.

Notes
[20] - 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: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	275	255
Units: Subjects
Any	87	131
Any unsolicited AEs ( vaccination 1)	87	96
Any unsolicited AEs (vaccination 2)	0	73

No statistical analyses for this end point

Primary: Number of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs.

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End point title

Number of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs. ^[21]

End point description

A serious adverse event is any untoward medical occurrence that at any dose results in death or is life threatening or requires prolonged hospitalization, leads to Persistent or significant disability/incapacity.

End point type

Primary

End point timeframe

Group 3B: from Day 1 to Day 31 (30 days after the vaccination) and Group B_0_1: from Day 1 to Day 61 (30 days after the second dose)

Notes
[21] - 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: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	275	255
Units: Subjects
Any SAEs	0	1
Any Medically Attended AEs	17	34
Any AEs leading to premature withdrawal	0	1

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA ≥1:5 after booster dose/first vaccination of rMenB+OMV NZ.

Top of page

End point title

Percentage of subjects with hSBA ≥1:5 after booster dose/first vaccination of rMenB+OMV NZ.

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713.

End point type

Secondary

End point timeframe

Group 3B: 1 month after booster dose, Group B_0_1 : 30 days after first vaccination.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	268	253
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	99 (96.8 to 99.77)	79 (73.5 to 83.9)
5/99	100 (98.4 to 100.0)	84 (78.9 to 88.6)
NZ98/254	93 (88.9 to 95.6)	52 (45.4 to 58.1)
M10713	99 (96.8 to 99.77)	87 (82.1 to 90.8)

Statistical analysis 1

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[22]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

25.4

Notes
[22] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 2

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[23]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

11.7

upper limit

Notes
[23] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 3

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[24]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

33.9

upper limit

47.8

Notes
[24] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 4

Statistical analysis description

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[25]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

16.8

Notes
[25] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Secondary: Percentage of subjects with hSBA ≥1:8 after booster dose/first vaccination of rMenB+OMV NZ

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End point title

Percentage of subjects with hSBA ≥1:8 after booster dose/first vaccination of rMenB+OMV NZ

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713.

End point type

Secondary

End point timeframe

Group 3B : 1 month after booster dose, Group B_0_1 : 30 days after first vaccination.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	268	253
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	99 (96.8 to 99.77)	72 (65.6 to 77.0)
5/99	100 (98.4 to 100.0)	81 (75.6 to 86.0)
NZ98/254	87 (82.8 to 91.2)	45 (38.4 to 51.0)
M10713	98 (95.7 to 99.4)	85 (79.9 to 89.1)

Statistical analysis 1

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[26]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

21.9

upper limit

33.3

Notes
[26] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 2

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[27]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

14.3

upper limit

24.3

Notes
[27] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 3

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[28]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

35.2

upper limit

49.9

Notes
[28] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 4

Statistical analysis description

The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen.

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[29]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.8

upper limit

18.3

Notes
[29] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Secondary: Percentage of subjects with hSBA ≥1:16 after booster dose/first vaccination of rMenB+OMV NZ

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End point title

Percentage of subjects with hSBA ≥1:16 after booster dose/first vaccination of rMenB+OMV NZ

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains.

End point type

Secondary

End point timeframe

Group 3B: 1 month after booster dose, Group B_0_1 : 30 days after first vaccination.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	268	253
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	99 (96.2 to 99.59)	58 (52.2 to 64.6)
5/99	100 (98.4 to 100.0)	73 (66.9 to 78.6)
NZ98/254	79 (73.6 to 83.8)	36 (29.9 to 42.1)
M10713	95 (91.8 to 97.4)	77 (70.9 to 81.7)

Statistical analysis 1

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[30]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

33.9

upper limit

46.3

Notes
[30] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 2

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[31]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

21.6

upper limit

Notes
[31] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 3

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[32]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

35.1

upper limit

50.6

Notes
[32] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Statistical analysis 4

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[33]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.9

upper limit

24.6

Notes
[33] - Vaccine comparison at 1 month after booster /1st dose in V72_75 (Group 3B vs. Group B_0_1)

Secondary: hSBA Geometric Mean Titers prior to booster/first dose of vaccination & post booster/first dose of vaccination.

Top of page

End point title

hSBA Geometric Mean Titers prior to booster/first dose of vaccination & post booster/first dose of vaccination.

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76, 5/99,NZ98/254 and M10713

End point type

Secondary

End point timeframe

Group 3B subjects: Day 1(pre-booster dose) and 1 month post-booster dose. Group B_0_1: Day 1 (pre-first dose) and 30 days post-first dose.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	268	253
Units: Titers
geometric mean (confidence interval 95%)
H44/76- pre booster/ pre first dose	3.10 (2.65 to 3.62)	1.19 (1.01 to 1.41)
H44/76-1 month post booster/first dose	188 (155 to 228)	16 (13 to 20)
5/99- pre booster/ pre first dose	24 (19 to 30)	1.51 (1.21 to 1.88)
5/99-1 month post booster/first dose	2089 (1690 to 2582)	31 (25 to 38)
NZ98/254-pre booster/ pre first dose	1.64 (1.44 to 1.86)	1.11 (0.97 to 1.28)
NZ98/254-1 month post booster/first dose	32 (26 to 39)	5.39 (4.33 to 6.72)
M10713-pre booster/ pre first dose	16 (13 to 20)	12 (9.62 to 15)
M10713-1 month post booster/first dose	78 (66 to 92)	30 (25 to 36)

Statistical analysis 1

Statistical analysis description

Pre booster/Pre first dose-Adjusted geometric mean titers for H44/76 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[34]

Method

ANOVA

Parameter type

Vaccine group ratios

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

3.2

Notes
[34] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 2

Statistical analysis description

Post booster/Post first dose-Adjusted geometric mean titers for H44/76 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[35]

Method

ANOVA

Parameter type

vaccine group ratios

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.85

upper limit

Notes
[35] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 3

Statistical analysis description

Pre booster/Pre first dose-Adjusted geometric mean titers for 5/99 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[36]

Method

ANOVA

Parameter type

vaccine group ratios

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[36] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 4

Statistical analysis description

Post booster/Post first dose-Adjusted geometric mean titers for 5/99 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[37]

Method

ANOVA

Parameter type

Vaccine group ratios

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[37] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 5

Statistical analysis description

Pre booster/Pre first dose-Adjusted geometric mean titers for NZ98/254 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[38]

Method

ANOVA

Parameter type

Vaccine group ratios

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.24

upper limit

1.75

Notes
[38] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 6

Statistical analysis description

post booster dose/ first dose-Adjusted geometric mean titers for NZ98/254 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[39]

Method

ANOVA

Parameter type

vaccine group ratios

Point estimate

5.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.49

upper limit

7.76

Notes
[39] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 7

Statistical analysis description

Pre booster/Pre first dose-Adjusted geometric mean titers for M10713 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[40]

Method

ANOVA

Parameter type

vaccine group ratios

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.75

Notes
[40] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 8

Statistical analysis description

Post booster/Post first dose-Adjusted geometric mean titers for M10713 indicator strain were obtained by exponentiating (base 10) the least square means and the lower and upper limits of the 95% confidence intervals of the log-transformed titers obtained from an ANOVA estimation adjusting for vaccine group and country

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

other ^[41]

Method

ANOVA

Parameter type

vaccine group ratios

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.08

upper limit

3.25

Notes
[41] - Vaccine comparison Pre-booster or pre-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Secondary: Geometric mean ratio (GMRs) of GMTs after booster dose/first rMenB+OMV NZ vaccination.

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End point title

Geometric mean ratio (GMRs) of GMTs after booster dose/first rMenB+OMV NZ vaccination.

End point description

Bactericidal activity was measured against each of the fout N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713 by calculating the GMRs of GMTs one month post-vaccination of a booster dose versus pre-booster dose (follow-on subjects) or first dose of rMenB+OMV NZ versus pre-first dose (naïve subjects) to each N. meningitidis group B indicator strain.

End point type

Secondary

End point timeframe

At Day 31 (30 days post booster dose/first dose of vaccination) versus Day 1 (prior to booster dose/first dose of vaccination).

End point values	Group 3B	Group B_0_1
Number of subjects analysed	268	253
Units: Ratio
geometric mean (confidence interval 95%)
H44/76	61 (50 to 74)	14 (11 to 17)
5/99	87 (67 to 112)	20 (16 to 26)
NZ98/254	19 (16 to 24)	4.92 (3.97 to 6.10)
M10713	4.85 (4.10 to 5.72)	2.44 (2.04 to 2.91)

No statistical analyses for this end point

Secondary: Percentages of subjects with at least 4-fold increase in hSBA titers pre vaccination compared to one month post-booster/first rMenB+OMV NZ vaccination

Top of page

End point title

Percentages of subjects with at least 4-fold increase in hSBA titers pre vaccination compared to one month post-booster/first rMenB+OMV NZ vaccination

End point description

The percentage of subjects with 4-fold rise at one month post-vaccination with a booster dose (follow-on subjects) /first dose (naive subjects) of rMenB+OMV NZ with respect to day 1 (follow-on subjects) / pre-first dose of rMenB+OMV NZ (naïve subjects)

End point type

Secondary

End point timeframe

Group 3B: 1 month after booster dose; Group B_0_1: 1 month after first vaccination

End point values	Group 3B	Group B_0_1
Number of subjects analysed	268	253
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	96 (93.2 to 98.2)	70 (63.5 to 75.2)
5/99	98 (94.6 to 99.2)	76 (69.9 to 81.4)
NZ98/254	80 (75.0 to 85.0)	43 (36.3 to 49.0)
M10713	49 (42.6 to 54.9)	26 (20.5 to 31.7)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA ≥1:5 after booster dose/second vaccination of rMenB+OMV NZ

Top of page

End point title

Percentage of subjects with hSBA ≥1:5 after booster dose/second vaccination of rMenB+OMV NZ

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. On day 1, subjects in the Group B_0_1 were to be randomized into 2 different blood draw schedules according to a 1:1 ratio : 2 blood samples at different time points: Group B_0_1_1: blood draws at 3 and 30 days after the second dose. Group B_0_1_2: blood draws at 7 and 30 days after the second dose.

End point type

Secondary

End point timeframe

Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose."

End point values	Group 3B	Group B_0_1
Number of subjects analysed	242	203
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 3 days post vaccination	36 (30.3 to 42.8)	80 (71.1 to 87.2)
H44/76 7 days post vaccination	98 (95.2 to 99.3)	99 (94.4 to 99.97)
H44/76 1 month post vaccination	99 (96.4 to 99.74)	99 (96.5 to 99.88)
5/99- 3 days post-vaccination	78 (71.7 to 84.1)	83 (72.9 to 89.9)
5/99- 7 days post-vaccination	100 (98.0 to 100.0)	99 (93.8 to 99.97)
5/99- 1 month post-vaccination	100 (98.0 to 100.0)	99 (95.9 to 99.86)
NZ98/254- 3 days post-vaccination	18 (12.9 to 23.1)	44 (34.1 to 53.8)
NZ98/254- 7 days post-vaccination	74 (67.7 to 79.3)	79 (69.1 to 86.2)
NZ98/254- 1 month post-vaccination	93 (88.6 to 95.7)	76 (69.9 to 82.0)
M10713- 3 days post-vaccination	78 (72.2 to 83.1)	82 (73.2 to 88.7)
M10713- 7 days post-vaccination	98 (94.7 to 99.1)	96 (89.9 to 98.9)
M10713- 1 month post-vaccination	99 (97.0 to 99.90)	93 (88.7 to 96.2)

Statistical analysis 1

Statistical analysis description

3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen.

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[42]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-44

Confidence interval

level

95%

sides

2-sided

lower limit

-52.7

upper limit

-33.1

Notes
[42] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 2

Statistical analysis description

7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[43]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

3.6

Notes
[43] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 3

Statistical analysis description

1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain H44/76 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[44]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

2.4

Notes
[44] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 4

Statistical analysis description

3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[45]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-13.6

upper limit

6.6

Notes
[45] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 5

Statistical analysis description

7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[46]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

6.2

Notes
[46] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 6

Statistical analysis description

1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain 5/99 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[47]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

4.1

Notes
[47] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 7

Statistical analysis description

3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[48]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-26

Confidence interval

level

95%

sides

2-sided

lower limit

-36.9

upper limit

-15.7

Notes
[48] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 8

Statistical analysis description

7 days post vaccination-The group difference in percentages of subjects with response N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[49]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

5.8

Notes
[49] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 9

Statistical analysis description

1 month post vaccination-The group difference in percentages of subjects with response N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[50]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

23.3

Notes
[50] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 10

Statistical analysis description

3 days post vaccination-The group difference in percentages of subjects with response N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[51]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-12.4

upper limit

5.8

Notes
[51] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 11

Statistical analysis description

7 days post vaccination-The group difference in percentages of subjects with response N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[52]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

7.7

Notes
[52] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 12

Statistical analysis description

1 month post vaccination-The group difference in percentages of subjects with response N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[53]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

10.5

Notes
[53] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Secondary: Percentage of subjects with hSBA ≥1:8 after booster dose/second vaccination of rMenB+OMV NZ

Top of page

End point title

Percentage of subjects with hSBA ≥1:8 after booster dose/second vaccination of rMenB+OMV NZ

End point description

End point type

Secondary

End point timeframe

Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	242	203
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 3 days post vaccination	30 (24.5 to 36.4)	75 (65.9 to 83.1)
H44/76 7 days post vaccination	96 (93.1 to 98.3)	97 (91.3 to 99.4)
H44/76 1 month post vaccination	99 (96.4 to 99.74)	98 (95.0 to 99.5)
5/99- 3 days post-vaccination	76 (69.4 to 82.2)	83 (72.9 to 89.9)
5/99- 7 days post-vaccination	100 (98.0 to 100.0)	99 (93.8 to 99.97)
5/99- 1 month post-vaccination	100 (98.0 to 100.0)	99 (95.9 to 99.86)
NZ98/254- 3 days post-vaccination	16 (11.4 to 21.2)	42 (32.3 to 51.9)
NZ98/254- 7 days post-vaccination	67 (60.1 to 72.6)	69 (59.3 to 78.3)
NZ98/254- 1 month post-vaccination	88 (82.6 to 91.5)	67 (60.1 to 73.4)
M10713- 3 days post-vaccination	70 (63.5 to 75.4)	73 (63.8 to 81.5)
M10713- 7 days post-vaccination	95 (92.0 to 97.7)	94 (87.1 to 97.7)
M10713- 1 month post-vaccination	98 (95.8 to 99.55)	90 (85.2 to 93.9)

Statistical analysis 1

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[54]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-45

Confidence interval

level

95%

sides

2-sided

lower limit

-54.4

upper limit

-34.3

Notes
[54] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 2

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[55]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

5.2

Notes
[55] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 3

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[56]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

3.9

Notes
[56] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 4

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[57]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-15.9

upper limit

4.6

Notes
[57] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[58]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

6.2

Notes
[58] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[59]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

4.1

Notes
[59] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 7

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[60]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-26

Confidence interval

level

95%

sides

2-sided

lower limit

-36.6

upper limit

-15.7

Notes
[60] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 8

Statistical analysis description

7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[61]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-13.3

upper limit

8.5

Notes
[61] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 9

Statistical analysis description

1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[62]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.8

upper limit

28.3

Notes
[62] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 10

Statistical analysis description

3 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[63]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-13.4

upper limit

7.1

Notes
[63] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 11

Statistical analysis description

7 days post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[64]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

8.5

Notes
[64] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 12

Statistical analysis description

1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain M10713 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[65]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.2

upper limit

13.2

Notes
[65] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Secondary: Percentage of subjects with hSBA ≥1:16 after booster dose/second vaccination of rMenB+OMV NZ

Top of page

End point title

Percentage of subjects with hSBA ≥1:16 after booster dose/second vaccination of rMenB+OMV NZ

End point description

End point type

Secondary

End point timeframe

Group 3B: 3, 7 and 30 days after third dose booster; Group B_0_1: At 3 (group B_0_1_1 only), 7 (sub-group B_0_1_2 only) and 30 days post-second dose

End point values	Group 3B	Group B_0_1
Number of subjects analysed	242	203
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 3 days post vaccination	21 (15.7 to 26.3)	50 (40.5 to 60.4)
H44/76 7 days post vaccination	95 (91.0 to 97.1)	92 (84.5 to 96.4)
H44/76 1 month post vaccination	99 (96.4 to 99.74)	91 (86.3 to 94.7)
5/99- 3 days post-vaccination	70 (63.1 to 76.8)	76 (65.1 to 84.2)
5/99- 7 days post-vaccination	100 (98.0 to 100.0)	99 (93.8 to 99.97)
5/99- 1 month post-vaccination	100 (98.0 to 100.0)	98 (95.0 to 99.64)
NZ98/254- 3 days post-vaccination	9 (6.0 to 13.9)	30 (21.0 to 39.2)
NZ98/254- 7 days post-vaccination	51 (44.5 to 57.7)	47 (36.8 to 57.3)
NZ98/254- 1 month post-vaccination	81 (75.0 to 85.6)	49 (41.7 to 55.9)
M10713- 3 days post-vaccination	59 (52.0 to 64.8)	64 (53.9 to 73.0)
M10713- 7 days post-vaccination	88 (83.2 to 91.8)	88 (79.6 to 93.5)
M10713- 1 month post-vaccination	95 (91.5 to 97.4)	84 (78.5 to 89.0)

Statistical analysis 1

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[66]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-30

Confidence interval

level

95%

sides

2-sided

lower limit

-40.4

upper limit

-19

Notes
[66] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 2

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[67]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

10.3

Notes
[67] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 3

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[68]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.9

upper limit

12.5

Notes
[68] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 4

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[69]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

6.5

Notes
[69] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[70]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

6.2

Notes
[70] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[71]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

Notes
[71] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 7

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[72]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-20

Confidence interval

level

95%

sides

2-sided

lower limit

-30

upper limit

-11.1

Notes
[72] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 8

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[73]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.6

upper limit

15.7

Notes
[73] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 9

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[74]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

23.2

upper limit

40.2

Notes
[74] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Statistical analysis 10

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[75]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

Notes
[75] - Vaccine comparison at Day 4 Group 3B vs Day 34 Group B_0_1 (3 days after booster or 2nd dose)

Statistical analysis 11

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[76]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

8.9

Notes
[76] - Vaccine comparison at Day 8 Group 3B vs Day 38 Group B_0_1 (7 days after booster or 2nd dose)

Statistical analysis 12

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[77]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.3

upper limit

16.9

Notes
[77] - Vaccine comparison at Day 31 Group 3B vs Day 61 Group B_0_1 (1 month after booster or 2nd dose)

Secondary: hSBA Geometric Mean Titers prior to booster/second dose of vaccination & post booster/second dose of vaccination.

Top of page

End point title

hSBA Geometric Mean Titers prior to booster/second dose of vaccination & post booster/second dose of vaccination.

End point description

End point type

Secondary

End point timeframe

Group 3B: Day 1 (pre-booster dose) and 3, 7 and 30 days after third dose booster; Group B_0_1: Pre 2nd dose and at 3 (group B_0_1_1 only), 7 (group B_0_1_2 only) and 30 days post second dose.

End point values	Group 3B	Group B_0_1
Number of subjects analysed	242	203
Units: Titers
geometric mean (confidence interval 95%)
H44/76 - pre-vaccination	2.99 (2.41 to 3.70)	17 (14 to 22)
H44/76 - 3 days post-vacc	3.20 (2.60 to 3.94)	17 (13 to 23)
H44/76 - 7 days post-vacc	115 (98 to 136)	57 (44 to 73)
H44/76 - 1 month post-vacc.	196 (170 to 228)	56 (48 to 66)
5/99- pre-vaccination	24 (18 to 32)	31 (23 to 41)
5/99- 3 days post-vacc	24 (18 to 31)	27 (19 to 41)
5/99- 7 days post-vacc	1787 (1477 to 2162)	337 (257 to 442)
5/99- 1 month post-vacc.	2026 (1714 to 2395)	248 (208 to 295)
NZ98/254- pre-vaccination	1.57 (1.29 to 1.92)	5.11 (4.10 to 6.38)
NZ98/254- 3 days post-vacc	1.62 (1.35 to 1.96)	4.45 (3.38 to 5.84)
NZ98/254- 7 days post-vacc	12 (10 to 15)	12 (8.46 to 16)
NZ98/254- 1 month post-vacc.	35 (29 to 42)	14 (11 to 17)
M10713- pre-vaccination	15 (12 to 19)	32 (25 to 41)
M10713- 3 days post-vacc	16 (13 to 21)	23 (17 to 33)
M10713- 7 days post-vacc	54 (46 to 62)	45 (36 to 57)
M10713- 1 month post-vacc.	78 (67 to 92)	41 (35 to 49)

Statistical analysis 1

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[78]

Method

ANOVA

Parameter type

vaccine group difference

Point estimate

3.49

Confidence interval

level

95%

sides

2-sided

lower limit

2.85

upper limit

4.29

Notes
[78] - Vaccine Comparison Day 31 Group 3B vs Day 61 Group B_0_1(1 month after booster or 2nd dose)

Statistical analysis 2

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[79]

Method

ANOVA

Parameter type

vaccine group difference

Point estimate

8.18

Confidence interval

level

95%

sides

2-sided

lower limit

6.51

upper limit

Notes
[79] - Vaccine Comparison Day 31 Group 3B vs Day 61 Group B_0_1(1 month after booster or 2nd dose)

Statistical analysis 3

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[80]

Method

ANOVA

Parameter type

vaccine group difference

Point estimate

2.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.98

upper limit

3.36

Notes
[80] - Vaccine Comparison Day 31 Group 3B vs Day 61 Group B_0_1(1 month after booster or 2nd dose)

Statistical analysis 4

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[81]

Method

ANOVA

Parameter type

vaccine group difference

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.52

upper limit

2.36

Notes
[81] - Vaccine Comparison Day 31 Group 3B vs Day 61 Group B_0_1(1 month after booster or 2nd dose)

Secondary: Geometric Mean Ratios (GMRs) of GMTs after booster/second vaccination versus before booster/second vaccination.

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End point title

Geometric Mean Ratios (GMRs) of GMTs after booster/second vaccination versus before booster/second vaccination.

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713 by calculating the GMRs of GMTs post-vaccination with a booster dose (Group 3B) versus pre-booster dose or second dose (Group B_0_1) of vaccination versus pre-second dose.

End point type

Secondary

End point timeframe

Group 3B: Day 1 and 30 days after third dose booster; Group B_0_1: 30 days post-first dose and at 30 days post-second dose

End point values	Group 3B	Group B_0_1
Number of subjects analysed	242	203
Units: Ratio
geometric mean (confidence interval 95%)
H44/76	66 (55 to 79)	3.27 (2.66 to 4.03)
5/99	85 (65 to 111)	8.10 (6.12 to 11)
NZ98/25	22 (19 to 27)	2.63 (2.15 to 3.21)
M10713	5.07 (4.33 to 5.94)	1.27 (1.07 to 1.52)

No statistical analyses for this end point

Secondary: Percentages of Subjects with at Least Four-fold Increase in hSBA Titers Pre-booster/Second dose vaccination- compared to 3, 7 and 30 Days Post- booster/Second Vaccination

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End point title

Percentages of Subjects with at Least Four-fold Increase in hSBA Titers Pre-booster/Second dose vaccination- compared to 3, 7 and 30 Days Post- booster/Second Vaccination

End point description

The percentage of subjects with 4-fold rise at three, seven, thirty days post-vaccination with a booster dose (follow-on subjects) /second dose (naive subjects) of rMenB+OMV NZ with respect to day 1 (follow-on subjects) / pre-second dose of rMenB+OMV NZ (naïve subjects). Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: • for a pre-vaccination titer < 4, a post-vaccination titer of at least 16; • for a pre-vaccination titer ≥ 4 but <LLOQ, a post vaccination titer of at least fourfold the LLOQ; • for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer

End point type

Secondary

End point timeframe

Group 3B: at 3, 7 and 30 days after third dose booster; Group B_0_1: at 3 (group B_0_1_1 only), 7 (group B_0_1_2 only) and 30 days post second dose

End point values	Group 3B	Group B_0_1
Number of subjects analysed	242	203
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 3 days post vaccination	2 (0.7 to 4.8)	4 (1.0 to 9.5)
H44/76 - 7 days post-vacc	88 (82.8 to 91.5)	35 (25.4 to 45.0)
H44/76 - 1 month post-vacc.	96 (93.1 to 98.3)	38 (31.7 to 45.5)
5/99- 3 days post-vacc	5 (2.0 to 8.8)	6 (2.0 to 13.5)
5/99- 7 days post-vacc	97 (92.7 to 98.7)	59 (48.2 to 69.8)
5/99- 1 month post-vacc.	97 (93.5 to 99.1)	64 (56.8 to 71.7)
NZ98/254- 3 days post-vacc	2 (0.7 to 5.0)	2 (0.23 to 6.8)
NZ98/254- 7 days post-vacc	55 (48.3 to 61.5)	19 (11.4 to 27.7)
NZ98/254- 1 month post-vacc.	81 (75.3 to 85.8)	27 (21.3 to 34.1)
M10713- 3 days post-vacc	3 (0.9 to 5.4)	0 (0.0 to 3.5)
M10713- 7 days post-vacc	34 (27.8 to 40.1)	6 (2.3 to 13.0)
M10713- 1 month post-vacc.	49 (42.3 to 55.3)	9 (5.8 to 14.3)

Statistical analysis 1

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[82]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

1.8

Notes
[82] - 3 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 2

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[83]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

42.1

upper limit

62.5

Notes
[83] - 7 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 3

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[84]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

50.5

upper limit

64.7

Notes
[84] - 1 Month Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 4

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[85]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-9.1

upper limit

Notes
[85] - 3 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[86]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

48.1

Notes
[86] - 7 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[87]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

25.2

upper limit

40.4

Notes
[87] - 1 Month Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 7

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[88]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

3.4

Notes
[88] - 3 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 8

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[89]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

25.6

upper limit

45.7

Notes
[89] - 7 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 9

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[90]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

45.2

upper limit

61.1

Notes
[90] - 1 Month Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 10

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[91]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

5.4

Notes
[91] - 3 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 11

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[92]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

19.1

upper limit

34.9

Notes
[92] - 7 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 12

Statistical analysis description

Comparison groups

Group B_0_1 v Group 3B

Number of subjects included in analysis

445

Analysis specification

Pre-specified

Analysis type

other ^[93]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

31.6

upper limit

46.6

Notes
[93] - 1 Month Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Secondary: Percentage of subjects with hSBA ≥1:5 after second vaccination of rMenB+OMV NZ

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End point title

Percentage of subjects with hSBA ≥1:5 after second vaccination of rMenB+OMV NZ ^[94]

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76,5/99,NZ98/254 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.

End point type

Secondary

End point timeframe

At Day 61 (30 days post second dose of vaccination.)

Notes
[94] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	Group B_0_1
Number of subjects analysed	215
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	99 (96.7 to 99.89)
5/99	98 (95.6 to 99.68)
NZ98/254	77 (70.5 to 82.2)
M10713	93 (88.7 to 96.0)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA ≥1:8 after second vaccination of rMenB+OMV NZ.

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End point title

Percentage of subjects with hSBA ≥1:8 after second vaccination of rMenB+OMV NZ. ^[95]

End point description

End point type

Secondary

End point timeframe

At Day 61 (30 days post second vaccination)

Notes
[95] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	Group B_0_1
Number of subjects analysed	215
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	98 (95.3 to 99.5)
5/99	98 (95.6 to 99.68)
NZ98/254	67 (60.3 to 73.2)
M10713	90 (85.4 to 93.8)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA ≥1:16 after second vaccination of rMenB+OMV NZ.

Top of page

End point title

Percentage of subjects with hSBA ≥1:16 after second vaccination of rMenB+OMV NZ. ^[96]

End point description

End point type

Secondary

End point timeframe

At Day 61 (30 days post second vaccination)

Notes
[96] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	Group B_0_1
Number of subjects analysed	215
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	91 (86.0 to 94.2)
5/99	98 (94.8 to 99.4)
NZ98/254	48 (41.5 to 55.3)
M10713	84 (78.5 to 88.7)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers (GMTs) after second vaccination of rMenB+OMV NZ.

Top of page

End point title

hSBA Geometric Mean Titers (GMTs) after second vaccination of rMenB+OMV NZ. ^[97]

End point description

End point type

Secondary

End point timeframe

At Day 1 & Day 61 (30 days post second dose of vaccination)

Notes
[97] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	Group B_0_1
Number of subjects analysed	215
Units: Titers
geometric mean (confidence interval 95%)
H44/76 Day 1	1.32 (1.18 to 1.47)
H44/76 1 month post 2nd vaccination	61 (53 to 70)
5/99 Day 1	1.63 (1.35 to 1.96)
5/99 1 month post 2nd vaccination	257 (217 to 305)
NZ98/254 Day 1	1.28 (1.15 to 1.42)
NZ98/254 1 month post 2nd vaccination	14 (11 to 17)
M10713 Day 1	14 (11 to 18)
M10713 1 month post 2nd vaccination	46 (38 to 55)

No statistical analyses for this end point

Secondary: Geometric mean ratio (GMRs) of GMTs one month post second vaccination versus pre vaccination at Day 1

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End point title

Geometric mean ratio (GMRs) of GMTs one month post second vaccination versus pre vaccination at Day 1 ^[98]

End point description

End point type

Secondary

End point timeframe

At Day 1 & Day 61 (30 days post 2nd vaccination)

Notes
[98] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	Group B_0_1
Number of subjects analysed	215
Units: Ratio
geometric mean (confidence interval 95%)
H44/76	46 (39 to 54)
5/99	156 (117 to 209)
NZ98/254	11 (8.88 to 14)
M10713	3.23 (2.76 to 3.77)

No statistical analyses for this end point

Secondary: Percentages of Subjects with at Least Four-fold Increase in hSBA Titers at pre-First Vaccination compared to One Month Post-Second Vaccination

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End point title

Percentages of Subjects with at Least Four-fold Increase in hSBA Titers at pre-First Vaccination compared to One Month Post-Second Vaccination ^[99]

End point description

The percentage of subjects with 4-fold rise at one month post-vaccination with a second dose (naïve subjects) of rMenB+OMV NZ with respect to day 1, to each and any one, two, three or all 4 indicator strains. Percentage of subjects with four-fold rise in hSBA titers relative to baseline were defined as: • for a pre-vaccination titer < 4, a post-vaccination titer of at least 16; • for a pre-vaccination titer ≥ 4 but <LLOQ, a post vaccination titer of at least fourfold the LLOQ; • for a pre-vaccination titer ≥LLOQ, a post vaccination titer of at least fourfold the pre-vaccination titer. Only subjects receiving the second dose of vaccination(group B_0_1) were considered for this outcome measure.

End point type

Secondary

End point timeframe

At Day 61 (30 days post second dose of vaccination)

Notes
[99] - 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: The results in this study were tabulated by age group and study period. Hence for each related endpoint, they are presented for only the respective groups in the baseline period, while the results for multiple endpoints account for all baseline groups.

End point values	Group B_0_1
Number of subjects analysed	215
Units: Percentage of Subjects
number (confidence interval 95%)
H44/76	95 (91.6 to 97.7)
5/99	97 (92.9 to 98.8)
NZ98/254	67 (59.9 to 73)
M10713	35 (28.2 to 41.4)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited AEs were collected until 7 days after vaccinations. Unsolicited AEs were collected 30 days after vaccination at day 31 (all subjects) and at day 61 (group B_0_1 subjects only).

Adverse event reporting additional description

Serious Adverse Events (SAEs) were collected until study termination (1 month for group 3B subjects/ 2 months for group B_0_1 subjects)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Group B_0_1

Reporting group description

Subjects who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

Reporting group title

Group 3B

Reporting group description

Serious adverse events	Group B_0_1	Group 3B
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 255 (0.39%)	0 / 275 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 255 (0.39%)	0 / 275 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Group B_0_1	Group 3B
Total subjects affected by non serious adverse events
subjects affected / exposed	253 / 255 (99.22%)	266 / 275 (96.73%)
Nervous system disorders
Headache
subjects affected / exposed	126 / 255 (49.41%)	150 / 275 (54.55%)
occurrences all number	442	361
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	251 / 255 (98.43%)	259 / 275 (94.18%)
occurrences all number	2029	1088
Injection site erythema
subjects affected / exposed	135 / 255 (52.94%)	162 / 275 (58.91%)
occurrences all number	724	575
Fatigue
subjects affected / exposed	141 / 255 (55.29%)	156 / 275 (56.73%)
occurrences all number	489	394
Injection site induration
subjects affected / exposed	136 / 255 (53.33%)	135 / 275 (49.09%)
occurrences all number	834	548
Injection site swelling
subjects affected / exposed	111 / 255 (43.53%)	123 / 275 (44.73%)
occurrences all number	675	475
Pyrexia
subjects affected / exposed	9 / 255 (3.53%)	17 / 275 (6.18%)
occurrences all number	16	22
Gastrointestinal disorders
Nausea
subjects affected / exposed	53 / 255 (20.78%)	56 / 275 (20.36%)
occurrences all number	128	113
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	100 / 255 (39.22%)	121 / 275 (44.00%)
occurrences all number	313	291
Arthralgia
subjects affected / exposed	63 / 255 (24.71%)	85 / 275 (30.91%)
occurrences all number	212	203
Infections and infestations
Viral upper respiratory tract infection
subjects affected / exposed	23 / 255 (9.02%)	13 / 275 (4.73%)
occurrences all number	26	13

More information

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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

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of subjects with human serum bactericidal activity (hSBA) ≥1:5

Primary: Percentage of subjects with human serum bactericidal activity (hSBA) ≥1:5

Primary: Percentage of subjects with hSBA≥1:8

Primary: Percentage of subjects with hSBA≥1:8

Primary: Percentage of subjects with hSBA≥1:16

Primary: Percentage of subjects with hSBA≥1:16

Primary: hSBA Geometric Mean Titers (GMTs) after the last dose of rMenB+OMV NZ vaccination in the parent study.

Primary: hSBA Geometric Mean Titers (GMTs) after the last dose of rMenB+OMV NZ vaccination in the parent study.

Primary: Geometric Mean Ratios (GMRs) of GMTs after the last dose of rMenB+OMV NZ Vaccination in the Parent Study.

Primary: Geometric Mean Ratios (GMRs) of GMTs after the last dose of rMenB+OMV NZ Vaccination in the Parent Study.

Primary: Number of subjects with solicited local and systemic AEs.

Primary: Number of subjects with solicited local and systemic AEs.

Primary: Number of subjects with any unsolicited adverse events (AEs).

Primary: Number of subjects with any unsolicited adverse events (AEs).

Primary: Number of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs.

Primary: Number of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs.

Secondary: Percentage of subjects with hSBA ≥1:5 after booster dose/first vaccination of rMenB+OMV NZ.

Secondary: Percentage of subjects with hSBA ≥1:5 after booster dose/first vaccination of rMenB+OMV NZ.

Secondary: Percentage of subjects with hSBA ≥1:8 after booster dose/first vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:8 after booster dose/first vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:16 after booster dose/first vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:16 after booster dose/first vaccination of rMenB+OMV NZ

Secondary: hSBA Geometric Mean Titers prior to booster/first dose of vaccination & post booster/first dose of vaccination.

Secondary: hSBA Geometric Mean Titers prior to booster/first dose of vaccination & post booster/first dose of vaccination.

Secondary: Geometric mean ratio (GMRs) of GMTs after booster dose/first rMenB+OMV NZ vaccination.

Secondary: Geometric mean ratio (GMRs) of GMTs after booster dose/first rMenB+OMV NZ vaccination.

Secondary: Percentages of subjects with at least 4-fold increase in hSBA titers pre vaccination compared to one month post-booster/first rMenB+OMV NZ vaccination

Secondary: Percentages of subjects with at least 4-fold increase in hSBA titers pre vaccination compared to one month post-booster/first rMenB+OMV NZ vaccination

Secondary: Percentage of subjects with hSBA ≥1:5 after booster dose/second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:5 after booster dose/second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:8 after booster dose/second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:8 after booster dose/second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:16 after booster dose/second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:16 after booster dose/second vaccination of rMenB+OMV NZ

Secondary: hSBA Geometric Mean Titers prior to booster/second dose of vaccination & post booster/second dose of vaccination.

Secondary: hSBA Geometric Mean Titers prior to booster/second dose of vaccination & post booster/second dose of vaccination.

Secondary: Geometric Mean Ratios (GMRs) of GMTs after booster/second vaccination versus before booster/second vaccination.

Secondary: Geometric Mean Ratios (GMRs) of GMTs after booster/second vaccination versus before booster/second vaccination.

Secondary: Percentages of Subjects with at Least Four-fold Increase in hSBA Titers Pre-booster/Second dose vaccination- compared to 3, 7 and 30 Days Post- booster/Second Vaccination

Secondary: Percentages of Subjects with at Least Four-fold Increase in hSBA Titers Pre-booster/Second dose vaccination- compared to 3, 7 and 30 Days Post- booster/Second Vaccination

Secondary: Percentage of subjects with hSBA ≥1:5 after second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:5 after second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:8 after second vaccination of rMenB+OMV NZ.

Secondary: Percentage of subjects with hSBA ≥1:8 after second vaccination of rMenB+OMV NZ.

Secondary: Percentage of subjects with hSBA ≥1:16 after second vaccination of rMenB+OMV NZ.

Secondary: Percentage of subjects with hSBA ≥1:16 after second vaccination of rMenB+OMV NZ.

Secondary: hSBA Geometric Mean Titers (GMTs) after second vaccination of rMenB+OMV NZ.

Secondary: hSBA Geometric Mean Titers (GMTs) after second vaccination of rMenB+OMV NZ.

Secondary: Geometric mean ratio (GMRs) of GMTs one month post second vaccination versus pre vaccination at Day 1

Secondary: Geometric mean ratio (GMRs) of GMTs one month post second vaccination versus pre vaccination at Day 1

Secondary: Percentages of Subjects with at Least Four-fold Increase in hSBA Titers at pre-First Vaccination compared to One Month Post-Second Vaccination

Secondary: Percentages of Subjects with at Least Four-fold Increase in hSBA Titers at pre-First Vaccination compared to One Month Post-Second Vaccination

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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