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Clinical Trial Results:
A Phase 3b, Open-Label, Randomized, Multicenter Study to Assess the Safety and Immunogenicity of GlaxoSmithKline Biologicals Meningococcal group B Vaccine When Administered Concomitantly with GlaxoSmithKline Biologicals MenACWY Conjugate Vaccine to Healthy Infants

Summary
EudraCT number	2016-005117-44
Trial protocol	Outside EU/EEA
Global end of trial date	14 Oct 2016

Results information
Results version number	v2(current)
This version publication date	07 Feb 2018
First version publication date	22 Oct 2017
Other versions	v1
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

205240

ISRCTN number

US NCT number

NCT02106390

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

11 Aug 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

14 Oct 2016

Global end of trial reached?

Yes

Global end of trial date

14 Oct 2016

Was the trial ended prematurely?

Main objective of the trial

The purpose of this trial was to assess the immunological non-inferiority of rMenB+OMV NZ and MenACWY when concomitantly administered compared to either alone in healthy infants at 3, 5, 7 and 13 months of age, as measured by the ratio of hSBA Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains (for rMenB+OMV NZ) and serogroups A, C, W-135 and Y (for MenACWY) at one month after the fourth vaccination.

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

05 Jun 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 163

Country: Number of subjects enrolled

Mexico: 587

Worldwide total number of subjects

750

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)

750

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

750 healthy infants, aged 3 months were recruited from 3 sites in Argentina and 4 sites in Mexico.

Screening details

All enrolled subjects were included in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

This trial is designed as an open-trial; therefore, no blinding procedures were used.

Are arms mutually exclusive

Yes

rMenB+ACWY Group

Arm description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ / MenACWY vaccines, concomitantly administered at 3, 5, 7 and 13 months of age.

Arm type

Experimental

Investigational medicinal product name

GlaxoSmithKline Biologicals Meningococcal group B Vaccine

Investigational medicinal product code

Other name

rMENB+OMVNZ; Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 mL Pre-filled syringe. The volume delivered in a single dose was 0.5 mL.

Investigational medicinal product name

GlaxoSmithKline Biologicals Meningococcal ACWY Conjugate Vaccine

Investigational medicinal product code

Other name

MenACWY; Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Powder (vial)+ Solution (syringe or vial). The volume delivered after reconstitution was 0.5 mL.

rMenB Group

Arm description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ administered at 3, 5, 7 and 13 months of age.

Arm type

Active comparator

Investigational medicinal product name

GlaxoSmithKline Biologicals Meningococcal group B Vaccine

Investigational medicinal product code

Other name

rMENB+OMVNZ; Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 mL Pre-filled syringe. The volume delivered in a single dose was 0.5 mL.

MenACWY Group

Arm description

Approximately 250 healthy infants aged 3 months who received 4 doses of MenACWY administered at 3, 5, 7 and 13 months of age.

Arm type

Active comparator

Investigational medicinal product name

GlaxoSmithKline Biologicals Meningococcal ACWY Conjugate Vaccine

Investigational medicinal product code

Other name

MenACWY; Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Powder (vial)+ Solution (syringe or vial). The volume delivered after reconstitution was 0.5 mL.

Number of subjects in period 1	rMenB+ACWY Group	rMenB Group	MenACWY Group
Started	252	250	248
Completed	203	202	205
Not completed	49	48	43
Consent withdrawn by subject	15	16	15
Adverse event, non-fatal	-	2	1
Other: Administrative Reason	8	5	12
Other: Unspecified	1	4	2
Lost to follow-up	25	20	13
Protocol deviation	-	1	-

Baseline characteristics

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Reporting group title

rMenB+ACWY Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ / MenACWY vaccines, concomitantly administered at 3, 5, 7 and 13 months of age.

Reporting group title

rMenB Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ administered at 3, 5, 7 and 13 months of age.

Reporting group title

MenACWY Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of MenACWY administered at 3, 5, 7 and 13 months of age.

Reporting group values	rMenB+ACWY Group	rMenB Group	MenACWY Group	Total
Number of subjects	252	250	248	750
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestation age<37 weeks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	252	250	248	750
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	0	0	0	0
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age continuous
Units: days
arithmetic mean (standard deviation)	104.0 ( 10.72 )	101.4 ( 10.57 )	102.7 ( 10.9 )	-
Gender categorical
Units: Subjects
Female	120	118	139	377
Male	132	132	109	373
Race/Ethnicity, Customized
Units: Subjects
White	17	20	17	54
Other	235	230	231	696

End points

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Reporting group title

rMenB+ACWY Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ / MenACWY vaccines, concomitantly administered at 3, 5, 7 and 13 months of age.

Reporting group title

rMenB Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ administered at 3, 5, 7 and 13 months of age.

Reporting group title

MenACWY Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of MenACWY administered at 3, 5, 7 and 13 months of age.

Primary: Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains

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End point title

Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains ^[1]

End point description

Human serum bactericidal activity (hSBA) titers against each of the serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 after receiving 4 doses of rMenB+OMV NZ / MenACWY vaccines, concomitantly administered, versus corresponding response in subjects who received rMenB+OMV NZ administered alone, were presented in terms of vaccine group specific geometric mean titers (GMTs). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Primary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[1] - 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	148	158
Units: Titers
geometric mean (confidence interval 95%)
H44/76	92 (67 to 128)	104 (77 to 141)
5/99	1850 (1122 to 3050)	1790 (1128 to 2842)
NZ98/254	39 (29 to 53)	38 (28 to 52)
M10713	13 (7.82 to 21)	12 (7.72 to 20)

Statistical analysis 1

Statistical analysis description

H44/76- The comparison of adjusted GMTs ratio (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ) was performed for the H44/76 serogroup B indicator strain,at one month after the fourth vaccination."

Comparison groups

rMenB+ACWY Group v rMenB Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.1

Notes
[2] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ is > 0.5 for all serogroup B indicator strains.

Statistical analysis 2

Statistical analysis description

5/99-The comparison of adjusted GMTs ratio (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ) was performed for the 5/99 serogroup B indicator strain,at one month after the fourth vaccination.

Comparison groups

rMenB+ACWY Group v rMenB Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.45

Notes
[3] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ is > 0.5 for all serogroup B indicator strains.

Statistical analysis 3

Statistical analysis description

NZ98/254-The comparison of adjusted GMTs ratio (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ) was performed for the NZ98/254 serogroup B indicator strain,at one month after the fourth vaccination.

Comparison groups

rMenB+ACWY Group v rMenB Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.25

Notes
[4] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ is > 0.5 for all serogroup B indicator strains.

Statistical analysis 4

Statistical analysis description

M10713-The comparison of adjusted GMTs ratio (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ) was performed for the M10713 serogroup B indicator strain,at one month after the fourth vaccination.

Comparison groups

rMenB+ACWY Group v rMenB Group

Number of subjects included in analysis

306

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.4

Notes
[5] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMV NZ + MenACWY versus rMenB+OMV NZ is > 0.5 for all serogroup B indicator strains.

Primary: hSBA Geometric Mean Titers (GMTs) against each of the serogroups A, C, W-135 and Y

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End point title

hSBA Geometric Mean Titers (GMTs) against each of the serogroups A, C, W-135 and Y ^[6]

End point description

hSBA titers against N. meningitidis serogroups A, C, W-135 and Y after receiving four doses of either rMenB+OMV NZ / MenACWY concomitantly administered versus corresponding response in subjects who received MenACWY administered alone were presented in terms of vaccine group specific GMTs. This outcome measure applies to only rMenB+ACWY and MenACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups.

End point type

Primary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	161	156
Units: Titers
geometric mean (confidence interval 95%)
Serogroup A	409 (300 to 556)	165 (122 to 224)
Serogroup C	452 (312 to 655)	421 (294 to 602)
Serogroup W	721 (493 to 1053)	536 (370 to 776)
Serogroup Y	410 (293 to 575)	391 (280 to 546)

Statistical analysis 1

Statistical analysis description

Serogroup A-The comparison of adjusted GMTs ratio (rMenB+OMV NZ + Men ACWY versus MenACWY) was performed for serogroup A at one month after the fourth vaccination.

Comparison groups

MenACWY Group v rMenB+ACWY Group

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.97

upper limit

3.11

Notes
[7] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMVNZ + MenACWY versus MenACWY) was > 0.5 for all serogroups A, C, W-135 and Y.

Statistical analysis 2

Statistical analysis description

Serogroup C-The comparison of adjusted GMTs ratio (rMenB+OMV NZ + Men ACWY versus MenACWY) was performed for the serogroup C at one month after the fourth vaccination.

Comparison groups

MenACWY Group v rMenB+ACWY Group

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.38

Notes
[8] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMVNZ + MenACWY versus MenACWY) was > 0.5 for all serogroups A, C, W-135 and Y.

Statistical analysis 3

Statistical analysis description

Serogroup W-The comparison of adjusted GMTs ratio (rMenB+OMV NZ + Men ACWY versus MenACWY) was performed for the serogroup W-135 at one month after the fourth vaccination.

Comparison groups

MenACWY Group v rMenB+ACWY Group

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.34

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

1.74

Notes
[9] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMVNZ + MenACWY versus MenACWY) was > 0.5 for all serogroups A, C, W-135 and Y.

Statistical analysis 4

Statistical analysis description

Serogroup Y-The comparison of adjusted GMTs ratio (rMenB+OMV NZ + Men ACWY versus MenACWY) was performed for the serogroup Y at one month after the fourth vaccination.

Comparison groups

MenACWY Group v rMenB+ACWY Group

Number of subjects included in analysis

317

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.35

Notes
[10] - Non-inferiority was to be concluded if, at one month following the fourth vaccination, the lower limits of the two-sided 95% confidence interval for the between-group ratios of GMTs (rMenB+OMVNZ + MenACWY versus MenACWY) was > 0.5 for all serogroups A, C, W-135 and Y.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

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End point title

hSBA Geometric Mean Titers against each of the serogroup B indicator strains. ^[11]

End point description

hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 1

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	191	206
Units: Titers
geometric mean (confidence interval 95%)
H44/76	1.03 (0.99 to 1.08)	1.02 (0.98 to 1.07)
5/99	1.09 (0.99 to 1.21)	1.07 (0.97 to 1.17)
NZ98/254	1.06 (1.01 to 1.12)	1.07 (1.02 to 1.12)
M10713	1.88 (1.51 to 2.34)	1.59 (1.29 to 1.96)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

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End point title

hSBA Geometric Mean Titers against each of the serogroup B indicator strains. ^[12]

End point description

hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 151 (one month after the third vaccination)

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	181	206
Units: Titers
geometric mean (confidence interval 95%)
H44/76	116 (100 to 135)	129 (113 to 147)
5/99	891 (752 to 1055)	935 (803 to 1088)
NZ98/254	32 (26 to 39)	33 (27 to 40)
M10713	9.09 (6.57 to 13)	10 (7.50 to 14)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

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End point title

hSBA Geometric Mean Titers against each of the serogroup B indicator strains. ^[13]

End point description

hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 301 (before the fourth vaccination)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	173	204
Units: Titers
geometric mean (confidence interval 95%)
H44/76	7.68 (5.91 to 9.99)	8.31 (6.54 to 11)
5/99	131 (107 to 161)	109 (90 to 132)
NZ98/254	3.21 (2.44 to 4.21)	2.93 (2.25 to 3.81)
M10713	2.48 (1.89 to 3.27)	2.40 (1.85 to 3.10)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

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End point title

hSBA Geometric Mean Titers against each of the serogroup B indicator strains. ^[14]

End point description

hSBA GMTs against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	181	196
Units: Titers
geometric mean (confidence interval 95%)
H44/76	122 (98 to 151)	126 (104 to 154)
5/99	1404 (1016 to 1939)	1262 (934 to 1706)
NZ98/254	37 (30 to 45)	36 (30 to 44)
M10713	18 (14 to 24)	17 (13 to 22)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

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End point title

hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y. ^[15]

End point description

hSBA GMTs against each of the N. meningitidis serogroups A, C, W-135, Y at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 1

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	213	210
Units: Titers
geometric mean (confidence interval 95%)
Serogroup A	2.05 (1.97 to 2.15)	2.08 (1.99 to 2.17)
Serogroup C	2.16 (1.98 to 2.35)	2.09 (1.92 to 2.27)
Serogroup W	2.33 (2.13 to 2.55)	2.31 (2.11 to 2.52)
Serogroup Y	2.06 (1.95 to 2.17)	2.16 (2.05 to 2.28)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers against each of the serogroups A, C, W-135 and Y

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End point title

hSBA Geometric Mean Titers against each of the serogroups A, C, W-135 and Y ^[16]

End point description

hSBA GMTs against each of the N. meningitidis serogroups A, C, W-135, Y at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 151 (one month after the third vaccination)

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	215	214
Units: Titers
geometric mean (confidence interval 95%)
Serogroup A	303 (242 to 379)	136 (108 to 169)
Serogroup C	388 (320 to 469)	416 (345 to 502)
Serogroup W	347 (282 to 427)	298 (244 to 364)
Serogroup Y	226 (182 to 282)	283 (228 to 351)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

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End point title

hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y. ^[17]

End point description

hSBA GMTs against each of the N. meningitidis serogroups A, C, W-135, Y before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 301 (before the fourth vaccination)

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	203	204
Units: Titers
geometric mean (confidence interval 95%)
Serogroup A	20 (15 to 28)	15 (11 to 21)
Serogroup C	31 (23 to 41)	43 (32 to 58)
Serogroup W	48 (37 to 63)	47 (36 to 62)
Serogroup Y	38 (30 to 49)	43 (33 to 55)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

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End point title

hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y. ^[18]

End point description

hSBA GMTs against each of the N.meningitidis serogroups A, C, W-135, Y at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups A,C,W-135 & Y were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	199	204
Units: Titers
geometric mean (confidence interval 95%)
Serogroup A	329 (269 to 403)	132 (108 to 161)
Serogroup C	331 (268 to 409)	311 (252 to 384)
Serogroup W	576 (458 to 723)	428 (342 to 537)
Serogroup Y	377 (304 to 466)	363 (294 to 448)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains

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End point title

Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains ^[19]

End point description

Percentage of subjects with hSBA titers≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 before the first vaccination (Day 1). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 1

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	191	206
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	0 (0.0 to 2.3)	1 (0.01 to 2.8)
5/99	1 (0.15 to 4.5)	1 (0.13 to 3.7)
NZ98/254	1 (0.01 to 2.9)	1 (0.01 to 2.7)
M10713	16 (11.4 to 22.7)	11 (6.9 to 15.9)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains

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End point title

Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains ^[20]

End point description

Percentage of subjects with hSBA titers ≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 151 (one month after the third vaccination)

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	181	206
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	100 (97.6 to 100.0)	100 (98.2 to 100.0)
5/99	100 (97.3 to 100.0)	100 (98.1 to 100.0)
NZ98/254	96 (92.2 to 98.4)	97 (93.7 to 98.9)
M10713	70 (62.7 to 77.0)	68 (61.1 to 74.3)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains.

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End point title

Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains. ^[21]

End point description

Percentage of subjects with hSBA titers ≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 301 (before the fourth vaccination)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	173	204
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	74 (65.4 to 81.2)	75 (67.9 to 80.7)
5/99	100 (97.4 to 100.0)	97 (93.9 to 99.1)
NZ98/254	42 (34.2 to 49.3)	36 (29.7 to 43.3)
M10713	33 (25.7 to 41.2)	31 (24.5 to 37.7)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains.

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End point title

Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains. ^[22]

End point description

Percentage of subjects with hSBA titers ≥ 1:5 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 331 (One month after the fourth vaccination)

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	181	196
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	100 (97.4 to 100.0)	99 (97.1 to 99.99)
5/99	99 (95.0 to 99.83)	97 (93.0 to 98.8)
NZ98/254	100 (98.0 to 100.0)	98 (94.9 to 99.4)
M10713	87 (80.8 to 91.7)	87 (81.6 to 91.5)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

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End point title

Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains ^[23]

End point description

Percentage of subjects with hSBA titers ≥ 1:8 against each of the N. meningitidis serogroup B indicator strains at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 1

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	191	206
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	0 (0.0 to 2.3)	0 (0.0 to 1.8)
5/99	1 (0.02 to 3.5)	1 (0.01 to 2.9)
NZ98/254	1 (0.01 to 2.9)	1 (0.01 to 2.7)
M10713	12 (7.3 to 17.1)	8 (4.6 to 12.5)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Top of page

End point title

Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains ^[24]

End point description

Percentage of subjects with hSBA titers ≥ 1:8 against each of the N. meningitidis serogroup B indicator strains at one month after third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 151 (one month after the third vaccination)

Notes
[24] - 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	181	206
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	100 (97.6 to 100.0)	100 (98.2 to 100.0)
5/99	100 (97.3 to 100.0)	100 (98.1 to 100.0)
NZ98/254	92 (87.4 to 95.7)	92 (87.6 to 95.5)
M10713	65 (57.2 to 72.1)	59 (52.2 to 66.0)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Top of page

End point title

Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains ^[25]

End point description

Percentage of subjects with hSBA titers ≥ 1:8 against each of the N. meningitidis serogroup B indicator strains before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 301 (before the fourth vaccination)

Notes
[25] - 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	173	204
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	58 (49.5 to 67.0)	56 (48.9 to 63.5)
5/99	100 (97.4 to 100.0)	97 (93.2 to 98.8)
NZ98/254	26 (19.6 to 33.2)	26 (20.6 to 33.1)
M10713	21 (14.4 to 27.9)	23 (17.5 to 29.7)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroup B indicator strains

Top of page

End point title

Percentage of subjects with hSBA titers≥1:8 against each of the serogroup B indicator strains ^[26]

End point description

Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and rMenB groups as the serogroup B indicator strains were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[26] - 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	181	196
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	100 (97.4 to 100.0)	99 (97.1 to 99.99)
5/99	99 (95.0 to 99.83)	97 (93.0 to 98.8)
NZ98/254	98 (94.4 to 99.4)	94 (90.2 to 97.2)
M10713	83 (76.5 to 88.6)	82 (76.4 to 87.5)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers ≥1:4 against each of the serogroups A, C, W-135 and Y

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End point title

Percentage of subjects with hSBA titers ≥1:4 against each of the serogroups A, C, W-135 and Y ^[27]

End point description

Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y before the first vaccination (Day 1). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 1

Notes
[27] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	213	210
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	1 (0.11 to 3.4)	1 (0.12 to 3.5)
Serogroup C	4 (1.7 to 7.5)	3 (1.4 to 6.9)
Serogroup W	4 (1.8 to 8.0)	4 (1.4 to 7.2)
Serogroup Y	2 (0.5 to 4.7)	5 (2.3 to 8.6)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Top of page

End point title

Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y ^[28]

End point description

Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 151 (one month after the third vaccination)

Notes
[28] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	215	214
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	99 (97.4 to 99.99)	96 (92.0 to 98.0)
Serogroup C	100 (98.2 to 100.0)	100 (98.2 to 100.0)
Serogroup W	100 (97.9 to 100.0)	100 (98.1 to 100.0)
Serogroup Y	99 (96.0 to 99.71)	100 (98.3 to 100.0)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Top of page

End point title

Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y ^[29]

End point description

Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 301 (before the fourth vaccination)

Notes
[29] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	203	204
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	68 (60.5 to 73.9)	63 (55.4 to 69.2)
Serogroup C	88 (82.3 to 92.0)	89 (84.1 to 93.4)
Serogroup W	93 (88.7 to 96.7)	96 (91.3 to 98.0)
Serogroup Y	91 (85.8 to 94.3)	95 (90.6 to 97.3)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Top of page

End point title

Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y ^[30]

End point description

Percentage of subjects with hSBA titers≥ 1:4 against each of the N. meningitidis serogroups A, C, W-135 and Y at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[30] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	199	204
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	100 (98.1 to 100.0)	98 (94.3 to 99.2)
Serogroup C	100 (98.1 to 100.0)	100 (98.1 to 100.0)
Serogroup W	100 (98.0 to 100.0)	100 (98.0 to 100.0)
Serogroup Y	100 (98.2 to 100.0)	99 (97.3 to 99.99)

No statistical analyses for this end point

Secondary: Within-subject Geometric Mean Ratios (GMRs) against each of the serogroup B indicator strains

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End point title

Within-subject Geometric Mean Ratios (GMRs) against each of the serogroup B indicator strains ^[31]

End point description

Geometric Mean Ratios(GMRs) of GMTs against each of the serogroup B indicator strains- H44/76, 5/99, N98/254 & M10713 were calculated at one month after the fourth vaccination (Day 331) versus pre fourth vaccination(Day 301).

End point type

Secondary

End point timeframe

At Day 331 (one month after fourth vaccination)

Notes
[31] - 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	155	195
Units: Ratio
geometric mean (confidence interval 95%)
H44/76	17 (13 to 22)	16 (12 to 20)
5/99	9.60 (6.99 to 13)	12 (8.86 to 16)
NZ98/254	11 (8.35 to 15)	12 (9.39 to 16)
M10713	5.99 (4.20 to 8.54)	6.75 (4.90 to 9.29)

No statistical analyses for this end point

Secondary: Within-subject Geometric Mean Ratios (GMRs) against each of serogroups A, C, W-135 and Y

Top of page

End point title

Within-subject Geometric Mean Ratios (GMRs) against each of serogroups A, C, W-135 and Y ^[32]

End point description

Geometric Mean Ratios(GMRs) of GMTs against each of the serogroups A,C,W-135 & Y were calculated at one month after the fourth vaccination (Day 331) versus pre fourth vaccination (Day 301).

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[32] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	197	201
Units: Ratio
geometric mean (confidence interval 95%)
Serogroup A	16 (13 to 21)	8.75 (6.69 to 11)
Serogroup C	11 (8.86 to 14)	7.79 (6.25 to 9.71)
Serogroup W	13 (10 to 16)	9.44 (7.52 to 12)
Serogroup Y	9.75 (8.00 to 12)	8.97 (7.36 to 11)

No statistical analyses for this end point

Secondary: Percentage of subjects with four-fold increases in hSBA titers against each of the serogroup B indicator strains

Top of page

End point title

Percentage of subjects with four-fold increases in hSBA titers against each of the serogroup B indicator strains ^[33]

End point description

Percentage of subjects with four-fold increase in hSBA titers against each of the N. meningitidis serogroup B indicator strains-H44/76,5/99,NZ98/254 & M10713 at one month after the fourth vaccination (Day 331) over pre-fourth vaccination (Day 301). This outcome measure applies to only groups rMenB+ACWY and rMenB as the serogroup B indicator strains were assessed only for these two groups. For serogroup B strains, 4-fold increase in titers was defined as post 4th vaccination titer ≥8 (if pre 4th vaccination titer was <2) or post 4th vaccination titer ≥ 4 x pre 4th vaccination titer (if pre 4th vaccination titer was ≥2).

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[33] - 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	rMenB+ACWY Group	rMenB Group
Number of subjects analysed	155	195
Units: Percentage of subjects
number (confidence interval 95%)
H44/76	93 (86.0 to 96.8)	92 (87.2 to 95.6)
5/99	94 (88.2 to 97.6)	95 (90.9 to 97.9)
NZ98/254	81 (73.5 to 86.5)	79 (73.1 to 84.9)
M10713	58 (48.7 to 66.3)	60 (52.5 to 67.0)

No statistical analyses for this end point

Secondary: Percentage of subjects with four-fold increases in hSBA titers against each of the serogroups A, C, W-135 and Y

Top of page

End point title

Percentage of subjects with four-fold increases in hSBA titers against each of the serogroups A, C, W-135 and Y ^[34]

End point description

Percentages of subjects with four-fold increases in hSBA against each of the N. meningitidis serogroups A,C,W & Y at one month after the fourth vaccination (Day 331) over pre-fourth vaccination(Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups. For serogroups A, C, W and Y, 4-fold increase in titers was defined as post 4th vaccination titer ≥16 (if pre 4th vaccination titer was <4) or post 4th vaccination titer ≥ 4 x pre 4th vaccination titer (if pre 4th vaccination titer was ≥4).

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[34] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	197	201
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	90 (84.4 to 93.5)	71 (64.6 to 77.6)
Serogroup C	88 (81.9 to 92.0)	77 (70.1 to 82.9)
Serogroup W	89 (83.0 to 93.5)	84 (77.9 to 89.7)
Serogroup Y	82 (75.6 to 86.9)	81 (74.4 to 85.8)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

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End point title

Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y ^[35]

End point description

Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 and Y at baseline (Day 1). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 1

Notes
[35] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	213	210
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	1 (0.01 to 2.6)	1 (0.01 to 2.7)
Serogroup C	2 (0.8 to 5.6)	2 (0.5 to 4.9)
Serogroup W	4 (1.5 to 7.3)	3 (0.8 to 5.9)
Serogroup Y	0 (0.0 to 1.7)	2 (0.5 to 4.8)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

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End point title

Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y ^[36]

End point description

Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 & Y at one month after the third vaccination (Day 151). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 151 (one month before the third vaccination)

Notes
[36] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	215	214
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	99 (97.4 to 99.99)	96 (92.0 to 98.0)
Serogroup C	100 (98.2 to 100.0)	100 (98.2 to 100.0)
Serogroup W	100 (97.9 to 100.0)	99 (97.1 to 99.99)
Serogroup Y	98 (95.3 to 99.5)	99 (97.4 to 99.99)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

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End point title

Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y ^[37]

End point description

Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 & Y before the fourth vaccination (Day 301). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 301 (before the fourth vaccination)

Notes
[37] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	203	204
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	65 (58.0 to 71.6)	58 (50.8 to 64.9)
Serogroup C	77 (70.5 to 82.7)	85 (79.3 to 89.9)
Serogroup W	92 (86.5 to 95.4)	91 (85.8 to 94.8)
Serogroup Y	86 (80.1 to 90.2)	91 (85.8 to 94.3)

No statistical analyses for this end point

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

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End point title

Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y ^[38]

End point description

Percentage of subjects with hSBA titers≥ 1:8 against each of the N. meningitidis serogroups A, C, W-135 & Y at one month after the fourth vaccination (Day 331). This outcome measure applies to only rMenB+ACWY and MENACWY groups as the serogroups were assessed only for these two groups.

End point type

Secondary

End point timeframe

At Day 331 (one month after the fourth vaccination)

Notes
[38] - 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	rMenB+ACWY Group	MenACWY Group
Number of subjects analysed	199	204
Units: Percentage of subjects
number (confidence interval 95%)
Serogroup A	100 (98.1 to 100.0)	96 (92.4 to 98.3)
Serogroup C	99 (97.1 to 99.99)	100 (98.1 to 100.0)
Serogroup W	100 (98.0 to 100.0)	100 (98.0 to 100.0)
Serogroup Y	98 (95.7 to 99.69)	99 (97.3 to 99.99)

No statistical analyses for this end point

Secondary: Number of subjects with solicited local and systemic Adverse Events (AEs)

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End point title

Number of subjects with solicited local and systemic Adverse Events (AEs)

End point description

Number of subjects with solicited local and systemic AEs during the 7 days (including the day of vaccination) after any vaccination

End point type

Secondary

End point timeframe

From Day 1 (6 hours) to Day 7 after each vaccination (Days 1, 61, 121 and 301)

End point values	rMenB+ACWY Group	rMenB Group	MenACWY Group
Number of subjects analysed	240	232	237
Units: Participants
Any	235	226	194
Any local	220	214	157
Any Systemic	217	217	178
Erythema (vaccination 1)	101	102	44
Induration (vaccination 1)	111	102	22
Swelling (vaccination 1)	82	86	22
Tenderness (vaccination 1)	162	159	73
Change in Eating Habits (vaccination 1)	53	47	34
Diarrhea (vaccination 1)	46	41	42
Irritability (vaccination 1)	111	121	87
Persistent Crying (vaccination 1)	124	132	85
Rash (vaccination 1)	19	28	18
Sleepiness (vaccination 1)	69	78	54
Vomiting (vaccination 1)	14	28	23
Fever (vaccination 1)	49	54	10
Treatment of Pain/Fever (vaccination 1)	82	98	25
Erythema (vaccination 2)	97	102	47
Induration (vaccination 2)	99	110	32
Swelling (vaccination 2)	78	83	24
Tenderness (vaccination 2)	142	138	66
Change in Eating Habits (vaccination 2)	46	44	31
Diarrhea (vaccination 2)	37	36	24
Irritability (vaccination 2)	99	95	70
Persistent Crying (vaccination 2)	104	108	66
Rash (vaccination 2)	16	21	13
Sleepiness (vaccination 2)	51	55	45
Vomiting (vaccination 2)	10	21	17
Fever (vaccination 2)	48	54	15
Treatment of Pain/Fever (vaccination 2)	74	91	29
Erythema (vaccination 3)	86	96	35
Induration (vaccination 3)	92	103	30
Swelling (vaccination 3)	73	82	19
Tenderness (vaccination 3)	139	128	59
Change in Eating Habits (vaccination 3)	42	45	33
Diarrhea (vaccination 3)	24	40	25
Irritability (vaccination 3)	83	84	61
Persistent Crying (vaccination 3)	90	92	60
Rash (vaccination 3)	10	11	11
Sleepiness (vaccination 3)	39	46	39
Vomiting (vaccination 3)	7	27	14
Fever (vaccination 3)	37	38	25
Treatment of Pain/Fever (vaccination 3)	57	69	31
Erythema (vaccination 4)	73	88	37
Induration (vaccination 4)	84	93	29
Swelling (vaccination 4)	75	74	21
Tenderness (vaccination 4)	126	129	64
Change in Eating Habits (vaccination 4)	59	45	40
Diarrhea (vaccination 4)	29	28	23
Irritability (vaccination 4)	81	74	57
Persistent Crying (vaccination 4)	84	89	56
Rash (vaccination 4)	11	13	6
Sleepiness (vaccination 4)	50	37	33
Vomiting (vaccination 4)	15	14	11
Fever (vaccination 4)	53	46	19
Treatment of Pain/Fever (vaccination 4)	71	67	31

No statistical analyses for this end point

Secondary: Number of subjects with unsolicited adverse events

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End point title

Number of subjects with unsolicited adverse events

End point description

An unsolicited adverse event (AE) is defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product at any dose that does not necessarily have to have a causal relationship with this treatment.

End point type

Secondary

End point timeframe

From Day 1 to Day 7 after each vaccination (Days 1, 61, 121 and 301)

End point values	rMenB+ACWY Group	rMenB Group	MenACWY Group
Number of subjects analysed	249	249	246
Units: Participants
Any	103	116	70
Any unsolicited AEs( vaccination 1)	63	62	20
Any unsolicited AEs( vaccination 2)	60	69	29
Any unsolicited AEs( vaccination 3)	57	63	23
Any unsolicited AEs( vaccination 4)	44	58	13

No statistical analyses for this end point

Secondary: Number of subjects with SAEs, AEs leading to withdrawal and medically attended AEs (MAEs)

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End point title

Number of subjects with SAEs, AEs leading to withdrawal and medically attended AEs (MAEs)

End point description

A serious adverse event is any untoward medical occurrence that at any dose results in death/ is life threatening/requires prolonged hospitalization/Persistent or significant disability/incapacity/congenital anomaly/or birth defect.

End point type

Secondary

End point timeframe

Throughout the whole study period (from Day 1 upto Day 331)

End point values	rMenB+ACWY Group	rMenB Group	MenACWY Group
Number of subjects analysed	249	249	246
Units: Participants
Any SAEs	6	13	11
Any Medically Attended AEs	177	188	183
Any AEs leading to premature withdrawal	0	2	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited local and systemic AEs were collected from day 1 (6 hours) upto day 7 after each vaccination. Unsolicited AEs were collected from day 1 to day 7.

Adverse event reporting additional description

Serious Adverse Events (SAEs) were collected throughout the whole study period (from day 1 to day 331). All the unsolicited AEs were reported by non-systematic assessment and the solicited AEs were reported by systematic assessment

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

rMenB+ACWY Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ / MenACWY vaccines, concomitantly administered at 3, 5, 7 and 13 months of age.

Reporting group title

rMenB Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of rMenB + OMV NZ administered at 3, 5, 7 and 13 months of age

Reporting group title

MenACWY Group

Reporting group description

Approximately 250 healthy infants aged 3 months who received 4 doses of MenACWY administered at 3, 5, 7 and 13 months of age.

Serious adverse events	rMenB+ACWY Group	rMenB Group	MenACWY Group
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 249 (2.41%)	13 / 249 (5.22%)	11 / 246 (4.47%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Limb injury
subjects affected / exposed	0 / 249 (0.00%)	1 / 249 (0.40%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 249 (0.00%)	1 / 249 (0.40%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	0 / 249 (0.00%)	0 / 249 (0.00%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Kawasaki's disease
subjects affected / exposed	1 / 249 (0.40%)	0 / 249 (0.00%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	0 / 249 (0.00%)	0 / 249 (0.00%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 249 (0.00%)	1 / 249 (0.40%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Milk allergy
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 249 (0.00%)	0 / 249 (0.00%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	0 / 249 (0.00%)	1 / 249 (0.40%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	0 / 249 (0.00%)	0 / 249 (0.00%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	1 / 249 (0.40%)	3 / 249 (1.20%)	4 / 246 (1.63%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 249 (0.00%)	1 / 249 (0.40%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Exanthema subitum
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 249 (0.40%)	0 / 249 (0.00%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 249 (0.40%)	2 / 249 (0.80%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 249 (0.00%)	1 / 249 (0.40%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pertussis
subjects affected / exposed	0 / 249 (0.00%)	0 / 249 (0.00%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 249 (0.00%)	2 / 249 (0.80%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 249 (0.40%)	3 / 249 (1.20%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 249 (0.00%)	1 / 249 (0.40%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 249 (0.40%)	0 / 249 (0.00%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 249 (0.40%)	0 / 249 (0.00%)	1 / 246 (0.41%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 249 (0.40%)	0 / 249 (0.00%)	0 / 246 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	rMenB+ACWY Group	rMenB Group	MenACWY Group
Total subjects affected by non serious adverse events
subjects affected / exposed	240 / 249 (96.39%)	232 / 249 (93.17%)	221 / 246 (89.84%)
Nervous system disorders
Somnolence
subjects affected / exposed	106 / 249 (42.57%)	115 / 249 (46.18%)	87 / 246 (35.37%)
occurrences all number	226	236	189
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	212 / 249 (85.14%)	207 / 249 (83.13%)	131 / 246 (53.25%)
occurrences all number	593	583	267
Crying
subjects affected / exposed	176 / 249 (70.68%)	184 / 249 (73.90%)	129 / 246 (52.44%)
occurrences all number	434	463	301
Injection site erythema
subjects affected / exposed	147 / 249 (59.04%)	162 / 249 (65.06%)	104 / 246 (42.28%)
occurrences all number	424	480	211
Injection site induration
subjects affected / exposed	144 / 249 (57.83%)	152 / 249 (61.04%)	57 / 246 (23.17%)
occurrences all number	575	609	116
Injection site swelling
subjects affected / exposed	130 / 249 (52.21%)	138 / 249 (55.42%)	56 / 246 (22.76%)
occurrences all number	380	403	88
Pyrexia
subjects affected / exposed	125 / 249 (50.20%)	121 / 249 (48.59%)	60 / 246 (24.39%)
occurrences all number	201	210	79
Gastrointestinal disorders
Diarrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	108 / 249 (43.37%)	98 / 249 (39.36%)	89 / 246 (36.18%)
occurrences all number	181	196	163
Vomiting
alternative assessment type: Non-systematic
subjects affected / exposed	36 / 249 (14.46%)	64 / 249 (25.70%)	49 / 246 (19.92%)
occurrences all number	51	105	82
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
alternative assessment type: Non-systematic
subjects affected / exposed	17 / 249 (6.83%)	12 / 249 (4.82%)	15 / 246 (6.10%)
occurrences all number	25	16	26
Bronchospasm
alternative assessment type: Non-systematic
subjects affected / exposed	9 / 249 (3.61%)	12 / 249 (4.82%)	13 / 246 (5.28%)
occurrences all number	13	16	23
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	46 / 249 (18.47%)	57 / 249 (22.89%)	42 / 246 (17.07%)
occurrences all number	62	81	62
Dermatitis diaper
subjects affected / exposed	12 / 249 (4.82%)	16 / 249 (6.43%)	14 / 246 (5.69%)
occurrences all number	16	16	15
Dermatitis atopic
subjects affected / exposed	6 / 249 (2.41%)	11 / 249 (4.42%)	17 / 246 (6.91%)
occurrences all number	6	12	20
Psychiatric disorders
Irritability
alternative assessment type: Non-systematic
subjects affected / exposed	155 / 249 (62.25%)	170 / 249 (68.27%)	125 / 246 (50.81%)
occurrences all number	409	418	320
Eating disorder
alternative assessment type: Non-systematic
subjects affected / exposed	110 / 249 (44.18%)	100 / 249 (40.16%)	85 / 246 (34.55%)
occurrences all number	214	194	162
Infections and infestations
Nasopharyngitis
subjects affected / exposed	81 / 249 (32.53%)	87 / 249 (34.94%)	78 / 246 (31.71%)
occurrences all number	161	164	135
Viral upper respiratory tract infection
subjects affected / exposed	72 / 249 (28.92%)	82 / 249 (32.93%)	86 / 246 (34.96%)
occurrences all number	104	127	123
Pharyngitis
subjects affected / exposed	50 / 249 (20.08%)	50 / 249 (20.08%)	50 / 246 (20.33%)
occurrences all number	57	59	60
Bronchiolitis
subjects affected / exposed	34 / 249 (13.65%)	34 / 249 (13.65%)	37 / 246 (15.04%)
occurrences all number	40	37	37
Gastroenteritis
subjects affected / exposed	31 / 249 (12.45%)	40 / 249 (16.06%)	38 / 246 (15.45%)
occurrences all number	37	44	43
Conjunctivitis
subjects affected / exposed	20 / 249 (8.03%)	18 / 249 (7.23%)	24 / 246 (9.76%)
occurrences all number	23	18	25
Candida nappy rash
subjects affected / exposed	15 / 249 (6.02%)	12 / 249 (4.82%)	6 / 246 (2.44%)
occurrences all number	16	14	6
Rhinitis
subjects affected / exposed	14 / 249 (5.62%)	13 / 249 (5.22%)	19 / 246 (7.72%)
occurrences all number	17	16	21
Viral rash
subjects affected / exposed	13 / 249 (5.22%)	14 / 249 (5.62%)	13 / 246 (5.28%)
occurrences all number	13	14	13

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 3b, Open-Label, Randomized, Multicenter Study to Assess the Safety and Immunogenicity of GlaxoSmithKline Biologicals Meningococcal group B Vaccine When Administered Concomitantly with GlaxoSmithKline Biologicals MenACWY Conjugate Vaccine to Healthy Infants

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains

Primary: Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains

Primary: hSBA Geometric Mean Titers (GMTs) against each of the serogroups A, C, W-135 and Y

Primary: hSBA Geometric Mean Titers (GMTs) against each of the serogroups A, C, W-135 and Y

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroup B indicator strains.

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

Secondary: hSBA Geometric Mean Titers against each of the serogroups A, C, W-135 and Y

Secondary: hSBA Geometric Mean Titers against each of the serogroups A, C, W-135 and Y

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

Secondary: hSBA Geometric Mean Titers against each of the serogroups A,C,W-135 & Y.

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains.

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains.

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains.

Secondary: Percentage of subjects with hSBA titers ≥1:5 against each of the serogroup B strains.

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroup B indicator strains

Secondary: Percentage of subjects with hSBA titers ≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers ≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:4 against each of the serogroups A, C, W-135 and Y

Secondary: Within-subject Geometric Mean Ratios (GMRs) against each of the serogroup B indicator strains

Secondary: Within-subject Geometric Mean Ratios (GMRs) against each of the serogroup B indicator strains

Secondary: Within-subject Geometric Mean Ratios (GMRs) against each of serogroups A, C, W-135 and Y

Secondary: Within-subject Geometric Mean Ratios (GMRs) against each of serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with four-fold increases in hSBA titers against each of the serogroup B indicator strains

Secondary: Percentage of subjects with four-fold increases in hSBA titers against each of the serogroup B indicator strains

Secondary: Percentage of subjects with four-fold increases in hSBA titers against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with four-fold increases in hSBA titers against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Percentage of subjects with hSBA titers≥1:8 against each of the serogroups A, C, W-135 and Y

Secondary: Number of subjects with solicited local and systemic Adverse Events (AEs)

Secondary: Number of subjects with solicited local and systemic Adverse Events (AEs)

Secondary: Number of subjects with unsolicited adverse events

Secondary: Number of subjects with unsolicited adverse events

Secondary: Number of subjects with SAEs, AEs leading to withdrawal and medically attended AEs (MAEs)

Secondary: Number of subjects with SAEs, AEs leading to withdrawal and medically attended AEs (MAEs)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
A Phase 3b, Open-Label, Randomized, Multicenter Study to Assess the Safety and Immunogenicity of GlaxoSmithKline Biologicals Meningococcal group B Vaccine When Administered Concomitantly with GlaxoSmithKline Biologicals MenACWY Conjugate Vaccine to Healthy Infants