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Clinical Trial Results:
A Phase 2b, Randomized, Controlled, Observer-Blind, Multi-Center Study Assessing the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Meningococcal ABCWY Vaccine Administered at Different Schedules Compared to GSK Meningococcal group B vaccine, in Healthy Adolescents

Summary
EudraCT number	2013-002451-15
Trial protocol	FI PL
Global end of trial date	03 Mar 2016

Results information
Results version number	v2
This version publication date	10 Mar 2018
First version publication date	18 May 2017
Other versions	v1 , 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

205215

ISRCTN number

US NCT number

NCT02212457

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

10 Mar 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

22 May 2015

Global end of trial reached?

Yes

Global end of trial date

03 Mar 2016

Was the trial ended prematurely?

Main objective of the trial

To demonstrate the non-inferiority of the Meningococcal (groups A, C, W and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant (MenABCWY) vaccine to that of the Meningococcal (group B) multicomponent recombinant adsorbed (rMenB +OMV) vaccine administered according to 0, 2 month schedule, as measured by hSBA GMTs against N. meningitidis serogroup B test strains1 at 1 month after the last meningococcal vaccination.

Protection of trial subjects

Standard immunization practices were observed and care was taken to administer the injection intramuscularly. As with all injectable vaccines, appropriate medical treatment and supervision was readily available in case of rare anaphylactic reactions following administration of the study vaccine. Epinephrine 1:1000 and diphenhydramine was available in case of any anaphylactic reactions. Care was taken to ensure that the vaccine is not injected into a blood vessel. The measures of safety used in this study are routine clinical procedures. They include a close vigilance for, and stringent reporting of, selected local and systemic adverse events routinely monitored in vaccine clinical studies as indicators of reactogenicity. The period of observation for AEs extended from the time a subject signed an informed consent until he or she completed the final study visit (Visit Month 13) or terminated the study early (whichever came first).

Background therapy

Evidence for comparator

The comparator regimen of rMenB+OMV, Havrix Junior Monodose Havrix Monodose vaccines is already approved by the European Union (rMenB+OMV) and the United Kingdom (Havrix Junior Monodose and Havrix Monodose) for prophylactic use.

Actual start date of recruitment

21 Aug 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Finland: 495

Country: Number of subjects enrolled

Poland: 433

Country: Number of subjects enrolled

United States: 135

Worldwide total number of subjects

1063

EEA total number of subjects

928

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)

289

Adolescents (12-17 years)

448

Adults (18-64 years)

326

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects were recruited from 32 centers.

Screening details

All subjects were included in the trial.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

The trial was designed as an observer-blind study. Observer-blind means that during the course of study, the subject, the parents/guardians of the subjects and the study personnel responsible for the evaluation of any study endpoint (e.g. safety and reactogenicity) were unaware which vaccine was administered.

Are arms mutually exclusive

Yes

rMenB_0_2 Group

Arm description

Subjects received two injections of Bexsero™ vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Arm type

Active comparator

Investigational medicinal product name

Havrix® Vaccine

Investigational medicinal product code

Other name

Hepatitis A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects between 1 and 15 years of age received one pediatric dose (0.5 mL) of Havrix® Junior Monodose® Vaccine (Hepatitis A virus antigen, 720 ELISA units/0.5 mL dose), administered in the deltoid muscle. Subjects 16 years of age or older received one adult dose (1.0 mL) of Havrix® Monodose® Vaccine (Hepatitis A virus antigen, 1440 ELISA units/1 mL dose of hepatitis A virus antigen), administered in the deltoid muscle.

Investigational medicinal product name

Bexsero®

Investigational medicinal product code

rMenB+OMV

Other name

GSK Meningococcal B Recombinant vaccine

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.5 milliliters (mL) dose of injectable suspension administered into the deltoid area of the non-dominant arm

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable saline solution administered into the deltoid area of the non-dominant arm

ABCWY_ 0_2 Group

Arm description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

GSK Meningococcal ABCWY Vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable suspension administered into the deltoid area of the non-dominant arm

Investigational medicinal product name

Havrix® Vaccine

Investigational medicinal product code

Other name

Hepatitis A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable saline solution administered into the deltoid area of the non-dominant arm

ABCWY_0_1 Group

Arm description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 1, Havrix® vaccine at Visit Month 2 and Visit Month 12 and saline placebo at Visit Month 6.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

GSK Meningococcal ABCWY Vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable suspension administered into the deltoid area of the non-dominant arm

Investigational medicinal product name

Havrix® Vaccine

Investigational medicinal product code

Other name

Hepatitis A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable saline solution administered into the deltoid area of the non-dominant arm

ABCWY_0_6 Group

Arm description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 6, Havrix® vaccine at Visit Month 1 and Visit Month 12 and saline placebo at Visit Month 2.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

GSK Meningococcal ABCWY Vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable suspension administered into the deltoid area of the non-dominant arm

Investigational medicinal product name

Havrix® Vaccine

Investigational medicinal product code

Other name

Hepatitis A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable saline solution administered into the deltoid area of the non-dominant arm

ABCWY_0_11 Group

Arm description

Subjects received MenABCWY vaccine at Visit Month 1 and Visit Month 12, Havrix® vaccine at Visit Month 0 and Visit Month 6 and saline placebo at Visit Month 2.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

GSK Meningococcal ABCWY Vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable suspension administered into the deltoid area of the non-dominant arm

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Saline solution

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable saline solution administered into the deltoid area of the non-dominant arm

Investigational medicinal product name

Havrix® Vaccine

Investigational medicinal product code

Other name

Hepatitis A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

ABCWY_0_2_6 Group

Arm description

Subjects received MenABCWY vaccine at Visit Month 0, Visit Month 2 and Visit Month 6 and Havrix® vaccine at Visit Month 1 and Visit Month 12.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

GSK Meningococcal ABCWY Vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose of injectable suspension administered into the deltoid area of the non-dominant arm

Investigational medicinal product name

Havrix® Vaccine

Investigational medicinal product code

Other name

Hepatitis A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 1	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group
Started	228	232	157	134	152	160
Completed	209	211	141	123	137	147
Not completed	19	21	16	11	15	13
Consent withdrawn by subject	8	10	8	6	5	4
Adverse event, non-fatal	1	2	2	2	-	1
Unspecified	2	1	2	1	-	1
Lost to follow-up	6	7	4	1	8	4
Protocol deviation	2	1	-	1	2	3

Baseline characteristics

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Reporting group title

rMenB_0_2 Group

Reporting group description

Subjects received two injections of Bexsero™ vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Reporting group title

ABCWY_ 0_2 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Reporting group title

ABCWY_0_1 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 1, Havrix® vaccine at Visit Month 2 and Visit Month 12 and saline placebo at Visit Month 6.

Reporting group title

ABCWY_0_6 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 6, Havrix® vaccine at Visit Month 1 and Visit Month 12 and saline placebo at Visit Month 2.

Reporting group title

ABCWY_0_11 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 1 and Visit Month 12, Havrix® vaccine at Visit Month 0 and Visit Month 6 and saline placebo at Visit Month 2.

Reporting group title

ABCWY_0_2_6 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0, Visit Month 2 and Visit Month 6 and Havrix® vaccine at Visit Month 1 and Visit Month 12.

Reporting group values	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group	Total
Number of subjects	228	232	157	134	152	160	1063
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	56	73	39	35	39	47	289
Adolescents (12-17 years)	96	93	72	59	64	64	448
Adults (18-64 years)	76	66	46	40	49	49	326
From 65-84 years	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	14.5 ( 3.09 )	14.2 ( 3.17 )	14.4 ( 3.01 )	14.4 ( 3.06 )	14.5 ( 3.1 )	14.3 ( 3.16 )	-
Gender categorical
Units: Subjects
Female	130	119	101	76	89	96	611
Male	98	113	56	58	63	64	452

End points

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Reporting group title

rMenB_0_2 Group

Reporting group description

Subjects received two injections of Bexsero™ vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Reporting group title

ABCWY_ 0_2 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Reporting group title

ABCWY_0_1 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 1, Havrix® vaccine at Visit Month 2 and Visit Month 12 and saline placebo at Visit Month 6.

Reporting group title

ABCWY_0_6 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 6, Havrix® vaccine at Visit Month 1 and Visit Month 12 and saline placebo at Visit Month 2.

Reporting group title

ABCWY_0_11 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 1 and Visit Month 12, Havrix® vaccine at Visit Month 0 and Visit Month 6 and saline placebo at Visit Month 2.

Reporting group title

ABCWY_0_2_6 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0, Visit Month 2 and Visit Month 6 and Havrix® vaccine at Visit Month 1 and Visit Month 12.

Primary: Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup B test strains

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End point title

Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup B test strains ^[1]

End point description

The non-inferiority of the Meningococcal (groups A, C, W and Y) oligosaccharide diphtheria CRM-197 conjugate combined with meningococcal (group B) multicomponent recombinant (MenABCWY) vaccine to Meningococcal (group B) multicomponent recombinant adsorbed (Bexsero™) vaccine, administered according to 0, 2 month schedule, as measured by hSBA GMTs against N.meningitidis serogroup B test strains at 1 month after the last meningococcal vaccination, is reported. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. This outcome measure was evaluated only in the rMenB_0_2 and ABCWY_ 0_2 Groups. The analysis was performed on the PPS (Per Protocol Set) Month 3 population, which included all subjects in the All Enrolled Set who received a study vaccination and provided evaluable serum samples at pre- (Visit Month 0) and at least one post-vaccination (Visit Month 3).

End point type

Primary

End point timeframe

At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 3)

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_0_2 Group	ABCWY_ 0_2 Group
Number of subjects analysed	150	158
Units: Titers
geometric mean (confidence interval 95%)
M14459 strain (Month 0) [N=155;147]	1.31 (1.09 to 1.57)	1.28 (1.07 to 1.53)
M14459 strain (Month 3) [N=158;150]	15.78 (12 to 22)	11.64 (8.61 to 16)
M07-0241084 strain (Month 0) [N=151;148]	2.16 (1.61 to 2.89)	2.12 (1.60 to 2.82)
M07-0241084 strain (Month 3) [N=154;150]	11.56 (8.86 to 15)	8.19 (6.31 to 11)
96217 strain (Month 0) [N=152;143]	2.36 (1.70 to 3.28)	2.93 (2.13 to 4.03)
96217 strain (Month 3) [N=156;149]	229.29 (179 to 294)	150.82 (118 to 192)
NZ98/254 strain (Month 0) [N=154;147]	1.15 (0.95 to 1.39)	1.27 (1.06 to 1.53)
NZ98/254 strain (Month 3) [N=157;150]	24.31 (18 to 32)	11.95 (9.10 to 16)

Statistical analysis 1

Statistical analysis description

Non-inferiority response against N. meningitidis serogroup B test strain M14459 of the MenABCWY vaccine to that of the Bexsero™ vaccine, administered according to 0, 2 month schedule.

Comparison groups

ABCWY_ 0_2 Group v rMenB_0_2 Group

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

ANCOVA

Parameter type

Between Group Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.03

Notes
[2] - Non-inferiority criterion was met if at 1 month after the second meningococcal vaccination (Visit Month 3) the lower limit of the two-sided 95% confidence interval for the between-group ratios of GMTs (ABCWY_0_2 versus rMenB_0_2) was greater than 0.5 for each of the four serogroup B test strains.

Statistical analysis 2

Statistical analysis description

Non-inferiority response against N. meningitidis serogroup B test strain M07-0241084 of the MenABCWY vaccine to that of the Bexsero™ vaccine, administered according to 0, 2 month schedule.

Comparison groups

rMenB_0_2 Group v ABCWY_ 0_2 Group

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

ANCOVA

Parameter type

Between Group Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

0.92

Notes
[3] - Non-inferiority criterion was met if at 1 month after the second meningococcal vaccination (Visit Month 3)the lower limit of the two-sided 95% confidence interval for the between-group ratios of GMTs (ABCWY_0_2 versus rMenB_0_2) was greater than 0.5 for each of the four serogroup B test strains.

Statistical analysis 3

Statistical analysis description

Non-inferiority response against N. meningitidis serogroup B test strain 96217 of the MenABCWY vaccine to that of the Bexsero™ vaccine, administered according to 0, 2 month schedule.

Comparison groups

rMenB_0_2 Group v ABCWY_ 0_2 Group

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

ANCOVA

Parameter type

Between Group Ratio

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

0.85

Notes
[4] - Non-inferiority criterion was met if at 1 month after the second meningococcal vaccination (Visit Month 3) the lower limit of the two-sided 95% confidence interval for the between-group ratios of GMTs (ABCWY_0_2 versus rMenB_0_2) was greater than 0.5 for each of the four serogroup B test strains.

Statistical analysis 4

Statistical analysis description

Non-inferiority response against N. meningitidis serogroup B test strain NZ98/254 of the MenABCWY vaccine to that of the Bexsero™ vaccine, administered according to 0, 2 month schedule.

Comparison groups

rMenB_0_2 Group v ABCWY_ 0_2 Group

Number of subjects included in analysis

308

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

ANCOVA

Parameter type

Between Group Ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

0.66

Notes
[5] - Non-inferiority criterion was met if at 1 month after the second meningococcal vaccination (Visit Month 3) the lower limit of the two-sided 95% confidence interval for the between-group ratios of GMTs (ABCWY_0_2 versus rMenB_0_2) was greater than 0.5 for each of the four serogroup B test strains.

Secondary: hSBA GMTs against N. meningitidis serogroup B test strains

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End point title

hSBA GMTs against N. meningitidis serogroup B test strains ^[6]

End point description

The immunogenicity of MenABCWY vaccine, administered according to 0, 2, 6 months schedule is compared with those administered according to 0, 2 months schedule, as measured by hSBA GMTs against N. meningitidis serogroup B test strains at 1 month after the last meningococcal vaccination. The test strains assessed were Meningitis B NZ98/254 Ab, Meningitis B M14459 Ab, Meningitis B M07-0241084 Ab and Meningitis B 96217 Ab. This outcome measure was evaluated only in the ABCWY_ 0_2 and ABCWY_0_2_6 Groups. The analysis was performed on the Full analysis set (FAS) 1 month after the last meningococcal vaccination. 1 month post last meningococcal vaccination corresponds to Month 3 for ABCWY_0_2 Group and Month 7 for ABCWY_0_2_6 Group.

End point type

Secondary

End point timeframe

At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 3/Month 7)

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	ABCWY_ 0_2 Group	ABCWY_0_2_6 Group
Number of subjects analysed	212	151
Units: Titers
geometric mean (confidence interval 95%)
M14459 strain (Month 0) [N=207;151]	1.21 (1.07 to 1.37)	1.12 (0.98 to 1.28)
M14459 strain (Month 3/Month 7) [N=211;151]	12.17 (9.60 to 15)	27.09 (21 to 35)
M07-0241084 strain (Month 0) [N=201;145]	2.36 (1.85 to 3.01)	2.05 (1.58 to 2.67)
M07-0241084 strain (Month 3/Month 7) [N=206;148]	8.91 (7.10 to 11)	18.03 (14 to 23)
96217 strain (Month 0) [N=205;146]	2.31 (1.75 to 3.06)	2.28 (1.68 to 3.07)
96217 strain (Month 3/Month 7) [N=210;150]	174.27 (142 to 215)	298.76 (239 to 374)
NZ98/254 strain (Month 0) [N=208;151]	1.24 (1.09 to 1.41)	1.07 (0.93 to 1.23)
NZ98/254 strain (Month 3/Month 7) [N=212;151]	12.57 (9.81 to 16)	17.55 (13 to 23)

No statistical analyses for this end point

Secondary: Percentages of subjects with hSBA titers ≥ Lower Limit of Quantitation (LLQ) against N. meningitidis serogroup B test strains

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End point title

Percentages of subjects with hSBA titers ≥ Lower Limit of Quantitation (LLQ) against N. meningitidis serogroup B test strains ^[7]

End point description

The immunogenicity of MenABCWY vaccine, administered according to 0, 2, 6 month schedule, was compared with those administered according to 0, 2 month schedule, as measured by the percentages of subjects with hSBA titers ≥ LLQ (≥ 5, ≥ 8 and ≥ 16) against N. meningitidis serogroup B test strains at 1 month after the last meningococcal vaccination. The analysis was performed on FAS 1 month after the last meningococcal vaccination. The analysis for this outcome measure was carried out only on the subjects in the ABCWY_0_2 Group and ABCWY_0_2_6 Group in the FAS 1 month after the last meningococcal vaccination, at each visit.

End point type

Secondary

End point timeframe

At baseline (Month 0) and 1 month after the last meningococcal vaccination (Month 3/Month 7)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: 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	ABCWY_ 0_2 Group	ABCWY_0_2_6 Group
Number of subjects analysed	212	151
Units: Percentages of subjects
number (confidence interval 95%)
M14459 strain; ≥ 5 (Month 0) [N=207;151]	8 (4.5 to 12.2)	3 (1.1 to 7.6)
M14459 strain; ≥ 8 (Month 0) [N=207;151]	5 (2.7 to 9.3)	2 (0.41 to 5.7)
M14459 strain; ≥ 16 (Month 0) [N=207;151]	2 (0.5 to 4.9)	1 (0.16 to 4.7)
M14459 strain; ≥ 5 (Month 3/Month 7) [N=211;151]	75 (69 to 81)	94 (89 to 97.2)
M14459 strain; ≥ 8 (Month 3/Month 7) [N=211;151]	70 (63.5 to 76.2)	89 (83.4 to 93.8)
M14459 strain; ≥ 16 (Month 3/Month 7)[N=211;151]	53 (45.6 to 59.5)	73 (65 to 79.8)
M07-0241084 strain ≥ 5 (Month 0) [N=201;145]	27 (21.3 to 34.1)	21 (14.4 to 28.2)
M07-0241084 strain ≥ 8 (Month 0) [N=201;145]	20 (14.6 to 26.1)	19 (13.2 to 26.7)
M07-0241084 strain ≥ 16 (Month 0) [N=201;145]	14 (9.5 to 19.5)	14 (9.2 to 21.3)
M07-0241084 strain ≥5(Month 3/Month 7)[N=206;148]	71 (64.7 to 77.4)	82 (75.3 to 88.2)
M07-0241084 strain ≥8(Month 3/Month 7)[N=206;148]	56 (48.8 to 62.7)	79 (71.6 to 85.3)
M07-0241084 strain≥16(Month 3/Month 7)[N=206;148]	33 (26.6 to 39.9)	58 (49.7 to 66.2)
96217 strain; ≥ 5 (Month 0) [N=205;146]	35 (28.1 to 41.6)	29 (22.2 to 37.6)
96217 strain; ≥ 8 (Month 0) [N=205;146]	30 (24 to 37)	28 (21 to 36.1)
96217 strain; ≥ 16 (Month 0) [N=205;146]	17 (12.2 to 22.9)	18 (12 to 25)
96217 strain; ≥ 5 (Month 3/Month 7) [N=210;150]	98 (94.5 to 99.2)	99 (96.3 to 99.98)
96217 strain; ≥ 8 (Month 3/Month 7) [N=210;150]	97 (93.3 to 98.6)	99 (96.3 to 99.98)
96217 strain; ≥ 16 (Month 3/Month 7) [N=210;150]	95 (91.4 to 97.7)	99 (96.3 to 99.98)
NZ98/254 strain ≥ 5 (Month 0) [N= 208;151]	8 (4.5 to 12.2)	3 (0.7 to 6.6)
NZ98/254 strain ≥ 8 (Month 0) [N= 208;151]	6 (3.4 to 10.5)	2 (0.41 to 5.7)
NZ98/254 strain ≥ 16 (Month 0) [N= 208;151]	5 (2.7 to 9.3)	1 (0.02 to 3.6)
NZ98/254 strain ≥ 5(Month 3/Month 7) [N=212;151]	77 (70.6 to 82.4)	82 (75.1 to 87.9)
NZ98/254 strain ≥ 8 (Month 3/Month 7) [N=212;151]	64 (57.3 to 70.6)	75 (67.1 to 81.5)
NZ98/254 strain ≥ 16 (Month 3/Month 7)[N=212;151]	47 (40.3 to 54.1)	57 (48.7 to 65)

No statistical analyses for this end point

Secondary: Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

Top of page

End point title

Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

End point description

The number of subjects with any and Grade 3 solicited local or systemic AEs and other indicators of reactogenicity within 30 minutes after each vaccination. Assessed solicited local symptoms were: pain, erythema and induration. Assessed solicited systemic symptoms were: fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills, and fever (body temperature ≥38.0°C). Other solicited data included: Prevention of Pain and/or Fever and Treatment of Pain and/or Fever. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. The analysis was performed on the Solicited Safety Set population, which included all screened subjects who provided informed consent, demographic and/or baseline screening assessments, regardless of the subject's randomization and treatment status in the study, received a Subject ID and a study vaccination, and who provided post-vaccination reactogenicity data.

End point type

Secondary

End point timeframe

Within 30 minutes after vaccination

End point values	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group
Number of subjects analysed	228	232	155	134	151	159
Units: Subjects
Any Induration (1st) [N=217,219,146,128,143,151]	0	0	0	0	0	0
Grade3 Induration(1st)[N=217,219,146,128,143,151]	0	0	0	0	0	0
Any Induration (2nd) [N=215,217,150,125,144,151]	0	0	0	0	0	0
Grade3 Induration(2nd)[N=215,217,150,125,144,151]	0	0	0	0	0	0
Any Induration (3rd) [N=212,219,146,125,141,151]	0	0	0	0	0	0
Grade3 Induration(3rd)[N=212,219,146,125,141,151]	0	0	0	0	0	0
Any Induration (4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Grade3 Induration(4th)[N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Induration (5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Grade3 Induration(5th)[N=207,206,141,122,134,149]	0	0	0	0	0	0
Any Erythema (1st) [N=217,219,146,128,143,151]	1	0	0	0	1	0
Grade 3 Erythema(1st) [N=217,219,146,128,143,151]	0	0	0	0	0	0
Any Erythema (2nd) [N=215,217,150,125,144,151]	2	0	0	1	0	0
Grade 3 Erythema (2nd)[N=215,217,150,125,144,151]	0	0	0	0	0	0
Any Erythema (3rd) [N=212,219,146,125,141,151]	0	1	0	1	0	0
Grade 3 Erythema (3rd) [N=212,219,146,125,141,151]	0	0	0	0	0	0
Any Erythema (4th) [N=212,214,141,124,138,152]	0	1	0	0	0	1
Grade 3 Erythema(4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Erythema (5th) [N=206,206,141,122,133,149]	0	0	0	0	0	0
Grade 3 Erythema(5th) [N=206,206,141,122,133,149]	0	0	0	0	0	0
Any Pain(1st) [N=228,231,155,134,151,159]	19	4	12	8	17	13
Grade 3 Pain (1st) [N=228,231,155,134,151,159]	0	0	0	0	0	0
Any Pain (2nd) [N=216,221,150,129,145,153]	10	12	11	9	14	9
Grade 3 Pain (2nd) [N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Pain (3rd) [N=213,219,146,126,141,152]	10	11	8	7	5	13
Grade 3 Pain (3rd) [N=213,219,146,126,141,152]	0	0	0	0	0	0
Any Pain (4th) [N=212,214,141,124,138,152]	28	22	7	14	8	17
Grade 3 Pain (4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Pain (5th) [N=207,206,141,122,133,149]	19	16	12	15	13	12
Grade 3 Pain (5th) [N=207,206,141,122,133,149]	0	0	0	0	0	0
Any Nausea (1st) [N=228,231,155,134,151,158]	0	0	2	1	2	2
Grade 3 Nausea (1st) [N=228,231,155,134,151,159]	0	0	0	0	0	0
Any Nausea (2nd) [N=216,221,150,129,145,153]	2	0	1	1	0	0
Grade 3 Nausea (2nd) [N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Nausea (3rd) [N=213,219,146,126,141,152]	2	0	2	0	0	1
Grade 3 Nausea (3rd) [N=213,219,146,126,141,152]	0	0	0	0	0	0
Any Nausea (4th) [N=212,214,141,124,138,152]	2	0	2	0	1	0
Grade 3 Nausea (4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Nausea (5th) [N=207,206,141,122,134,149]	1	0	3	1	0	1
Grade 3 Nausea (5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Any Fatigue (1st) [N=228,231,155,134,151,158]	4	6	6	1	2	1
Grade 3 Fatigue (1st) [N=228,231,155,134,151,158]	0	0	0	0	0	0
Any Fatigue (2nd) [N=216,221,150,129,145,153]	4	3	1	1	2	0
Grade 3 Fatigue (2nd) [N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Fatigue (3rd) [N=213,219,146,126,141,152]	2	4	0	1	1	2
Grade 3 Fatigue(3rd) [N=213,219,146,126,141,152]	0	0	0	1	0	0
Any Fatigue (4th) [N=212,214,141,124,138,152]	2	1	1	0	1	3
Grade 3 Fatigue (4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Fatigue (5th) [N=207,206,141,122,134,149]	1	2	1	3	1	1
Grade 3 Fatigue (5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Any Myalgia (1st) [N=228,231,155,134,151,158]	0	1	0	0	0	0
Grade 3 Myalgia (1st) [N=228,231,155,134,151,158]	0	0	0	0	0	0
Any Myalgia (2nd) [N=216,221,150,129,145,153]	0	0	1	0	3	1
Grade 3 Myalgia (2nd) [N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Myalgia (3rd) [N=213,219,146,126,141,152]	0	0	0	1	0	0
Grade 3 Myalgia (3rd) [N=213,219,146,126,141,152]	0	0	0	0	0	0
Any Myalgia (4th) [N=212,214,141,124,138,152]	0	0	0	0	1	0
Grade 3 Myalgia (4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Myalgia (5th) [N=207,206,141,122,134,149]	0	4	1	0	1	0
Grade 3 Myalgia (5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Any Arthralgia (1st) [N=228,231,155,134,151,158]	0	0	0	0	0	0
Grade3 Arthralgia(1st)[N=228,231,155,134,151,158]	0	0	0	0	0	0
Any Arthralgia (2nd) [N=216,221,150,129,145,153]	0	0	0	0	0	0
Grade3 Arthralgia(2nd)[N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Arthralgia (3rd) [N=213,219,146,126,141,152]	0	0	0	0	0	0
Grade3 Arthralgia(3rd)[N=213,219,146,126,141,152]	0	0	0	0	0	0
Any Arthralgia (4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Grade3 Arthralgia(4th)[N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Arthralgia (5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Grade3 Arthralgia(5th)[N=207,206,141,122,134,149]	0	0	0	0	0	0
Any Headache (1st) [N=228,231,155,134,151,158]	2	3	1	1	1	0
Grade 3 Headache(1st) [N=228,231,155,134,151,158]	0	0	0	0	0	0
Any Headache (2nd) [N=216,221,150,129,145,153]	3	1	2	1	1	1
Grade 3 Headache (2nd)[N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Headache (3rd) [N=213,219,146,126,141,152]	2	1	2	0	1	1
Grade 3 Headache(3rd) [N=213,219,146,126,141,152]	0	0	0	0	0	0
Any Headache (4th) [N=212,214,141,124,138,152]	3	2	0	0	1	1
Grade 3 Headache (4th)[N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Headache (5th) [N=207,206,141,122,134,149]	2	1	0	0	0	1
Grade 3 Headache(5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Any Chills (1st) [N=228,231,155,134,151,158]	0	1	1	0	2	2
Grade 3 Chills (1st) [N=228,231,155,134,151,158]	0	0	0	0	0	0
Any Chills (2nd) [N=216,221,150,129,145,153]	1	1	1	1	0	0
Grade 3 Chills (2nd) [N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Chills (3rd) [N=213,219,146,126,141,152]	1	1	0	0	0	0
Grade 3 Chills (3rd) [N=213,219,146,126,141,152]	0	0	0	0	0	0
Any Chills (4th) [N=212,214,141,124,138,152]	1	1	0	0	0	0
Grade 3 Chills (4th) [N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Chills (5th) [N=207,206,141,122,134,149]	1	1	0	0	0	0
Grade 3 Chills (5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Any Appetite Loss(1)[N=228,231,155,134,151,158]	0	0	0	0	0	0
Grade3AppetiteLoss(1)[N=228,231,155,134,151,158]	0	0	0	0	0	0
Any Appetite Loss(2)[N=216,221,150,129,145,153]	0	0	0	0	0	0
Grade3AppetiteLoss(2)[N=216,221,150,129,145,153]	0	0	0	0	0	0
Any Appetite Loss(3)[N=213,219,146,126,141,152]	0	0	0	0	0	0
Grade3AppetiteLoss(3)[N=213,219,146,126,141,152]	0	0	0	0	0	0
Any Appetite Loss(4)[N=212,214,141,124,138,152]	0	0	0	0	0	0
Grade3AppetiteLoss(4)[N=212,214,141,124,138,152]	0	0	0	0	0	0
Any Appetite Loss(5)[N=207,206,141,122,134,149]	0	0	0	0	0	0
Grade3AppetiteLoss(5)[N=207,206,141,122,134,149]	0	0	0	0	0	0
Fever (1st) [N=228,232,155,133,151,158]	0	0	0	0	0	0
Fever (2nd) [N=216,221,150,128,145,153]	0	0	0	0	0	0
Fever (3rd) [N=213,218,146,125,141,152]	0	0	0	0	0	0
Fever (4th) [N=211,214,140,124,137,152]	0	0	0	0	0	0
Fever (5th) [N=207,206,141,122,134,149]	0	0	0	0	0	0
Pain/Fever prevention(1)N=228,232,155,134,151,159	0	0	0	0	0	0
Pain/Fever prevention(2)N=216,221,150,129,145,153	0	2	0	0	0	0
Pain/Fever prevention(3)N=213,219,146,126,141,152	1	0	0	0	0	0
Pain/Fever prevention(4)N=211,214,141,124,138,152	0	0	0	0	0	0
Pain/Fever prevention(5)N=207,206,141,122,134,149	0	0	0	0	0	0
Pain/Fever treatment(1)N=227,232,155,134,151,159	0	0	1	0	0	0
Pain/Fever treatment(2)N=216,221,150,129,145,153	1	0	0	0	0	1
Pain/Fever treatment(3)N=213,219,146,126,141,152	0	0	0	0	0	0
Pain/Fever treatment(4)N=212,214,141,124,138,152	0	1	0	0	0	0
Pain/Fever treatment(5)N=207,206,141,122,134,149	0	0	0	0	1	0

No statistical analyses for this end point

Secondary: Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

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End point title

Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

End point description

The number of subjects with any or Grade 3 solicited local or systemic AEs and other indicators of reactogenicity from Day 1 (6 hours) to Day 7 after each vaccination is reported. Assessed solicited local symptoms were: pain, erythema and induration. Assessed solicited systemic symptoms were: fatigue, headache, myalgia, arthralgia, loss of appetite, nausea, chills, and fever (body temperature ≥38.0°C). Other solicited data included: Prevention of Pain and/or Fever and Treatment of Pain and/or Fever. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. The analysis was performed on the Solicited Safety Set population, which included all screened subjects who provided informed consent, demographic and/or baseline screening assessments, regardless of the subject's randomization and treatment status in the study, received a Subject ID and a study vaccination, and who provided post-vaccination reactogenicity data.

End point type

Secondary

End point timeframe

From Day 1 (6 hours) to Day 7 after each vaccination

End point values	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group
Number of subjects analysed	228	231	155	134	151	159
Units: Subjects
Any AE [N= 228, 231, 155, 134, 151, 159]	224	227	153	131	151	157
Any Local AE [N= 228, 231, 155, 134, 151, 159]	221	225	148	129	147	156
Any Systemic AE [N= 228, 231, 155, 134, 151, 159]	201	201	143	117	134	143
Any Pain (1st) [N=227,231,154,134,151,159]	213	223	142	126	80	146
Grade 3 Pain (1st) [N=227,231,154,134,151,159]	9	13	2	10	0	6
Any Pain (2nd) [N=214,216,150,128,144,151]	32	34	122	41	135	51
Grade 3 Pain (2nd) [N=214,216,150,128,144,151]	0	1	5	0	11	0
Any Pain (3rd) [N=212,217,144,125,138,150]	193	185	38	26	16	133
Grade 3 Pain (3rd) [N=212,217,144,125,138,150]	11	7	0	0	0	5
Any Pain (4th) [N=206,211,139,120,136,152]	79	77	19	106	44	138
Grade 3 Pain (4th) [N=206,211,139,120,136,152]	1	0	0	10	0	9
Any Pain (5th) [N=206,206,140,121,132,147]	83	80	58	48	119	64
Grade 3 Pain (5th) [N=206,206,140,121,132,147]	0	1	1	0	11	1
Any Erythema (1st) [N=227,231,154,134,151,159]	23	24	18	12	1	23
Grade 3 Erythema (1st)[N=227,231,154,134,151,159]	0	3	1	0	0	2
Any Erythema (2nd) [N=214,216,150,128,144,151]	3	5	9	1	17	3
Grade3Erythema(2nd)[N=214,216,150,128,144,151]	0	0	2	0	4	1
Any Erythema (3rd) [N=212,217,144,125,138,150]	33	29	0	2	0	20
Grade 3 Erythema (3rd)[N=212,217,144,125,138,150]	2	6	0	0	0	1
Any Erythema (4th) [N=206,211,139,120,136,152]	1	1	0	12	0	16
Grade 3 Erythema(4th) [N=206,211,139,120,136,152]	0	0	0	1	0	5
Any Erythema (5th) [N=206,206,140,121,132,147]	1	1	1	0	11	0
Grade 3 Erythema(5th) [N=206,206,140,121,132,147]	0	0	0	0	1	0
Any Induration (1st) [N=227,231,154,134,151,159]	24	23	14	13	3	21
Grade 3 Induration(1st)[N=227,231,154,134,151,159]	0	0	0	1	0	1
Any Induration(2nd) [N=214,216,150,128,144,151]	2	2	12	0	12	2
Grade3 Induration(2nd)[N=214,216,150,128,144,151]	0	0	0	0	0	0
Any Induration (3rd) [N=212,217,144,125,138,150]	27	18	1	0	1	22
Grade3 Induration(3rd)[N=212,217,144,125,138,150]	2	1	0	0	0	0
Any Induration(4th) [N=206,211,139,120,136,152]	2	3	0	10	0	14
Grade3 Induration(4th)[N=206,211,139,120,136,152]	0	0	0	1	0	1
Any Induration (5th) [N=206,206,140,121,132,147]	2	3	1	2	16	1
Grade3 Induration(5th)[N=206,206,140,121,132,147]	0	0	0	1	1	0
Any Fatigue (1st) [N=227,231,154,134,151,159]	126	121	84	68	68	76
Grade3 Fatigue(1st) [N=227,231,154,134,151,159]	7	7	4	3	3	4
Any Fatigue (2nd) [N=214,216,150,128,144,151]	61	64	64	40	64	49
Grade 3 Fatigue(2nd) [N=214,216,150,128,144,151]	0	3	4	2	1	0
Any Fatigue (3rd) [N=212,217,144,125,138,150]	106	96	44	32	32	55
Grade 3 Fatigue(3rd) [N=212,217,144,125,138,150]	4	5	1	0	1	1
Any Fatigue (4th) [N=206,211,139,120,136,152]	50	56	37	51	35	73
Grade 3 Fatigue(4th) [N=206,211,139,120,136,152]	2	3	0	5	2	3
Any Fatigue (5th) [N=206,206,140,121,132,147]	62	59	37	41	51	46
Grade 3 Fatigue(5th) [N=206,206,140,121,132,147]	1	2	4	0	6	3
Any Headache (1st) [N=227,231,154,134,151,159]	103	92	65	52	63	64
Grade 3 Headache(1st) [N=227,231,154,134,151,159]	4	3	5	2	2	3
Any Headache (2nd) [N=214,216,150,128,144,151]	67	47	70	36	63	41
Grade 3 Headache(2nd) [N=214,216,150,128,144,151]	1	2	3	2	4	2
Any Headache (3rd) [N=212,217,144,125,138,150]	90	76	42	28	30	53
Grade 3 Headache(3rd) [N=212,217,144,125,138,150]	3	4	1	0	3	0
Any Headache (4th) [N=206,211,139,120,136,152]	49	35	26	44	26	52
Grade 3 Headache(4th) [N=206,211,139,120,136,152]	3	3	0	2	0	4
Any Headache (5th) [N=206,206,140,121,132,147]	64	40	33	33	52	37
Grade 3 Headache(5th) [N=206,206,140,121,132,147]	1	1	2	1	2	2
Any Myalgia (1st) [N=227,231,154,134,151,159]	62	53	39	34	33	40
Grade 3 Myalgia (1st)[N=227,231,154,134,151,159]	2	4	2	2	0	3
Any Myalgia (2nd) [N=214,216,150,128,144,151]	15	20	27	15	37	18
Grade 3 Myalgia(2nd) [N=214,216,150,128,144,151]	0	3	1	1	1	0
Any Myalgia (3rd) [N=212,217,144,125,138,150]	52	40	13	10	13	34
Grade 3 Myalgia (3rd) [N=212,217,144,125,138,150]	2	2	0	0	2	2
Any Myalgia (4th) [N=206,211,139,120,136,152]	17	20	11	26	13	39
Grade 3 Myalgia(4th) [N=206,211,139,120,136,152]	1	1	1	2	0	2
Any Myalgia (5th) [N=206,206,140,121,132,147]	16	26	19	12	21	19
Grade 3 Myalgia (5th) [N=206,206,140,121,132,147]	0	1	0	0	1	1
Any Appetite Loss(1st)[N=227,231,154,134,151,159]	41	33	28	22	14	18
Grade3AppetiteLoss(1st)[N=227,231,154,134,151,159	2	3	0	0	0	0
AnyAppetiteLoss(2nd)[N=214,216,150,128,144,151]	17	11	15	12	19	9
Grade3AppetiteLoss(2nd)[N=214,216,150,128,144,151	0	1	0	0	2	0
AnyAppetiteLoss(3rd)[N=212,217,144,125,138,150]	28	28	7	7	11	17
Grade3AppetiteLoss(3rd)[N=212,217,144,125,138,150	1	0	1	0	1	0
Any Appetite Loss(4th)[N=206,211,139,120,136,152]	11	10	4	13	11	23
Grade3AppetiteLoss(4th)[N=206,211,139,120,136,152	0	0	0	0	0	0
Any Appetite Loss(5th)[N=206,206,140,121,132,147]	18	14	9	9	22	7
Grade3AppetiteLoss(5th)[N=206,206,140,121,132,147	0	0	1	0	0	0
Any Nausea (1st) [N=227,231,154,134,151,159]	42	36	28	17	26	21
Grade 3 Nausea (1st) [N=227,231,154,134,151,159]	1	0	0	0	0	1
Any Nausea (2nd) [N=214,216,150,128,144,151]	17	15	20	10	26	15
Grade 3 Nausea (2nd) [N=214,216,150,128,144,151]	0	0	0	0	0	0
Any Nausea (3rd) [N=212,217,144,125,138,150]	35	24	10	8	4	21
Grade 3 Nausea (3rd) [N=212,217,144,125,138,150]	0	0	0	0	0	0
Any Nausea (4th) [N=206,211,139,120,136,152]	21	13	9	11	14	23
Grade 3 Nausea (4th) [N=206,211,139,120,136,152]	1	0	0	0	0	0
Any Nausea (5th) [N=206,206,140,121,132,147]	16	15	8	11	21	12
Grade 3 Nausea(5th) [N=206,206,140,121,132,147]	0	0	0	0	0	0
Any Chills (1st) [N=227,231,154,134,151,159]	45	36	41	24	27	40
Grade 3 Chills (1st) [N=227,231,154,134,151,159]	1	0	1	1	2	1
Any Chills (2nd) [N=214,216,150,128,144,151]	17	26	26	12	32	15
Grade 3 Chills (2nd) [N=214,216,150,128,144,151]	0	1	1	0	0	0
Any Chills(3rd) [N=212,217,144,125,138,150]	33	33	9	7	12	22
Grade 3 Chills(3rd) [N=212,217,144,125,138,150]	1	1	0	0	1	0
Any Chills (4th) [N=206,211,139,120,136,152]	11	11	10	12	9	31
Grade 3 Chills (4th) [N=206,211,139,120,136,152]	2	0	0	0	0	1
Any Chills (5th) [N=206,206,140,121,132,147]	19	23	17	11	22	13
Grade 3 Chills(5th) [N=206,206,140,121,132,147]	0	0	0	1	0	0
Fever (1st) [N=227,231,154,133,151,158]	5	4	5	1	2	3
Fever (2nd) [N=214,216,149,127,144,151]	2	6	4	2	9	3
Fever (3rd) [N=212,217,143,124,138,150]	6	3	2	0	4	4
Fever (4th) [N=206,211,138,119,136,151]	0	2	0	3	0	7
Fever (5th) [N=206,206,139,120,132,147]	5	1	2	0	3	1
Pain/Fever prevention(1)N=227,231,154,134,151,159	28	34	21	26	5	34
Pain/Fever prevention(2)N=214,216,150,128,144,151	5	7	18	5	24	7
Pain/Fever prevention(3)N=212,217,144,125,138,150	32	34	3	2	3	21
Pain/Fever prevention(4)N=206,211,139,120,136,152	6	5	3	19	3	25
Pain/Fever prevention(5)N=206,206,140,121,132,147	5	9	4	1	26	3
Pain/Fever treatment(1)N=227,231,154,134,151,159	31	45	27	32	6	31
Pain/Fever treatment(2)N=214,216,150,128,144,151	3	4	20	3	29	4
Pain/Fever treatment(3)N=212,217,144,125,138,150	38	37	2	4	2	23
Pain/Fever treatment(4)N=206,211,139,120,136,152	7	4	2	22	2	27
Pain/Fever treatment(5)N=206,206,140,121,132,147	3	8	2	3	29	2
Any Arthralgia (1st) [N=227,231,154,134,151,159]	25	14	13	17	12	14
Grade3Arthralgia(1st) [N=227,231,154,134,151,159]	0	1	0	0	1	2
Any Arthralgia (2nd) [N=214,216,150,128,144,151]	7	11	10	9	8	7
Grade3Arthralgia(2nd)[N=214,216,150,128,144,151]	0	0	0	1	0	1
Any Arthralgia (3rd) [N=212,217,144,125,138,150]	16	17	4	3	6	11
Grade3Arthralgia(3rd)[N=212,217,144,125,138,150]	0	1	0	0	0	0
Any Arthralgia (4th) [N=206,211,139,120,136,152]	8	10	5	10	7	18
Grade3Arthralgia(4th)[N=206,211,139,120,136,152]	1	0	0	0	0	2
Any Arthralgia(5th)[N=206,206,140,121,132,147]	8	9	8	6	11	11
Grade3Arthralgia(5th)[N=206,206,140,121,132,147]	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reporting unsolicited AEs after any vaccination

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End point title

Number of subjects reporting unsolicited AEs after any vaccination

End point description

The number of subjects reporting unsolicited AEs and possibly or probably related unsolicited AEs is reported. An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Possibly or probably related AE = AE assessed by the investigator as related to the vaccination. The analysis was performed on the Unsolicited Safety Set population, which included all subjects who received a study vaccination and who had post-vaccination unsolicited adverse event records.

End point type

Secondary

End point timeframe

From Day 1 through Day 30 after any vaccination

End point values	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group
Number of subjects analysed	221	228	151	129	147	157
Units: Subjects
Any AE(s)	146	148	93	76	97	104
Possibly or Probably Related AE(s)	25	31	23	16	18	27

No statistical analyses for this end point

Secondary: Number of subjects reporting any serious adverse events (SAEs) and other significant AE(s)

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End point title

Number of subjects reporting any serious adverse events (SAEs) and other significant AE(s)

End point description

The number of subjects reporting any SAE, possibly or probably related SAE(s), medically attended AE(s) (MAEs), AE(s) leading to premature withdrawal,AE(s) leading to death,AE(s) leading to hospitalization and AE(s) leading to dose reduction, interruption and delay in study vaccination during the entire study period is reported. SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.Possibly or probably related SAE=SAE assessed by the investigator as related to the vaccination.MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel for any reason. The analysis was performed on the Unsolicited Safety Set population, which included all subjects who received a study vaccination and who had post-vaccination unsolicited AE records.

End point type

Secondary

End point timeframe

During the entire study period (from Month 0 up to Month 13)

End point values	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group
Number of subjects analysed	221	228	151	129	147	157
Units: Subjects
Any SAE(s)	9	3	8	7	2	6
Possibly or Probably Related SAE(s)	0	1	1	0	0	0
Medically Attended AE(s)	103	97	68	57	67	79
AE(s) leading to premature withdrawal	2	6	4	2	1	3
AE(s) leading to Death	0	0	0	0	0	0
AE(s) leading to Hospitalization	9	1	7	6	1	6
AE(s)leadingtodosereduction,interruption,vaccdelay	8	8	7	2	4	5

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited AEs were collected from Day 1 (6 hours) to Day 7; Unsolicited AEs were collected from Day 1 to Day 30; SAEs, AEs leading to withdrawal and medically attended AEs were collected throughout the entire study period (from Month 0 up to Month 13).

Adverse event reporting additional description

SAEs were assessed for the Unsolicited safety set of subjects and the frequent adverse events were assessed for the Overall safety set. Therefore, the total number of participants at risk for SAEs are different from the total number of participants at risk for other adverse events.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

rMenB_0_2 Group

Reporting group description

Subjects received two injections of Bexsero™ vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Reporting group title

ABCWY_ 0_2 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 2, Havrix® vaccine at Visit Month 6 and Visit Month 12 and saline placebo at Visit Month 1.

Reporting group title

ABCWY_0_1 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 1, Havrix® vaccine at Visit Month 2 and Visit Month 12 and saline placebo at Visit Month 6.

Reporting group title

ABCWY_0_6 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0 and Visit Month 6, Havrix® vaccine at Visit Month 1 and Visit Month 12 and saline placebo at Visit Month 2.

Reporting group title

ABCWY_0_11 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 1 and Visit Month 12, Havrix® vaccine at Visit Month 0 and Visit Month 6 and saline placebo at Visit Month 2.

Reporting group title

ABCWY_0_2_6 Group

Reporting group description

Subjects received MenABCWY vaccine at Visit Month 0, Visit Month 2 and Visit Month 6 and Havrix® vaccine at Visit Month 1 and Visit Month 12.

Serious adverse events	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group
Total subjects affected by serious adverse events
subjects affected / exposed	9 / 228 (3.95%)	3 / 231 (1.30%)	8 / 155 (5.16%)	7 / 134 (5.22%)	2 / 151 (1.32%)	6 / 159 (3.77%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast
subjects affected / exposed ^[1]	0 / 221 (0.00%)	0 / 228 (0.00%)	1 / 151 (0.66%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Tooth extraction
subjects affected / exposed ^[2]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion incomplete
subjects affected / exposed ^[3]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed ^[4]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed ^[5]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Testicular torsion
subjects affected / exposed ^[6]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	1 / 157 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed ^[7]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental disorder
subjects affected / exposed ^[8]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed ^[9]	0 / 221 (0.00%)	1 / 228 (0.44%)	1 / 151 (0.66%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Carbon monoxide poisoning
subjects affected / exposed ^[10]	0 / 221 (0.00%)	1 / 228 (0.44%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed ^[11]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	1 / 157 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed ^[12]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed ^[13]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	1 / 157 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrioventricular block second degree
subjects affected / exposed ^[14]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Partial seizures
subjects affected / exposed ^[15]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	1 / 147 (0.68%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed ^[16]	0 / 221 (0.00%)	1 / 228 (0.44%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed ^[17]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	1 / 147 (0.68%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed ^[18]	2 / 221 (0.90%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal migraine
subjects affected / exposed ^[19]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed ^[20]	0 / 221 (0.00%)	0 / 228 (0.00%)	1 / 151 (0.66%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed ^[21]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed ^[22]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Tubulointerstitial nephritis
subjects affected / exposed ^[23]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hypothyroidism
subjects affected / exposed ^[24]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	1 / 157 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed ^[25]	0 / 221 (0.00%)	0 / 228 (0.00%)	1 / 151 (0.66%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Connective tissue disorder
subjects affected / exposed ^[26]	0 / 221 (0.00%)	0 / 228 (0.00%)	1 / 151 (0.66%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Torticollis
subjects affected / exposed ^[27]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	1 / 157 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed ^[28]	1 / 221 (0.45%)	0 / 228 (0.00%)	2 / 151 (1.32%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed ^[29]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed ^[30]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infectious mononucleosis
subjects affected / exposed ^[31]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed ^[32]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic inflammatory disease
subjects affected / exposed ^[33]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	1 / 157 (0.64%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed ^[34]	0 / 221 (0.00%)	0 / 228 (0.00%)	1 / 151 (0.66%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed ^[35]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed ^[36]	1 / 221 (0.45%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Failure to thrive
subjects affected / exposed ^[37]	0 / 221 (0.00%)	0 / 228 (0.00%)	1 / 151 (0.66%)	0 / 129 (0.00%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obesity
subjects affected / exposed ^[38]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	0 / 129 (0.00%)	0 / 147 (0.00%)	1 / 157 (0.64%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed ^[39]	0 / 221 (0.00%)	0 / 228 (0.00%)	0 / 151 (0.00%)	1 / 129 (0.78%)	0 / 147 (0.00%)	0 / 157 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[27] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[28] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[29] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[30] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[31] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[32] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[33] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[34] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[35] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[36] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[37] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[38] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.
[39] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed.

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

Non-serious adverse events	rMenB_0_2 Group	ABCWY_ 0_2 Group	ABCWY_0_1 Group	ABCWY_0_6 Group	ABCWY_0_11 Group	ABCWY_0_2_6 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	226 / 228 (99.12%)	229 / 231 (99.13%)	153 / 155 (98.71%)	131 / 134 (97.76%)	151 / 151 (100.00%)	158 / 159 (99.37%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Arthralgia
subjects affected / exposed	48 / 228 (21.05%)	48 / 231 (20.78%)	28 / 155 (18.06%)	31 / 134 (23.13%)	27 / 151 (17.88%)	38 / 159 (23.90%)
occurrences all number	109	125	57	96	68	101
Injury, poisoning and procedural complications
Respiratory tract infection
subjects affected / exposed	15 / 228 (6.58%)	12 / 231 (5.19%)	10 / 155 (6.45%)	5 / 134 (3.73%)	6 / 151 (3.97%)	10 / 159 (6.29%)
occurrences all number	24	15	16	12	12	13
Nervous system disorders
Headache
subjects affected / exposed	165 / 228 (72.37%)	149 / 231 (64.50%)	114 / 155 (73.55%)	93 / 134 (69.40%)	110 / 151 (72.85%)	117 / 159 (73.58%)
occurrences all number	830	593	496	450	478	530
General disorders and administration site conditions
Chills
subjects affected / exposed	80 / 228 (35.09%)	76 / 231 (32.90%)	61 / 155 (39.35%)	40 / 134 (29.85%)	62 / 151 (41.06%)	70 / 159 (44.03%)
occurrences all number	236	216	172	136	173	208
Fatigue
subjects affected / exposed	169 / 228 (74.12%)	165 / 231 (71.43%)	119 / 155 (76.77%)	98 / 134 (73.13%)	105 / 151 (69.54%)	120 / 159 (75.47%)
occurrences all number	956	891	534	533	559	633
Injection site erythema
subjects affected / exposed	131 / 228 (57.46%)	131 / 231 (56.71%)	80 / 155 (51.61%)	80 / 134 (59.70%)	89 / 151 (58.94%)	97 / 159 (61.01%)
occurrences all number	465	367	271	268	284	398
Injection site induration
subjects affected / exposed	110 / 228 (48.25%)	98 / 231 (42.42%)	67 / 155 (43.23%)	53 / 134 (39.55%)	70 / 151 (46.36%)	85 / 159 (53.46%)
occurrences all number	437	359	260	176	248	458
Injection site pain
subjects affected / exposed	221 / 228 (96.93%)	225 / 231 (97.40%)	148 / 155 (95.48%)	129 / 134 (96.27%)	148 / 151 (98.01%)	154 / 159 (96.86%)
occurrences all number	1870	1598	1003	1065	1087	1592
Pyrexia
subjects affected / exposed	27 / 228 (11.84%)	27 / 231 (11.69%)	20 / 155 (12.90%)	13 / 134 (9.70%)	25 / 151 (16.56%)	26 / 159 (16.35%)
occurrences all number	37	34	26	16	33	32
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	16 / 228 (7.02%)	9 / 231 (3.90%)	6 / 155 (3.87%)	5 / 134 (3.73%)	9 / 151 (5.96%)	9 / 159 (5.66%)
occurrences all number	22	9	6	6	12	12
Nausea
subjects affected / exposed	74 / 228 (32.46%)	68 / 231 (29.44%)	51 / 155 (32.90%)	47 / 134 (35.07%)	56 / 151 (37.09%)	62 / 159 (38.99%)
occurrences all number	232	145	136	85	167	149
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	12 / 228 (5.26%)	5 / 231 (2.16%)	6 / 155 (3.87%)	1 / 134 (0.75%)	1 / 151 (0.66%)	3 / 159 (1.89%)
occurrences all number	14	6	7	1	1	3
Oropharyngeal pain
subjects affected / exposed	12 / 228 (5.26%)	13 / 231 (5.63%)	9 / 155 (5.81%)	7 / 134 (5.22%)	5 / 151 (3.31%)	7 / 159 (4.40%)
occurrences all number	14	13	13	9	6	8
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	103 / 228 (45.18%)	99 / 231 (42.86%)	69 / 155 (44.52%)	54 / 134 (40.30%)	65 / 151 (43.05%)	81 / 159 (50.94%)
occurrences all number	271	315	169	178	213	244
Infections and infestations
Gastroenteritis
subjects affected / exposed	15 / 228 (6.58%)	11 / 231 (4.76%)	13 / 155 (8.39%)	9 / 134 (6.72%)	10 / 151 (6.62%)	10 / 159 (6.29%)
occurrences all number	16	11	13	11	12	10
Nasopharyngitis
subjects affected / exposed	37 / 228 (16.23%)	30 / 231 (12.99%)	28 / 155 (18.06%)	21 / 134 (15.67%)	24 / 151 (15.89%)	25 / 159 (15.72%)
occurrences all number	53	50	40	38	34	44
Pharyngitis
subjects affected / exposed	16 / 228 (7.02%)	21 / 231 (9.09%)	7 / 155 (4.52%)	8 / 134 (5.97%)	11 / 151 (7.28%)	15 / 159 (9.43%)
occurrences all number	16	21	9	8	14	15
Rhinitis
subjects affected / exposed	15 / 228 (6.58%)	18 / 231 (7.79%)	7 / 155 (4.52%)	6 / 134 (4.48%)	5 / 151 (3.31%)	11 / 159 (6.92%)
occurrences all number	18	21	10	6	5	14
Tonsillitis
subjects affected / exposed	7 / 228 (3.07%)	10 / 231 (4.33%)	3 / 155 (1.94%)	6 / 134 (4.48%)	9 / 151 (5.96%)	5 / 159 (3.14%)
occurrences all number	9	11	4	8	10	5
Upper respiratory tract infection
subjects affected / exposed	53 / 228 (23.25%)	58 / 231 (25.11%)	37 / 155 (23.87%)	31 / 134 (23.13%)	35 / 151 (23.18%)	37 / 159 (23.27%)
occurrences all number	74	92	52	46	51	51
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	69 / 228 (30.26%)	64 / 231 (27.71%)	45 / 155 (29.03%)	43 / 134 (32.09%)	45 / 151 (29.80%)	52 / 159 (32.70%)
occurrences all number	208	164	107	91	131	121

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Were there any global substantial amendments to the protocol? Yes

23 Apr 2014

The protocol was amended primarily to address comments from CBER on the previous version of the protocol, relating to addition of secondary immunogenicity objective and inclusion of detail on safety data collection and randomization procedures. Additional changes were made to ensure that the subjects/parents/legal guardians were encouraged to contact sites during the entire study in case medically-attended AEs or any AEs which was perceived as being of concern. Additionally the placebo was provided as ampoules instead of the vials and the protocol text was amended accordingly.

03 Feb 2015

The protocol was amended to further clarify certain sections and to correct the content errors/typographical errors which were recognized in the protocol version 3.0.

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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Baseline characteristics

Baseline characteristics

End points

End points

Primary: Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup B test strains

Primary: Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup B test strains

Secondary: hSBA GMTs against N. meningitidis serogroup B test strains

Secondary: hSBA GMTs against N. meningitidis serogroup B test strains

Secondary: Percentages of subjects with hSBA titers ≥ Lower Limit of Quantitation (LLQ) against N. meningitidis serogroup B test strains

Secondary: Percentages of subjects with hSBA titers ≥ Lower Limit of Quantitation (LLQ) against N. meningitidis serogroup B test strains

Secondary: Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

Secondary: Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

Secondary: Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

Secondary: Number of subjects reporting any and Grade 3 solicited local or systemic adverse events (AEs) and other indicators of reactogenicity

Secondary: Number of subjects reporting unsolicited AEs after any vaccination

Secondary: Number of subjects reporting unsolicited AEs after any vaccination

Secondary: Number of subjects reporting any serious adverse events (SAEs) and other significant AE(s)

Secondary: Number of subjects reporting any serious adverse events (SAEs) and other significant AE(s)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

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