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Clinical Trial Results:
A Phase IIIB, Randomized, Observer-blind, Multicenter Study to Assess the Safety and Immunogenicity of GSK's Meningococcal Group B Vaccine When Administered Concomitantly With GSK's Meningococcal MenACWY Conjugate Vaccine to Healthy Subjects of 16-18 Years of Age

Summary
EudraCT number	2016-003722-16
Trial protocol	Outside EU/EEA IT
Global end of trial date	22 Jul 2024

Results information
Results version number	v1
This version publication date	02 Feb 2025
First version publication date	02 Feb 2025
Other versions	v2

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

205419

ISRCTN number

US NCT number

NCT04318548

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

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

Public contact

GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 044 8664357343, 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

03 Oct 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Nov 2023

Global end of trial reached?

Yes

Global end of trial date

22 Jul 2024

Was the trial ended prematurely?

Main objective of the trial

• To assess the safety and tolerability of rMenB+OMV NZ and MenACWY, when administered concomitantly or alone, in healthy subjects 16-18 years of age. • To demonstrate the non-inferiority of the antibody response to rMenB+OMV NZ given concomitantly with MenACWY to healthy subjects 16-18 years of age compared to rMenB+OMV NZ administered alone, as measured by serum bactericidal assay using human complement (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup B indicator strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at 1 month after the second vaccination with rMenB+OMV NZ. • To demonstrate the non-inferiority of the antibody response to MenACWY given concomitantly with rMenB+OMV NZ to healthy subjects 16-18 years of age compared to MenACWY administered alone, as measured by hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y, at 1 month after the (study) vaccination with MenACWY.

Protection of trial subjects

Vaccine administration was preceded by a review of the subjects’ medical history (including previous vaccination and occurrence of undesirable events) and a general physical examination at the first visit and symptom-directed physical examination before subsequent vaccinations. Protocol procedures, including blood sampling, were done by a qualified healthcare professional. The subjects were observed closely for at least 30 minutes following the administration of the vaccine(s)/product(s), with appropriate medical treatment readily available in case of anaphylaxis and syncope.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Aug 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Italy: 111

Country: Number of subjects enrolled

United States: 834

Worldwide total number of subjects

945

EEA total number of subjects

111

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

864

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study ended on Day 271 for participants who had not reached Day 271 when Protocol Amendment 7 took effect, and on Day 451 for those who had already passed Day 271.Safety follow-up period for each participant was from Day 1 up to Day 451 or Day 271 for participants who have not reached Day 271 at the time Protocol Amendment 7 took effect.

Screening details

A total of 945 participants were enrolled in the study, of which only 940 were randomized into the 3 treatment groups. After randomization, 2 participants did not receive the vaccine and making it a total of 938 participants in the exposed set.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Monitor, Data analyst, Subject, Investigator

Are arms mutually exclusive

Yes

MenB+MenACWY Group

Arm description

Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of MenACWY vaccine, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of placebo at Day 91.

Arm type

Experimental

Investigational medicinal product name

MenACWY

Investigational medicinal product code

Other name

Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of MenACWY vaccine administered intramuscularly.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of Placebo administered intramuscularly.

Investigational medicinal product name

rMenB+OMV NZ

Investigational medicinal product code

Other name

Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 dose of rMenB+OMV NZ vaccine administered intramuscularly.

MenB Group

Arm description

Participants received 1 dose of rMenB+OMV NZ vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day 1, 1 dose of rMenB+OMV NZ vaccine at Day 61 and 1 dose of MenACWY at Day 91.

Arm type

Experimental

Investigational medicinal product name

rMenB+OMV NZ

Investigational medicinal product code

Other name

Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 dose of rMenB+OMV NZ vaccine administered intramuscularly.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of Placebo administered intramuscularly.

Investigational medicinal product name

MenACWY

Investigational medicinal product code

Other name

Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of MenACWY vaccine administered intramuscularly.

MenACWY Group

Arm description

Participants received 1 dose of MenACWY vaccine administered concomitantly with 1 dose of placebo, as separate injections in each arm at Day1, 1 dose of rMenB+OMV NZ vaccine each administered at Day 61 and at Day 91.

Arm type

Experimental

Investigational medicinal product name

rMenB+OMV NZ

Investigational medicinal product code

Other name

Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 dose of rMenB+OMV NZ vaccine administered intramuscularly.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of Placebo administered intramuscularly.

Investigational medicinal product name

MenACWY

Investigational medicinal product code

Other name

Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of MenACWY vaccine administered intramuscularly.

Number of subjects in period 1 ^[1]	MenB+MenACWY Group	MenB Group	MenACWY Group
Started	310	308	320
Completed	297	284	298
Not completed	13	24	22
Adverse event, non-fatal	-	-	1
Migrated / moved from the study area	-	-	1
Not specified	1	2	3
Lost to follow-up	6	13	9
Consent withdrawal, not due to a (S)AE	5	9	6
Protocol deviation	1	-	2

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: A total of 945 participants were enrolled in the study, of which only 940 were randomized into the 3 treatment groups. After randomization, 2 participants did not receive the vaccine and making it a total of 938 participants in the exposed set.

Baseline characteristics

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Reporting group title

MenB+MenACWY Group

Reporting group description

Reporting group title

MenB Group

Reporting group description

Reporting group title

MenACWY Group

Reporting group description

Reporting group values	MenB+MenACWY Group	MenB Group	MenACWY Group	Total
Number of subjects	310	308	320	938
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	286	283	288	857
Adults (18-64 years)	24	25	32	81
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	16.4 ( 0.7 )	16.4 ( 0.7 )	16.5 ( 0.7 )	-
Sex: Female, Male
Units: Participants
Male	154	170	157	481
Female	156	138	163	457
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	46	38	37	121
Not Hispanic or Latino	263	270	282	815
Unknown or Not Reported	1	0	1	2

End points

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Reporting group title

MenB+MenACWY Group

Reporting group description

Reporting group title

MenB Group

Reporting group description

Reporting group title

MenACWY Group

Reporting group description

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 1

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End point title

Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 1 ^[1]

End point description

Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs = occurrence of the symptom regardless of intensity grade. Analysis was performed on the Exposed set (ES), which included all participants who received at least one dose of the study treatment and had the electronic diary (eDiary) for solicited events completed after the administration of study treatment and for whom data were available during the specified period. Allocation per group is based on the treatment administered. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 7 days after the rMenB+OMV NZ vaccination at Day 1

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	307	306	0 ^[2]
Units: Participants
Erythema	12	12
Induration	14	22
Pain	246	247
Swelling	15	18

Notes
[2] - Participants in this group did not receive rMenB+OMV NZ on Day 1 hence zero participants.

No statistical analyses for this end point

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 61

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End point title

Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 61 ^[3]

End point description

End point type

Primary

End point timeframe

During 7 days after the rMenB+OMV NZ vaccination at Day 61

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	307	306	287
Units: Participants
Erythema	17	17	8
Induration	18	19	6
Pain	240	228	238
Swelling	16	16	7

No statistical analyses for this end point

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 91

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End point title

Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 91 ^[4]

End point description

End point type

Primary

End point timeframe

During 7 days after the rMenB+OMV NZ vaccination at Day 91

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	0 ^[5]	0 ^[6]	287
Units: Participants
Erythema			14
Induration			11
Pain			205
Swelling			13

Notes
[5] - Participants in this group did not receive rMenB+OMV NZ on Day 91 hence zero participants.
[6] - Participants in this group did not receive rMenB+OMV NZ on Day 91 hence zero participants.

No statistical analyses for this end point

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 1

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End point title

Number of participants with solicited local AEs after the vaccination with MenACWY at Day 1 ^[7]

End point description

Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs= occurrence of the symptom regardless of intensity grade. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 7 days after the MenACWY vaccination at Day 1

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	307	0 ^[8]	319
Units: Participants
Erythema	5		6
Induration	7		7
Pain	93		104
Swelling	5		5

Notes
[8] - Participants in this group did not receive MenACWY on Day 1 hence zero participants.

No statistical analyses for this end point

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 61

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End point title

Number of participants with solicited local AEs after the vaccination with MenACWY at Day 61 ^[9]

End point description

Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs= occurrence of the symptom regardless of intensity grade. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis. 1 participant in MenB Group received wrong study treatment at Day 61 (MenACWY vaccine instead of rMenB+OMV NZ), hence was considered in the analysis population.

End point type

Primary

End point timeframe

During 7 days after the MenACWY vaccination at Day 61

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	0 ^[10]	1	0 ^[11]
Units: Participants
Erythema		0
Induration		0
Pain		1
Swelling		0

Notes
[10] - Participants in this group did not receive MenACWY on Day 61 hence zero participants.
[11] - Participants in this group did not receive MenACWY on Day 61 hence zero participants.

No statistical analyses for this end point

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 91

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End point title

Number of participants with solicited local AEs after the vaccination with MenACWY at Day 91 ^[12]

End point description

Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs= occurrence of the symptom regardless of intensity grade. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 7 days after the MenACWY vaccination at Day 91

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	0 ^[13]	265	0 ^[14]
Units: Participants
Erythema		4
Induration		1
Pain		38
Swelling		5

Notes
[13] - Participants in this group did not receive MenACWY on Day 91 hence zero participants.
[14] - Participants in this group did not receive MenACWY on Day 91 hence zero participants.

No statistical analyses for this end point

Primary: Number of participants with solicited local AEs after the vaccination with Placebo at Day 1

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End point title

Number of participants with solicited local AEs after the vaccination with Placebo at Day 1 ^[15]

End point description

Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs = occurrence of the symptom regardless of intensity grade. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 7 days after the Placebo vaccination at Day 1

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	0 ^[16]	306	320
Units: Participants
Erythema		2	2
Induration		5	0
Pain		78	77
Swelling		2	1

Notes
[16] - Participants in this group did not receive Placebo on Day 1 hence zero participants.

No statistical analyses for this end point

Primary: Number of participants with solicited local AEs after the vaccination with Placebo at Day 91

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End point title

Number of participants with solicited local AEs after the vaccination with Placebo at Day 91 ^[17]

End point description

Solicited local adverse events assessed are injection site pain, erythema, swelling, induration. Any solicited local AEs = occurrence of the symptom regardless of intensity grade. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis. 1 participant in MenACWY Group received wrong study treatment at Day 91 (placebo instead of rMenB+OMV NZ), hence was considered in the analysis population.

End point type

Primary

End point timeframe

During 7 days after the Placebo vaccination at Day 91

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	282	0 ^[18]	320
Units: Participants
Erythema	1		0
Induration	1		0
Pain	25		0
Swelling	0		0

Notes
[18] - Participants in this group did not receive Placebo on Day 91 hence zero participants.

No statistical analyses for this end point

Primary: Number of participants with solicited systemic AEs at Day 1

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End point title

Number of participants with solicited systemic AEs at Day 1 ^[19]

End point description

Solicited systemic adverse events assessed are fever [temperature >= 38.0°C], nausea, fatigue, myalgia, arthralgia, and headache. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 7 days after the first study intervention administration occurring at Day 1

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	307	306	320
Units: Participants
Arthralgia	24	32	24
Fatigue	114	118	108
Headache	128	135	134
Myalgia	36	49	31
Nausea	46	57	51
Fever	7	10	2

No statistical analyses for this end point

Primary: Number of participants with solicited systemic AEs at Day 61

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End point title

Number of participants with solicited systemic AEs at Day 61 ^[20]

End point description

End point type

Primary

End point timeframe

During 7 days after the second study intervention administration occurring at Day 61

Notes
[20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	307	306	320
Units: Participants
Arthralgia	28	24	27
Fatigue	96	101	88
Headache	112	103	93
Myalgia	41	42	43
Nausea	37	37	40
Fever	4	8	6

No statistical analyses for this end point

Primary: Number of participants with solicited systemic AEs at Day 91

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End point title

Number of participants with solicited systemic AEs at Day 91 ^[21]

End point description

End point type

Primary

End point timeframe

During 7 days after the third study intervention administration occurring at Day 91

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	307	306	320
Units: Participants
Arthralgia	7	8	24
Fatigue	38	59	86
Headache	56	53	84
Myalgia	7	16	39
Nausea	20	18	31
Fever	2	2	6

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 1

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End point title

Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 1 ^[22]

End point description

Unsolicited adverse events are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms are reported as an unsolicited adverse event. Any solicited AE that has not resolved within 30 days post vaccination and is reported during clinic visits or safety follow-up calls is entered into the subject's electronic Case Report Form (eCRF) as an unsolicited AE. Serious Adverse Events (SAEs) are any untoward medical occurrence that result in death, are life-threatening, require hospitalization or prolongation of existing hospitalization, result in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 30 days after the first study intervention administration occurring at Day 1

Notes
[22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	49	54	55

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 61

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End point title

Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 61 ^[23]

End point description

End point type

Primary

End point timeframe

During 30 days after the second study intervention administration occurring at Day 61

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	51	47	44

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 91

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End point title

Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 91 ^[24]

End point description

End point type

Primary

End point timeframe

During 30 days after the third study intervention administration occurring at Day 91

Notes
[24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	37	37	38

No statistical analyses for this end point

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 1

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End point title

Number of participants with any AEs/SAEs leading to withdrawal at Day 1 ^[25]

End point description

Unsolicited AEs are any AE reported beyond those solicited during the clinical study. A solicited symptom reported outside the designated follow-up period is considered an unsolicited AE. Any solicited AE that has not resolved within 30 days post vaccination and is reported during clinic visits/safety follow-up calls is entered into the subject's eCRF as an unsolicited AE. SAEs are any untoward medical occurrence that result in death, are life-threatening, require hospitalization/prolongation of existing hospitalization, result in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. A participant was considered a ‘withdrawal’ from study when no study procedure has occurred, no follow-up has been performed and no further information has been collected for this participant from the date of withdrawal/last contact. Analysis was performed on ES population,participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 30 days after the first study intervention administration occurring at Day 1

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	0	0	1

No statistical analyses for this end point

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 61

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End point title

Number of participants with any AEs/SAEs leading to withdrawal at Day 61 ^[26]

End point description

End point type

Primary

End point timeframe

During 30 days after the second study intervention administration occurring at Day 61

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	0	0	0

No statistical analyses for this end point

Primary: Number of participants with any medically attended AEs at Day 1

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End point title

Number of participants with any medically attended AEs at Day 1 ^[27]

End point description

Medically attended AEs are symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

During 30 days after the first study intervention administration occurring at Day 1

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	28	36	26

No statistical analyses for this end point

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 91

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End point title

Number of participants with any AEs/SAEs leading to withdrawal at Day 91 ^[28]

End point description

End point type

Primary

End point timeframe

During 30 days after the third study intervention administration occurring at Day 91

Notes
[28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	0	0	0

No statistical analyses for this end point

Primary: Number of participants with any medically attended AEs at Day 61

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End point title

Number of participants with any medically attended AEs at Day 61 ^[29]

End point description

End point type

Primary

End point timeframe

During 30 days after the second study intervention administration occurring at Day 61

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	28	32	25

No statistical analyses for this end point

Primary: Number of participants with any medically attended AEs at Day 91

Top of page

End point title

Number of participants with any medically attended AEs at Day 91 ^[30]

End point description

End point type

Primary

End point timeframe

During 30 days after the third study intervention administration occurring at Day 91

Notes
[30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	19	21	17

No statistical analyses for this end point

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

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End point title

Number of participants with any SAEs, AEs leading to withdrawal and medically attended AEs ^[31]

End point description

SAEs, AEs leading to withdrawal and medically attended AEs were assessed throughout the study period and are reported in this outcome measure. Analysis was performed on the ES population, which included all participants who received at least one dose of the study treatment. Allocation per group is based on the treatment administered.

End point type

Primary

End point timeframe

Throughout the study period (Day 1 to Day 271)

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants
SAEs	2	3	5
AEs leading to withdrawal	0	0	1
Medically attended AEs	93	103	96

No statistical analyses for this end point

Primary: Number of participants who received rMenB+OMV NZ with adverse events of special interest (AESI)

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End point title

Number of participants who received rMenB+OMV NZ with adverse events of special interest (AESI) ^[32]

End point description

AESIs are predefined (serious or non-serious) adverse events of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation in order to characterize and understand it. Analysis was performed on ES population. Only participants with data available at specified timepoints were included in the analysis.

End point type

Primary

End point timeframe

Throughout the study period (Day 1 to Day 271)

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: Participants	0	0	0

No statistical analyses for this end point

Primary: Number of participants with any SAEs and AEs leading to withdrawal

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End point title

Number of participants with any SAEs and AEs leading to withdrawal ^[33]

End point description

Unsolicited AEs are any AE reported beyond those solicited during the clinical study. A solicited symptom reported outside the designated follow-up period is considered an unsolicited AE. Any solicited AE that has not resolved within 30 days post vaccination and is reported during clinic visits/safety follow-up calls is entered into the subject's eCRF as an unsolicited AE. SAEs are any untoward medical occurrence that result in death, are life-threatening, require hospitalization or prolongation, causing disability/incapacity and is a congenital anomaly/birth defect in the offspring of study subject. A participant is considered a 'withdrawal' from the study if no further study procedures, follow-ups, or data collection have occurred since the withdrawal/last contact date. Analysis was performed on ES population,participants with data available at specified timepoints (during safety follow-up period from Day 271 to Day 451) were included in the analysis.

End point type

Primary

End point timeframe

During safety follow-up (Day 271 to Day 451)

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	88	90	87
Units: Participants
SAEs	0	1	2
AEs leading to withdrawal	0	0	0

No statistical analyses for this end point

Primary: Number of participants who received rMenB+OMV NZ with AESI

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End point title

Number of participants who received rMenB+OMV NZ with AESI ^[34]

End point description

End point type

Primary

End point timeframe

During safety follow-up (Day 271 to Day 451)

Notes
[34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	88	90	87
Units: Participants	0	0	0

No statistical analyses for this end point

Primary: Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against each of the N. meningitidis serogroup B strains at 1 month after the second vaccination with rMenB+OMV NZ (groups MenB+MenACWY and MenB), and between-group GMT ratios

Top of page

End point title

Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against each of the N. meningitidis serogroup B strains at 1 month after the second vaccination with rMenB+OMV NZ (groups MenB+MenACWY and MenB), and between-group GMT ratios ^[35]

End point description

hSBA titers were measured by serum bactericidal assay and expressed as Geometric Mean Titers (GMTs) against N. meningitidis serogroup B indicator strains (M14459 [fHbp], 96217 [NadA], NZ98/254 [PorA] and M13520 [NHBA]). Analysis was performed on the Per Protocol Set (PPS), which included participants who received at least 1 dose of the study intervention to which they were randomized and had post-vaccination data available at the specified timepoint minus participants with protocol deviations that led to exclusion from the PPS.

End point type

Primary

End point timeframe

At Day 91 (1 month after the second vaccination with rMenB+OMV NZ in MenB+MenACWY and MenB groups)

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: As specified in the Protocol, the analysis assess the imqmune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the second vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	274	267
Units: Titers
geometric mean (confidence interval 95%)
fHbp (M14459)	16.9 (14.4 to 19.8)	18.7 (15.9 to 21.9)
NadA (96217)	239.6 (202.9 to 283.0)	272.4 (231.1 to 321.0)
PorA (NZ98/254)	18.8 (15.6 to 22.6)	21.3 (17.7 to 25.6)
NHBA (M13520)	19.0 (15.6 to 23.1)	20.5 (16.9 to 24.9)

Statistical Analysis 1

Statistical analysis description

To demonstrate the non-inferiority (NI) of the antibody response to rMenB+OMV NZ given concomitantly with MenACWY compared to rMenB+OMV NZ administered alone, measured by hSBA GMTs against N. meningitidis serogroup B indicator strains at one month after the second vaccination with rMenB+OMV NZ (at Day 91).

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

^[36]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.06

Notes
[36] - NI was to be demonstrated if the lower limit (LL) of the 2-sided 95% CI of the GMT ratio between the MenB+MenACWY group and MenB group for hSBA titers against M14459 (fHbp) strain was above (>) 0.5

Statistical Analysis 2

Statistical analysis description

To demonstrate the non-inferiority of the antibody response to rMenB+OMV NZ given concomitantly with MenACWY compared to rMenB+OMV NZ administered alone, measured by hSBA GMTs against N. meningitidis serogroup B indicator strains at one month after the second vaccination with rMenB+OMV NZ (at Day 91).

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

^[37]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.04

Notes
[37] - NI was to be demonstrated if LL of the 2-sided 95% CI of the GMT ratio between the MenB+MenACWY group and MenB group for hSBA titers against 96217 (NadA) strain was >0.5

Statistical Analysis 3

Statistical analysis description

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

^[38]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.12

Notes
[38] - NI was to be demonstrated if LL of the 2-sided 95% CI of the GMT ratio between the MenB+MenACWY group and MenB group for hSBA titers against NZ98/254 (PorA) strain was >0.5.

Statistical Analysis 4

Statistical analysis description

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

^[39]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.06

Notes
[39] - NI was to be demonstrated if LL of the 2-sided 95% CI of the GMT ratio between the MenB+MenACWY group and MenB group for hSBA titers against M13520 (NHBA) strain was >0.5

Primary: hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y after vaccination with MenACWY (groups MenB+MenACWY and MenACWY), and between-group GMT ratios

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End point title

hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y after vaccination with MenACWY (groups MenB+MenACWY and MenACWY), and between-group GMT ratios ^[40]

End point description

hSBA titers were measured by serum bactericidal assay and expressed as GMTs against each of the 4 serogroups Men A, Men C, Men W and Men Y. Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Primary

End point timeframe

At Day 31 (1 month after the vaccination with MenACWY in MenACWY and MenB+MenACWY groups)

Notes
[40] - 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: As specified in the Protocol, the analysis assess the immune response to MenACWY in healthy subjects 16-18 years of age against each of the serogroups A, C, W and Y, at one month after the (study) vaccination with MenACWY.

End point values	MenB+MenACWY Group	MenACWY Group
Number of subjects analysed	295	303
Units: Titers
geometric mean (confidence interval 95%)
Men A	2388.8 (1977.2 to 2886.1)	2536.1 (2095.7 to 3069.1)
Men C	2075.9 (1602.5 to 2689.3)	1867.6 (1438.7 to 2424.2)
Men W	2299.3 (1902.5 to 2778.9)	2305.7 (1905.3 to 2790.4)
Men Y	2897.3 (2359.2 to 3558.3)	2802.0 (2278.3 to 3446.2)

Statistical Analysis 1

Statistical analysis description

To demonstrate the non-inferiority of the antibody response to MenACWY given concomitantly with rMenB+OMV NZ compared to MenACWY administered alone, as measured by hSBA GMTs against the N. meningitidis serogroup Men A, at one month after the vaccination with MenACWY (at Day 31).

Comparison groups

MenB+MenACWY Group v MenACWY Group

Number of subjects included in analysis

598

Analysis specification

Pre-specified

Analysis type

^[41]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.14

Notes
[41] - NI was to be demonstrated if LL of the 2-sided 95% CI of the between-group ratio of hSBA GMTs between MenB+MenACWY group and MenACWY group for Men A serogroup was >0.5.

Statistical Analysis 4

Statistical analysis description

To demonstrate the non-inferiority of the antibody response to MenACWY given concomitantly with rMenB+OMV NZ compared to MenACWY administered alone, as measured by hSBA GMTs against the N. meningitidis serogroup Men Y, at one month after the vaccination with MenACWY (at Day 31).

Comparison groups

MenB+MenACWY Group v MenACWY Group

Number of subjects included in analysis

598

Analysis specification

Pre-specified

Analysis type

^[42]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.27

Notes
[42] - NI was to be demonstrated if LL of the 2-sided 95% CI of the between-group ratio of hSBA GMTs between MenB+MenACWY group and MenACWY group for Men Y serogroup was >0.5.

Statistical Analysis 3

Statistical analysis description

To demonstrate the non-inferiority of the antibody response to MenACWY given concomitantly with rMenB+OMV NZ compared to MenACWY administered alone, as measured by hSBA GMTs against the N. meningitidis serogroup Men W, at one month after the vaccination with MenACWY (at Day 31).

Comparison groups

MenB+MenACWY Group v MenACWY Group

Number of subjects included in analysis

598

Analysis specification

Pre-specified

Analysis type

^[43]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.21

Notes
[43] - NI was to be demonstrated if LL of the 2-sided 95% CI of the between-group ratio of hSBA GMTs between MenB+MenACWY group and MenACWY group for Men W serogroup was >0.5.

Statistical Analysis 2

Statistical analysis description

To demonstrate the non-inferiority of the antibody response to MenACWY given concomitantly with rMenB+OMV NZ compared to MenACWY administered alone, as measured by hSBA GMTs against the N. meningitidis serogroup Men C, at one month after the vaccination with MenACWY (at Day 31).

Comparison groups

MenB+MenACWY Group v MenACWY Group

Number of subjects included in analysis

598

Analysis specification

Pre-specified

Analysis type

^[44]

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.44

Notes
[44] - NI was to be demonstrated if LL of the 2-sided 95% CI of the between-group ratio of hSBA GMTs between MenB+MenACWY group and MenACWY group for Men C serogroup was >0.5.

Secondary: hSBA Geometric Mean Concentrations (GMCs) measured by ECL against each of the N. meningitidis serogroups after MenACWY vaccination

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End point title

hSBA Geometric Mean Concentrations (GMCs) measured by ECL against each of the N. meningitidis serogroups after MenACWY vaccination

End point description

Immune response to MenACWY given with or without rMenB+OMV NZ, as measured by lectrochemiluminescence-based multiplex (ECL) GMCs against each of the serogroups A, C, W and Y. ECL (validated assay) was used because ELISA is not validated. Analysis was performed on the PPS population, which included participants who received at least 1 dose of the study intervention to which they were randomized and had post-vaccination data available at the specified timepoint minus participants with protocol deviations that led to exclusion from the PPS. 99999" is used as a placeholder value for the results for all the groups since the analysis of final results for these groups is ongoing and will be updated subsequently.

End point type

Secondary

End point timeframe

At Day 31 (1 month after the vaccination of MenACWY in MenACWY and MenB+MenACWY groups)

End point values	MenB+MenACWY Group	MenB Group	MenACWY Group
Number of subjects analysed	310	308	320
Units: IU/L
geometric mean (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: hSBA GMTs against each of the serogroup B strains in both MenB+MenACWY and MenB Groups after first rMenB+OMV NZ vaccination and between-group GMT ratios

Top of page

End point title

hSBA GMTs against each of the serogroup B strains in both MenB+MenACWY and MenB Groups after first rMenB+OMV NZ vaccination and between-group GMT ratios ^[45]

End point description

hSBA titers were measured by bactericidal activity against N. meningitidis serogroup B indicator strains (M14459 [fHbp], 96217 [NadA], NZ98/254 [PorA] and M13520 [NHBA]) and expressed in GMTs. Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At Day 31 (1 month after first vaccination with rMenB+OMV NZ)

Notes
[45] - 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: As specified in the Protocol, the analysis assess the imqmune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the first vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	294	294
Units: Titers
geometric mean (confidence interval 95%)
fHbp (M14459)	4.3 (3.6 to 5.1)	5.6 (4.7 to 6.7)
NadA (96217)	45.2 (36.0 to 56.9)	73.4 (58.5 to 91.9)
PorA (NZ98/254)	4.2 (3.5 to 5.0)	5.6 (4.7 to 6.6)
NHBA (M13520)	6.4 (5.1 to 8.1)	8.8 (7.0 to 11.1)

Statistical Analysis 1

Statistical analysis description

To assess the immune response to rMenB+OMV NZ given concomitantly with MenACWY compared to rMenB+OMV NZ administered alone, measured by hSBA GMTs against N. meningitidis M14459 (fHbp) strain at one month after the fisrt vaccination with rMenB+OMV NZ (at Day 31).

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

588

Analysis specification

Pre-specified

Analysis type

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.91

Statistical Analysis 4

Statistical analysis description

To assess the immune response to rMenB+OMV NZ given concomitantly with MenACWY compared to rMenB+OMV NZ administered alone, measured by hSBA GMTs against N. meningitidis M13520 (NHBA) at one month after the second vaccination with rMenB+OMV NZ (at Day 31).

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

588

Analysis specification

Pre-specified

Analysis type

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.9

Statistical Analysis 3

Statistical analysis description

To assess the immune response to rMenB+OMV NZ given concomitantly with MenACWY compared to rMenB+OMV NZ administered alone, measured by hSBA GMTs against N. meningitidis NZ98/254 (PorA) strain at one month after the second vaccination with rMenB+OMV NZ (at Day 31).

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

588

Analysis specification

Pre-specified

Analysis type

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

0.91

Statistical Analysis 2

Statistical analysis description

To assess the immune response to rMenB+OMV NZ given concomitantly with MenACWY compared to rMenB+OMV NZ administered alone, measured by hSBA GMTs against N. meningitidis 96217 (NadA) strain at one month after the second vaccination with rMenB+OMV NZ (at Day 31).

Comparison groups

MenB+MenACWY Group v MenB Group

Number of subjects included in analysis

588

Analysis specification

Pre-specified

Analysis type

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

0.77

Secondary: Geometric mean ratios (GMRs) against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Top of page

End point title

Geometric mean ratios (GMRs) against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination ^[46]

End point description

The immune response to rMenB+OMV NZ was measured by bactericidal activity against N. meningitidis serogroup B indicator strains (M14459 [fHbp], 96217 [NadA], NZ98/254 [PorA] and M13520 [NHBA]) in terms of GMRs (after vaccination/baseline). Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At Day 31 (1 month after first rMenB+OMV NZ vaccination) compared to the baseline (Day 1)

Notes
[46] - 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: As specified in the Protocol, the analysis assess the immune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the first vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	294	294
Units: Ratio
geometric mean (confidence interval 95%)
fHbp (M14459)	1.6 (1.4 to 1.9)	2.0 (1.7 to 2.4)
NadA (96217)	5.9 (4.7 to 7.4)	9.3 (7.5 to 11.6)
PorA (NZ98/254)	1.4 (1.2 to 1.6)	1.8 (1.5 to 2.1)
NHBA (M13520)	1.8 (1.5 to 2.2)	2.3 (1.9 to 2.8)

No statistical analyses for this end point

Secondary: GMRs against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination

Top of page

End point title

GMRs against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination ^[47]

End point description

End point type

Secondary

End point timeframe

At Day 91 (1 month after the second rMenB+OMV NZ vaccination) compared to the baseline (Day 1)

Notes
[47] - 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: As specified in the Protocol, the analysis assess the imqmune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the second vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	274	267
Units: Ratio
geometric mean (confidence interval 95%)
fHbp (M14459)	6.4 (5.5 to 7.5)	7.0 (5.9 to 8.1)
NadA (96217)	30.7 (25.8 to 36.6)	35.1 (29.5 to 41.7)
PorA (NZ98/254)	6.0 (5.0 to 7.2)	6.9 (5.8 to 8.3)
NHBA (M13520)	5.2 (4.4 to 6.2)	5.6 (4.7 to 6.6)

No statistical analyses for this end point

Secondary: Percentage of participants with hSBA titers >= lower limit of quantitation (LLOQ) for each and all serogroup B test strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Top of page

End point title

Percentage of participants with hSBA titers >= lower limit of quantitation (LLOQ) for each and all serogroup B test strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination ^[48]

End point description

The immune response to rMenB+OMV NZ vaccine is evaluated by measuring bactericidal activity in terms of participants with hSBA titers >= LLOQ against N. meningitidis serogroup B test strains (M14459 [fHbp], 96217 [NadA], NZ98/254 [PorA] and M13520 [NHBA]). Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At Day 31 (one month after the first rMenB+OMV NZ vaccination)

Notes
[48] - 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: As specified in the Protocol, the analysis assess the imqmune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the first vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	294	294
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459)	32.3 (27.0 to 38.0)	44.9 (39.1 to 50.8)
NadA (96217)	77.9 (72.7 to 82.5)	85.7 (81.2 to 89.5)
PorA ( NZ98/254)	21.1 (16.6 to 26.2)	30.4 (25.2 to 36.0)
NHBA (M13520)	37.1 (31.5 to 42.9)	44.4 (38.6 to 50.3)

No statistical analyses for this end point

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all of the serogroup B test strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination

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End point title

Percentage of participants with hSBA titers >= LLOQ for each and all of the serogroup B test strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination ^[49]

End point description

End point type

Secondary

End point timeframe

At Day 91 (1 month after the second rMenB+OMV NZ vaccination)

Notes
[49] - 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: As specified in the Protocol, the analysis assess the imqmune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the second vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	274	267
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459 )	92.3 (88.5 to 95.2)	92.5 (88.6 to 95.3)
NadA (96217)	99.6 (98.0 to 100)	99.6 (97.9 to 100)
PorA (NZ98/254)	83.2 (78.2 to 87.4)	85.0 (80.1 to 89.0)
NHBA (M13520)	84.2 (79.4 to 88.4)	90.2 (86.0 to 93.5)

No statistical analyses for this end point

Secondary: Percentage of participants with 4-fold increase in hSBA titers relative to baseline in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

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End point title

Percentage of participants with 4-fold increase in hSBA titers relative to baseline in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination ^[50]

End point description

The immune response to rMenB+OMV NZ vaccine is evaluated by measuring bactericidal activity against each of N. meningitidis serogroup B test strains (M14459 [fHbp], 96217 [NadA], NZ98/254 [PorA] and M13520 [NHBA]) in terms of the Four-fold increase defined as: - For a pre-vaccination titer < limit of detection (LOD), a post-vaccination titer of >= 4-fold the LOD or >= LLOQ, whichever is greater, - For a pre-vaccination titer >= LOD but <LLOQ, a post vaccination titer of at least 4-fold the LLOQ, - For a pre-vaccination titer >= LLOQ, a post vaccination titer of at least 4-fold the pre-vaccination titer. Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At 1 month after the first rMenB+OMV NZ vaccination (i.e at Day 31) relative to baseline (i.e. Day 1)

Notes
[50] - 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: As specified in the Protocol, the analysis assess the imqmune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the first vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	293	293
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459)	14.7 (10.8 to 19.3)	21.0 (16.4 to 26.1)
NadA (96217)	68.9 (63.3 to 74.2)	78.4 (73.3 to 83.0)
PorA (NZ98/254)	8.9 (5.9 to 12.7)	16.4 (12.4 to 21.2)
NHBA (M13520)	17.4 (13.2 to 22.2)	25.3 (20.4 to 30.6)

No statistical analyses for this end point

Secondary: Percentage of participants with hSBA titers >=LLOQ for each of the serogroup A, C, W and Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination

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End point title

Percentage of participants with hSBA titers >=LLOQ for each of the serogroup A, C, W and Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination ^[51]

End point description

The immune response to MenACWY vaccines is expressed in terms of percentage of participants with hSBA titers >=LLOQ for each of the serogroup Men A, Men C, Men W and Men Y. Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At baseline (Day 1) and at one month after the MenACWY vaccination (i.e. Day 31)

Notes
[51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As specified in the Protocol, the analysis assesses the immune response to MenACWY in healthy subjects 16-18 years of age against each of the serogroups A, C, W and Y, at one month after the (study) vaccination with MenACWY.

End point values	MenB+MenACWY Group	MenACWY Group
Number of subjects analysed	295	303
Units: Percentage of participants
number (confidence interval 95%)
Men A, Baseline (Day 1)	28.1 (22.8 to 33.9)	30.0 (24.7 to 35.9)
Men A, Day 31	99.7 (98.1 to 100)	99.3 (97.5 to 99.9)
Men C, Baseline (Day 1)	46.3 (40.5 to 52.1)	44.4 (38.7 to 50.3)
Men C, Day 31	99.0 (97.1 to 99.8)	98.7 (96.6 to 99.6)
Men W, Baseline (Day 1)	27.4 (22.4 to 32.9)	28.4 (23.3 to 34.0)
Men W, Day 31	100 (98.8 to 100)	100 (98.8 to 100)
Men Y, Baseline (Day 1)	23.4 (18.6 to 28.7)	23.0 (18.3 to 28.2)
Men Y, Day 31	99.7 (98.1 to 100)	99.7 (98.2 to 100)

No statistical analyses for this end point

Secondary: GMRs against each of the N. meningitidis serogroup Men A, Men C, Men W and Men Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination

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End point title

GMRs against each of the N. meningitidis serogroup Men A, Men C, Men W and Men Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination ^[52]

End point description

Immune response to MenACWY given with or without rMenB+OMV NZ was measured by bactericidal activity against the four serogroups Men A, Men C, Men W and Men Y in terms of GMRs at one month after MenACWY vaccination compared to the baseline at Day 1/Month 0. GMR was measured within-group. Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At 1 month after MenACWY vaccination (i.e.at Day 31) compared to the baseline (Day 1)

Notes
[52] - 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: As specified in the Protocol, the analysis assesses the immune response to MenACWY in healthy subjects 16-18 years of age against each of the serogroups A, C, W and Y, at one month after the (study) vaccination with MenACWY.

End point values	MenB+MenACWY Group	MenACWY Group
Number of subjects analysed	295	303
Units: Ratio
geometric mean (confidence interval 95%)
Men A	150.2 (120.1 to 187.8)	145.0 (115.4 to 182.2)
Men C	130.0 (97.7 to 173.1)	131.9 (98.8 to 176.1)
Men W	294.2 (229.0 to 378.1)	279.3 (216.6 to 360.1)
Men Y	324.3 (252.2 to 417.0)	300.0 (232.9 to 386.4)

No statistical analyses for this end point

Secondary: Percentage of participants with 4-fold increase in hSBA titers against each of the N. meningitidis serogroup Men A, Men C, Men W and Men Y relative to baseline in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination

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End point title

Percentage of participants with 4-fold increase in hSBA titers against each of the N. meningitidis serogroup Men A, Men C, Men W and Men Y relative to baseline in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination ^[53]

End point description

The immune response to MenACWY vaccine is evaluated by measuring percentage of participants with 4-fold increase for the four serogroups Men A, Men C, Men W and Men Y. The Four-fold increase defined as: - For a pre-vaccination titer <LOD, a post-vaccination titer of >= 4-fold the LOD or >= LLOQ, whichever is greater, - For a pre-vaccination titer >=LOD but <LLOQ, a post vaccination titer of at least 4-fold the LLOQ, - For a pre-vaccination titer >= LLOQ, a post vaccination titer of at least 4-fold the pre-vaccination titer. Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At 1 month after MenACWY vaccination (i.e at Day 31) relative to baseline (i.e. Day 1)

Notes
[53] - 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: As specified in the Protocol, the analysis assesses the immune response to MenACWY in healthy subjects 16-18 years of age against each of the serogroups A, C, W and Y, at one month after the (study) vaccination with MenACWY.

End point values	MenB+MenACWY Group	MenACWY Group
Number of subjects analysed	293	296
Units: Percentage of participants
number (confidence interval 95%)
Men A	98.5 (96.1 to 99.6)	98.1 (95.6 to 99.4)
Men C	95.2 (92.1 to 97.4)	95.6 (92.6 to 97.6)
Men W	98.6 (96.5 to 99.6)	97.9 (95.6 to 99.2)
Men Y	98.6 (96.5 to 99.6)	98.3 (96.1 to 99.4)

No statistical analyses for this end point

Secondary: Percentage of participants with 4-fold increase in hSBA titers relative to baseline in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination

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End point title

Percentage of participants with 4-fold increase in hSBA titers relative to baseline in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination ^[54]

End point description

The immune response to rMenB+OMV NZ vaccine is evaluated by measuring bactericidal activity against each of the N. meningitidis serogroup B test strains (M14459 [fHbp], 96217 [NadA], NZ98/254 [PorA] and M13520 [NHBA]) in terms of the Four-fold increase defined as: - For a pre-vaccination titer <LOD, a post-vaccination titer of >= 4-fold the LOD or >= LLOQ, whichever is greater, - For a pre-vaccination titer >=LOD but <LLOQ, a post vaccination titer of at least 4-fold the LLOQ, - For a pre-vaccination titer >=LLOQ, a post vaccination titer of at least 4-fold the pre-vaccination titer. Analysis was performed on PPS population. Only those participants with data available at specified timepoint were included in analysis.

End point type

Secondary

End point timeframe

At 1 month after the second rMenB+OMV vaccination (i.e at Day 91) relative to baseline (i.e. Day 1)

Notes
[54] - 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: As specified in the Protocol, the analysis assess the imqmune response to rMenB+OMV NZ in healthy subjects 16-18 years of age against N. meningitidis serogroup B test strains M14459 (fHbp), 96217 (NadA), NZ98/254 (PorA) and M07-0241084 (NHBA), at one month after the second vaccination with rMenB+OMV NZ.

End point values	MenB+MenACWY Group	MenB Group
Number of subjects analysed	273	266
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459)	57.1 (51.0 to 63.1)	64.6 (58.5 to 70.4)
NadA (96217)	96.0 (92.9 to 98.0)	98.9 (96.7 to 99.8)
PorA (NZ98/254)	51.5 (45.4 to 57.5)	56.6 (50.4 to 62.7)
NHBA (M13520)	55.1 (49.0 to 61.2)	53.0 (46.8 to 59.1)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited AEs: within 7 days post-vaccination. Unsolicited AEs: within 30 days post-vaccination. All-cause mortality,SAEs,MAAEs, AEs leading to withdrawal, and AESIs: monitored from Day 1 to study end at Day 271 or Day 451, depending on participation date

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

MenB+MenACWY Group

Reporting group description

Reporting group title

MenACWY Group

Reporting group description

Reporting group title

MenB Group

Reporting group description

Serious adverse events	MenB+MenACWY Group	MenACWY Group	MenB Group
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 310 (0.65%)	7 / 320 (2.19%)	4 / 308 (1.30%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Lumbar vertebral fracture
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (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
Fibula fracture
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (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
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (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
Psychiatric disorders
Adjustment disorder with depressed mood
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (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
Depression
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (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
Drug abuse
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (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
Major depression
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (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
Suicidal ideation
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	2 / 308 (0.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (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
Rhabdomyolysis
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (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
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	MenB+MenACWY Group	MenACWY Group	MenB Group
Total subjects affected by non serious adverse events
subjects affected / exposed	293 / 310 (94.52%)	289 / 320 (90.31%)	293 / 308 (95.13%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Vascular disorders
Pallor
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
General disorders and administration site conditions
Feeling of body temperature change
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Fatigue
subjects affected / exposed	152 / 310 (49.03%)	159 / 320 (49.69%)	160 / 308 (51.95%)
occurrences all number	265	303	306
Chills
subjects affected / exposed	2 / 310 (0.65%)	3 / 320 (0.94%)	2 / 308 (0.65%)
occurrences all number	2	3	3
Chest pain
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	0	1	1
Chest discomfort
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Administration site swelling
subjects affected / exposed	31 / 310 (10.00%)	26 / 320 (8.13%)	32 / 308 (10.39%)
occurrences all number	38	33	44
Administration site pain
subjects affected / exposed	281 / 310 (90.65%)	268 / 320 (83.75%)	282 / 308 (91.56%)
occurrences all number	589	629	597
Administration site induration
subjects affected / exposed	31 / 310 (10.00%)	25 / 320 (7.81%)	35 / 308 (11.36%)
occurrences all number	46	33	56
Administration site erythema
subjects affected / exposed	28 / 310 (9.03%)	28 / 320 (8.75%)	31 / 308 (10.06%)
occurrences all number	39	30	37
Swelling
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	0	1	1
Peripheral swelling
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Pain
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	1	0	1
Malaise
subjects affected / exposed	2 / 310 (0.65%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	2	0	0
Injection site swelling
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Injection site reaction
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	1	1	0
Injection site pruritus
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Injection site pain
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	1	0	1
Injection site hypoaesthesia
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Injection site bruising
subjects affected / exposed	3 / 310 (0.97%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	3	0	2
Influenza like illness
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	2 / 308 (0.65%)
occurrences all number	1	0	2
Induration
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Vaccination site bruising
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Vaccination site erythema
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Vaccination site rash
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Vaccination site swelling
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Pyrexia
subjects affected / exposed	14 / 310 (4.52%)	19 / 320 (5.94%)	23 / 308 (7.47%)
occurrences all number	17	21	26
Immune system disorders
Multiple allergies
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	5 / 310 (1.61%)	5 / 320 (1.56%)	2 / 308 (0.65%)
occurrences all number	7	5	2
Abnormal uterine bleeding
subjects affected / exposed	2 / 310 (0.65%)	0 / 320 (0.00%)	2 / 308 (0.65%)
occurrences all number	2	0	2
Varicocele
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Vaginal discharge
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Pelvic pain
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Heavy menstrual bleeding
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Gynaecomastia
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	1	1	1
Cough
subjects affected / exposed	1 / 310 (0.32%)	8 / 320 (2.50%)	3 / 308 (0.97%)
occurrences all number	1	8	3
Upper respiratory tract congestion
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Throat irritation
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Sneezing
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Sinus congestion
subjects affected / exposed	2 / 310 (0.65%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	2	0	1
Rhinorrhoea
subjects affected / exposed	1 / 310 (0.32%)	3 / 320 (0.94%)	1 / 308 (0.32%)
occurrences all number	1	3	1
Rhinitis allergic
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Respiratory symptom
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Respiratory disorder
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Oropharyngeal pain
subjects affected / exposed	13 / 310 (4.19%)	10 / 320 (3.13%)	11 / 308 (3.57%)
occurrences all number	13	10	11
Nasal congestion
subjects affected / exposed	7 / 310 (2.26%)	5 / 320 (1.56%)	3 / 308 (0.97%)
occurrences all number	7	5	3
Epistaxis
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Dyspnoea
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	1	1	1
Dysphonia
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Wheezing
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Depression
subjects affected / exposed	2 / 310 (0.65%)	1 / 320 (0.31%)	2 / 308 (0.65%)
occurrences all number	2	1	2
Generalised anxiety disorder
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Intentional self-injury
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Investigations
Arthroscopy
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Blood cholesterol increased
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Injury, poisoning and procedural complications
Breast procedural complication
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Abdominal injury
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Joint injury
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Head injury
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Foot fracture
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Fibula fracture
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Face injury
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Eye injury
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Distal clavicular osteolysis
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Contusion
subjects affected / exposed	0 / 310 (0.00%)	3 / 320 (0.94%)	1 / 308 (0.32%)
occurrences all number	0	3	1
Concussion
subjects affected / exposed	2 / 310 (0.65%)	0 / 320 (0.00%)	3 / 308 (0.97%)
occurrences all number	2	0	3
Ligament injury
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Seroma
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Scar
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Procedural pain
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	2 / 308 (0.65%)
occurrences all number	1	1	2
Open globe injury
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Muscle strain
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	1	1	1
Lip injury
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Limb injury
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	4 / 308 (1.30%)
occurrences all number	0	0	5
Ligament sprain
subjects affected / exposed	0 / 310 (0.00%)	3 / 320 (0.94%)	1 / 308 (0.32%)
occurrences all number	0	3	1
Ligament rupture
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Skin laceration
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	1	0	1
Thermal burn
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Torus fracture
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Vulvovaginal injury
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Suture related complication
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Congenital, familial and genetic disorders
Os trigonum
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 310 (0.32%)	2 / 320 (0.63%)	3 / 308 (0.97%)
occurrences all number	1	2	3
Headache
subjects affected / exposed	178 / 310 (57.42%)	185 / 320 (57.81%)	185 / 308 (60.06%)
occurrences all number	320	345	317
Migraine
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	1	0	1
Paraesthesia
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Sciatica
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Sinus headache
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	2 / 310 (0.65%)	2 / 320 (0.63%)	0 / 308 (0.00%)
occurrences all number	2	2	0
Neutropenia
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 310 (0.00%)	3 / 320 (0.94%)	0 / 308 (0.00%)
occurrences all number	0	3	0
Cerumen impaction
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	0	1	1
Tympanic membrane perforation
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Eustachian tube dysfunction
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	1	1	0
Eye disorders
Photophobia
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Myopia
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Episcleritis
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Lacrimation increased
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Astigmatism
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Blepharitis
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Gastrointestinal disorders
Colitis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Cheilitis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Aphthous ulcer
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Abdominal pain upper
subjects affected / exposed	0 / 310 (0.00%)	5 / 320 (1.56%)	4 / 308 (1.30%)
occurrences all number	0	5	5
Abdominal pain
subjects affected / exposed	2 / 310 (0.65%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	2	1	1
Abdominal discomfort
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	2 / 308 (0.65%)
occurrences all number	1	0	2
Vomiting
subjects affected / exposed	4 / 310 (1.29%)	6 / 320 (1.88%)	3 / 308 (0.97%)
occurrences all number	4	6	3
Salivary gland mucocoele
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Tooth impacted
subjects affected / exposed	1 / 310 (0.32%)	2 / 320 (0.63%)	0 / 308 (0.00%)
occurrences all number	1	2	0
Toothache
subjects affected / exposed	5 / 310 (1.61%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	5	1	0
Nausea
subjects affected / exposed	74 / 310 (23.87%)	94 / 320 (29.38%)	90 / 308 (29.22%)
occurrences all number	105	132	119
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Dyspepsia
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Diarrhoea
subjects affected / exposed	1 / 310 (0.32%)	4 / 320 (1.25%)	2 / 308 (0.65%)
occurrences all number	1	6	2
Constipation
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	1	0	1
Sensitive skin
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Rash pruritic
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Rash
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	4 / 308 (1.30%)
occurrences all number	0	0	4
Pruritus
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	2 / 308 (0.65%)
occurrences all number	0	1	2
Pityriasis rosea
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Dermatitis contact
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Dermatitis atopic
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Cold sweat
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Alopecia
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Acne
subjects affected / exposed	1 / 310 (0.32%)	2 / 320 (0.63%)	1 / 308 (0.32%)
occurrences all number	1	2	1
Hirsutism
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 310 (0.00%)	3 / 320 (0.94%)	0 / 308 (0.00%)
occurrences all number	0	3	0
Micturition urgency
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Endocrine disorders
Polycystic ovarian syndrome
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	0	1	1
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	1 / 310 (0.32%)	2 / 320 (0.63%)	3 / 308 (0.97%)
occurrences all number	1	2	3
Neck pain
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	1	0	1
Myalgia
subjects affected / exposed	73 / 310 (23.55%)	88 / 320 (27.50%)	81 / 308 (26.30%)
occurrences all number	86	116	112
Musculoskeletal pain
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Medial tibial stress syndrome
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Joint swelling
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	0	1	1
Joint range of motion decreased
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Bone swelling
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Back pain
subjects affected / exposed	2 / 310 (0.65%)	2 / 320 (0.63%)	0 / 308 (0.00%)
occurrences all number	2	2	0
Arthralgia
subjects affected / exposed	53 / 310 (17.10%)	58 / 320 (18.13%)	46 / 308 (14.94%)
occurrences all number	65	77	66
Tendon pain
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Synovial cyst
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Rotator cuff syndrome
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Pain in jaw
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Tendonitis
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	0	1	1
Infections and infestations
Acute sinusitis
subjects affected / exposed	0 / 310 (0.00%)	3 / 320 (0.94%)	3 / 308 (0.97%)
occurrences all number	0	3	3
Bacterial vaginosis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Bacterial vulvovaginitis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Beta haemolytic streptococcal infection
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Bronchitis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Bronchitis viral
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
COVID-19
subjects affected / exposed	9 / 310 (2.90%)	9 / 320 (2.81%)	5 / 308 (1.62%)
occurrences all number	9	9	5
Chlamydial infection
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	1	0	1
Conjunctivitis
subjects affected / exposed	3 / 310 (0.97%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	3	0	0
Conjunctivitis bacterial
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Eye infection
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	0	1	0
Fungal infection
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	2 / 308 (0.65%)
occurrences all number	0	0	2
Gastroenteritis
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	2 / 308 (0.65%)
occurrences all number	1	1	2
Gastroenteritis viral
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	1	1	0
Gonorrhoea
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Hordeolum
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Impetigo
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Influenza
subjects affected / exposed	4 / 310 (1.29%)	2 / 320 (0.63%)	10 / 308 (3.25%)
occurrences all number	4	2	10
Nasopharyngitis
subjects affected / exposed	11 / 310 (3.55%)	18 / 320 (5.63%)	4 / 308 (1.30%)
occurrences all number	11	18	5
Otitis externa
subjects affected / exposed	2 / 310 (0.65%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	2	0	0
Otitis media acute
subjects affected / exposed	3 / 310 (0.97%)	1 / 320 (0.31%)	2 / 308 (0.65%)
occurrences all number	3	1	3
Sinusitis bacterial
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Rhinitis
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	2 / 308 (0.65%)
occurrences all number	1	1	3
Respiratory tract infection viral
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	0 / 308 (0.00%)
occurrences all number	1	1	0
Pyuria
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Pilonidal disease
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Pharyngotonsillitis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Pharyngitis streptococcal
subjects affected / exposed	1 / 310 (0.32%)	2 / 320 (0.63%)	3 / 308 (0.97%)
occurrences all number	1	2	3
Pharyngitis
subjects affected / exposed	2 / 310 (0.65%)	4 / 320 (1.25%)	3 / 308 (0.97%)
occurrences all number	2	4	3
Staphylococcal infection
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Stitch abscess
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Upper respiratory tract infection
subjects affected / exposed	4 / 310 (1.29%)	10 / 320 (3.13%)	1 / 308 (0.32%)
occurrences all number	5	10	1
Urethritis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Urinary tract infection
subjects affected / exposed	0 / 310 (0.00%)	2 / 320 (0.63%)	1 / 308 (0.32%)
occurrences all number	0	2	1
Viral infection
subjects affected / exposed	3 / 310 (0.97%)	0 / 320 (0.00%)	3 / 308 (0.97%)
occurrences all number	3	0	3
Viral pharyngitis
subjects affected / exposed	0 / 310 (0.00%)	0 / 320 (0.00%)	1 / 308 (0.32%)
occurrences all number	0	0	1
Viral upper respiratory tract infection
subjects affected / exposed	1 / 310 (0.32%)	1 / 320 (0.31%)	2 / 308 (0.65%)
occurrences all number	1	1	2
Sinusitis
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	2 / 308 (0.65%)
occurrences all number	1	0	2
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 310 (0.00%)	1 / 320 (0.31%)	1 / 308 (0.32%)
occurrences all number	0	1	1
Dehydration
subjects affected / exposed	1 / 310 (0.32%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	1	0	0
Vitamin D deficiency
subjects affected / exposed	2 / 310 (0.65%)	0 / 320 (0.00%)	0 / 308 (0.00%)
occurrences all number	2	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

14 Aug 2019

As per the recommendation from CBER the study has been amended to include an update in development and validation of a new “agar-overlay” serum bactericidal assay using human serum complement (hSBA). Additional changes include validation of the MenB manual to measure immunogenicity of the meningococcal group B vaccine, a modification in the definition of 4-fold increase in post-vaccination hSBA titer definition when the pre-vaccination titer is below the limit of detection, and a modification in the population set to be used for safety analysis wherein the exposed set is to be used for all safety analyses.

23 Jan 2020

The inclusion of a booster recommendation in Menveo’s US Prescription Insert, with the recommendation to administer the booster at least 4 years after the priming dose, has only been approved by US FDA in December 2019. As a result, the company intends to align the inclusion criterion in the V72_79 study with the recently introduced booster recommendation in the US and amend the protocol accordingly to allow inclusion of subjects who have received a meningococcal ACWY vaccine 4 years or greater in the past.

21 Jun 2022

The purpose of the amendment is to update the exclusion criteria of the protocol, align COVID-19 reporting requirements to local guidelines, and to update the definition of End of Study (EoS).

11 Oct 2022

The purpose of the amendment is to shorten the safety follow-up period to 6 months in subjects who have not reached the 6-month safety follow-up after the last dose and to extend the visit window to 28 days post reference day to mitigate the impact of COVID pandemic, including quarantine, mandatory vaccination, or other disturbances in the study procedures.

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 IIIB, Randomized, Observer-blind, Multicenter Study to Assess the Safety and Immunogenicity of GSK's Meningococcal Group B Vaccine When Administered Concomitantly With GSK's Meningococcal MenACWY Conjugate Vaccine to Healthy Subjects of 16-18 Years of Age

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 1

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 1

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 61

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 61

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 91

Primary: Number of participants with solicited local adverse events (AEs) after the vaccination with rMenB+OMV NZ at Day 91

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 1

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 1

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 61

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 61

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 91

Primary: Number of participants with solicited local AEs after the vaccination with MenACWY at Day 91

Primary: Number of participants with solicited local AEs after the vaccination with Placebo at Day 1

Primary: Number of participants with solicited local AEs after the vaccination with Placebo at Day 1

Primary: Number of participants with solicited local AEs after the vaccination with Placebo at Day 91

Primary: Number of participants with solicited local AEs after the vaccination with Placebo at Day 91

Primary: Number of participants with solicited systemic AEs at Day 1

Primary: Number of participants with solicited systemic AEs at Day 1

Primary: Number of participants with solicited systemic AEs at Day 61

Primary: Number of participants with solicited systemic AEs at Day 61

Primary: Number of participants with solicited systemic AEs at Day 91

Primary: Number of participants with solicited systemic AEs at Day 91

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 1

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 1

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 61

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 61

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 91

Primary: Number of participants with any unsolicited AEs (including all Serious Adverse Events) at Day 91

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 1

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 1

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 61

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 61

Primary: Number of participants with any medically attended AEs at Day 1

Primary: Number of participants with any medically attended AEs at Day 1

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 91

Primary: Number of participants with any AEs/SAEs leading to withdrawal at Day 91

Primary: Number of participants with any medically attended AEs at Day 61

Primary: Number of participants with any medically attended AEs at Day 61

Primary: Number of participants with any medically attended AEs at Day 91

Primary: Number of participants with any medically attended AEs at Day 91

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

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

Primary: Number of participants who received rMenB+OMV NZ with adverse events of special interest (AESI)

Primary: Number of participants who received rMenB+OMV NZ with adverse events of special interest (AESI)

Primary: Number of participants with any SAEs and AEs leading to withdrawal

Primary: Number of participants with any SAEs and AEs leading to withdrawal

Primary: Number of participants who received rMenB+OMV NZ with AESI

Primary: Number of participants who received rMenB+OMV NZ with AESI

Primary: Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against each of the N. meningitidis serogroup B strains at 1 month after the second vaccination with rMenB+OMV NZ (groups MenB+MenACWY and MenB), and between-group GMT ratios

Primary: Human Serum Bactericidal Assay (hSBA) Geometric Mean Titers (GMTs) against each of the N. meningitidis serogroup B strains at 1 month after the second vaccination with rMenB+OMV NZ (groups MenB+MenACWY and MenB), and between-group GMT ratios

Primary: hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y after vaccination with MenACWY (groups MenB+MenACWY and MenACWY), and between-group GMT ratios

Primary: hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y after vaccination with MenACWY (groups MenB+MenACWY and MenACWY), and between-group GMT ratios

Secondary: hSBA Geometric Mean Concentrations (GMCs) measured by ECL against each of the N. meningitidis serogroups after MenACWY vaccination

Secondary: hSBA Geometric Mean Concentrations (GMCs) measured by ECL against each of the N. meningitidis serogroups after MenACWY vaccination

Secondary: hSBA GMTs against each of the serogroup B strains in both MenB+MenACWY and MenB Groups after first rMenB+OMV NZ vaccination and between-group GMT ratios

Secondary: hSBA GMTs against each of the serogroup B strains in both MenB+MenACWY and MenB Groups after first rMenB+OMV NZ vaccination and between-group GMT ratios

Secondary: Geometric mean ratios (GMRs) against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Secondary: Geometric mean ratios (GMRs) against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Secondary: GMRs against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination

Secondary: GMRs against each of the N. meningitidis serogroup B strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination

Secondary: Percentage of participants with hSBA titers >= lower limit of quantitation (LLOQ) for each and all serogroup B test strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Secondary: Percentage of participants with hSBA titers >= lower limit of quantitation (LLOQ) for each and all serogroup B test strains in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all of the serogroup B test strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all of the serogroup B test strains in both MenB+MenACWY and MenB Groups after the second rMenB+OMV NZ vaccination

Secondary: Percentage of participants with 4-fold increase in hSBA titers relative to baseline in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Secondary: Percentage of participants with 4-fold increase in hSBA titers relative to baseline in both MenB+MenACWY and MenB Groups after the first rMenB+OMV NZ vaccination

Secondary: Percentage of participants with hSBA titers >=LLOQ for each of the serogroup A, C, W and Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination

Secondary: Percentage of participants with hSBA titers >=LLOQ for each of the serogroup A, C, W and Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination

Secondary: GMRs against each of the N. meningitidis serogroup Men A, Men C, Men W and Men Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination

Secondary: GMRs against each of the N. meningitidis serogroup Men A, Men C, Men W and Men Y in both MenB+MenACWY and MenACWY Groups after MenACWY vaccination

Clinical Trial Results:
A Phase IIIB, Randomized, Observer-blind, Multicenter Study to Assess the Safety and Immunogenicity of GSK's Meningococcal Group B Vaccine When Administered Concomitantly With GSK's Meningococcal MenACWY Conjugate Vaccine to Healthy Subjects of 16-18 Years of Age