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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	v4(current)
This version publication date	24 Oct 2018
First version publication date	14 Oct 2017
Other versions	v1 , v2 , v3
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

23 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 & 2 sites in Chile.Analysis were performed on the study population (Groups 3B and B_0_1), but also repeated & stratified by parent study (i.e., V72_41 subjects using naïve subjects in Australia and Canada as controls, and V72P10 subjects using naïve subjects in Chile as controls)

Screening details

All enrolled subjects were included in the study. Only groups 3B & B_0_1 were accounted for enrollment number as subjects from parent studies are included in the group 3B.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Blinding implementation details

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

Are arms mutually exclusive

Yes

Group 3B

Arm description

Subjects who received two doses of rMenB+OMV NZ administered at 0, 1 or 0,2 or 0,6 month schedule in study V72P10 (NCT00661713) and at 0,1 month schedule in study V72_41(NCT0142384), and who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during parent studies, 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

Naive subjects from Australia,Canada and Chile, 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

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/Ethnicity American Indian or Alaska Native	11	1	12
Race/Ethnicity Asian	22	18	40
Race/Ethnicity Black or African American	3	2	5
Race/Ethnicity Native Hawaiian/Pacific Islander	3	8	11
Race/Ethnicity White	98	74	172
Race/Ethnicity 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

Subject analysis set title

Group 3B (V72_41)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who received two doses of rMenB+OMV NZ administered at 0,1-month schedule in study V72_41 (NCT0142384) and who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during study V72_41, and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster.

Subject analysis set title

Group 3B (V72P10)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who received two doses of rMenB+OMV NZ administered at 0,1 or 0,2 or 0,6 month schedule in study V72P10 (NCT00661713) and who received a third dose booster of rMenB+OMV NZ at 4 to 7.5 years after the last dose received during study V72P10, and had blood collected at baseline and at 3, 7 and 30 days after the third dose booster.

Subject analysis set title

Group B_0_1 (V72_41)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Naive subjects from Australia and Canada, who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule in this study and had blood collected at baseline, 30 days after the first dose and 3 or 7, and 30 days after the second dose.

Subject analysis set title

Group B_0_1 (V72P10)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Naive subjects from Chile, who received two doses of rMenB+OMV NZ at a 0 and 1 month schedule in this study 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)≥1:4

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End point title

Percentage of subjects with Human Serum Bactericidal Activity (hSBA)≥1:4

End point description

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99, NZ98/254.Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set,& all naïve subjects (group B_0_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1,for at least one indicator strain. This outcome measure was assessed only for strains 5/99 & NZ98/254.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	273	253	144	129	148	105
Units: Percentage of subjects
number (confidence interval 95%)
5/99 (N-254,239,134,120,100,139)	84 (79.2 to 88.5)	17 (12.2 to 22.1)	84 (77 to 90)	84 (76.4 to 90.2)	24 (16.9 to 31.7)	7 (2.9 to 13.9)
NZ98/254 (N-273,253,144,129,105,148)	18 (13.9 to 23.4)	8 (5.2 to 12.4)	9 (4.9 to 14.9)	29 (21.1 to 37.3)	14 (9 to 20.9)	0 (0 to 3.5)

Statistical Analysis 1

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 (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

292

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

68.1

upper limit

84.1

Notes
[1] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [(Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical Analysis 2

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

234

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

49.9

upper limit

69.2

Notes
[2] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical Analysis 3

Statistical analysis description

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

526

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

60.5

upper limit

73.5

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 NZ98/254 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen.

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

292

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

5.3

upper limit

14.8

Notes
[4] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical Analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

234

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

4.9

upper limit

24.2

Notes
[5] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10 vs. Group B_0_1 (V72P10)]

Statistical Analysis 6

Statistical analysis description

Comparison groups

Group 3B v Group B_0_1

Number of subjects included in analysis

526

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

4.3

upper limit

15.9

Notes
[6] - 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 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 and M10713.Analysis was performed on the Full analysis set (FAS) persistence.The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (group B_0_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.This outcome measure was assessed only for strains H44/76 & 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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	275	255	144	131	105	150
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 (N-275,255,144,131,105,150)	33 (27.9 to 39.4)	9 (5.5 to 12.8)	26 (19.4 to 34.4)	41 (32.7 to 50.2)	5 (1.6 to 10.8)	11 (6.7 to 17.5)
M10713(N-274,255,143,131,105,150)	74 (68.9 to 79.5)	70 (64.2 to 75.7)	71 (63.2 to 78.6)	78 (69.8 to 84.6)	59 (49.0 to 68.5)	78 (70.5 to 84.3)

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 ^[7]

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
[7] - 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 B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[8]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine groups difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.2

upper limit

30.1

Notes
[8] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [(Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 3

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

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

upper limit

39.6

Notes
[9] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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 ^[10]

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

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[11]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group differences

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

24.2

Notes
[11] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1(V72_41)]

Statistical analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

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

-10

upper limit

9.5

Notes
[12] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1(V72P10)]

Primary: Percentage of subjects with hSBA titers≥1:5 in parent studies- V72P10 and V72_41

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End point title

Percentage of subjects with hSBA titers≥1:5 in parent studies- V72P10 and V72_41 ^[13]

End point description

Bactericidal activity was measured against the N. meningitidis group B indicator strains H44/76 and M10713. Analysis was performed on the FAS persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (group B_0_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

End point type

Primary

End point timeframe

At one month after last vaccination in parent studies- V72P10 (Month 7) and V72_41 (Month 2)

Notes
[13] - 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 (V72_41)	Group 3B (V72P10)
Number of subjects analysed	144	131
Units: Percentage of subjects
number (confidence interval 95%)
H44/76- Baseline in Parent study(N-144,131)	1 (0.17 to 4.9)	23 (16 to 31.1)
H44/76-1MTHafterlastvacc in Parentstudy(N-144,131)	99 (95.1 to 99.83)	100 (97.2 to 100)
M10713- Baseline in Parent study(N-143,131)	34 (25.9 to 41.9)	73 (64 to 80)
M10713-1MTHafterlastvacc in Parentstudy(N-140,131)	68 (59.4 to 75.5)	98 (94.6 to 99.81)

No statistical analyses for this end point

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.Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (B_0_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	275	255	144	131	105	150
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N=275,255,144,131,105,150)	28 (23.1 to 34.1)	6 (3.3 to 9.5)	22 (15.7 to 29.9)	35 (27.0 to 43.9)	1 (0.02 to 5.2)	9 (5.2 to 15.2)
5/99(N=254,239,134,120,100,139)	81 (75.3 to 85.4)	13 (9.0 to 17.9)	78 (70.4 to 85.0)	83 (75.4 to 89.5)	4 (1.1 to 9.9)	19 (13.2 to 27.0)
NZ98/254(N=273,253,144,129,105,148)	14 (10.4 to 19.0)	6 (3.1 to 9.1)	7 (3.4 to 12.4)	22 (15.6 to 30.7)	0 (0.0 to 3.5)	9 (5.3 to 15.4)
M10713(N=274,255,143,131,105,150)	68 (62.0 to 73.4)	63 (56.9 to 69.1)	62 (53.0 to 69.5)	75 (66.5 to 82.0)	52 (42.4 to 62.2)	71 (62.7 to 77.8)

Statistical analysis 1

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 ^[14]

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
[14] - 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 (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[15]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

14.6

upper limit

28.9

Notes
[15] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 3

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 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[16]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

16.4

upper limit

35.3

Notes
[16] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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 ^[17]

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

Statistical analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[18]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

65.3

upper limit

81.3

Notes
[18] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[19]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

53.6

upper limit

72.3

Notes
[19] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 7

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 ^[20]

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

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[21]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.3

upper limit

12.3

Notes
[21] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 9

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

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

4.5

upper limit

Notes
[22] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 10

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 ^[23]

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

Statistical analysis 11

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

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

-3.3

upper limit

21.4

Notes
[24] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 12

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

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

-6.4

upper limit

14.5

Notes
[25] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Primary: Percentage of subjects with hSBA≥1:16

Top of page

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.Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (B_0_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	275	255	144	131	105	150
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N=275,255,144,131,105,150)	20 (15.1 to 24.8)	4 (2.2 to 7.6)	12 (7.0 to 18.2)	28 (20.7 to 36.8)	0 (0.0 to 3.5)	7 (3.7 to 12.7)
5/99(N=254,239,134,120,100,139)	75 (69.0 to 80.0)	8 (5.2 to 12.6)	72 (63.2 to 79.1)	78 (69.9 to 85.3)	2 (0.24 to 7.0)	13 (7.9 to 19.7)
NZ98/254(N=273,253,144,129,105,148)	11 (7.8 to 15.7)	2 (0.9 to 5.1)	5 (2.0 to 9.8)	19 (12.3 to 26.4)	0 (0.0 to 3.5)	4 (1.5 to 8.6)
M10713(N=274,255,143,131,105,150)	57 (51.2 to 63.2)	56 (49.4 to 61.9)	50 (41.9 to 58.8)	65 (56.1 to 73.0)	48 (37.8 to 57.6)	61 (53.0 to 69.2)

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 ^[26]

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
[26] - 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 (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

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

7.5

upper limit

18.1

Notes
[27] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 3

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

281

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

12.3

upper limit

29.9

Notes
[28] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 4

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 ^[29]

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

Statistical analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

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

60.8

upper limit

Notes
[30] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

281

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

55.2

upper limit

73.7

Notes
[31] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 7

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 ^[32]

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

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

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

1.2

upper limit

9.7

Notes
[33] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 9

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[34]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.5

upper limit

22.6

Notes
[34] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 10

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 ^[35]

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

Statistical analysis 11

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[36]

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

15.2

Notes
[36] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 12

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[37]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

14.7

Notes
[37] - Vaccine comparison at Persistence at 4/7.5 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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

Top of page

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.Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (B_0_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain. 1 month post last vaccination in parent study was abbreviated as 1MTHLastvaccPRNTSTDY in the endpoint categories.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	275	255	144	131	105	150
Units: Titers
geometric mean (confidence interval 95%)
H44/76(1MTHLastvaccPRNTSTDY)N-275,0,144,131,0,0	124 (108 to 143)	0 (0 to 0)	99 (82 to 119)	197 (165 to 235)	0 (0 to 0)	0 (0 to 0)
H44/76( Day 1)N- 275,255,144,131,105,150	3.05 (2.61 to 3.56)	1.20 (1.02 to 1.42)	2.43 (2.04 to 2.89)	4.51 (3.57 to 5.69)	1.14 (0.93 to 1.40)	1.52 (1.23 to 1.90)
5/99(1MTHLastvaccPRNTSTDY)N- 254,0,134,120,0,0	270 (234 to 311)	0 (0 to 0)	180 (153 to 211)	606 (492 to 746)	0 (0 to 0)	0 (0 to 0)
5/99 (Day 1)N- 254,239,134,120,100,139	26 (21 to 31)	1.57 (1.26 to 1.95)	24 (19 to 30)	31 (23 to 42)	1.20 (0.91 to 1.58)	2.30 (1.75 to 3.04)
NZ98/254(1MTHLastvaccPRNTSTDY)N273,0,144,129,0,0	22 (19 to 27)	0 (0 to 0)	11 (8.67 to 14)	93 (75 to 117)	0 (0 to 0)	0 (0 to 0)
NZ98/254( Day 1)N- 273,253,144,129,105,148	1.66 (1.46 to 1.89)	1.11 (0.97 to 1.27)	1.31 (1.17 to 1.45)	2.56 (2.07 to 3.17)	1.01 (0.89 to 1.14)	1.50 (1.23 to 1.84)
M10713(1MTHLastvaccPRNTSTDY)N-271,0,140,131,0,0	19 (16 to 24)	0 (0 to 0)	10 (7.65 to 14)	66 (53 to 81)	0 (0 to 0)	0 (0 to 0)
M10713(Day 1)N- 271,255,140,131,105,150	16 (13 to 20)	12 (9.86 to 16)	13 (9.86 to 18)	22 (16 to 29)	10 (7.13 to 15)	18 (14 to 24)

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 ^[38]

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

Statistical analysis 2

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[39]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

2.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.66

upper limit

2.72

Notes
[39] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 3

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[40]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

2.96

Confidence interval

level

95%

sides

2-sided

lower limit

2.15

upper limit

4.07

Notes
[40] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 4

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 ^[41]

Method

ANOVA

Parameter type

Vaccine group ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

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

Statistical analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[42]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[42] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[43]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.05

upper limit

Notes
[43] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 7

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 ^[44]

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

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[45]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

1.51

Notes
[45] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 9

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[46]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.28

Notes
[46] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 10

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 ^[47]

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

Statistical analysis 11

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

249

Analysis specification

Pre-specified

Analysis type

other ^[48]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

2.05

Notes
[48] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 12

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

281

Analysis specification

Pre-specified

Analysis type

other ^[49]

Method

ANOVA

Parameter type

vaccine group ratio of GMTs

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.78

Notes
[49] - Vaccine Comparison at Persistence at 4 years/Baseline in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Primary: Geometric Mean Ratios (GMRs) of GMTs after the last dose of rMenB+OMV NZ Vaccination in the Parent Study versus day 1

Top of page

End point title

Geometric Mean Ratios (GMRs) of GMTs after the last dose of rMenB+OMV NZ Vaccination in the Parent Study versus day 1 ^[50] ^[51]

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.Analysis was performed on the Full analysis set (FAS) persistence. The FAS included all follow-on subjects (Group 3B) in the All Enrolled Set, and all naïve subjects (B_0_1) in the All Enrolled Set who provided evaluable immunogenicity result at day 1, for at least one indicator strain.

End point type

Primary

End point timeframe

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

Notes
[50] - 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.
[51] - 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	Group 3B (V72_41)	Group 3B (V72P10)
Number of subjects analysed	275	144	131
Units: Ratio
geometric mean (confidence interval 95%)
H44/76(N-275,144,131)	0.025 (0.020 to 0.030)	0.026 (0.020 to 0.033)	0.023 (0.018 to 0.029)
5/99(N-254,134,120)	0.098 (0.079 to 0.12)	0.13 (0.10 to 0.18)	0.052 (0.039 to 0.068)
NZ98/254(N-273,144,129)	0.073 (0.059 to 0.089)	0.12 (0.092 to 0.15)	0.027 (0.021 to 0.036)
M10713(N-271,140,131)	0.81 (0.65 to 1.01)	1.26 (0.92 to 1.73)	0.33 (0.25 to 0.43)

No statistical analyses for this end point

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

Top of page

End point title

Number of subjects with solicited local and systemic AEs. ^[52]

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. Threshold for any Erythema, Swelling and Induration: >= 25 mm.The analysis was done on the Solicited Safety Set. The solicited safety set included all subjects in the exposed set with any solicited adverse event data and/indicators of solicited adverse events.

End point type

Primary

End point timeframe

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

Notes
[52] - 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 (N-266,254)	263	251
Any Local (vaccination 1) (N-266,253)	258	247
Injection site pain (vaccination 1) (N-264,252)	258	247
Erythema (vaccination 1) (N-261,248)	54	18
Swelling (vaccination 1)(261,249)	60	34
Induration (vaccination 1)(N-261,248)	54	26
Any systemic (vaccination 1)(N-266,253)	203	163
Fever (≥ 38.0°C) (vaccination 1)(N-265,253)	16	4
High fever (≥ 39.5°C) (vaccination 1)(N-265,253)	0	0
Nausea (vaccination 1)(N-264,252)	56	30
Fatigue (vaccination 1)(N-266,252)	155	110
Myalgia (vaccination 1)(N-265,252)	120	71
Arthralgia (vaccination 1)(N-265,252)	84	47
Headache (vaccination 1)(N-266,253)	146	94
Any Local (vaccination 2)(N-0,248)	0	226
Injection site pain (vaccination 2)(N-0,247)	0	226
Erythema (vaccination 2)(N-0,247)	0	21
Swelling (vaccination 2)(N-0,248)	0	32
Induration (vaccination 2)(N-0,247)	0	31
Any systemic (vaccination 2)(N-0,248)	0	140
Fever (≥ 38.0°C) (vaccination 2)(N-0,248)	0	5
High fever (≥ 39.5°C) (vaccination 2)(N-0,248)	0	0
Nausea (vaccination 2)(N-0,248)	0	33
Fatigue (vaccination 2)(N-0,248)	0	92
Myalgia (vaccination 2)(N-0,248)	0	64
Arthralgia (vaccination 2)(N-0,248)	0	36
Headache (vaccination 2)(N-0,248)	0	84

No statistical analyses for this end point

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

Top of page

End point title

Number of subjects with any unsolicited adverse events (AEs). ^[53]

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.Analysis was performed on the unsolicited safety set. The unsolicited safety set included all subjects who received a study vaccination with unsolicited adverse event data.

End point type

Primary

End point timeframe

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

Notes
[53] - 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(N-275,255)	87	131
Any unsolicited AEs ( vaccination 1)(N-275,255)	87	96
Any unsolicited AEs (vaccination 2)(N-0,250)	0	73

No statistical analyses for this end point

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

Top of page

End point title

Number of subjects with any SAEs, AEs leading to withdrawal and medically attended AEs. ^[54]

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.Analysis was performed on the Overall safety set. The overall safety set included all screened subjects in the solicited and unsolicited safety set who provided informed consent and provided demographic and/or baseline screening assessments, regardless of the subject’s randomization and treatment status in the study and received a Subject ID.

End point type

Primary

End point timeframe

Group 3B: from Day 1 to Day 31 (study termination visit) and Group B_0_1: from Day 1 to Day 61 (study termination visit)

Notes
[54] - 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(N-275,255)	0	1
Any Medically Attended AEs(N-275,255)	17	34
Any AEs leading to premature withdrawal(N-275,255)	0	1

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA ≥1:4 after booster dose/first vaccination of rMenB+OMV NZ.

Top of page

End point title

Percentage of subjects with hSBA ≥1:4 after booster dose/first vaccination of rMenB+OMV NZ.

End point description

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain. This outcome measure was assessed only for strains 5/99 & NZ98/254.

End point type

Secondary

End point timeframe

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

End point values	Group 3B	Group B_0_1	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	262	251	142	120	103	148
Units: Percentage of subjects
number (confidence interval 95%)
5/99 (N-226,234,124,102,97,137)	100 (98.4 to 100.0)	85 (79.8 to 89.4)	100 (97.1 to 100.0)	100 (96.4 to 100.0)	87 (78.2 to 92.7)	84 (76.7 to 89.7)
NZ98/254 (N-262,251,142,120,103,148)	94 (90.3 to 96.5)	53 (47.0 to 59.7)	94 (89.2 to 97.5)	93 (87.3 to 97.1)	41 (31.2 to 50.9)	62 (53.8 to 70.0)

Statistical Analysis 1

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 (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

245

Analysis specification

Pre-specified

Analysis type

other ^[55]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

21.6

Notes
[55] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

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 (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

268

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

10.8

upper limit

23.1

Notes
[56] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 3

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

513

Analysis specification

Pre-specified

Analysis type

other ^[57]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

20.1

Notes
[57] - 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 NZ98/254 and the associated confidence interval for the difference were calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

245

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

upper limit

63.3

Notes
[58] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical Analysis 5

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 (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

268

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

upper limit

40.1

Notes
[59] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical Analysis 6

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

513

Analysis specification

Pre-specified

Analysis type

other ^[60]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

33.6

upper limit

47.2

Notes
[60] - 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 ≥1:5 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 and M10713.Analysis was performed on the Full Analysis set( FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for at least one indicator strain.This outcome measure was assessed only for strains H44/76 & M10713.

End point type

Secondary

End point timeframe

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

End point values	Group 3B	Group B_0_1	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	268	253	142	127	104	149
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N- 268,253,141,127,104,149)	99 (96.8 to 99.77)	79 (73.5 to 83.9)	98 (93.9 to 99.56)	100 (97.1 to 100.0)	80 (70.8 to 87.0)	79 (71.1 to 84.8)
M10713(N- 268,252,141,127,103,149)	99 (96.8 to 99.77)	87 (82.1 to 90.8)	99 (96.1 to 99.98)	98 (94.4 to 99.81)	80 (70.5 to 86.9)	92 (86.4 to 95.8)

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 ^[61]

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
[61] - 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 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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

246

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

10.7

upper limit

Notes
[62] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 3

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 (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[63]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

15.6

upper limit

28.8

Notes
[63] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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 ^[64]

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

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

246

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

12.8

upper limit

28.6

Notes
[65] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[66]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

12.2

Notes
[66] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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

Top of page

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.Analysis was performed on the Full Analysis set (FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for atleast one indicator strain.

End point type

Secondary

End point timeframe

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

End point values	Group 3B	Group B_0_1	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	268	253	142	127	104	149
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N-268,253,141,127,104,149)	99 (96.8 to 99.77)	72 (65.6 to 77.0)	98 (93.9 to 99.56)	100 (97.1 to 100.0)	67 (57.4 to 76.2)	74 (66.7 to 81.3)
5/99(N-226,234,124,102,97,137)	100 (98.4 to 100.0)	81 (75.6 to 86.0)	100 (97.1 to 100)	100 (96.4 to 100)	81 (72.3 to 88.6)	81 (73.4 to 87.2)
NZ98/254(N- 262,251,142,120,103,148)	87 (82.8 to 91.2)	45 (38.4 to 51.0)	86 (79.1 to 91.2)	89 (82.2 to 94.1)	28 (19.7 to 37.9)	56 (47.7 to 64.2)
M10713(N- 268,252,141,127,103,149)	98 (95.7 to 99.4)	85 (79.9 to 89.1)	99 (95.0 to 99.83)	98 (93.3 to 99.51)	79 (69.5 to 86.1)	89 (83.1 to 93.7)

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 ^[67]

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
[67] - 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 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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

246

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

21.8

upper limit

40.3

Notes
[68] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 3

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 (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[69]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

19.2

upper limit

33.1

Notes
[69] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 4

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 ^[70]

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

Statistical analysis 5

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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

246

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

12.1

upper limit

27.5

Notes
[71] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 6

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 (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[72]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.3

upper limit

26.4

Notes
[72] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 7

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 ^[73]

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

Statistical analysis 8

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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

246

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

46.6

upper limit

67.3

Notes
[74] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 9

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 (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[75]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

42.5

Notes
[75] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 10

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 ^[76]

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

Statistical analysis 11

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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

246

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

12.6

upper limit

Notes
[77] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 12

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 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[78]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

14.7

Notes
[78] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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

Top of page

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 H44/76, 5/99, NZ98/254 & M10713.Analysis was performed on the Full Analysis set (FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for atleast one indicator strain.

End point type

Secondary

End point timeframe

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

End point values	Group 3B	Group B_0_1	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	268	253	142	127	104	149
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N- 268,253,141,127,104,149)	99 (96.2 to 99.59)	58 (52.2 to 64.6)	98 (93.9 to 99.56)	99 (95.7 to 99.98)	49 (39.1 to 59.0)	65 (56.9 to 72.7)
5/99(N-226,234,124,102,97,137)	100 (98.4 to 100.0)	73 (66.9 to 78.6)	100 (97.1 to 100)	100 (96.4 to 100)	77 (67.7 to 85.2)	70 (61.7 to 77.6)
NZ98/254(N- 262,251,142,120,103,148)	79 (73.6 to 83.8)	36 (29.9 to 42.1)	73 (65.2 to 80.3)	86 (78.3 to 91.5)	22 (14.7 to 31.6)	45 (37.1 to 53.7)
M10713(N- 268,252,141,127,103,149)	95 (91.8 to 97.4)	77 (70.9 to 81.7)	94 (88.2 to 97.0)	97 (92.1 to 99.1)	66 (56.0 to 75.1)	84 (77.0 to 89.4)

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 ^[79]

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
[79] - 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 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[80]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

38.9

upper limit

58.5

Notes
[80] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 3

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[81]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

26.6

upper limit

42.2

Notes
[81] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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 ^[82]

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

Statistical analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

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

15.5

upper limit

Notes
[83] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

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

22.9

upper limit

38.1

Notes
[84] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 7

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 ^[85]

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

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

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

39.3

upper limit

60.9

Notes
[86] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 9

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

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

29.9

upper limit

50.2

Notes
[87] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 10

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 ^[88]

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

Statistical analysis 11

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

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

17.9

upper limit

37.8

Notes
[89] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 12

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

276

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

6.4

upper limit

20.1

Notes
[90] - Vaccine comparison at 1 month after booster /1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

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. Analysis was performed on the Full Analysis set (FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for atleast one indicator strain. pre booster/pre first dose was abbreviated as Pre B/1st dose and post booster/post first dose was abbreviated as Post B/1st dose in the endpoint category respectively.

End point type

Secondary

End point timeframe

Group 3B subjects: Day 1(pre-booster dose) and 30 days 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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	268	253	142	127	104	149
Units: Titers
geometric mean (confidence interval 95%)
H44/76-PreB/1stdose(N-268,253,141,127,104,149)	3.10 (2.65 to 3.62)	1.19 (1.01 to 1.41)	2.45 (2.06 to 2.92)	4.65 (3.66 to 5.89)	1.13 (0.92 to 1.38)	1.53 (1.23 to 1.90)
H44/76-1MTHpostB/1stdose(N268,253,141,127,104,149)	188 (155 to 228)	16 (13 to 20)	158 (123 to 204)	269 (206 to 351)	13 (10 to 18)	24 (19 to 31)
5/99-PreB/1stdose(N-211,225,118,93,96,129)	24 (19 to 30)	1.51 (1.21 to 1.88)	22 (17 to 28)	31 (22 to 43)	1.19 (0.89 to 1.59)	2.19 (1.65 to 2.92)
5/99-1MTHpostB/1stdose(N-226,234,124,102,97,137)	2089 (1690 to 2582)	31 (25 to 38)	2191 (1681 to 2856)	1951 (1425 to 2671)	30 (22 to 40)	31 (24 to 41)
NZ98/254-PreB/1stdose(N-260,249,142,118,103,146)	1.64 (1.44 to 1.86)	1.11 (0.97 to 1.28)	1.31 (1.18 to 1.46)	2.48 (1.99 to 3.09)	1.00 (0.88 to 1.13)	1.51 (1.24 to 1.84)
NZ98/254-1MTHpostB/1dose(N-262,251,142,120,103,148	32 (26 to 39)	5.39 (4.33 to 6.72)	30 (23 to 38)	41 (30 to 56)	3.58 (2.70 to 4.76)	9.43 (7.15 to 12)
M10713-PreB/1stdose(N-267,252,140,127,103,149)	16 (13 to 20)	12 (9.62 to 15)	14 (10 to 19)	22 (16 to 29)	9.82 (6.87 to 14)	18 (14 to 23)
M10713-1MTHpostB/1dose(N-268,252,141,127,103,149)	78 (66 to 92)	30 (25 to 36)	65 (52 to 81)	113 (90 to 142)	23 (18 to 30)	46 (37 to 57)

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 ^[91]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

3.2

Notes
[91] - 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 ^[92]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.85

upper limit

Notes
[92] - Vaccine comparison Post-booster or post-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 3

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[93]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.18

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

2.79

Notes
[93] - Vaccine comparison-Pre-booster or pre-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 4

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[94]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.22

upper limit

Notes
[94] - Vaccine comparison-post-booster or post-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[95]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.04

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

4.2

Notes
[95] - Vaccine comparison- Pre-booster or pre-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[96]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.75

upper limit

Notes
[96] - Vaccine comparison- post-booster or post-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 7

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 ^[97]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[97] - 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 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 ^[98]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[98] - Vaccine comparison Post-booster or post-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 9

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[99]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[99] - Vaccine comparison- Pre-booster or pre-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 10

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[100]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

107

Notes
[100] - Vaccine comparison- post-booster or post-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 11

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[101]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.99

upper limit

Notes
[101] - Vaccine comparison- Pre-booster or pre-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 12

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[102]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Notes
[102] - Vaccine comparison- post-booster or post-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 13

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 ^[103]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.24

upper limit

1.75

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

Statistical analysis 14

Statistical analysis description

Post booster dose/ post 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 ^[104]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

5.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.49

upper limit

7.76

Notes
[104] - Vaccine comparison Post-booster or post-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 15

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[105]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

1.54

Notes
[105] - Vaccine comparison- Pre-booster or pre-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 16

Statistical analysis description

Post booster/Post 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 (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[106]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

8.27

Confidence interval

level

95%

sides

2-sided

lower limit

5.83

upper limit

Notes
[106] - Vaccine comparison- post-booster or post-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 17

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[107]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.2

Notes
[107] - Vaccine comparison- Pre-booster or pre-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 18

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[108]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.36

Confidence interval

level

95%

sides

2-sided

lower limit

2.88

upper limit

6.58

Notes
[108] - Vaccine comparison- post-booster or post-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 19

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 ^[109]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.75

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

Statistical analysis 20

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 ^[110]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.08

upper limit

3.25

Notes
[110] - Vaccine comparison Post-booster or post-1st dose in V72_75 (Group 3B vs. Group B _0_1)

Statistical analysis 21

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[111]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

2.18

Notes
[111] - Vaccine comparison- Pre-booster or pre-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 22

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[112]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.79

Confidence interval

level

95%

sides

2-sided

lower limit

2.04

upper limit

3.81

Notes
[112] - Vaccine comparison- post-booster or post-1st dose in V72_75 [Group 3B (V72_41) vs. Group B_0_1 (V72_41)]

Statistical analysis 23

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[113]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.82

Notes
[113] - Vaccine comparison- Pre-booster or pre-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Statistical analysis 24

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[114]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.45

Confidence interval

level

95%

sides

2-sided

lower limit

1.79

upper limit

3.36

Notes
[114] - Vaccine comparison- post-booster or post-1st dose in V72_75 [Group 3B (V72P10) vs. Group B_0_1 (V72P10)]

Secondary: Geometric mean ratio (GMRs) of GMTs after booster dose/first rMenB+OMV NZ vaccination versus day 1.

Top of page

End point title

Geometric mean ratio (GMRs) of GMTs after booster dose/first rMenB+OMV NZ vaccination versus day 1.

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 prefirst dose (naïve subjects) to each N. meningitidis group B indicator strain.Analysis was performed on the Full Analysis set (FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for atleast one 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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	268	253	142	127	104	149
Units: Ratio
geometric mean (confidence interval 95%)
H44/76(N-268,253,141,127,104,149)	61 (50 to 74)	14 (11 to 17)	65 (49 to 85)	58 (44 to 76)	12 (8.69 to 16)	16 (12 to 20)
5/99(N-211,225,118,93,96,129)	87 (67 to 112)	20 (16 to 26)	100 (72 to 139)	64 (44 to 93)	25 (18 to 36)	14 (9.90 to 19)
NZ98/254(N-260,249,142,118,103,146)	19 (16 to 24)	4.92 (3.97 to 6.10)	23 (18 to 29)	16 (12 to 22)	3.60 (2.69 to 4.81)	6.43 (4.95 to 8.34)
M10713(N-267,252,140,127,103,149)	4.85 (4.10 to 5.72)	2.44 (2.04 to 2.91)	4.69 (3.72 to 5.92)	5.16 (4.14 to 6.42)	2.37 (1.81 to 3.10)	2.58 (2.11 to 3.16)

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). 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.Analysis was performed on the Full Analysis set (FAS) booster. The FAS booster included all follow on subjects and all naive subjects in the All enrolled set who received vaccination at day 1 and provided evaluable immunogenicity result at day 31 for atleast one indicator strain.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	268	253	142	127	104	149
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N-268,253,141,127,104,149)	96 (93.2 to 98.2)	70 (63.5 to 75.2)	95 (90.0 to 98.0)	98 (93.3 to 99.51)	66 (56.4 to 75.3)	72 (63.9 to 78.9)
5/99(N-211,225,118,93,96,129)	98 (94.6 to 99.2)	76 (69.9 to 81.4)	98 (94.0 to 99.79)	97 (90.9 to 99.3)	79 (69.7 to 86.8)	74 (65.2 to 81.0)
NZ98/254(N-260,249,142,118,103,146)	80 (75.0 to 85.0)	43 (36.3 to 49.0)	83 (75.9 to 88.9)	77 (68.5 to 84.3)	28 (19.7 to 37.9)	53 (44.3 to 61.1)
M10713(N-267,252,140,127,103,149)	49 (42.6 to 54.9)	26 (20.5 to 31.7)	49 (40.0 to 57.2)	49 (39.9 to 57.8)	24 (16.4 to 33.7)	27 (19.9 to 34.7)

Statistical analysis 1

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 ^[115]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

20.7

upper limit

Notes
[115] - 1 month post booster/first dose of vaccination: Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 2

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[116]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

19.3

upper limit

38.7

Notes
[116] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41) Difference

Statistical analysis 3

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[117]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

18.3

upper limit

33.9

Notes
[117] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10) Difference

Statistical analysis 4

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 or 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

521

Analysis specification

Pre-specified

Analysis type

other ^[118]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

15.9

upper limit

27.9

Notes
[118] - 1 month post booster/first dose of vaccination: Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[119]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

11.5

upper limit

28.5

Notes
[119] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41) Difference

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[120]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

14.6

upper limit

31.9

Notes
[120] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10) Difference

Statistical analysis 7

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 ^[121]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

29.8

upper limit

45.4

Notes
[121] - 1 month post booster/first dose of vaccination: Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[122]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

43.5

upper limit

64.7

Notes
[122] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41) Difference

Statistical analysis 9

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[123]

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

35.1

Notes
[123] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10) Difference

Statistical analysis 10

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 ^[124]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

14.7

upper limit

30.8

Notes
[124] - 1 month post booster/first dose of vaccination: Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 11

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

246

Analysis specification

Pre-specified

Analysis type

other ^[125]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.2

upper limit

35.5

Notes
[125] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41) Difference

Statistical analysis 12

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

other ^[126]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

10.6

upper limit

32.9

Notes
[126] - 1 month post booster/first dose of vaccination: Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10) Difference

Secondary: Percentage of Subjects With hSBA ≥1:4 After Booster Dose/Second Vaccination of rMenB+OMV NZ

Top of page

End point title

Percentage of Subjects With hSBA ≥1:4 After Booster Dose/Second Vaccination of rMenB+OMV NZ

End point description

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. 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.Analysis was performed on PPS kinetics which included all subjects who correctly received the vaccination at day 1/ day 1 & day 31 (naive subjects) & provided evaluable immunogenicity result at all of days 4, 8 & 31 (for follow-on subjects) or at all of days 34,38 and 61 (naive subjects). This outcome measure was assessed only for strains 5/99 & NZ98/254. Days post vaccination has been abbreviated as DPV in the endpoint categories. Month post vaccination has been abbreviated as MPV in the endpoint categories.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	233	203	130	103	94	109
Units: Percentage of subjects
number (confidence interval 95%)
5/99-3 days post vaccination(N-185,86,103,82,44,42	79 (72.3 to 84.6)	85 (75.5 to 91.7)	78 (68.4 to 85.3)	80 (70.3 to 88.4)	82 (67.3 to 91.8)	88 (74.4 to 96.0)
5/99-7 days post vaccination(N-185,88,103,82,40,48	100 (98.0 to 100.0)	99 (93.8 to 99.97)	100 (96.5 to 100.0)	100 (95.6 to 100.0)	100 (95.7 to 100.0)	98 (92.2 to 99.73)
5/99-1 MTH post vaccination(N-185,174,103,82,84,90	100 (98.0 to 100.0)	99 (95.9 to 99.86)	100 (96.5 to 100.0)	100 (95.6 to 100.0)	100 (95.7 to 100.0)	98 (92.2 to 99.73)
NZ98/254-3 days post vacc(N-233,105,130,103,50,55)	19 (14.1 to 24.5)	47 (36.9 to 56.7)	12 (6.6 to 18.3)	28 (19.7 to 37.9)	32 (19.5 to 46.7)	60 (45.9 to 73.0)
NZ98/254- 7 days post vacc(N-233,98,130,103,44,54)	76 (70.0 to 81.3)	81 (71.4 to 87.9)	73 (64.6 to 80.5)	80 (70.5 to 86.9)	80 (64.7 to 90.2)	81 (68.6 to 90.7)
NZ98/254-1 MTH post vacc(N-233,203,130,103,94,109)	94 (90.1 to 96.7)	80 (74.1 to 85.5)	94 (88.2 to 97.3)	94 (87.8 to 97.8)	82 (72.6 to 89.1)	79 (70.0 to 86.1)

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 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

436

Analysis specification

Pre-specified

Analysis type

other ^[127]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-15

upper limit

4.5

Notes
[127] - 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 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[128]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-17

upper limit

11.4

Notes
[128] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical Analysis 3

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

other ^[129]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-8

Confidence interval

level

95%

sides

2-sided

lower limit

-20

upper limit

7.3

Notes
[129] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical Analysis 4

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

436

Analysis specification

Pre-specified

Analysis type

other ^[130]

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

Statistical Analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[131]

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

8.8

Notes
[131] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical Analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

other ^[132]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

Notes
[132] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical Analysis 7

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

436

Analysis specification

Pre-specified

Analysis type

other ^[133]

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

Statistical Analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[134]

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

4.4

Notes
[134] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1(V72_41) (1 month after booster or 2nd dose)

Statistical Analysis - 9

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

other ^[135]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

7.8

Notes
[135] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (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 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

436

Analysis specification

Pre-specified

Analysis type

other ^[136]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-28

Confidence interval

level

95%

sides

2-sided

lower limit

-38.4

upper limit

-17.1

Notes
[136] - 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 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[137]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-20

Confidence interval

level

95%

sides

2-sided

lower limit

-35.2

upper limit

-7.5

Notes
[137] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical Analysis 12

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

other ^[138]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-32

Confidence interval

level

95%

sides

2-sided

lower limit

-46.5

upper limit

-15.7

Notes
[138] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical Analysis 13

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 3B v Group B_0_1

Number of subjects included in analysis

436

Analysis specification

Pre-specified

Analysis type

other ^[139]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-13.6

upper limit

5.6

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

Statistical Analysis 14

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[140]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-19.2

upper limit

9.2

Notes
[140] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical Analysis 15

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

other ^[141]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

12.3

Notes
[141] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical Analysis 16

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 3B v Group B_0_1

Number of subjects included in analysis

436

Analysis specification

Pre-specified

Analysis type

other ^[142]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Diffference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

7.6

upper limit

20.3

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

Statistical Analysis 17

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[143]

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

21.6

Notes
[143] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical Analysis 18

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

other ^[144]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine Group Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

6.4

upper limit

24.6

Notes
[144] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month after booster or 2nd dose)

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 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.Analysis was performed on the PPS kinetics which included all subjects who correctly received the vaccination at day 1/ day 1 & day 31 (naive subjects) & provided evaluable immunogenicity result at all of days 4, 8 & 31 (for follow-on subjects) or at all of days 34,38 & 61 (naive subjects).This outcome measure was assessed only for strains H44/76 & M10713. Days post vaccination has been abbreviated as DPV in the endpoint categories. Month post vaccination has been abbreviated as MPV in the endpoint categories.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	242	203	130	112	94	109
Units: Percentage of subjects
number (confidence interval 95%)
H44/76- 3 DPV (N-242,105,130,112,50,55)	36 (30.3 to 42.8)	80 (71.1 to 87.2)	28 (20.9 to 37.0)	46 (36.1 to 55.2)	74 (59.7 to 85.4)	85 (73.3 to 93.5)
H44/76- 7 DPV(N-242,98,130,112,44,54)	98 (95.2 to 99.3)	99 (94.4 to 99.97)	97 (92.3 to 99.2)	99 (95.1 to 99.98)	100 (92.0 to 100.0)	98 (90.1 to 99.95)
H44/76- 1MPV(N-242,203,130,112,94,109)	99 (96.4 to 99.74)	99 (96.5 to 99.88)	98 (93.4 to 99.52)	100 (96.8 to 100.0)	99 (94.2 to 99.97)	99 (95.0 to 99.98)
M10713- 3 DPV(N-241,105,129,112 ,50,55)	78 (72.2 to 83.1)	82 (73.2 to 88.7)	71 (62.7 to 78.9)	86 (77.8 to 91.6)	76 (61.8 to 86.9)	87 (75.5 to 94.7)
M10713- 7 DPV(N-241,98,129,112,44,54)	98 (94.7 to 99.1)	96 (89.9 to 98.9)	98 (93.4 to 99.52)	97 (92.4 to 99.4)	95 (84.5 to 99.4)	96 (87.3 to 99.55)
M10713- 1 MPV(N-241,203,129,112,94,109)	99 (97.0 to 99.90)	93 (88.7 to 96.2)	99 (95.8 to 99.98)	99 (95.1 to 99.98)	90 (82.6 to 95.5)	95 (89.6 to 98.5)

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 ^[145]

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
[145] - 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 ^[146]

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
[146] - 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 ^[147]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

2.4

Notes
[147] - 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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[148]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-46

Confidence interval

level

95%

sides

2-sided

lower limit

-58.4

upper limit

-29.8

Notes
[148] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[149]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.7

upper limit

5.1

Notes
[149] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[150]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

3.7

Notes
[150] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 7

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[151]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

-40

Confidence interval

level

95%

sides

2-sided

lower limit

-51.8

upper limit

-25.4

Notes
[151] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[152]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

Notes
[152] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 9

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[153]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

Notes
[153] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (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 ^[154]

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
[154] - 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 ^[155]

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
[155] - 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 ^[156]

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

Statistical analysis 13

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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[157]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-17.8

upper limit

10.6

Notes
[157] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 14

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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[158]

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

Notes
[158] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 15

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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[159]

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

16.5

Notes
[159] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 16

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[160]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-11.8

upper limit

Notes
[160] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 17

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[161]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

10.1

Notes
[161] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 18

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[162]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

9.5

Notes
[162] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month days 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

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.Analysis was performed on PPS kinetics which included all subjects who had no protocol deviations/any other reason defined prior to analysis, leading to exclusion & correctly received the vaccination at day 1/day 31 & day 1 & provided evaluable immunogenicity result at all of days 4, 8 & 31 (follow-on subjects)or at all of days 34, 38 & 61(naive) Days post vaccination has been abbreviated as DPV in the endpoint categories. Month post vaccination has been abbreviated as MPV in the endpoint categories.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	242	203	130	112	94	109
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 3 DPV(N-242,105,130,112,50,55)	30 (24.5 to 36.4)	75 (65.9 to 83.1)	22 (15.5 to 30.4)	39 (30.2 to 49.0)	70 (55.4 to 82.1)	80 (67.0 to 89.6)
H44/76 7 DPV(N-242,98,130,112,44,54)	96 (93.1 to 98.3)	97 (91.3 to 99.4)	95 (89.2 to 97.8)	98 (93.7 to 99.78)	95 (84.5 to 99.4)	98 (90.1 to 99.95)
H44/76 1 MPV(N-242,203,130,112,94,109)	99 (96.4 to 99.74)	98 (95.0 to 99.5)	98 (93.4 to 99.52)	100 (96.8 to 100.0)	99 (94.2 to 99.97)	97 (92.2 to 99.4)
5/99- 3 DPV(N-185,86,103,82,44,42)	76 (69.4 to 82.2)	83 (72.9 to 89.9)	74 (64.2 to 82.0)	79 (68.9 to 87.4)	80 (64.7 to 90.2)	86 (71.5 to 94.6)
5/99- 7 DPV(N-185,88,103,82,40,48)	100 (98.0 to 100.0)	99 (93.8 to 99.97)	100 (96.5 to 100.0)	100 (95.6 to 100.0)	100 (91.2 to 100.0)	98 (88.9 to 99.95)
5/99- 1 MPV(N-185,174,103,82,84,90)	100 (98.0 to 100.0)	99 (95.9 to 99.86)	100 (96.5 to 100.0)	100 (95.6 to 100.0)	100 (95.7 to 100.0)	98 (92.2 to 99.73)
NZ98/254- 3DPV(N-233,105,130,103,50,55)	16 (11.4 to 21.2)	42 (32.3 to 51.9)	10 (5.4 to 16.5)	23 (15.5 to 32.7)	28 (16.2 to 42.5)	55 (40.6 to 68.0)
NZ98/254- 7 DPV(N-233,98,130,103,44,54)	67 (60.1 to 72.6)	69 (59.3 to 78.3)	61 (51.8 to 69.2)	74 (64.2 to 82.0)	68 (52.4 to 81.4)	70 (56.4 to 82.0)
NZ98/254- 1 MPV(N-233,203,130,103,94,109)	88 (82.6 to 91.5)	67 (60.1 to 73.4)	85 (77.2 to 90.3)	91 (84.1 to 95.9)	65 (54.4 to 74.5)	69 (59.2 to 77.3)
M10713- 3DPV(N-241,105,129,112,50,55)	70 (63.5 to 75.4)	73 (63.8 to 81.5)	62 (53.1 to 70.4)	79 (69.8 to 85.8)	62 (47.2 to 75.3)	84 (71.2 to 92.2)
M10713- 7 DPV(N-241,98,129,112,44,54)	95 (92.0 to 97.7)	94 (87.1 to 97.7)	95 (90.2 to 98.3)	96 (89.9 to 98.5)	93 (81.3 to 98.6)	94 (84.6 to 98.8)
M10713- 1 MPV(N-241,203,129,112,94,109)	98 (95.8 to 99.55)	90 (85.2 to 93.9)	98 (94.5 to 99.81)	98 (93.7 to 99.78)	86 (77.5 to 92.4)	94 (87.2 to 97.4)

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 ^[163]

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
[163] - 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 ^[164]

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
[164] - 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 ^[165]

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
[165] - 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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[166]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-48

Confidence interval

level

95%

sides

2-sided

lower limit

-60.8

upper limit

-32

Notes
[166] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[167]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-7.3

upper limit

10.1

Notes
[167] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[168]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

3.7

Notes
[168] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 7

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[169]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-41

Confidence interval

level

95%

sides

2-sided

lower limit

-53.3

upper limit

-25.5

Notes
[169] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[170]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

8.1

Notes
[170] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 9

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[171]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

7.8

Notes
[171] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month days 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 ^[172]

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
[172] - 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 ^[173]

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
[173] - 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 ^[174]

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

Statistical analysis 13

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[175]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-19.2

upper limit

10.3

Notes
[175] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 14

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[176]

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

8.8

Notes
[176] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 15

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[177]

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

4.4

Notes
[177] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 16

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[178]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-19.4

upper limit

9.1

Notes
[178] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 17

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[179]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

Notes
[179] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 18

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[180]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

7.8

Notes
[180] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month days after booster or 2nd dose)

Statistical analysis 19

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 ^[181]

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

Statistical analysis 20

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 ^[182]

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

Statistical analysis 21

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 ^[183]

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

Statistical analysis 22

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[184]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-18

Confidence interval

level

95%

sides

2-sided

lower limit

-32.5

upper limit

-5.8

Notes
[184] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 23

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[185]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-22.3

upper limit

9.5

Notes
[185] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 24

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[186]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.4

upper limit

31.3

Notes
[186] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 25

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[187]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-31

Confidence interval

level

95%

sides

2-sided

lower limit

-46

upper limit

-15.5

Notes
[187] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 26

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[188]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.8

upper limit

18.8

Notes
[188] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 27

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[189]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.1

upper limit

32.8

Notes
[189] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month days after booster or 2nd dose)

Statistical analysis 28

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 ^[190]

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

Statistical analysis 29

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 ^[191]

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

Statistical analysis 30

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 ^[192]

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

Statistical analysis 31

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[193]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-15.1

upper limit

16.1

Notes
[193] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 32

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[194]

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

13.9

Notes
[194] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 33

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[195]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.9

upper limit

20.9

Notes
[195] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 34

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[196]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-16.7

upper limit

8.6

Notes
[196] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 35

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[197]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

11.1

Notes
[197] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 36

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[198]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

11.1

Notes
[198] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	242	203	130	112	94	109
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 3 DPV(N-242,105,130,112,50,55)	21 (15.7 to 26.3)	50 (40.5 to 60.4)	13 (7.8 to 20.1)	29 (21.2 to 38.8)	40 (26.4 to 54.8)	60 (45.9 to 73.0)
H44/76 7 DPV(N-242,98,130,112,44,54)	95 (91.0 to 97.1)	92 (84.5 to 96.4)	92 (85.4 to 95.7)	98 (93.7 to 99.78)	89 (75.4 to 96.2)	94 (84.6 to 98.8)
H44/76 1 MPV(N-242,203,130,112,94,109)	99 (96.4 to 99.74)	91 (86.3 to 94.7)	98 (93.4 to 99.52)	100 (96.8 to 100.0)	90 (82.6 to 95.5)	92 (84.9 to 96.2)
5/99- 3 DPV(N-185,86,103,82,44,42)	70 (63.1 to 76.8)	76 (65.1 to 84.2)	69 (59.1 to 77.7)	72 (60.9 to 81.3)	75 (59.7 to 86.8)	76 (60.5 to 87.9)
5/99- 7 DPV(N-185,88,103,82,40,48)	100 (98.0 to 100.0)	99 (93.8 to 99.97)	100 (96.5 to 100)	100 (95.6 to 100)	100 (91.2 to 100)	98 (88.9 to 99.95)
5/99- 1 MPV(N-185,174,103,82,84,90)	100 (98.0 to 100.0)	98 (95.0 to 99.64)	100 (96.5 to 100.0)	100 (95.6 to 100.0)	100 (95.7 to 100.0)	97 (90.6 to 99.3)
NZ98/254- 3 DPV(N-233,105,130,103,50,55)	9 (6.0 to 13.9)	30 (21.0 to 39.2)	5 (2.2 to 10.8)	15 (8.4 to 22.9)	18 (8.6 to 31.4)	40 (27.0 to 54.1)
NZ98/254- 7 DPV(N-233,98,130,103,44,54)	51 (44.5 to 57.7)	47 (36.8 to 57.3)	41 (32.2 to 49.7)	64 (54.0 to 73.3)	41 (26.3 to 56.8)	52 (37.8 to 65.7)
NZ98/254- 1 MPV(N-233,203,130,103,94,109)	81 (75.0 to 85.6)	49 (41.7 to 55.9)	74 (65.4 to 81.2)	89 (81.7 to 94.5)	40 (30.4 to 51.0)	56 (46.1 to 65.5)
M10713- 3 DPV(N-241,105,129,112,50,55)	59 (52.0 to 64.8)	64 (53.9 to 73.0)	48 (39.2 to 57.0)	71 (61.2 to 78.8)	50 (35.5 to 64.5)	76 (63.0 to 86.8)
M10713- 7 DPV(N-241,98,129,112,44,54)	88 (83.2 to 91.8)	88 (79.6 to 93.5)	85 (78.0 to 90.9)	91 (84.2 to 95.6)	84 (69.9 to 93.4)	91 (79.7 to 96.9)
M10713- 1 MPV(N-241,203,129,112,94,109)	95 (91.5 to 97.4)	84 (78.5 to 89.0)	93 (87.2 to 96.8)	97 (92.4 to 99.4)	76 (65.6 to 83.8)	92 (84.9 to 96.2)

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 ^[199]

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
[199] - 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 ^[200]

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
[200] - 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 ^[201]

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
[201] - 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 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[202]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-27

Confidence interval

level

95%

sides

2-sided

lower limit

-41.8

upper limit

-12.9

Notes
[202] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 5

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[203]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

16.2

Notes
[203] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 6

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[204]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

15.2

Notes
[204] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 7

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[205]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-31

Confidence interval

level

95%

sides

2-sided

lower limit

-45.1

upper limit

-14.6

Notes
[205] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 8

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[206]

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

13.5

Notes
[206] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 9

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[207]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

4.4

upper limit

Notes
[207] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (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 ^[208]

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
[208] - 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 ^[209]

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
[209] - 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 ^[210]

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

Statistical analysis 13

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[211]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-20.5

upper limit

10.6

Notes
[211] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 14

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[212]

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

8.8

Notes
[212] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 15

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[213]

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

4.4

Notes
[213] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 16

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[214]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-19.4

upper limit

Notes
[214] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 17

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[215]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

Notes
[215] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 18

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[216]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

9.4

Notes
[216] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month after booster or 2nd dose)

Statistical analysis 19

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 ^[217]

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

Statistical analysis 20

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 ^[218]

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

Statistical analysis 21

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 ^[219]

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

Statistical analysis 22

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[220]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-13

Confidence interval

level

95%

sides

2-sided

lower limit

-25.9

upper limit

-3

Notes
[220] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 23

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[221]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-17.1

upper limit

15.9

Notes
[221] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 24

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[222]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

20.5

upper limit

45.3

Notes
[222] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 25

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[223]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-25

Confidence interval

level

95%

sides

2-sided

lower limit

-40.1

upper limit

-11.2

Notes
[223] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 26

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[224]

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

28.1

Notes
[224] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 27

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[225]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

44.1

Notes
[225] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month after booster or 2nd dose)

Statistical analysis 28

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 ^[226]

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

Statistical analysis 29

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 ^[227]

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

Statistical analysis 30

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 ^[228]

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

Statistical analysis 31

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[229]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-18

upper limit

14.1

Notes
[229] - Vaccine comparison at Day 4 Group 3B (V72_41) vs Day 34 Group B_0_1 (V72_41) (3 days after booster or 2nd dose)

Statistical analysis 32

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[230]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-9.7

upper limit

15.7

Notes
[230] - Vaccine comparison at Day 8 Group 3B (V72_41) vs Day 38 Group B_0_1 (V72_41) (7 days after booster or 2nd dose)

Statistical analysis 33

Statistical analysis description

Comparison groups

Group B_0_1 (V72_41) v Group 3B (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[231]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

8.2

upper limit

27.8

Notes
[231] - Vaccine comparison at Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 34

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[232]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-19.1

upper limit

9.1

Notes
[232] - Vaccine comparison at Day 4 Group 3B (V72P10) vs Day 34 Group B_0_1 (V72P10) (3 days after booster or 2nd dose)

Statistical analysis 35

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[233]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

11.8

Notes
[233] - Vaccine comparison at Day 8 Group 3B (V72P10) vs Day 38 Group B_0_1 (V72P10) (7 days after booster or 2nd dose)

Statistical analysis 36

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[234]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

12.6

Notes
[234] - Vaccine comparison at Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	242	203	130	112	94	109
Units: Titers
geometric mean (confidence interval 95%)
H44/76 -Pre Vacc(N-242,203,130,112,94,109)	2.99 (2.41 to 3.70)	17 (14 to 22)	2.41 (1.86 to 3.13)	4.61 (3.34 to 6.38)	14 (10 to 19)	27 (19 to 37)
H44/76 - 3 DPV(N-242,105,130,112,50,55)	3.20 (2.60 to 3.94)	17 (13 to 23)	2.68 (2.06 to 3.48)	4.57 (3.38 to 6.18)	14 (9.55 to 22)	24 (16 to 37)
H44/76 - 7 DPV(N-242,98,130,112,44,54)	115 (98 to 136)	57 (44 to 73)	97 (77 to 123)	153 (123 to 191)	62 (42 to 90)	60 (44 to 83)
H44/76 - 1 MPV(N-242,203,130,112,94,109)	196 (170 to 228)	56 (48 to 66)	157 (127 to 193)	285 (234 to 345)	57 (45 to 73)	64 (52 to 78)
5/99-Pre Vacc(N-175,169,100,75,82,87)	24 (18 to 32)	31 (23 to 41)	20 (14 to 29)	30 (20 to 47)	33 (23 to 50)	30 (20 to 44)
5/99- 3 DPV(N-185,86,103,82,44,42)	24 (18 to 31)	27 (19 to 41)	23 (16 to 34)	25 (17 to 35)	27 (15 to 49)	28 (17 to 47)
5/99- 7 DPV(N-185,88,103,82,40,48)	1787 (1477 to 2162)	337 (257 to 442)	1969 (1516 to 2556)	1547 (1191 to 2009)	294 (197 to 439)	365 (259 to 514)
5/99- 1 MPV(N-185,174,103,82,84,90)	2026 (1714 to 2395)	248 (208 to 295)	2147 (1749 to 2635)	1903 (1469 to 2466)	224 (179 to 281)	276 (215 to 353)
NZ98/254-Pre Vacc(N-231,201,130,101,93,108)	1.57 (1.29 to 1.92)	5.11 (4.10 to 6.38)	1.31 (1.06 to 1.63)	2.40 (1.72 to 3.37)	3.44 (2.66 to 4.43)	9.79 (7.07 to 14)
NZ98/254- 3 DPV(N-233,105,130,103,50,55)	1.62 (1.35 to 1.96)	4.45 (3.38 to 5.84)	1.40 (1.15 to 1.70)	2.34 (1.72 to 3.20)	2.75 (2.02 to 3.74)	8.94 (5.84 to 14)
NZ98/254- 7 DPV(N-233,98,130,103,44,54)	12 (10 to 15)	12 (8.46 to 16)	10 (7.80 to 13)	18 (13 to 25)	11 (6.96 to 17)	15 (9.79 to 24)
NZ98/254- 1 MPV(N-233,203,130,103,94,109)	35 (29 to 42)	14 (11 to 17)	32 (25 to 40)	44 (33 to 59)	12 (9.04 to 16)	17 (13 to 23)
M10713-Pre Vacc(N-240,202,128,112,93,109)	15 (12 to 19)	32 (25 to 41)	13 (9.76 to 18)	22 (16 to 29)	25 (18 to 35)	50 (38 to 67)
M10713- 3DPV(N-241,105,129,112,50,55)	16 (13 to 21)	23 (17 to 33)	14 (9.96 to 19)	24 (18 to 32)	18 (11 to 30)	37 (24 to 56)
M10713- 7 DPV(N-241,98,129,112,44,54)	54 (46 to 62)	45 (36 to 57)	48 (39 to 59)	68 (56 to 82)	42 (30 to 59)	56 (42 to 73)
M10713- 1 MPV(N-241,203,129,112,94,109)	78 (67 to 92)	41 (35 to 49)	64 (52 to 80)	116 (94 to 143)	34 (26 to 44)	61 (49 to 75)

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 ^[235]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

3.49

Confidence interval

level

95%

sides

2-sided

lower limit

2.85

upper limit

4.29

Notes
[235] - 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 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[236]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.73

Confidence interval

level

95%

sides

2-sided

lower limit

2.02

upper limit

3.69

Notes
[236] - Vaccine Comparison Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 3

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[237]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

4.46

Confidence interval

level

95%

sides

2-sided

lower limit

3.38

upper limit

5.88

Notes
[237] - Vaccine Comparison Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (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 ^[238]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

8.18

Confidence interval

level

95%

sides

2-sided

lower limit

6.51

upper limit

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

Statistical analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[239]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

9.58

Confidence interval

level

95%

sides

2-sided

lower limit

7.17

upper limit

Notes
[239] - Vaccine Comparison Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[240]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

6.9

Confidence interval

level

95%

sides

2-sided

lower limit

4.82

upper limit

9.87

Notes
[240] - Vaccine Comparison Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (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 ^[241]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.98

upper limit

3.36

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

Statistical analysis 8

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[242]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.89

upper limit

3.73

Notes
[242] - Vaccine Comparison Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 9

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[243]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

2.51

Confidence interval

level

95%

sides

2-sided

lower limit

1.67

upper limit

3.78

Notes
[243] - Vaccine Comparison Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (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 ^[244]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.52

upper limit

2.36

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

Statistical analysis 11

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[245]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.88

Confidence interval

level

95%

sides

2-sided

lower limit

1.37

upper limit

2.59

Notes
[245] - Vaccine Comparison Day 31 Group 3B (V72_41) vs Day 61 Group B_0_1 (V72_41) (1 month after booster or 2nd dose)

Statistical analysis 12

Statistical analysis description

Comparison groups

Group 3B (V72P10) v Group B_0_1 (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[246]

Method

ANOVA

Parameter type

Ratio of GMTs

Point estimate

1.91

Confidence interval

level

95%

sides

2-sided

lower limit

1.41

upper limit

2.58

Notes
[246] - Vaccine Comparison Day 31 Group 3B (V72P10) vs Day 61 Group B_0_1 (V72P10) (1 month after booster or 2nd dose)

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

Top of page

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.Analysis was performed on PPS kinetics which included all subjects who had no protocol deviations/any other reason defined prior to analysis, leading to exclusion & correctly received the vaccination at day 1/day 31 & day 1 & provided evaluable immunogenicity result at all of days 4, 8 & 31 (follow-on subjects)or at all of days 34, 38 & 61(naive)

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	242	203	130	112	94	109
Units: Ratio
geometric mean (confidence interval 95%)
H44/76(N-242,203,130,112,94,109)	66 (55 to 79)	3.27 (2.66 to 4.03)	65 (49 to 85)	62 (49 to 78)	4.21 (3.05 to 5.80)	2.37 (1.87 to 3.00)
5/99(N-175,169,100,75,82,87)	85 (65 to 111)	8.10 (6.12 to 11)	105 (76 to 145)	62 (41 to 96)	6.86 (4.82 to 9.78)	9.09 (6.10 to 14)
NZ98/25(N-231,201,130,101,93,108)	22 (19 to 27)	2.63 (2.15 to 3.21)	24 (19 to 30)	18 (14 to 24)	3.42 (2.59 to 4.51)	1.76 (1.36 to 2.29)
M10713(N-240,202,128,112,93,109)	5.07 (4.33 to 5.94)	1.27 (1.07 to 1.52)	4.87 (3.92 to 6.05)	5.30 (4.29 to 6.55)	1.36 (1.06 to 1.75)	1.20 (0.97 to 1.49)

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

Top of page

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 3, 7, 30 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. Days post vaccination has been abbreviated as DPV in the endpoint categories. Month post vaccination has been abbreviated as MPV in the endpoint categories.

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	Group 3B (V72_41)	Group 3B (V72P10)	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	242	203	130	112	94	109
Units: Percentage of subjects
number (confidence interval 95%)
H44/76 3 DPV (N-242,105,130,112,50,55)	2 (0.7 to 4.8)	4 (1.0 to 9.5)	2 (0.48 to 6.6)	2 (0.22 to 6.3)	6 (1.3 to 16.5)	2 (0.05 to 9.7)
H44/76 - 7 DPV(N-242,98,130,112,44,54)	88 (82.8 to 91.5)	35 (25.4 to 45.0)	89 (82.6 to 94.0)	86 (77.8 to 91.6)	45 (30.4 to 61.2)	26 (15.0 to 39.7)
H44/76 - 1 MPV(N-242,203,130,112,94,109)	96 (93.1 to 98.3)	38 (31.7 to 45.5)	95 (89.2 to 97.8)	98 (93.7 to 99.78)	51 (40.5 to 61.5)	28 (19.4 to 36.9)
5/99-3 MPV(N-175,83,100,75,44,39)	5 (2.0 to 8.8)	6 (2.0 to 13.5)	7 (2.9 to 13.9)	1 (0.03 to 7.2)	5 (0.6 to 15.5)	8 (1.6 to 20.9)
5/99- 7 DPV(N-175,86,100,75,38,48)	97 (92.7 to 98.7)	59 (48.2 to 69.8)	98 (93.0 to 99.76)	95 (86.9 to 98.5)	55 (38.3 to 71.4)	63 (47.4 to 76.0)
5/99- 1 MPV(N-175,169,100,75,82,87)	97 (93.5 to 99.1)	64 (56.8 to 71.7)	98 (93.0 to 99.76)	96 (88.8 to 99.2)	56 (44.7 to 67.0)	72 (61.8 to 81.5)
NZ98/254-3 DPV(N-231,104,130,101,50,54)	2 (0.7 to 5.0)	2 (0.23 to 6.8)	2 (0.48 to 6.6)	2 (0.24 to 7.0)	2 (0.05 to 10.6)	2 (0.05 to 9.9)
NZ98/254- 7 DPV(N-231,97,130,101,43,54)	55 (48.3 to 61.5)	19 (11.4 to 27.7)	55 (45.7 to 63.4)	55 (45.2 to 65.3)	26 (13.5 to 41.2)	13 (5.4 to 24.9)
NZ98/254- 1 MPV(N-231,201,130,101,93,108)	81 (75.3 to 85.8)	27 (21.3 to 34.1)	82 (73.8 to 87.8)	80 (71.1 to 87.5)	35 (25.8 to 46.1)	20 (13.2 to 29.2)
M10713- 3 DPV(N-240,105,128,112,50,55)	3 (0.9 to 5.4)	0 (0.0 to 3.5)	2 (0.49 to 6.7)	3 (0.6 to 7.6)	0 (0.0 to 7.1)	0 (0.0 to 6.5)
M10713- 7 DPV(N-240,97,128,112,43,54)	34 (27.8 to 40.1)	6 (2.3 to 13.0)	39 (30.6 to 48.1)	28 (19.6 to 36.9)	14 (5.3 to 27.9)	0 (0.0 to 6.6)
M10713- 1 MPV(N-240,202,128,112,93,109)	49 (42.3 to 55.3)	9 (5.8 to 14.3)	48 (39.5 to 57.4)	49 (39.5 to 58.7)	12 (6.1 to 20.2)	7 (3.2 to 14.0)

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 ^[247]

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
[247] - 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 ^[248]

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
[248] - 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 ^[249]

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
[249] - 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 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[250]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-14.1

upper limit

Notes
[250] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 5

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[251]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

28.1

upper limit

58.5

Notes
[251] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 6

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[252]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

32.7

upper limit

54.1

Notes
[252] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 7

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[253]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

4.8

Notes
[253] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 8

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[254]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

71.5

Notes
[254] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 9

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[255]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

61.2

upper limit

78.5

Notes
[255] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] 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 ^[256]

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
[256] - 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 ^[257]

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
[257] - 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 ^[258]

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
[258] - 1 Month Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 13

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[259]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

10.2

Notes
[259] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 14

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[260]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

27.7

upper limit

58.6

Notes
[260] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 15

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[261]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

31.1

upper limit

Notes
[261] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 16

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[262]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-19.2

upper limit

0.9

Notes
[262] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 17

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[263]

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

Notes
[263] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 18

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[264]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.2

upper limit

34.4

Notes
[264] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 19

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 ^[265]

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
[265] - 3 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 20

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 ^[266]

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
[266] - 7 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 21

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 ^[267]

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
[267] - 1 Month Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 22

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[268]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

Notes
[268] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 23

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[269]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

12.1

upper limit

Notes
[269] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 24

Statistical analysis description

1 month post vaccination-The group difference in percentages of subjects with response against N. meningitidis serogroup B indicator strain NZ98/154 and the associated confidence interval for the difference was calculated using the method of Miettinen and Nurminen

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[270]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

33.6

upper limit

57.1

Notes
[270] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 25

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[271]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

5.4

Notes
[271] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 26

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[272]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

27.8

upper limit

54.5

Notes
[272] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 27

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[273]

Method

Miettinen and Nurminen score method

Parameter type

vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

47.9

upper limit

69.6

Notes
[273] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 28

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 ^[274]

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
[274] - 3 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 29

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 ^[275]

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
[275] - 7 Days Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 30

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 ^[276]

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
[276] - 1 Month Post Booster/Second Vaccination. Four-fold Increase (Group 3B vs. Group B_0_1) Difference

Statistical analysis 31

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[277]

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

6.7

Notes
[277] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 32

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[278]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.7

upper limit

37.1

Notes
[278] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 33

Statistical analysis description

Comparison groups

Group 3B (V72_41) v Group B_0_1 (V72_41)

Number of subjects included in analysis

224

Analysis specification

Pre-specified

Analysis type

other ^[279]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

25.1

upper limit

Notes
[279] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72_41) vs. Group B_0_1 (V72_41)] Difference

Statistical analysis 34

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[280]

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

7.6

Notes
[280] - 3 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 35

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[281]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

20.2

upper limit

36.6

Notes
[281] - 7 Days Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Statistical analysis 36

Statistical analysis description

Comparison groups

Group B_0_1 (V72P10) v Group 3B (V72P10)

Number of subjects included in analysis

221

Analysis specification

Pre-specified

Analysis type

other ^[282]

Method

Miettinen and Nurminen score method

Parameter type

Vaccine group difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

51.9

Notes
[282] - 1 month Post Booster/Second Vaccination. Four-fold Increase [Group 3B (V72P10) vs. Group B_0_1 (V72P10)] Difference

Secondary: Percentage of subjects with hSBA ≥1:4 after second vaccination of rMenB+OMV NZ

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End point title

Percentage of subjects with hSBA ≥1:4 after second vaccination of rMenB+OMV NZ ^[283]

End point description

Bactericidal activity was measured against the N. meningitidis group B indicator strains 5/99 and NZ98/254. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B_0_1 who correctly received two vaccinations at day 1 and day 31 & provided evaluable immunogenicity result at day 61 for atleast one indicator strain. The analysis was performed only on strains 5/99 and NZ98/254.

End point type

Secondary

End point timeframe

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

Notes
[283] - 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	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	215	98	117
Units: Percentage of subjects
number (confidence interval 95%)
5/99 (N-195,91,104)	98 (95.6 to 99.68)	100 (96.0 to 100.0)	97 (91.8 to 99.4)
NZ98/254 (N-215,98,117)	80 (74.5 to 85.5)	82 (72.5 to 88.7)	79 (71.0 to 86.4)

No statistical analyses for this end point

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 ^[284]

End point description

Bactericidal activity was measured against each of the four N. meningitidis group B indicator strains H44/76 and M10713. Only subjects receiving a second vaccination (group B_0_1) were assessed for this outcome measure.Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B_0_1 who correctly received two vaccinations at day 1 and day 31 & provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

End point type

Secondary

End point timeframe

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

Notes
[284] - 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	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	215	98	117
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N-215,98,117)	99 (96.7 to 99.89)	99 (94.4 to 99.97)	99 (95.3 to 99.98)
M10713(N-214,98,116)	93 (88.7 to 96.0)	90 (82.0 to 95.0)	96 (90.2 to 98.6)

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. ^[285]

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.Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B_0_1 who correctly received two vaccinations at day 1 and day 31 & provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

End point type

Secondary

End point timeframe

At Day 61 (30 days post second vaccination)

Notes
[285] - 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	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	215	98	117
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N-215,98,117)	98 (95.3 to 99.5)	99 (94.4 to 99.97)	97 (92.7 to 99.5)
5/99(N-195,91,104)	98 (95.6 to 99.68)	100 (96.0 to 100.0)	97 (91.8 to 99.4)
NZ98/254(N-215,98,117)	67 (60.3 to 73.2)	64 (54.0 to 73.7)	69 (60.0 to 77.4)
M10713(N-214,98,116)	90 (85.4 to 93.8)	86 (77.2 to 92.0)	94 (88.0 to 97.5)

No statistical analyses for this end point

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

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End point title

Percentage of subjects with hSBA ≥1:16 after second vaccination of rMenB+OMV NZ. ^[286]

End point description

End point type

Secondary

End point timeframe

At Day 61 (30 days post second vaccination)

Notes
[286] - 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	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	215	98	117
Units: Percentage of subjects
number (confidence interval 95%)
H44/76(N-215,98,117)	91 (86.0 to 94.2)	91 (83.3 to 95.7)	91 (83.8 to 95.2)
5/99(N-195,91,104)	98 (94.8 to 99.4)	100 (96.0 to 100)	96 (90.4 to 98.9)
NZ98/254(N-215,98,117)	48 (41.5 to 55.3)	40 (30.0 to 50.2)	56 (46.1 to 64.7)
M10713(N-214,98,116)	84 (78.5 to 88.7)	74 (64.7 to 82.8)	92 (85.8 to 96.4)

No statistical analyses for this end point

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

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End point title

hSBA Geometric Mean Titers (GMTs) after second vaccination of rMenB+OMV NZ. ^[287]

End point description

End point type

Secondary

End point timeframe

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

Notes
[287] - 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	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	215	98	117
Units: Titers
geometric mean (confidence interval 95%)
H44/76-Day 1(N-215,98,117)	1.32 (1.18 to 1.47)	1.08 (1.00 to 1.17)	1.56 (1.29 to 1.89)
H44/76-1MTH post 2nd vacc(N-215,98,117)	61 (53 to 70)	57 (47 to 68)	64 (53 to 78)
5/99-Day 1(N-181,86,95)	1.63 (1.35 to 1.96)	1.18 (1.03 to 1.35)	2.18 (1.58 to 3.00)
5/99-1 MTH post 2nd vacc(N-195,91,104)	257 (217 to 305)	239 (200 to 285)	274 (207 to 363)
NZ98/254-Day 1(N-213,98,115)	1.28 (1.15 to 1.42)	1.00 (1.00 to 1.00)	1.58 (1.30 to 1.91)
NZ98/254-1MTH post 2nd vacc(N-215,98,117)	14 (11 to 17)	11 (8.41 to 14)	18 (13 to 24)
M10713-Day 1(N-214,98,116)	14 (11 to 18)	10 (7.13 to 15)	19 (14 to 26)
M10713-1 MTH post 2nd vacc(N-214,98,116)	46 (38 to 55)	33 (25 to 44)	60 (48 to 75)

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 ^[288]

End point description

End point type

Secondary

End point timeframe

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

Notes
[288] - 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	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	215	98	117
Units: Ratio
geometric mean (confidence interval 95%)
H44/76(N-215,98,117)	46 (39 to 54)	52 (42 to 65)	41 (33 to 51)
5/99(N-181,86,95)	156 (117 to 209)	204 (162 to 257)	123 (74 to 204)
NZ98/254(N-213,98,115)	11 (8.88 to 14)	11 (8.41 to 14)	11 (7.94 to 16)
M10713(N-214,98,116)	3.23 (2.76 to 3.77)	3.24 (2.57 to 4.08)	3.22 (2.60 to 3.98)

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 ^[289]

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.Analysis was performed on the PPS( per protocol set) catch up. The PPS catch up included all subjects who were randomized to group B_0_1 who correctly received two vaccinations at day 1 and day 31 & provided evaluable immunogenicity result at day 61 for atleast one indicator strain.

End point type

Secondary

End point timeframe

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

Notes
[289] - 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	Group B_0_1 (V72_41)	Group B_0_1 (V72P10)
Number of subjects analysed	215	98	117
Units: Percentage of Subjects
number (confidence interval 95%)
H44/76(N-215,98,117)	95 (91.6 to 97.7)	97 (91.3 to 99.4)	94 (88.1 to 97.6)
5/99(N-181,86,95)	97 (92.9 to 98.8)	100 (95.8 to 100)	94 (86.8 to 97.6)
NZ98/254(N-213,98,115)	67 (59.9 to 73)	64 (54.0 to 73.7)	69 (59.4 to 77.0)
M10713(N-214,98,116)	35 (28.2 to 41.4)	37 (27.2 to 47.1)	33 (24.3 to 42.1)

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 each 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 3B

Reporting group description

Reporting group title

Group B_0_1

Reporting group description

Serious adverse events	Group 3B	Group B_0_1
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 275 (0.00%)	1 / 255 (0.39%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 275 (0.00%)	1 / 255 (0.39%)
occurrences causally related to treatment / all	0 / 0	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 3B	Group B_0_1
Total subjects affected by non serious adverse events
subjects affected / exposed	266 / 275 (96.73%)	253 / 255 (99.22%)
Nervous system disorders
Headache
subjects affected / exposed	150 / 275 (54.55%)	126 / 255 (49.41%)
occurrences all number	361	442
General disorders and administration site conditions
Injectioon site pain
subjects affected / exposed	259 / 275 (94.18%)	251 / 255 (98.43%)
occurrences all number	1088	2029
Injection site erythema
subjects affected / exposed	162 / 275 (58.91%)	135 / 255 (52.94%)
occurrences all number	575	724
Fatigue
subjects affected / exposed	156 / 275 (56.73%)	141 / 255 (55.29%)
occurrences all number	394	489
Injection site induration
subjects affected / exposed	135 / 275 (49.09%)	136 / 255 (53.33%)
occurrences all number	548	834
Injection site swelling
subjects affected / exposed	123 / 275 (44.73%)	111 / 255 (43.53%)
occurrences all number	475	675
Pyrexia
subjects affected / exposed	17 / 275 (6.18%)	9 / 255 (3.53%)
occurrences all number	22	16
Gastrointestinal disorders
Nausea
subjects affected / exposed	56 / 275 (20.36%)	53 / 255 (20.78%)
occurrences all number	113	128
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	121 / 275 (44.00%)	100 / 255 (39.22%)
occurrences all number	291	313
Arthralgia
subjects affected / exposed	85 / 275 (30.91%)	63 / 255 (24.71%)
occurrences all number	203	212
Infections and infestations
Viral upper respiratory tract infection
subjects affected / exposed	13 / 275 (4.73%)	23 / 255 (9.02%)
occurrences all number	13	26

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)≥1:4

Primary: Percentage of subjects with Human Serum Bactericidal Activity (hSBA)≥1:4

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 titers≥1:5 in parent studies- V72P10 and V72_41

Primary: Percentage of subjects with hSBA titers≥1:5 in parent studies- V72P10 and V72_41

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 versus day 1

Primary: Geometric Mean Ratios (GMRs) of GMTs after the last dose of rMenB+OMV NZ Vaccination in the Parent Study versus day 1

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 ≥1:4 after booster dose/first vaccination of rMenB+OMV NZ.

Secondary: Percentage of subjects with hSBA ≥1:4 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 ≥1:5 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 versus day 1.

Secondary: Geometric mean ratio (GMRs) of GMTs after booster dose/first rMenB+OMV NZ vaccination versus day 1.

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 ≥1:4 After Booster Dose/Second Vaccination of rMenB+OMV NZ

Secondary: Percentage of Subjects With hSBA ≥1:4 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 ≥1:5 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 ≥1:4 after second vaccination of rMenB+OMV NZ

Secondary: Percentage of subjects with hSBA ≥1:4 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 ≥1:5 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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