Clinical Trial Results:
A Phase 2, Observer Blinded, Controlled, Randomized Multi-Center Study in Adolescents, to Evaluate Safety, Tolerability and Immunogenicity of Four Different rMenB plus MenACWY Formulations.

Due to a system error, the data reported in v1 is not correct and has been removed from public view.

Summary
EudraCT number	2014-005160-15
Trial protocol	Outside EU/EEA
Global end of trial date	27 Jul 2011

Results information
Results version number	v2(current)
This version publication date	04 Jun 2016
First version publication date	06 Jun 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set re-QC of this study is necessary because of the EudraCT system glitch and updates to results are required.

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

V102_02

ISRCTN number

US NCT number

NCT01210885

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Vaccines and Diagnostics

Sponsor organisation address

Via Fiorentina, 1, Siena, Italy, 53100

Public contact

Posting Director, Novartis Vaccines and Diagnostics , RegistryContactVaccinesUS@novartis.com

Scientific contact

Posting Director, Novartis Vaccines and Diagnostics , RegistryContactVaccinesUS@novartis.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001260-PIP01-11

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

06 Mar 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

27 Jul 2011

Global end of trial reached?

Yes

Global end of trial date

27 Jul 2011

Was the trial ended prematurely?

Main objective of the trial

To evaluate the immunogenicity, safety and tolerability of two doses of four different formulations of Meningococcal B Recombinant Vaccine (rMenB) (± Outer Membrane Vesicles (OMV)) + Meningococcal ACWY Conjugate (MenACWY), when administered to healthy adolescents aged 11-18 years, in order to select the formulation to bring into clinical development.

Protection of trial subjects

This clinical study was designed, implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practices (GCP), with applicable local regulations (including the European Directive 2001/20/EC, the US Code of Federal Regulation (CFR) Title 21, and the Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of Helsinki.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Dec 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Colombia: 121

Country: Number of subjects enrolled

Chile: 48

Country: Number of subjects enrolled

Panama: 326

Worldwide total number of subjects

495

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

383

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study centres were located in Panama (6 centres), Chile (2 centres) and Columbia (3 centres).

Screening details

All subjects enrolled were included in the trial.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Are arms mutually exclusive

Yes

MenABCWY

Arm description

MenABCWY combination vaccine containing rMenB without outer membrane vesicle (OMV) at a 0, 2-month schedule.

Arm type

Experimental

Investigational medicinal product name

Combined MenABCWY vaccine (rMenB (no OMV) + MenACWY lyophilized)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5mL was administered.

MenAB (X2)CWY

Arm description

MenABCWY combination vaccine containing rMenBx2doses at a 0, 2-month schedule.

Arm type

Experimental

Investigational medicinal product name

Combined MenABCWY vaccine (rMenBx2doses (no OMV) + MenACWY lyophilized)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 1.0mL was administered.

MenABCWY+OMV

Arm description

MenABCWY combination vaccine containing rMenB + OMV at 0, 2-month schedule.

Arm type

Experimental

Investigational medicinal product name

Combined MenABCWY vaccine (rMenB + OMV liquid suspension + MenACWY lyophilized)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5mL was administered.

MenABCWY+¼OMV

Arm description

MenABCWY combination vaccine containing rMenB + ¼ OMV at 0, 2-month schedule.

Arm type

Experimental

Investigational medicinal product name

Combined MenABCWY vaccine (rMenB + 1/4 OMV liquid suspension)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5mL was administered.

MenB

Arm description

rMenB (no OMV) at a 0, 2-month schedule.

Arm type

Active comparator

Investigational medicinal product name

Recombinant MenB (no OMV) vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Each dose of 0.5mL was administered.

MenACWY/Placebo

Arm description

1 dose of MenACWY, 1 dose of placebo at a 0, 2-month schedule.

Arm type

Placebo

Investigational medicinal product name

Menveo® Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine/Placebo.

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

MenACWY: Each dose of 0.5mL Placebo: Each dose of 0.5 mL was administered.

Number of subjects in period 1	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Started	80	82	83	82	85	83
Completed	79	80	81	81	81	83
Not completed	1	2	2	1	4	0
Consent withdrawn by subject	1	-	1	-	4	-
Adverse event, non-fatal	-	1	-	-	-	-
Lost to follow-up	-	1	-	-	-	-
Administrative reason	-	-	1	-	-	-
Protocol deviation	-	-	-	1	-	-

Baseline characteristics

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Reporting group title

MenABCWY

Reporting group description

MenABCWY combination vaccine containing rMenB without outer membrane vesicle (OMV) at a 0, 2-month schedule.

Reporting group title

MenAB (X2)CWY

Reporting group description

MenABCWY combination vaccine containing rMenBx2doses at a 0, 2-month schedule.

Reporting group title

MenABCWY+OMV

Reporting group description

MenABCWY combination vaccine containing rMenB + OMV at 0, 2-month schedule.

Reporting group title

MenABCWY+¼OMV

Reporting group description

MenABCWY combination vaccine containing rMenB + ¼ OMV at 0, 2-month schedule.

Reporting group title

MenB

Reporting group description

rMenB (no OMV) at a 0, 2-month schedule.

Reporting group title

MenACWY/Placebo

Reporting group description

1 dose of MenACWY, 1 dose of placebo at a 0, 2-month schedule.

Reporting group values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo	Total
Number of subjects	80	82	83	82	85	83	495
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	13.6 ± 2.1	13.8 ± 2.1	13.8 ± 2.3	13.9 ± 1.9	14.4 ± 2.2	14.2 ± 2.2	-
Gender categorical
Units: Subjects
Female	47	44	44	38	44	45	262
Male	33	38	39	44	41	38	233

End points

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Reporting group title

MenABCWY

Reporting group description

MenABCWY combination vaccine containing rMenB without outer membrane vesicle (OMV) at a 0, 2-month schedule.

Reporting group title

MenAB (X2)CWY

Reporting group description

MenABCWY combination vaccine containing rMenBx2doses at a 0, 2-month schedule.

Reporting group title

MenABCWY+OMV

Reporting group description

MenABCWY combination vaccine containing rMenB + OMV at 0, 2-month schedule.

Reporting group title

MenABCWY+¼OMV

Reporting group description

MenABCWY combination vaccine containing rMenB + ¼ OMV at 0, 2-month schedule.

Reporting group title

MenB

Reporting group description

rMenB (no OMV) at a 0, 2-month schedule.

Reporting group title

MenACWY/Placebo

Reporting group description

1 dose of MenACWY, 1 dose of placebo at a 0, 2-month schedule.

Subject analysis set title

All enrolled population

Subject analysis set type

Intention-to-treat

Subject analysis set description

all subjects who had signed an informed consent, undergone screening procedure (s) and were randomized.

Subject analysis set title

Safety population

Subject analysis set type

Safety analysis

Subject analysis set description

all subjects in the Exposed population who: - had received at least one dose of study vaccine, - provided some post-vaccination safety data.

Subject analysis set title

Modified Intention-to-treat (MITT) population, Immunogenicity

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

all subjects in the enrolled population who: - actually received a study vaccination; - provided at least one evaluable serum sample at the relevant time points and whose assay result was available for at least one serogroup or strain.

Subject analysis set title

Per protocol (PP) population, Immunogenicity

Subject analysis set type

Per protocol

Subject analysis set description

all subjects in the MITT Immunogenicity population who: - correctly received the vaccine, - provided evaluable serum samples at the relevant time points, - had no major protocol violation as defined prior to unblinding.

Primary: 1. Percentage of Subjects with Seroresponse to Neisseria Meningitidis Serogroups A, C, W and Y.

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End point title

1. Percentage of Subjects with Seroresponse to Neisseria Meningitidis Serogroups A, C, W and Y. ^[1]

End point description

Percentages of Subjects with a Seroresponse against N. Meningitidis serogroups A, C, W and Y. The data were reported based on the Per Protocol Set (PPS).

End point type

Primary

End point timeframe

1 month after the second vaccination (Day 91).

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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	77	80	80	81	78	82
Units: Percentages of Subjects
number (confidence interval 95%)
MenA (Day 91; N=77,79,80,79,77,81)	97 (91 to 100)	97 (91 to 100)	98 (91 to 100)	97 (91 to 100)	87 (77 to 94)	69 (58 to 79)
MenC (Day 91; N=77,78,79,77,77,79)	95 (87 to 99)	96 (89 to 99)	95 (88 to 99)	97 (91 to 100)	29 (19 to 40)	65 (53 to 75)
MenW (Day 91; N=77,76,80,77,76,81)	74 (63 to 83)	82 (71 to 90)	76 (65 to 85)	86 (76 to 93)	47 (36 to 59)	52 (40 to 63)
MenY (Day 91; N=77,78,80,81,78,82)	95 (87 to 99)	92 (84 to 97)	96 (89 to 99)	93 (85 to 97)	4 (1 to 11)	73 (62 to 82)

No statistical analyses for this end point

Primary: 2. Percentage of subjects with hSBA ≥ 1:8 to N. Meningitidis Serogroups A, C, W and Y.

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End point title

2. Percentage of subjects with hSBA ≥ 1:8 to N. Meningitidis Serogroups A, C, W and Y. ^[2]

End point description

Percentages of subjects with human serum bactericidal assay (hSBA) ≥ 1:8 to N. Meningitidis Serogroups A, C, W and Y after receiving 2 doses of MenABCWY vaccine. The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vaccination (Day 91).

Notes
[2] - 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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[3]	80	80	81	78	82
Units: Percentages of Subjects
number (confidence interval 95%)
MenA (Day 1; N=80,80,82,81,82,82)	9 (4 to 17)	5 (1 to 12)	4 (1 to 10)	1 (0.031 to 7)	1 (0.031 to 7)	5 (1 to 12)
MenA (Day 91; N=77,79,80,80,77,81)	99 (93 to 100)	100 (95 to 100)	98 (91 to 100)	99 (93 to 100)	87 (77 to 94)	72 (60 to 81)
MenC (Day 1; N=80,80,82,80,82,81)	33 (22 to 44)	29 (19 to 40)	38 (27 to 49)	33 (22 to 44)	29 (20 to 40)	32 (22 to 43)
MenC (Day 91; N=77,78,79,79,77,80)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	71 (60 to 81)	86 (77 to 93)
MenW (Day 1; N=80,79,82,80,81,82)	70 (59 to 80)	65 (53 to 75)	68 (57 to 78)	70 (59 to 80)	74 (63 to 83)	68 (57 to 78)
MenW (Day 91; N=77,77,80,79,77,81)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	99 (93 to 100)	98 (91 to 100)
MenY (Day 1; N=80,79,82,82,82,82)	26 (17 to 37)	25 (16 to 36)	28 (19 to 39)	28 (19 to 39)	26 (17 to 36)	40 (30 to 52)
MenY (Day 91; N=77,79,80,81,78,82)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (96 to 100)	28 (19 to 40)	100 (96 to 100)

Notes
[3] - On day 1 PPs included 80 subjects. On day 91, PPs included 77 subjects.

No statistical analyses for this end point

Primary: 3. Percentage of subjects with hSBA Titers ≥ 1:4 to N. Meningitidis Serogroups A, C, W and Y.

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End point title

3. Percentage of subjects with hSBA Titers ≥ 1:4 to N. Meningitidis Serogroups A, C, W and Y. ^[4]

End point description

Percentages of subjects with hSBA≥1:4 against N. Meningitidis serogroups A, C, W and Y after receiving 2 doses of MenABCWY vaccine. The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vaccination (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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[5]	80	80	81	78	82
Units: Percentages of Subjects
number (confidence interval 95%)
MenA (Day 1; N=80,80,82,81,82,82)	9 (4 to 17)	8 (3 to 16)	6 (2 to 14)	1 (0.031 to 7)	5 (1 to 12)	6 (2 to 14)
MenA (Day 91; N=77,79,80,80,77,81)	99 (93 to 100)	100 (95 to 100)	99 (93 to 100)	99 (93 to 100)	88 (79 to 95)	72 (60 to 81)
MenC (Day 1; N=80,80,82,80,82,81)	45 (34 to 57)	41 (30 to 53)	50 (39 to 61)	53 (41 to 64)	46 (35 to 58)	48 (37 to 60)
MenC (Day 91; N=77,78,79,79,77,80)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	84 (74 to 92)	95 (88 to 99)
MenW (Day 1; N=80,79,82,80,81,82)	71 (60 to 81)	67 (56 to 77)	70 (58 to 79)	75 (64 to 84)	75 (64 to 84)	72 (61 to 81)
MenW (Day 91; N=77,77,80,79,77,81)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	99 (93 to 100)	99 (93 to 100)
MenY (Day 1; N=80,79,82,82,82,82)	33 (22 to 44)	29 (19 to 40)	32 (22 to 43)	33 (23 to 44)	32 (22 to 43)	44 (33 to 55)
MenY (Day 91; N=77,79,80,81,78,82)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (96 to 100)	33 (23 to 45)	100 (96 to 100)

Notes
[5] - On day 1 PPs included 80 subjects. On day 91, PPs included 77 subjects.

No statistical analyses for this end point

Primary: 4. Percentage of Subjects with Fourfold Increase in hSBA Titers for MenB strains.

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End point title

4. Percentage of Subjects with Fourfold Increase in hSBA Titers for MenB strains. ^[6]

End point description

Percentages of Subjects with Fourfold Increase in hSBA Titers for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vaccination (Day 91).

Notes
[6] - 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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	77	80	80	81	78	82
Units: Percentages of Subjects
number (confidence interval 95%)
S.44/76-SL (Day 91; N=77,78,77,79,78,81)	95 (87 to 99)	96 (89 to 99)	99 (93 to 100)	97 (91 to 100)	87 (78 to 94)	1 (0.031 to 7)
S.5/99 (Day 91; N=76,79,80,77,77,80)	95 (87 to 99)	100 (95 to 100)	99 (93 to 100)	100 (95 to 100)	99 (93 to 100)	3 (0 to 9)
S.NZ98/254 (Day 91; N=77,79,80,78,77,81)	10 (5 to 19)	14 (7 to 24)	46 (35 to 58)	46 (35 to 58)	5 (1 to 13)	1 (0.031 to 7)

No statistical analyses for this end point

Primary: 5. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains.

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End point title

5. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains. ^[7]

End point description

Percentages of Subjects with hSBA ≥ 1:5 to N. Meningitidis for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vacciantion (Day 91).

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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[8]	80	80	81	78	82
Units: Percentages of Subjects
number (confidence interval 95%)
S.44/76-SL (Day 1; N=80,79,81,81,82,82)	4 (1 to 11)	8 (3 to 16)	7 (3 to 15)	6 (2 to 14)	6 (2 to 14)	7 (3 to 15)
S.44/76-SL (Day 91; N=77,79,78,80,78,81)	96 (89 to 99)	99 (93 to 100)	100 (95 to 100)	99 (93 to 100)	94 (86 to 98)	7 (3 to 15)
S.5/99 (Day 1; N=80,80,82,81,82,82)	14 (7 to 23)	13 (6 to 22)	10 (4 to 18)	14 (7 to 23)	21 (13 to 31)	13 (7 to 23)
S.5/99 (Day 91; N=76,79,80,78,77,80)	99 (93 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	16 (9 to 26)
S.NZ98/254 (Day 1; N=80,80,82,81,82,82)	3 (0 to 9)	6 (2 to 14)	5 (1 to 12)	2 (0 to 9)	9 (4 to 17)	4 (1 to 10)
S.NZ98/254 (Day 91; N=77,79,80,79,77,81)	16 (8 to 26)	19 (11 to 29)	78 (67 to 86)	71 (60 to 81)	18 (10 to 29)	2 (0 to 9)

Notes
[8] - On day 1 PPs included 80 subjects. On day 91, PPs included 77 subjects.

No statistical analyses for this end point

Primary: 6. Percentage of Subjects with hSBA ≥ 1:8 for MenB strains.

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End point title

6. Percentage of Subjects with hSBA ≥ 1:8 for MenB strains. ^[9]

End point description

Percentages of Subjects with hSBA ≥1:8 to N. Meningitidis for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vaccination (Day 91).

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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[10]	80	80	81	78	82
Units: Percentages of Subjects
number (confidence interval 95%)
S.44/76-SL (Day 1; N=80,79,81,81,82,82)	3 (0 to 9)	6 (2 to 14)	6 (2 to 14)	4 (1 to 10)	4 (1 to 10)	6 (2 to 14)
S.44/76-SL (Day 91; N=77,79,78,80,78,81)	96 (89 to 99)	99 (93 to 100)	100 (95 to 100)	99 (93 to 100)	91 (82 to 96)	5 (1 to 12)
S.5/99 (Day 1; N=80,80,82,81,82,82)	10 (4 to 19)	8 (3 to 16)	5 (1 to 12)	4 (1 to 10)	13 (7 to 23)	11 (5 to 20)
S.5/99 (Day 91; N=76,79,80,78,77,80)	99 (93 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	100 (95 to 100)	11 (5 to 20)
S.NZ98/254 (Day 1; N=80,80,82,81,82,82)	3 (0 to 9)	5 (1 to 12)	5 (1 to 12)	2 (0 to 9)	6 (2 to 14)	2 (0 to 9)
S.NZ98/254 (Day 91; N=77,79,80,79,77,81)	13 (6 to 23)	15 (8 to 25)	55 (43 to 66)	53 (42 to 64)	17 (9 to 27)	1 (0.031 to 7)

Notes
[10] - On day 1 PPs included 80 subjects. On day 91, PPs included 77 subjects.

No statistical analyses for this end point

Primary: 7. Geometric Mean hSBA Titers (GMTs), Serogroups A, C, W, Y.

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End point title

7. Geometric Mean hSBA Titers (GMTs), Serogroups A, C, W, Y. ^[11]

End point description

Geometric Mean hSBA Titers (95% CI) for N. Meningitidis Serogroups A, C, W, and Y. The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vaccination (Day 91).

Notes
[11] - 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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[12]	80	82	81	82	82
Units: Titers
geometric mean (confidence interval 95%)
MenA (Day 1; N=80,80,82,80,82,81)	1.45 (1.21 to 1.72)	1.34 (1.13 to 1.6)	1.28 (1.08 to 1.52)	1.22 (1.02 to 1.45)	1.2 (1.01 to 1.43)	1.4 (1.18 to 1.67)
MenA (Day 91; N=77,79,80,80,77,81)	146 (105 to 203)	205 (148 to 283)	172 (125 to 238)	157 (114 to 218)	60 (43 to 84)	33 (24 to 46)
MenC (Day 1; N=80,79,82,80,81,82)	4.6 (3.47 to 6.11)	3.8 (2.87 to 5.03)	4.57 (3.46 to 6.04)	4.56 (3.44 to 6.05)	4.59 (3.47 to 6.06)	4.04 (3.05 to 5.35)
MenC (Day 91; N=77,78,79,79,77,80)	317 (250 to 401)	380 (301 to 481)	286 (226 to 361)	340 (268 to 431)	15 (12 to 19)	39 (31 to 49)
MenW (Day 1; N=80,79,82,82,82,82)	19 (13 to 29)	17 (11 to 26)	20 (13 to 30)	18 (12 to 28)	22 (14 to 33)	19 (13 to 29)
MenW (Day 91; N=77,77,80,79,77,81)	344 (285 to 414)	440 (365 to 531)	356 (296 to 427)	385 (320 to 464)	131 (108 to 158)	146 (122 to 176)
MenY (Day 1; N=77,77,80,79,77,81)	4.3 (3.38 to 5.47)	4.11 (3.23 to 5.23)	4.35 (3.43 to 5.52)	4.24 (3.35 to 5.39)	4.45 (3.51 to 5.65)	5.76 (4.54 to 7.31)
MenY (Day 91; N=77,79,80,81,78,82)	196 (159 to 243)	219 (178 to 271)	187 (152 to 231)	180 (147 to 221)	4.26 (3.45 to 5.25)	62 (51 to 77)

Notes
[12] - On day 1 PPs included 80 subjects. On day 91, PPs included 77 subjects.

No statistical analyses for this end point

Primary: 8. hSBA GMTs, Serogroups B strains.

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End point title

8. hSBA GMTs, Serogroups B strains. ^[13]

End point description

Geometric Mean hSBA Titers (95% CI) for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vaccination (Day 91).

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[14]	80	80	81	78	82
Units: Titers
geometric mean (confidence interval 95%)
S.44/76-SL (Day 1; N=80,79,81,81,82,82)	1.17 (0.96 to 1.42)	1.33 (1.09 to 1.61)	1.34 (1.11 to 1.62)	1.24 (1.03 to 1.51)	1.31 (1.08 to 1.59)	1.34 (1.1 to 1.62)
S.44/76-SL (Day 91; N=77,79,78,80,78,81)	61 (49 to 77)	97 (78 to 123)	107 (85 to 135)	111 (88 to 139)	50 (40 to 63)	1.35 (1.08 to 1.7)
S.5/99 (Day 1; N=80,80,82,81,82,82)	2.38 (1.9 to 2.99)	2.09 (1.67 to 2.62)	1.83 (1.46 to 2.29)	2.01 (1.6 to 2.52)	2.59 (2.07 to 3.24)	2.26 (1.8 to 2.82)
S.5/99 (Day 91; N=76,79,80,78,77,80)	262 (217 to 317)	368 (306 to 442)	323 (269 to 389)	340 (282 to 410)	347 (288 to 419)	2.15 (1.78 to 2.58)
S.NZ98/254 (Day 1; N=80,80,82,81,82,82)	1.66 (1.4 to 1.96)	1.52 (1.29 to 1.79)	1.7 (1.44 to 2)	1.66 (1.4 to 1.96)	1.94 (1.65 to 2.29)	1.49 (1.27 to 1.76)
S.NZ98/254 (Day 91; N=77,79,80,79,77,81)	2.5 (1.99 to 3.14)	2.99 (2.39 to 3.74)	12 (9.98 to 16)	8.87 (7.08 to 11)	2.32 (1.84 to 2.91)	1.7 (1.36 to 2.13)

Notes
[14] - On day 1 PPs included 80 subjects. On day 91, PPs included 77 subjects.

No statistical analyses for this end point

Primary: 9. Geometric Mean Ratios (GMRs) for Serogroups A, C, W,Y.

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End point title

9. Geometric Mean Ratios (GMRs) for Serogroups A, C, W,Y. ^[15]

End point description

Geometric Mean Ratios for N. Meningitidis Serogroups A, C, W, and Y. The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after the second vaccination to pre-vaccination.

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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	77	80	80	81	78	82
Units: Ratio
geometric mean (confidence interval 95%)
MenA (Day 91/day 1; N=77,79,80,79,77,81)	104 (73 to 147)	154 (109 to 217)	133 (95 to 187)	125 (89 to 177)	49 (35 to 70)	24 (17 to 34)
MenC (Day 91/day 1; N=77,78,79,77,77,79)	70 (50 to 99)	100 (72 to 141)	65 (46 to 91)	74 (52 to 104)	3.32 (2.36 to 4.67)	9.61 (6.86 to 13)
MenW (Day 91/day 1; N=77,76,80,77,76,81)	18 (12 to 28)	27 (17 to 42)	18 (12 to 28)	20 (13 to 32)	5.97 (3.81 to 9.33)	7.78 (5.04 to 12)
MenY (Day 91/day 1; N=77,78,80,81,78,82)	45 (34 to 60)	52 (40 to 69)	43 (32 to 56)	43 (33 to 57)	0.94 (0.71 to 1.25)	12 (8.84 to 15)

No statistical analyses for this end point

Primary: 10. GMRs for Serogroups B strains.

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End point title

10. GMRs for Serogroups B strains. ^[16]

End point description

Geometric Mean Ratios for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data were reported based on the PPS.

End point type

Primary

End point timeframe

1 month after 2nd vaccination to pre-vaccination.

Notes
[16] - 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: No statistical analysis is associated to this end point. Analyses were run descriptively.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	77	80	80	82	78	82
Units: Ratio
geometric mean (confidence interval 95%)
S.44/76-SL (Day 91/day 1; N=77,78,77,79,78,81)	51 (39 to 66)	74 (57 to 96)	81 (62 to 105)	88 (68 to 114)	38 (30 to 50)	1.08 (0.84 to 1.4)
S.5/99 (Day 91/day 1; N=76,79,80,77,77,80)	111 (85 to 145)	174 (134 to 226)	172 (133 to 223)	165 (127 to 215)	141 (108 to 183)	1.01 (0.78 to 1.31)
S.NZ98/254 (Day 91/day 1; N=77,79,80,78,77,81)	1.5 (1.18 to 1.9)	1.86 (1.47 to 2.36)	7.41 (5.85 to 9.37)	5.3 (4.18 to 6.72)	1.31 (1.03 to 1.66)	1.07 (0.85 to 1.35)

No statistical analyses for this end point

Secondary: 11. Number of subjects reporting solicited local reaction during 7 days following each vaccination.

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End point title

11. Number of subjects reporting solicited local reaction during 7 days following each vaccination.

End point description

Safety was assessed as the number of subjects who reported solicited reaction from day 1 through day 7 after each vaccination (injection 1 and injection 2). The data were reported based on the Safety Set.

End point type

Secondary

End point timeframe

Day 1 through day 7 after each vaccination on day 1 and day 61.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[17]	81	83	82	85	82
Units: Number of Subjects
Pain (injection 1; N=81,81,83,82,85,82)	65	67	76	73	66	41
Pain (injection 2; N=80,80,81,81,81,82)	54	50	67	61	56	58
Erythema (injection 1; N=81,80,83,82,85,81)	19	26	31	26	23	20
Erythema (injection 2; N=80,80,81,81,81,82)	23	21	30	22	19	19
Induration (injection 1; N=81,79,83,82,84,81)	28	27	39	28	17	17
Induration (injection 2; N=80,80,81,81,81,82)	18	19	32	27	20	18
Swelling (injection 1; N=81,79,83,82,84,81)	10	22	43	20	16	12
Swelling (injection 2; N=80,80,81,81,80,82)	13	21	27	22	12	15

Notes
[17] - 81 actually treated as per Safety Set. Difference due to "as treated" vs "as randomized" situation.

No statistical analyses for this end point

Secondary: 12. Number of subjects reporting solicited Systemic reaction during 7 days following each vaccination.

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End point title

12. Number of subjects reporting solicited Systemic reaction during 7 days following each vaccination.

End point description

End point type

Secondary

End point timeframe

Day 1 through day 7 after each vaccination.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[18]	82	83	82	85	82
Units: Number of Subjects
Chills (injection 1; N=81,81,83,82,85,82)	12	13	13	22	10	14
Chills (injection 2; N=80,80,81,81,81,82)	10	14	14	10	8	11
Malaise (injection 1; N=81,81,83,82,85,82)	19	18	14	20	8	15
Malaise (injection 2; N=80,80,81,81,81,82)	10	19	17	14	15	13
Myalgia (injection 1; N=81,81,83,82,85,82)	39	42	42	45	34	31
Myalgia (injection 2; N=80,80,81,81,81,82)	27	29	41	30	31	29
Arthralgia (injection 1; N=81,81,83,82,85,82)	17	14	14	16	13	12
Arthralgia (injection 2; N=80,80,81,81,81,82)	9	8	20	12	12	9
Headache (injection 1; N=81,81,83,82,85,82)	34	33	41	31	30	34
Headache (injection 2 N=80,80,81,81,81,82)	21	24	31	22	23	28
Fatigue (injection 1; N=81,81,83,82,85,82)	18	12	9	15	18	12
Fatigue (injection 2; N=80,80,81,81,81,82)	9	7	11	9	9	7
Nausea (injection 1; N=81,81,83,82,85,82)	15	12	13	13	8	9
Nausea (injection 2; N=80,80,81,81,81,82)	6	10	7	7	7	7
Rash (injection 1; N=81,81,83,82,85,82)	4	1	3	4	3	4
Rash (injection 2; N=80,80,81,81,81,82)	3	4	3	3	5	2
Fever(>38°C) (injection 1; N=81,81,83,82,85,82)	2	5	4	5	2	2
Fever(>38°C) (injection 2; N=80,80,81,81,81,82)	2	5	6	5	3	4

Notes
[18] - 81 actually treated as per Safety Set.

No statistical analyses for this end point

Secondary: 13. Number of Subjects who reported Unsolicited AEs during 7 days after each vaccination

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End point title

13. Number of Subjects who reported Unsolicited AEs during 7 days after each vaccination

End point description

Safety was assessed as the number of subjects who reported unsolicited AEs reaction from day 1 through day 7 after each vaccination and SAEs for the entire study period. The data were reported based on the Safety Set.

End point type

Secondary

End point timeframe

Day 1 through day 7 after each vaccination and Day 1 to day 91 for SAEs.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80 ^[19]	81	83	82	85	82
Units: Number of Subjects
Any Adverse Events (AEs)	28	28	27	28	27	30
At least possibly related AEs	11	11	14	8	6	12
Serious Adverse Events (SAEs)	1	0	0	0	2	0
At least possibly related SAEs	0	0	0	0	0	0

Notes
[19] - 80 subjects started, 81 were actually analyzed in this group.

No statistical analyses for this end point

Secondary: 14. Percentage of subjects with hSBA ≥ 1:8 for Serogroups MenA, C, W and Y.

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End point title

14. Percentage of subjects with hSBA ≥ 1:8 for Serogroups MenA, C, W and Y.

End point description

Percentages of subjects with hSBA ≥ 1:8 against N. Meningitidis serogroups A, C, W and Y after the first dose of MenABCWY vaccine. The data were reported based on the PPS.

End point type

Secondary

End point timeframe

1 month after the 1st vaccination (Day 31).

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	79	78	80	81	79	81
Units: Percentages of Subjects
number (confidence interval 95%)
MenA (Day 31; N=78,78,79,81,78,78)	86 (76 to 93)	88 (79 to 95)	80 (69 to 88)	75 (64 to 84)	29 (20 to 41)	88 (79 to 95)
MenC (Day 31; N=79,78,80,80,78,79)	85 (75 to 92)	96 (89 to 99)	93 (84 to 97)	93 (84 to 97)	40 (29 to 51)	84 (74 to 91)
MenW (Day 31; N=79,78,79,80,77,80)	94 (86 to 98)	99 (93 to 100)	100 (95 to 100)	100 (95 to 100)	77 (66 to 86)	98 (91 to 100)
MenY (Day 31; N=79,78,79,81,78,81)	95 (88 to 99)	92 (84 to 97)	91 (83 to 96)	94 (86 to 98)	31 (21 to 42)	100 (96 to 100)

No statistical analyses for this end point

Secondary: 15. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains.

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End point title

15. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains.

End point description

Percentages of Subjects with hSBA ≥ 1:5 to N. Meningitidis for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data were reported based on the PPS.

End point type

Secondary

End point timeframe

1 month after the 1st vaccination (Day 31).

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	79	78	80	81	79	81
Units: Percentages of Subjects
number (confidence interval 95%)
S.44/76-SL (Day 31; N=79,78,80,80,78,81)	35 (25 to 47)	64 (52 to 75)	66 (55 to 76)	56 (45 to 68)	35 (25 to 46)	9 (4 to 18)
S.5/99 (Day 31; N=79,78,79,81,78,80)	94 (86 to 98)	99 (93 to 100)	81 (71 to 89)	85 (76 to 92)	99 (93 to 100)	20 (12 to 30)
S. NZ98/254 (Day 31; N=79,78,80,81,78,80)	4 (1 to 11)	12 (5 to 21)	38 (27 to 49)	30 (21 to 42)	11 (5 to 20)	4 (1 to 10)

No statistical analyses for this end point

Secondary: 16. hSBA GMTs, Serogroups A, C, W and Y.

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End point title

16. hSBA GMTs, Serogroups A, C, W and Y.

End point description

Geometric Mean hSBA Titers (95% CI) for N.Meningitidis Serogroups A, C, W, and Y. The data were reported based on the PPS.

End point type

Secondary

End point timeframe

1 month after 1st vaccination (Day 31).

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	79	78	80	81	79	81
Units: Titers
geometric mean (confidence interval 95%)
MenA (Day 31; N=78,78,79,81,78,78)	56 (36 to 85)	73 (48 to 112)	49 (32 to 74)	41 (27 to 62)	3.36 (2.2 to 5.14)	105 (68 to 160)
MenC (Day 31; N=79,78,80,80,78,79)	54 (39 to 76)	78 (56 to 110)	76 (54 to 107)	82 (58 to 115)	5.83 (4.14 to 8.2)	59 (42 to 84)
MenW (Day 31; N=79,78,79,80,77,80)	143 (108 to 189)	204 (154 to 270)	183 (138 to 241)	199 (151 to 264)	24 (18 to 32)	188 (142 to 248)
MenY (Day 31; N=79,78,79,81,78,81)	76 (56 to 103)	77 (57 to 104)	67 (50 to 91)	75 (56 to 101)	4.56 (3.38 to 6.16)	77 (57 to 104)

No statistical analyses for this end point

Secondary: 17. hSBA GMTs, Serogroups B strains.

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End point title

17. hSBA GMTs, Serogroups B strains.

End point description

Geometric Mean hSBA Titers (95% CI) for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data are reported based on the PPS.

End point type

Secondary

End point timeframe

1 month after 1st vaccination (Day 31).

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	80	79	81	82	82	82
Units: Titers
geometric mean (confidence interval 95%)
S. 44/76-SL (Day 31; N=79,78,80,80,78,81)	4.22 (3.01 to 5.92)	9.98 (7.1 to 14)	13 (9.06 to 18)	9.03 (6.45 to 13)	3.74 (2.67 to 5.25)	1.65 (1.18 to 2.31)
S. 5/99 (Day 31; N=79,78,79,81,78,80)	44 (33 to 59)	94 (71 to 124)	24 (18 to 32)	35 (26 to 46)	72 (54 to 95)	2.26 (1.71 to 2.99)
S. NZ98/254 (Day 31; N=79,78,80,81,78,80)	1.98 (1.59 to 2.46)	2.15 (1.73 to 2.68)	4.9 (3.94 to 6.08)	3.47 (2.8 to 4.31)	1.77 (1.42 to 2.2)	1.71 (1.38 to 2.13)

No statistical analyses for this end point

Secondary: 18. GMRs for Serogroups A, C, W, Y.

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End point title

18. GMRs for Serogroups A, C, W, Y.

End point description

Geometric Mean Ratios for N. meningitides Serogroups A, C, W and Y. The data were reported based on the PPS.

End point type

Secondary

End point timeframe

1 month after 1st vaccination to pre-vaccination.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	79	78	80	81	79	81
Units: Ratio
geometric mean (confidence interval 95%)
MenA (Day 31/day 1; N=78,78,79,80,78,78)	41 (26 to 63)	55 (36 to 85)	38 (24 to 58)	32 (21 to 49)	2.67 (1.74 to 4.11)	77 (50 to 118)
MenC (Day 31/day 1; N=79,78,80,79,78,78)	12 (8.37 to 18)	20 (14 to 29)	18 (12 to 26)	18 (13 to 27)	1.3 (0.88 to 1.91)	15 (10 to 22)
MenW (Day 31/day 1; N=79,77,79,78,76,80)	7.8 (5.2 to 12)	12 (7.8 to 18)	10 (6.69 to 15)	11 (7.02 to 16)	1.17 (0.77 to 1.77)	10 (7.01 to 16)
MenY (Day 31/day 1; N=79,77,79,81,78,81)	18 (13 to 25)	18 (13 to 26)	16 (11 to 22)	18 (13 to 25)	1.04 (0.75 to 1.46)	15 (11 to 21)

No statistical analyses for this end point

Secondary: 19. GMRs for Serogroups B strains.

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End point title

19. GMRs for Serogroups B strains.

End point description

Geometric Mean Ratio for the three major meningococcal B Strains (Strain 44/76-SL, Strain 5/99 and Strain NZ98/254). The data were reported based on the PPS.

End point type

Secondary

End point timeframe

1 month after 1st vaccination to pre-vaccination.

End point values	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Number of subjects analysed	79	78	80	81	79	81
Units: Ratio
geometric mean (confidence interval 95%)
S. 44/76-SL (Day 31/day 1; N=79,77,79,79,78,81)	3.36 (2.39 to 4.72)	7.73 (5.49 to 11)	9.81 (6.99 to 14)	7.09 (5.05 to 9.96)	2.9 (2.06 to 4.08)	1.28 (0.91 to 1.79)
S. 5/99 (Day 31/day 1; N=79,78,79,80,78,80)	19 (14 to 26)	44 (32 to 61)	12 (8.95 to 17)	17 (12 to 23)	29 (21 to 40)	1.02 (0.74 to 1.4)
S. NZ98 (Day 31/day 1; N=79,78,80,80,78,80)	1.19 (0.95 to 1.49)	1.33 (1.06 to 1.67)	2.91 (2.33 to 3.64)	2.09 (1.67 to 2.61)	1.01 (0.8 to 1.26)	1.07 (0.86 to 1.34)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Day 1 to Day 91.

Adverse event reporting additional description

All the unsolicited AEs were reported by non-systematic assessment and the solicited AEs were reported by systemic assessment.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.01

Reporting group title

MenABCWY

Reporting group description

MenABCWY combination vaccine containing rMenB without outer membrane vesicle (OMV) at a 0, 2-month schedule.

Reporting group title

MenAB (X2)CWY

Reporting group description

MenABCWY combination vaccine containing rMenBx2doses at a 0, 2-month schedule.

Reporting group title

MenABCWY+OMV

Reporting group description

MenABCWY combination vaccine containing rMenB + OMV at 0, 2-month schedule.

Reporting group title

MenABCWY+¼OMV

Reporting group description

MenABCWY combination vaccine containing rMenB + ¼ OMV at 0, 2-month schedule.

Reporting group title

MenB

Reporting group description

rMenB (no OMV) at a 0, 2-month schedule.

Reporting group title

MenACWY/Placebo

Reporting group description

1 dose of MenACWY, 1 dose of placebo at a 0, 2-month schedule.

Serious adverse events	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 81 (1.23%)	0 / 81 (0.00%)	0 / 83 (0.00%)	0 / 82 (0.00%)	2 / 85 (2.35%)	0 / 82 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Injury, poisoning and procedural complications
Craniocerebral injury
subjects affected / exposed	0 / 81 (0.00%)	0 / 81 (0.00%)	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 85 (1.18%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Intentional product misuse
subjects affected / exposed	1 / 81 (1.23%)	0 / 81 (0.00%)	0 / 83 (0.00%)	0 / 82 (0.00%)	0 / 85 (0.00%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Loss of consciousness
subjects affected / exposed	0 / 81 (0.00%)	0 / 81 (0.00%)	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 85 (1.18%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 81 (0.00%)	0 / 81 (0.00%)	0 / 83 (0.00%)	0 / 82 (0.00%)	1 / 85 (1.18%)	0 / 82 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	MenABCWY	MenAB (X2)CWY	MenABCWY+OMV	MenABCWY+¼OMV	MenB	MenACWY/Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	73 / 81 (90.12%)	75 / 81 (92.59%)	80 / 83 (96.39%)	76 / 82 (92.68%)	77 / 85 (90.59%)	74 / 82 (90.24%)
Nervous system disorders
Headache
subjects affected / exposed	40 / 81 (49.38%)	40 / 81 (49.38%)	48 / 83 (57.83%)	42 / 82 (51.22%)	39 / 85 (45.88%)	42 / 82 (51.22%)
occurrences all number	69	76	88	70	72	80
General disorders and administration site conditions
Chills
subjects affected / exposed	17 / 81 (20.99%)	23 / 81 (28.40%)	22 / 83 (26.51%)	26 / 82 (31.71%)	16 / 85 (18.82%)	21 / 82 (25.61%)
occurrences all number	27	30	28	36	22	28
Fatigue
subjects affected / exposed	21 / 81 (25.93%)	16 / 81 (19.75%)	17 / 83 (20.48%)	18 / 82 (21.95%)	23 / 85 (27.06%)	15 / 82 (18.29%)
occurrences all number	30	23	22	29	31	21
Injection site erythema
subjects affected / exposed	31 / 81 (38.27%)	35 / 81 (43.21%)	44 / 83 (53.01%)	33 / 82 (40.24%)	29 / 85 (34.12%)	28 / 82 (34.15%)
occurrences all number	47	47	67	49	42	39
Injection site induration
subjects affected / exposed	35 / 81 (43.21%)	33 / 81 (40.74%)	48 / 83 (57.83%)	38 / 82 (46.34%)	27 / 85 (31.76%)	26 / 82 (31.71%)
occurrences all number	47	47	76	55	39	35
Injection site pain
subjects affected / exposed	70 / 81 (86.42%)	69 / 81 (85.19%)	79 / 83 (95.18%)	76 / 82 (92.68%)	74 / 85 (87.06%)	66 / 82 (80.49%)
occurrences all number	127	128	151	141	131	106
Injection site swelling
subjects affected / exposed	18 / 81 (22.22%)	30 / 81 (37.04%)	46 / 83 (55.42%)	29 / 82 (35.37%)	23 / 85 (27.06%)	18 / 82 (21.95%)
occurrences all number	25	43	72	42	28	29
Malaise
subjects affected / exposed	22 / 81 (27.16%)	26 / 81 (32.10%)	25 / 83 (30.12%)	27 / 82 (32.93%)	17 / 85 (20.00%)	22 / 82 (26.83%)
occurrences all number	37	43	33	37	28	32
Pyrexia
subjects affected / exposed	5 / 81 (6.17%)	10 / 81 (12.35%)	10 / 83 (12.05%)	10 / 82 (12.20%)	5 / 85 (5.88%)	6 / 82 (7.32%)
occurrences all number	6	12	10	11	5	6
Gastrointestinal disorders
Nausea
subjects affected / exposed	18 / 81 (22.22%)	19 / 81 (23.46%)	16 / 83 (19.28%)	16 / 82 (19.51%)	14 / 85 (16.47%)	13 / 82 (15.85%)
occurrences all number	27	25	23	24	16	16
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	7 / 81 (8.64%)	5 / 81 (6.17%)	6 / 83 (7.23%)	7 / 82 (8.54%)	7 / 85 (8.24%)	6 / 82 (7.32%)
occurrences all number	9	5	6	7	8	7
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	22 / 81 (27.16%)	18 / 81 (22.22%)	28 / 83 (33.73%)	21 / 82 (25.61%)	22 / 85 (25.88%)	17 / 82 (20.73%)
occurrences all number	31	25	36	34	29	25
Myalgia
subjects affected / exposed	48 / 81 (59.26%)	48 / 81 (59.26%)	54 / 83 (65.06%)	50 / 82 (60.98%)	44 / 85 (51.76%)	41 / 82 (50.00%)
occurrences all number	82	80	91	80	72	67
Infections and infestations
Nasopharyngitis
subjects affected / exposed	5 / 81 (6.17%)	3 / 81 (3.70%)	6 / 83 (7.23%)	5 / 82 (6.10%)	11 / 85 (12.94%)	9 / 82 (10.98%)
occurrences all number	5	4	8	6	13	9

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 2, Observer Blinded, Controlled, Randomized Multi-Center Study in Adolescents, to Evaluate Safety, Tolerability and Immunogenicity of Four Different rMenB plus MenACWY Formulations.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1. Percentage of Subjects with Seroresponse to Neisseria Meningitidis Serogroups A, C, W and Y.

Primary: 1. Percentage of Subjects with Seroresponse to Neisseria Meningitidis Serogroups A, C, W and Y.

Primary: 2. Percentage of subjects with hSBA ≥ 1:8 to N. Meningitidis Serogroups A, C, W and Y.

Primary: 2. Percentage of subjects with hSBA ≥ 1:8 to N. Meningitidis Serogroups A, C, W and Y.

Primary: 3. Percentage of subjects with hSBA Titers ≥ 1:4 to N. Meningitidis Serogroups A, C, W and Y.

Primary: 3. Percentage of subjects with hSBA Titers ≥ 1:4 to N. Meningitidis Serogroups A, C, W and Y.

Primary: 4. Percentage of Subjects with Fourfold Increase in hSBA Titers for MenB strains.

Primary: 4. Percentage of Subjects with Fourfold Increase in hSBA Titers for MenB strains.

Primary: 5. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains.

Primary: 5. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains.

Primary: 6. Percentage of Subjects with hSBA ≥ 1:8 for MenB strains.

Primary: 6. Percentage of Subjects with hSBA ≥ 1:8 for MenB strains.

Primary: 7. Geometric Mean hSBA Titers (GMTs), Serogroups A, C, W, Y.

Primary: 7. Geometric Mean hSBA Titers (GMTs), Serogroups A, C, W, Y.

Primary: 8. hSBA GMTs, Serogroups B strains.

Primary: 8. hSBA GMTs, Serogroups B strains.

Primary: 9. Geometric Mean Ratios (GMRs) for Serogroups A, C, W,Y.

Primary: 9. Geometric Mean Ratios (GMRs) for Serogroups A, C, W,Y.

Primary: 10. GMRs for Serogroups B strains.

Primary: 10. GMRs for Serogroups B strains.

Secondary: 11. Number of subjects reporting solicited local reaction during 7 days following each vaccination.

Secondary: 11. Number of subjects reporting solicited local reaction during 7 days following each vaccination.

Secondary: 12. Number of subjects reporting solicited Systemic reaction during 7 days following each vaccination.

Secondary: 12. Number of subjects reporting solicited Systemic reaction during 7 days following each vaccination.

Secondary: 13. Number of Subjects who reported Unsolicited AEs during 7 days after each vaccination

Secondary: 13. Number of Subjects who reported Unsolicited AEs during 7 days after each vaccination

Secondary: 14. Percentage of subjects with hSBA ≥ 1:8 for Serogroups MenA, C, W and Y.

Secondary: 14. Percentage of subjects with hSBA ≥ 1:8 for Serogroups MenA, C, W and Y.

Secondary: 15. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains.

Secondary: 15. Percentage of Subjects with hSBA ≥ 1:5 for MenB strains.

Secondary: 16. hSBA GMTs, Serogroups A, C, W and Y.

Secondary: 16. hSBA GMTs, Serogroups A, C, W and Y.

Secondary: 17. hSBA GMTs, Serogroups B strains.

Secondary: 17. hSBA GMTs, Serogroups B strains.

Secondary: 18. GMRs for Serogroups A, C, W, Y.

Secondary: 18. GMRs for Serogroups A, C, W, Y.

Secondary: 19. GMRs for Serogroups B strains.

Secondary: 19. GMRs for Serogroups B strains.

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Observer Blinded, Controlled, Randomized Multi-Center Study in Adolescents, to Evaluate Safety, Tolerability and Immunogenicity of Four Different rMenB plus MenACWY Formulations.