Clinical Trial Results:
A Phase 3, Open Label, Multi-Center, Extension Study to Assess Antibody Persistence and Response to a Third or Fifth Dose of Novartis Meningococcal B Recombinant Vaccine in 4-Year-Old Children Who Previously Participated in Study V72P12E1

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

Summary
EudraCT number	2011-004931-30
Trial protocol	GB ES IT CZ
Global end of trial date	09 Apr 2014

Results information
Results version number	v2(current)
This version publication date	04 Jun 2016
First version publication date	19 Dec 2014
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set re-QC sutdy needed because of 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

V72P12E2

ISRCTN number

US NCT number

NCT01717638

WHO universal trial number (UTN)

Sponsor organisation name

NOVARTIS VACCINES AND DIAGNOSTICS S.R.L.

Sponsor organisation address

Via Fiorentina 1 , Siena, Italy, 53100

Public contact

Posting Director, Novartis Vaccines, RegistryContactVaccinesUS@novartis.com

Scientific contact

Posting Director, Novartis Vaccines, RegistryContactVaccinesUS@novartis.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

28 Aug 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Apr 2014

Was the trial ended prematurely?

Main objective of the trial

The main aim of the second extension study is to explore the bactericidal antibody persistence in 4-year-old children after a fourth dose boost of rMenB+OMV NZ given at 12, 18, or 24 months of age or after a two-dose catch-up schedule of rMenB+OMV NZ administered at either 12 and 14, 18 and 20, or 24 and 26 months of age in study V72P12E1.

Protection of trial subjects

Standard immunization practices should be observed and care should be taken to administer the injection intramuscularly. As with all injectable vaccines, appropriate medical treatment and supervision should be readily available in case of anaphylactic reactions following administration of the study vaccine, in accordance with local practice/guidelines such as epinephrine 1:1000 and diphenhydramine.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Nov 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 101

Country: Number of subjects enrolled

United Kingdom: 314

Country: Number of subjects enrolled

Czech Republic: 215

Country: Number of subjects enrolled

Italy: 175

Worldwide total number of subjects

805

EEA total number of subjects

805

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)

805

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects were enrolled from 4 centers in the UK; 4 centers in Italy; 4 centers in Spain; 19 centers in Czech Republic.

Screening details

All enrolled subjects were included in the trial.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

The trial was designed as an open-label study; all subjects scheduled to receive vaccination received MenB vaccine (rMenB+OMV NZ). The personnel analyzing the serum at the centralized laboratory were blinded to the study group of the subject.

Are arms mutually exclusive

Yes

B+R246_12_48

Arm description

Previously received rMenB+OMV NZ vaccine + routine vaccines at 2, 4 and 6 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 12 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B+R246_18_48

Arm description

Previously received rMenB+OMV NZ vaccine + routine vaccines at 2, 4 and 6 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 18 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B+R246_24_48

Arm description

Previously received rMenB+OMV NZ vaccine + routine vaccines at 2, 4 and 6 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 24 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B246_12_48

Arm description

Previously received 3 doses of rMenB+OMV NZ vaccine at 2, 4 and 6 months of age and routine vaccines at 3, 5 and 7 months of age, followed by a booster dose of rMenB+OMV NZ vaccine at 12 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B246_18_48

Arm description

Previously received 3 doses of rMenB+OMV NZ vaccine at 2, 4 and 6 months of age and routine vaccines at 3, 5 and 7 months of age, followed by a booster dose of rMenB+OMV NZ vaccine at 18 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B246_24_48

Arm description

Previously received 3 doses of rMenB+OMV NZ vaccine at 2, 4 and 6 months of age and routine vaccines at 3, 5 and 7 months of age, followed by a booster dose of rMenB+OMV NZ vaccine at 24 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B+R234_12_48

Arm description

Previously received rMenB+OMV NZ vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 12 months of age. All subjects received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B+R234_18_48

Arm description

Previously received rMenB+OMV NZ vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 18 months of age. All subjects received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B+R234_24_48

Arm description

Previously received rMenB+OMV NZ vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 24 months of age. All subjects received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B12 14_48

Arm description

Previously received two catch-up doses of rMenB+OMV NZ vaccine at 12 &14 months of age. All subjects received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B18 20_48

Arm description

Previously received two catch-up doses of rMenB+OMV NZ vaccine at 18 & 20 months of age. All subjects from this group received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B24 26_48

Arm description

Previously received two catch-up doses of rMenB+OMV NZ vaccine at 24 & 26 months of age. All subjects from this group received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

B48 50

Arm description

Newly recruited 4 year old naive subjects who received 2 catch-up doses of rMenB+OMV NZ vaccine, two months apart, in the present study.

Arm type

Experimental

Investigational medicinal product name

Novartis meningococcal B recombinant+ OMV NZ Vaccine

Investigational medicinal product code

rMenB+OMV NZ

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subject received one injection of a 0.5 mL dose.

Number of subjects in period 1	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B12 14_48	B18 20_48	B24 26_48	B48 50
Started	67	61	60	66	64	55	43	29	28	100	11	12	209
Completed	67	60	59	66	63	54	41	28	26	99	11	12	190
Not completed	0	1	1	0	1	1	2	1	2	1	0	0	19
Father in hospital	-	-	-	-	-	-	-	-	-	-	-	-	1
Consent withdrawn by subject	-	1	1	-	1	-	2	1	2	1	-	-	18
Lost to follow-up	-	-	-	-	-	1	-	-	-	-	-	-	-

Baseline characteristics

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Reporting group title

B+R246_12_48

Reporting group description

Reporting group title

B+R246_18_48

Reporting group description

Reporting group title

B+R246_24_48

Reporting group description

Reporting group title

B246_12_48

Reporting group description

Reporting group title

B246_18_48

Reporting group description

Reporting group title

B246_24_48

Reporting group description

Reporting group title

B+R234_12_48

Reporting group description

Reporting group title

B+R234_18_48

Reporting group description

Reporting group title

B+R234_24_48

Reporting group description

Reporting group title

B12 14_48

Reporting group description

Previously received two catch-up doses of rMenB+OMV NZ vaccine at 12 &14 months of age. All subjects received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Reporting group title

B18 20_48

Reporting group description

Reporting group title

B24 26_48

Reporting group description

Reporting group title

B48 50

Reporting group description

Newly recruited 4 year old naive subjects who received 2 catch-up doses of rMenB+OMV NZ vaccine, two months apart, in the present study.

Reporting group values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B12 14_48	B18 20_48	B24 26_48	B48 50	Total
Number of subjects	67	61	60	66	64	55	43	29	28	100	11	12	209	805
Age categorical
Units: Subjects
In utero														0
Preterm newborn infants (gestational age < 37 wks)														0
Newborns (0-27 days)														0
Infants and toddlers (28 days-23 months)														0
Children (2-11 years)														0
Adolescents (12-17 years)														0
Adults (18-64 years)														0
From 65-84 years														0
85 years and over														0
Age continuous
Analysis was done on the all enrolled population, ie, all subjects who have signed an informed consent, undergone screening procedure(s) and were randomized.
Units: months
arithmetic mean (standard deviation)	51.8 ± 3.4	52.1 ± 3.4	51.7 ± 3.5	51.7 ± 3.5	51.3 ± 3.7	52.3 ± 3.7	51.8 ± 3.4	51.4 ± 3.4	53.1 ± 3.5	51.7 ± 3.3	53.4 ± 4.3	56.8 ± 1.5	53.7 ± 3.6	-
Gender categorical
Analysis was done on the all enrolled set.
Units: Subjects
Female	23	28	33	28	32	30	24	17	13	50	6	4	99	387
Male	44	33	27	38	32	25	19	12	15	50	5	8	110	418

End points

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Reporting group title

B+R246_12_48

Reporting group description

Reporting group title

B+R246_18_48

Reporting group description

Reporting group title

B+R246_24_48

Reporting group description

Reporting group title

B246_12_48

Reporting group description

Reporting group title

B246_18_48

Reporting group description

Reporting group title

B246_24_48

Reporting group description

Reporting group title

B+R234_12_48

Reporting group description

Reporting group title

B+R234_18_48

Reporting group description

Reporting group title

B+R234_24_48

Reporting group description

Reporting group title

B12 14_48

Reporting group description

Previously received two catch-up doses of rMenB+OMV NZ vaccine at 12 &14 months of age. All subjects received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Reporting group title

B18 20_48

Reporting group description

Reporting group title

B24 26_48

Reporting group description

Reporting group title

B48 50

Reporting group description

Newly recruited 4 year old naive subjects who received 2 catch-up doses of rMenB+OMV NZ vaccine, two months apart, in the present study.

Primary: 1) Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules

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End point title

1) Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules ^[1] ^[2]

End point description

The antibody persistence at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the response in naïve children and reported as percentages of subjects with human serum bactericidal assay (hSBA) titers ≥1:5 and ≥1:8. Analysis was done on the Full Analysis set (FAS), Persistence, ie, all subjects in the enrolled population who provided at least one evaluable serum sample at baseline (visit 1).

End point type

Primary

End point timeframe

Day 1 (24-36 months post booster; baseline for naive)

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 endpoint.
[2] - 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: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B48 50
Number of subjects analysed	67	60	60	66	63	54	42	28	28	206
Units: Percentages of Subjects
number (confidence interval 95%)
H44/76 - ≥1:5; N=67,60,59,65,63,54,42,28,28,206	12 (5 to 22)	18 (10 to 30)	24 (14 to 37)	20 (11 to 32)	27 (17 to 40)	35 (23 to 49)	12 (4 to 26)	25 (11 to 45)	21 (8 to 41)	0 (0 to 3)
5/99 - ≥1:5; N=67,60,58,64,62,54,42,28,28,200	93 (83 to 98)	98 (91 to 100)	97 (88 to 100)	97 (89 to 100)	100 (94 to 100)	100 (93 to 100)	90 (77 to 97)	89 (72 to 98)	96 (82 to 100)	5 (2 to 8)
NZ 98/254 - ≥ 1:5	9 (3 to 18)	8 (3 to 18)	12 (5 to 23)	9 (3 to 19)	11 (5 to 22)	9 (3 to 20)	10 (3 to 23)	11 (2 to 28)	11 (2 to 28)	0 (0 to 3)
M10713 - ≥1:5; N=65,59,58,62,60,54,40,28,28,192	54 (41 to 66)	68 (54 to 79)	74 (61 to 85)	55 (42 to 68)	53 (40 to 66)	80 (66 to 89)	68 (51 to 81)	75 (55 to 89)	75 (55 to 89)	60 (53 to 67)
H44/76-≥1:8; N=67,60,59,65,63,54,42,28,28,206	7 (2 to 17)	10 (4 to 21)	17 (8 to 29)	11 (4 to 21)	24 (14 to 36)	28 (16 to 42)	7 (1 to 19)	21 (8 to 41)	21 (8 to 41)	0 (0 to 3)
5/99 - ≥1:8; N=67,60,58,64,62,54,42,28,28,200	91 (82 to 97)	97 (88 to 100)	93 (83 to 98)	94 (85 to 98)	94 (84 to 98)	100 (93 to 100)	90 (77 to 97)	86 (67 to 97)	96 (82 to 100)	3 (1 to 6)
NZ 98/254 - ≥ 1:8	4 (1 to 13)	5 (1 to 14)	8 (3 to 18)	8 (3 to 17)	3 (0 to 11)	4 (0 to 13)	2 (0.06 to 13)	7 (1 to 24)	11 (2 to 28)	0 (0 to 3)
M10713 - ≥1:8; N=65,59,58,62,60,54,40,28,28,192	49 (37 to 62)	53 (39 to 66)	60 (47 to 73)	48 (35 to 61)	45 (32 to 58)	65 (51 to 77)	60 (43 to 75)	61 (41 to 78)	61 (41 to 78)	56 (48 to 63)

No statistical analyses for this end point

Primary: 2) Persisting antibody titers in children (at 4 years of age), who had previously received three primary doses and one booster dose of rMenB+OMV NZ vaccine according to different schedules.

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End point title

2) Persisting antibody titers in children (at 4 years of age), who had previously received three primary doses and one booster dose of rMenB+OMV NZ vaccine according to different schedules. ^[3] ^[4]

End point description

The persisting antibody titers at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the titers in naive children and reported as geometric mean titers (GMTs). Analysis was done on FAS (Persistence).

End point type

Primary

End point timeframe

Day 1 (24-36 months post booster; baseline for naive)

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: No statistical analysis is associated to this endpoint.
[4] - 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: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B48 50
Number of subjects analysed	67	60	60	66	63	54	42	28	28	206
Units: Titers
geometric mean (confidence interval 95%)
H44/76; N=67,60,59,65,63,54,42,28,28,206	1.75 (1.36 to 2.25)	1.68 (1.29 to 2.19)	2.41 (1.83 to 3.19)	1.72 (1.29 to 2.29)	1.99 (1.49 to 2.65)	2.69 (1.96 to 3.7)	1.51 (1.04 to 2.18)	2.2 (1.38 to 3.49)	2.2 (1.37 to 3.53)	1.04 (1.01 to 1.07)
5/99; N=67,60,58,64,62,54,42,28,28,200	36 (27 to 48)	69 (50 to 94)	69 (50 to 96)	59 (45 to 78)	57 (43 to 75)	111 (82 to 151)	52 (34 to 81)	62 (36 to 108)	101 (57 to 177)	1.15 (1.05 to 1.27)
NZ 98/254	1.25 (1.03 to 1.52)	1.29 (1.05 to 1.59)	1.38 (1.11 to 1.72)	1.48 (1.2 to 1.83)	1.34 (1.08 to 1.66)	1.52 (1.2 to 1.92)	1.32 (1.05 to 1.65)	1.25 (0.94 to 1.66)	1.62 (1.21 to 2.16)	1.01 (0.99 to 1.03)
M10713; N=65,59,58,62,60,54,40,28,28,192	6.14 (4.19 to 8.99)	7.36 (4.94 to 11)	9.08 (5.97 to 14)	7.86 (5.17 to 12)	7.77 (5.07 to 12)	15 (9.49 to 24)	9.61 (5.81 to 16)	11 (5.92 to 20)	11 (5.9 to 21)	8.75 (6.74 to 11)

No statistical analyses for this end point

Primary: 3) Geometric mean ratio (GMR) in children (at 4 years of age) who had previously received three primary doses at 2, 4, 6 months of age and one booster dose of rMenB+OMV NZ vaccine according to different schedules

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End point title

3) Geometric mean ratio (GMR) in children (at 4 years of age) who had previously received three primary doses at 2, 4, 6 months of age and one booster dose of rMenB+OMV NZ vaccine according to different schedules ^[5] ^[6]

End point description

The geometric mean ratio (GMR) of GMTs (48 months/one month post booster vaccination) at 4 years of age in children who had previously received 3 primary doses at 2, 4, 6 months of age followed by a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is reported. GMTs against M10713 strain were not calculated for these groups in the parent study therefore the ratios cannot be available. Analysis was done on FAS (Persistence).

End point type

Primary

End point timeframe

Day 1 (24-36 months post booster dose; baseline for naive)

Notes
[5] - 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 endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48
Number of subjects analysed	63	57	54	59	56	47
Units: Ratio
geometric mean (confidence interval 95%)
H44/76; N=62,56,52,57,55,46,38,27,25,206	0.012 (0.0091 to 0.017)	0.013 (0.0096 to 0.018)	0.023 (0.016 to 0.033)	0.0092 (0.0066 to 0.013)	0.013 (0.0097 to 0.018)	0.023 (0.016 to 0.033)
5/99; N=61,57,50,57,55,44,37,27,25,200	0.029 (0.023 to 0.037)	0.032 (0.026 to 0.041)	0.043 (0.033 to 0.056)	0.031 (0.024 to 0.041)	0.034 (0.026 to 0.045)	0.054 (0.04 to 0.074)
NZ 98/254	0.028 (0.021 to 0.039)	0.094 (0.067 to 0.13)	0.071 (0.05 to 0.1)	0.043 (0.031 to 0.06)	0.081 (0.058 to 0.11)	0.11 (0.075 to 0.16)

No statistical analyses for this end point

Primary: 26) Geometric Mean Ratios (GMRs) in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses at 2, 3, 4 months of age and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules

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End point title

26) Geometric Mean Ratios (GMRs) in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses at 2, 3, 4 months of age and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules ^[7] ^[8]

End point description

The GMRs of GMTs (48 months/one month post booster vaccination) at 4 years of age in children who had previously received 3 primary doses at 2, 3, 4 months of age followed by a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is reported. Analysis was done on FAS (Persistence).

End point type

Primary

End point timeframe

Day 1 (24-36 months post booster dose; baseline for naive)

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 endpoint.
[8] - 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: No statistical analysis is associated to this endpoint.

End point values	B+R234_12_48	B+R234_18_48	B+R234_24_48
Number of subjects analysed	39	28	25
Units: Ratio
geometric mean (confidence interval 95%)
H44/76; N=38,27,25	0.0091 (0.0064 to 0.013)	0.023 (0.015 to 0.036)	0.023 (0.014 to 0.036)
5/99; N=37,27,25	0.035 (0.026 to 0.048)	0.037 (0.025 to 0.054)	0.055 (0.037 to 0.081)
NZ 98/254	0.03 (0.02 to 0.044)	0.082 (0.05 to 0.14)	0.066 (0.038 to 0.11)
M10713; N=26,24,25	0.67 (0.32 to 1.4)	0.91 (0.4 to 2.05)	0.47 (0.21 to 1.07)

No statistical analyses for this end point

Secondary: 4) Percentages of subjects with persisting serum bactericidal titers ≥1:5 and ≥1:8 (at 4 years of age), who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

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End point title

4) Percentages of subjects with persisting serum bactericidal titers ≥1:5 and ≥1:8 (at 4 years of age), who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules ^[9]

End point description

The antibody persistence in children at 4 year of age, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) according to different schedules is reported as number of subjects with hSBA titers ≥1:5 and hSBA titers ≥1:8. Analysis was done on FAS (Persistence).

End point type

Secondary

End point timeframe

Day 1 (22-34 months post last MenB vaccine)

Notes
[9] - 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: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48	B48 50
Number of subjects analysed	96	11	11	206
Units: Percentages of subjects
number (confidence interval 95%)
hSBA≥ 1:5 (H44/76 strain)	11 (6 to 20)	9 (0 to 41)	9 (0 to 41)	0 (0 to 3)
hSBA≥ 1:5 (5/99 strain; N=96,11,11,200)	84 (76 to 91)	100 (72 to 100)	100 (72 to 100)	5 (2 to 8)
hSBA≥ 1:5 (NZ 98/254 strain)	3 (1 to 9)	18 (2 to 52)	0 (0 to 28)	0 (0 to 3)
hSBA≥ 1:5 (M10713 strain; N=96,10,10,192)	59 (49 to 69)	60 (26 to 88)	60 (26 to 88)	60 (53 to 67)
hSBA≥ 1:8 (H44/76 strain)	8 (4 to 16)	9 (0 to 41)	0 (0 to 28)	0 (0 to 3)
hSBA≥ 1:8 (5/99 strain; N=96,11,11,200)	81 (72 to 88)	100 (72 to 100)	100 (72 to 100)	3 (1 to 6)
hSBA≥ 1:8 (NZ 98/254 strain)	2 (0 to 7)	18 (2 to 52)	0 (0 to 28)	0 (0 to 3)
hSBA≥ 1:8 (M10713 strain; N=96,10,10,192)	49 (39 to 59)	40 (12 to 74)	60 (26 to 88)	56 (48 to 63)

No statistical analyses for this end point

Secondary: 5) Persisting antibody titers in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

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End point title

5) Persisting antibody titers in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules ^[10]

End point description

The persisting GMTs in children at 4 years of age, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules are reported. Analysis was done on FAS (Persistence).

End point type

Secondary

End point timeframe

Day 1 (22-36 months post last MenB vaccine; baseline for naive)

Notes
[10] - 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: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48	B48 50
Number of subjects analysed	96	11	11	206
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain	1.61 (1.3 to 2)	2.03 (1.11 to 3.72)	1.69 (0.91 to 3.12)	1.04 (1.01 to 1.07)
5/99 strain; N=96, 11, 11, 200	23 (17 to 32)	47 (20 to 112)	69 (29 to 165)	1.15 (1.05 to 1.27)
NZ 98/254 strain	1.15 (0.96 to 1.37)	2.68 (1.65 to 4.36)	1.06 (0.65 to 1.75)	1.01 (0.99 to 1.03)
M10713 strain; N=96, 10, 10, 192	7.83 (5.54 to 11)	9.67 (3.54 to 26)	8.4 (3.03 to 23)	8.75 (6.74 to 11)

No statistical analyses for this end point

Secondary: 6) GMRs of GMTs in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

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End point title

6) GMRs of GMTs in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules ^[11]

End point description

The GMRs af GMTs (48 months/one month post last vaccination) in children at 4 years of age who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules. Analysis was done on FAS (Persistence).

End point type

Secondary

End point timeframe

Day 1 (22-36 months post last MenB vaccine)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48
Number of subjects analysed	88	9	10
Units: Ratio
geometric mean (confidence interval 95%)
H44/76 strain	0.092 (0.069 to 0.12)	0.18 (0.078 to 0.43)	0.2 (0.086 to 0.45)
5/99 strain	0.45 (0.34 to 0.59)	1.9 (0.84 to 4.29)	1.36 (0.62 to 3)
NZ 98/254 strain; N=88, 9, 8	0.28 (0.21 to 0.37)	0.73 (0.32 to 1.68)	0.42 (0.17 to 1.01)
M10713 strain; N=7, 7, 8	11 (3.34 to 38)	6.05 (1.45 to 25)	6.88 (1.68 to 28)

No statistical analyses for this end point

Secondary: 7) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a 5th dose of rMenB+OMV NZ vaccine (at 4 years of age) administered to children who had previously received 3 primary doses and a booster dose of the same vaccine

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End point title

7) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a 5th dose of rMenB+OMV NZ vaccine (at 4 years of age) administered to children who had previously received 3 primary doses and a booster dose of the same vaccine ^[12]

End point description

The percentages of subjects with hSBA titers ≥1:5 and ≥1:8, one month after a 5th dose of rMenB+OMV NZ vaccine was given children who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of the same vaccine according to different schedules is compared with the hSBA response of children who received first dose of rMenB+OMV NZ at 4 years of age. Analysis was done on FAS, Immunogenicity, ie, all subjects in the enrolled population who actually received a study vaccination, and provided at least one evaluable serum sample at post baseline.

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B48 50
Number of subjects analysed	26	18	16	16	26	15	40	26	26	175
Units: Percentages of subjects
geometric mean (confidence interval 95%)
H44/76 - ≥1:5; N=26,18,16,16,26,15,39,26,26,175	100 (87 to 100)	100 (81 to 100)	100 (79 to 100)	100 (79 to 100)	100 (87 to 100)	100 (78 to 100)	97 (87 to 100)	100 (87 to 100)	100 (87 to 100)	71 (64 to 78)
5/99 - ≥1:5; N=26,18,16,16,26,15,38,26,26,171	100 (87 to 100)	100 (81 to 100)	100 (79 to 100)	100 (79 to 100)	88 (70 to 98)	100 (78 to 100)	100 (91 to 100)	100 (87 to 100)	100 (87 to 100)	90 (85 to 94)
NZ 98/254 - ≥1:5; N=26,18,16,16,26,15,40,26,26,173	92 (75 to 99)	83 (59 to 96)	94 (70 to 100)	81 (54 to 96)	88 (70 to 98)	80 (52 to 96)	95 (83 to 99)	92 (75 to 99)	92 (75 to 99)	24 (18 to 31)
M10713 - ≥1:5; N=25,18,16,14,25,15,36,25,25,167	84 (64 to 95)	89 (65 to 99)	88 (62 to 98)	93 (66 to 100)	96 (80 to 100)	93 (68 to 100)	97 (85 to 100)	100 (86 to 100)	100 (86 to 100)	77 (70 to 83)
H44/76 - ≥1:8; N=26,18,16,16,26,15,39,26,26,175	96 (80 to 100)	100 (81 to 100)	100 (79 to 100)	100 (79 to 100)	96 (80 to 100)	100 (78 to 100)	97 (87 to 100)	100 (87 to 100)	96 (80 to 100)	63 (55 to 70)
5/99 - ≥1:8; N=26,18,16,16,26,15,38,26,26,171	100 (87 to 100)	100 (81 to 100)	100 (79 to 100)	100 (79 to 100)	100 (87 to 100)	100 (78 to 100)	100 (91 to 100)	100 (87 to 100)	100 (87 to 100)	87 (81 to 92)
NZ 98/254 - ≥1:8; N=26,18,16,16,26,15,40,26,26,173	85 (65 to 96)	61 (36 to 83)	81 (54 to 96)	75 (48 to 93)	88 (70 to 98)	80 (52 to 96)	88 (73 to 96)	81 (61 to 93)	88 (70 to 98)	17 (12 to 24)
M10713 - ≥1:8; N=25,18,16,14,25,15,36,25,25,167	76 (55 to 91)	89 (65 to 99)	88 (62 to 98)	93 (66 to 100)	96 (80 to 100)	93 (68 to 100)	97 (85 to 100)	100 (86 to 100)	96 (80 to 100)	74 (67 to 81)

No statistical analyses for this end point

Secondary: 8) GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age) in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules

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End point title

8) GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age) in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules ^[13]

End point description

The GMTs, at one month after a 5th dose of rMenB+OMV NZ vaccine in children who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules, are compared with the GMTs of children who received first dose of rMenB+OMV NZ at 4 years of age. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B48 50
Number of subjects analysed	26	18	16	16	26	15	40	26	26	175
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain; N=26,18,16,16,26,15,39,26,26,175	108 (70 to 168)	115 (68 to 195)	107 (61 to 188)	173 (98 to 303)	191 (123 to 297)	212 (199 to 379)	167 (109 to 258)	146 (85 to 251)	135 (78 to 235)	11 (8.51 to 14)
5/99 strain; N=26,18,16,16,26,15,38,26,26,171	754 (478 to 1190)	1719 (993 to 2976)	933 (518 to 1682)	1959 (1091 to 3517)	1387 (878 to 2191)	1954 (1068 to 3575)	1711 (1186 to 2470)	1239 (787 to 1953)	1280 (803 to 2041)	34 (27 to 42)
NZ 98/254 strain; N=26,18,16,16,26,15,40,26,26,173	22 (13 to 36)	11 (5.66 to 20)	28 (14 to 55)	16 (8.2 to 31)	21 (13 to 36)	15 (7.66 to 31)	26 (18 to 36)	18 (12 to 28)	27 (18 to 42)	2.25 (1.84 to 2.75)
M10713 strain; N=25,18,16,14,25,15,36,25,25,167	22 (13 to 37)	19 (10 to 36)	28 (14 to 54)	32 (16 to 65)	37 (22 to 63)	33 (17 to 64)	53 (40 to 71)	58 (40 to 84)	51 (35 to 73)	20 (15 to 25)

No statistical analyses for this end point

Secondary: 9) GMRs of GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules

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End point title

9) GMRs of GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules ^[14]

End point description

The GMRs of GMTs (one month post booster/48 months persistence), one month after a 5th dose of rMenB+OMV NZ vaccine in children who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules, are compared with the GMR (one month post 1 dose\baseline) of children who received first dose of rMenB+OMV NZ at 4 years of age. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B48 50
Number of subjects analysed	26	18	16	16	26	15	40	25	26	175
Units: Ratio
geometric mean (confidence interval 95%)
H44/76 strain; N=26,18,16,16,26,15,39,25,26,175	60 (40 to 92)	72 (44 to 120)	41 (24 to 71)	77 (45 to 132)	88 (58 to 134)	46 (26 to 80)	109 (71 to 167)	63 (37 to 108)	64 (37 to 110)	10 (8.2 to 13)
5/99 strain; N=26,18,16,15,25,15,38,25,26,168	32 (22 to 47)	23 (15 to 36)	15 (9.45 to 25)	30 (18 to 49)	20 (13 to 29)	18 (11 to 29)	33 (23 to 49)	20 (12 to 32)	12 (7.16 to 19)	29 (23 to 37)
NZ 98/254 strain; N=26,18,16,16,26,15,40,25,26,173	17 (10 to 29)	10 (5.43 to 19)	19 (9.54 to 37)	8.93 (4.75 to 17)	17 (10 to 29)	13 (6.48 to 26)	19 (14 to 27)	14 (9.35 to 22)	17 (11 to 26)	2.25 (1.84 to 2.75)
M10713 strain; N=24,17,16,12,23,15,35,24,25,158	3.15 (1.81 to 5.48)	4.46 (2.31 to 8.6)	3.36 (1.69 to 6.7)	3.49 (1.58 to 7.7)	3.74 (2.12 to 6.59)	4.21 (2.08 to 8.51)	5.35 (3.48 to 8.21)	3.86 (2.23 to 6.66)	4.04 (2.35 to 6.94)	2 (1.62 to 2.46)

No statistical analyses for this end point

Secondary: 10) Percentages of subjects with fourfold increase in hSBA titers after a 5th dose of rMenB+OMV NZ (at 4 years of age) was administered to children who previously received 3 primary and a booster dose of the same vaccine according to different schedules

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End point title

10) Percentages of subjects with fourfold increase in hSBA titers after a 5th dose of rMenB+OMV NZ (at 4 years of age) was administered to children who previously received 3 primary and a booster dose of the same vaccine according to different schedules ^[15]

End point description

The fourfold increase in hSBA titers, one month after a 5th dose of rMenB+OMV NZ vaccine was given to children who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules, is compared with the response in children who received the first dose of rMenB+OMV NZ vaccine at 4 years of age. Analysis was done on FAS, Immunogenicity.

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B48 50
Number of subjects analysed	26	18	16	16	26	15	40	25	26	175
Units: Percentages of subjects
number (confidence interval 95%)
H44/76 strain; N=26,18,16,16,26,15,39,25,26,175	92 (75 to 99)	100 (81 to 100)	100 (79 to 100)	100 (79 to 100)	96 (80 to 100)	93 (68 to 100)	97 (87 to 100)	96 (80 to 100)	96 (80 to 100)	63 (55 to 70)
5/99 strain; N=26,18,16,15,25,15,38,25,26,168	96 (80 to 100)	94 (73 to 100)	94 (70 to 100)	100 (78 to 100)	92 (74 to 99)	100 (78 to 100)	97 (86 to 100)	96 (80 to 100)	85 (65 to 96)	86 (80 to 91)
NZ 98/254 strain; N=26,18,16,16,26,15,40,25,26,173	81 (61 to 93)	61 (36 to 83)	81 (54 to 96)	69 (41 to 89)	88 (70 to 98)	73 (45 to 92)	88 (73 to 96)	72 (51 to 88)	85 (65 to 96)	17 (12 to 24)
M10713 strain; N=24,17,16,12,23,15,35,24,25,158	38 (19 to 59)	47 (23 to 72)	31 (11 to 59)	33 (10 to 65)	39 (20 to 61)	40 (16 to 68)	49 (31 to 66)	46 (26 to 67)	32 (15 to 54)	21 (15 to 28)

No statistical analyses for this end point

Secondary: 11) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a third dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who previously received 2 catch up doses of the same vaccine according to different schedules

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End point title

11) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a third dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who previously received 2 catch up doses of the same vaccine according to different schedules ^[16]

End point description

The percentages of subjects with hSBA titers ≥1:5 and hSBA titers ≥1:8 at one month after a third dose of rMenB+OMV NZ vaccine was given to children, who had previously received 2 catch up doses (at 12,14 or 18,20 or 24,26 months) of the same vaccine according to different schedules, are reported. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48	B48 50
Number of subjects analysed	97	10	12	175
Units: Percentages of subjects
number (confidence interval 95%)
hSBA≥ 1:5 (H44/76 strain)	100 (96 to 100)	100 (69 to 100)	100 (74 to 100)	71 (64 to 78)
hSBA≥ 1:5 (5/99 strain; N=94,10,12,171)	100 (96 to 100)	100 (69 to 100)	100 (74 to 100)	90 (85 to 94)
hSBA≥ 1:5 (NZ 98/254 strain; N=95,10,12,173)	96 (90 to 99)	70 (35 to 93)	100 (74 to 100)	24 (18 to 31)
hSBA≥ 1:5 (M10713 strain; N=90,9,10,167)	93 (86 to 98)	100 (66 to 100)	90 (55 to 100)	77 (70 to 83)
hSBA≥ 1:8 (H44/76 strain)	100 (96 to 100)	100 (69 to 100)	100 (74 to 100)	63 (55 to 70)
hSBA≥ 1:8 (5/99 strain; N=94,10,12,171)	100 (96 to 100)	100 (69 to 100)	100 (74 to 100)	87 (81 to 92)
hSBA≥ 1:8 (NZ 98/254 strain; N=95,10,12,173)	95 (88 to 98)	60 (26 to 88)	100 (74 to 100)	17 (12 to 24)
hSBA≥ 1:8 (M10713 strain; N=90,9,10,167)	92 (85 to 97)	100 (66 to 100)	90 (55 to 100)	74 (67 to 81)

No statistical analyses for this end point

Secondary: 12) GMTs Following a Third Dose of rMenB+OMV NZ Vaccine in Children (at 4 Years of Age) Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules

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End point title

12) GMTs Following a Third Dose of rMenB+OMV NZ Vaccine in Children (at 4 Years of Age) Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules ^[17]

End point description

The GMTs, one month following a third dose of rMenB+OMV NZ vaccine in 4 year old children who had previously received 2 catch up doses (at 12,14 or 18,20 or 24,26 months) of the same vaccine according to different schedules, are reported. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48	B48 50
Number of subjects analysed	97	10	12	175
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain	154 (124 to 191)	145 (76 to 277)	211 (116 to 383)	11 (8.51 to 14)
5/99 strain; N= 94,10,12,171	1575 (1219 to 2034)	2381 (1112 to 5095)	3604 (1785 to 7278)	34 (27 to 42)
NZ 98/254 strain; N=95,10,12,173	31 (25 to 39)	18 (8.87 to 35)	47 (25 to 88)	2.25 (1.84 to 2.75)
M10713 strain; N=90,9,10,167	38 (29 to 49)	74 (34 to 164)	84 (39 to 180)	20 (15 to 25)

No statistical analyses for this end point

Secondary: 13) GMRs of GMTs in Children Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules.

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End point title

13) GMRs of GMTs in Children Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules. ^[18]

End point description

The GMRs of GMTs following a third dose of rMenB+OMV NZ vaccine (one month post 3rd dose/persistence at 48 months) in children who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of the same vaccine according to different schedules are reported. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48	B48 50
Number of subjects analysed	95	10	11	175
Units: Ratio
geometric mean (confidence interval 95%)
H44/76 strain	99 (79 to 125)	67 (34 to 135)	133 (68 to 258)	10 (8.2 to 13)
5/99 strain; N=92,10,11,168	70 (57 to 86)	51 (27 to 95)	55 (30 to 99)	29 (23 to 37)
NZ 98/254 strain; N=93,10,11,173	27 (21 to 36)	5.96 (2.7 to 13)	38 (18 to 81)	2.25 (1.84 to 2.75)
M10713 strain; N=88,9,9,158	5.24 (3.91 to 7.02)	7.06 (2.92 to 17)	7.35 (3.03 to 18)	2 (1.62 to 2.46)

No statistical analyses for this end point

Secondary: 14) Percentages of Subjects With a 4-fold Increase in hSBA Titers Following a Third Dose of rMenB+OMV NZ Vaccine Given at 4 Years of Age to Children Who Previously Received 2 Catch up Doses of the Same Vaccine

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End point title

14) Percentages of Subjects With a 4-fold Increase in hSBA Titers Following a Third Dose of rMenB+OMV NZ Vaccine Given at 4 Years of Age to Children Who Previously Received 2 Catch up Doses of the Same Vaccine ^[19]

End point description

The percentage of subjects with a four-fold increase in hSBA titers following a third dose of rMenB+OMV NZ vaccine, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules,are reported. Fourfold increase is defined as- for subjects with a pre-vaccination titer <1:2 to a post-vaccination titer ≥1:8 and for subjects with a pre-vaccination titer ≥1:2 to a post-vaccination titer ≥ 4 fold pre-vaccination titer. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 31 (1 month post vaccination)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48	B48 50
Number of subjects analysed	95	10	11	175
Units: Percentages of subjects
number (confidence interval 95%)
H44/76 strain	99 (94 to 100)	90 (55 to 100)	100 (72 to 100)	63 (55 to 70)
5/99 strain; N=92,10,11,168	100 (96 to 100)	90 (55 to 100)	100 (72 to 100)	86 (80 to 91)
NZ 98/254 strain; N=93,10,11,173	94 (86 to 98)	50 (19 to 81)	100 (72 to 100)	17 (12 to 24)
M10713 strain; N=88,9,9,158	58 (47 to 68)	67 (30 to 93)	56 (21 to 86)	21 (15 to 28)

No statistical analyses for this end point

Secondary: 15) Percentages of Subjects With hSBA ≥1:5 and ≥1:8 in Response of Two Catch up Doses of rMenB+OMV NZ Vaccine When Administered to Children at 4 Years of Age

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End point title

15) Percentages of Subjects With hSBA ≥1:5 and ≥1:8 in Response of Two Catch up Doses of rMenB+OMV NZ Vaccine When Administered to Children at 4 Years of Age ^[20]

End point description

The sufficiency of immune response is reported in terms of percentages of subjects with hSBA ≥1:5 and ≥1:8 in response of two catch up doses of rMenB+OMV NZ vaccine, administered two months apart, in children at 4 years of age. Immune response was considered sufficient if the lower limit of the two-sided 95% CI for the percentage of subjects achieving hSBA ≥ 1:5 at one month after the two-dose series was > 70% for all three indicator (H44/76; 5/99 and NZ 98/254) strains. Immune sufficiency was not applicable for M10713 strain. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 91 (1 month post second vaccination)

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B48 50
Number of subjects analysed	175
Units: Percentages of subjects
number (confidence interval 95%)
hSBA≥ 1:5 (H44/76 strain)	100 (98 to 100)
hSBA≥ 1:5 (5/99 strain)	100 (98 to 100)
hSBA≥ 1:5 (NZ 98/254 strain; N=174)	91 (85 to 95)
hSBA≥ 1:8 (H44/76 strain)	100 (98 to 100)
hSBA≥ 1:8 (5/99 strain)	100 (98 to 100)
hSBA≥ 1:8 (NZ 98/254 strain; N=174)	80 (73 to 86)

No statistical analyses for this end point

Secondary: 16) GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

Top of page

End point title

16) GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age ^[21]

End point description

The GMTs in children who received two catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months of age are reported. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 91 (1 month post second vaccination)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B48 50
Number of subjects analysed	175
Units: Titers
geometric mean (confidence interval 95%)
H44/76 strain	109 (98 to 120)
5/99 strain	343 (302 to 389)
NZ 98/254 strain; N=174	17 (14 to 19)
M10713 strain; N=171	47 (40 to 56)

No statistical analyses for this end point

Secondary: 17) GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

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End point title

17) GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age ^[22]

End point description

The GMR of GMTs(one month post dose 2/baseline) in children following a two catch up dose of rMenB+OMV NZ at 48 and 50 months of age are reported. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 91 (1 month post second vaccination)

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B48 50
Number of subjects analysed	175
Units: Ratio
geometric mean (confidence interval 95%)
H44/76 strain	105 (94 to 116)
5/99 strain; N=172	299 (256 to 350)
NZ 98/254 strain; N=174	17 (14 to 19)
M10713 strain; N=171	5.12 (3.95 to 6.65)

No statistical analyses for this end point

Secondary: 18) Percentages of Subjects With 4-fold Increase in Serum Bactericidal Titers, Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

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End point title

18) Percentages of Subjects With 4-fold Increase in Serum Bactericidal Titers, Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age ^[23]

End point description

The percentages of subjects with 4-fold increase in hSBA titers, one month following a two catch up dose of rMenB+OMV NZ at 4 years of age are reported. Analysis was done on FAS (Immunogenicity).

End point type

Secondary

End point timeframe

Day 91 (1 month post second vaccination)

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B48 50
Number of subjects analysed	175
Units: Percentages of Subjects
number (confidence interval 95%)
H44/76 strain	100 (98 to 100)
5/99 strain; N=172	99 (97 to 100)
NZ 98/254 strain; N=174	80 (73 to 86)
M10713 strain; N=161	51 (43 to 59)

No statistical analyses for this end point

Secondary: 19) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

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End point title

19) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) ^[24]

End point description

The safety and tolerability of the 5th dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules in the earlier studies is reported as number of subjects with solicited local and systemic adverse events. Analysis was done on the safety population, ie, all subjects in the Exposed population who provided post vaccination and post-baseline safety data.

End point type

Secondary

End point timeframe

From day 1 to day 7 after vaccination

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48
Number of subjects analysed	29	20	17	19	27	17	43	29	27
Units: Number of subjects
Any local	27	18	17	16	24	17	38	28	27
Injection site Pain (mild)	4	5	1	6	5	2	4	6	7
Injection site Pain (moderate)	18	9	13	4	14	9	24	14	17
Injection site Pain (severe)	5	4	3	6	4	5	10	8	3
Injection site Erythema (25 - 50 mm)	2	3	3	5	6	3	5	6	5
Injection site Erythema (51 - 100 mm)	5	2	1	2	7	3	10	6	3
Injection site Erythema (>100 mm)	1	0	0	0	1	1	2	0	0
Injection site Induration (25 - 50 mm)	2	2	1	2	5	2	6	7	6
Injection site Induration (51 - 100 mm)	1	0	0	1	2	1	2	1	1
Injection site Induration (>100 mm)	1	0	0	0	0	1	1	0	0
Injection site Swelling (25 - 50 mm)	1	3	3	4	5	3	7	7	4
Injection site Swelling (51 - 100 mm)	1	0	1	2	3	2	7	5	1
Injection site Swelling (>100 mm)	1	0	0	0	0	1	1	0	0
Any Systemic	26	15	14	18	19	13	36	27	23
Change in eating habits	12	6	6	12	7	8	20	11	13
Rash	2	1	0	5	2	4	7	5	2
Arthralagia	12	4	6	9	8	5	11	8	12
Headache	5	1	6	3	2	3	7	5	8
Irritability	18	9	11	14	13	8	23	20	16
Diarrhea	4	1	1	2	4	2	6	4	3
Vomiting	0	1	0	0	1	0	5	3	2
Fever (≥ 38.0 °C)	6	3	3	2	1	1	5	4	2
Antipyretic used (prophylactically)	1	2	1	1	2	1	7	1	1
Antipyretic used (therapeutically)	5	5	4	3	3	1	10	4	3

No statistical analyses for this end point

Secondary: 20) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

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End point title

20) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) ^[25]

End point description

The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with solicited local and systemic adverse events. Analysis was done on the safety population.

End point type

Secondary

End point timeframe

From day 1 to day 7 after vaccination

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48
Number of subjects analysed	99	10	12
Units: Number of Subjects
Any local	94	9	11
Injection site Pain (mild)	33	2	2
Injection site Pain (moderate)	42	6	8
Injection site Pain (severe)	19	1	1
Injection site Erythema (25 - 50 mm)	12	2	0
Injection site Erythema (51 - 100 mm)	7	1	0
Injection site Erythema (>100 mm)	2	0	0
Injection site Induration (25 - 50 mm)	8	1	0
Injection site Induration (51 - 100 mm)	0	0	0
Injection site Induration (>100 mm)	1	0	0
Injection site Swelling (25 - 50 mm)	18	2	3
Injection site Swelling (51 - 100 mm)	2	0	1
Injection site Swelling (>100 mm)	0	0	0
Any Systemic	78	6	9
Change in eating habits	42	0	3
Rash	13	0	0
Arthralagia	28	1	6
Headache	20	2	4
Irritability	53	4	5
Diarrhea	5	0	2
Vomiting	6	2	1
Fever (≥ 38.0 °C)	16	4	5
Antipyretic used (prophylactically)	5	2	2
Antipyretic used (therapeutically)	18	4	5

No statistical analyses for this end point

Secondary: 21) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the first Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age

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End point title

21) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the first Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age ^[26]

End point description

The safety and tolerability of rMenB+OMV NZ vaccine in 4 year old children who received 2 catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months, is reported as number of subjects with solicited local and systemic adverse events after the first dose. Analysis was done on the safety population.

End point type

Secondary

End point timeframe

From day 1 to day 7 after first vaccination

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B48 50
Number of subjects analysed	205
Units: Number of Subjects
Any local	186
Injection site Pain (mild)	81
Injection site Pain (moderate)	77
Injection site Pain (severe)	27
Injection site Erythema (25 - 50 mm)	34
Injection site Erythema (51 - 100 mm)	8
Injection site Erythema (>100 mm)	1
Injection site Induration (25 - 50 mm)	23
Injection site Induration (51-100 mm)	3
Injection site Induration(>100 mm)	0
Injection site Swelling (25 - 50 mm)	26
Injection site Swelling (51 - 100 mm)	3
Injection site Swelling (>100 mm)	1
Any Systemic	137
Rash	15
Change in eating habits	49
Headache	25
Arthralagia	45
Irritability	67
Vomiting	8
Diarrhea	11
Fever (≥ 38.0 °C)	20
Antipyretic used (prophylactically)	17
Antipyretic used (therapeutically)	22

No statistical analyses for this end point

Secondary: 22) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the second Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age

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End point title

22) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the second Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age ^[27]

End point description

The safety and tolerability of rMenB+OMV NZ vaccine in 4 year old children who received 2 catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months, is reported as number of subjects with solicited local and systemic adverse events after the second dose. Analysis was done on the safety population.

End point type

Secondary

End point timeframe

From day 1 to day 7 after second vaccination

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B48 50
Number of subjects analysed	194
Units: Number of Subjects
Any local	161
Injection site Pain (mild)	70
Injection site Pain (moderate)	66
Injection site Pain (severe)	21
Injection site Erythema (25 - 50 mm)	15
Injection site Erythema (51 - 100 mm)	19
Injection site Erythema (>100 mm)	0
Injection site Induration (25 - 50 mm)	16
Injection site Induration (51-100 mm)	4
Injection site Induration(>100 mm)	0
Injection site Swelling (25 - 50 mm)	20
Injection site Swelling (51 - 100 mm)	4
Injection site Swelling (>100 mm)	0
Any Systemic	108
Rash	10
Change in eating habits	43
Headache	24
Arthralagia	40
Irritability	58
Vomiting	6
Diarrhea	8
Fever (≥ 38.0 °C)	16
Antipyretic used (prophylactically)	23
Antipyretic used (therapeutically)	24

No statistical analyses for this end point

Secondary: 23) Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Top of page

End point title

23) Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) ^[28]

End point description

The safety and tolerability of the 5th dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules in the earlier studies is reported as number of subjects with unsolicited AEs, Serious Adverse Events (SAE), AEs leading to premature withdrawal. Analysis was done on the safety population.

End point type

Secondary

End point timeframe

From day 1 to study termination

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B+R246_12_48	B+R246_18_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48
Number of subjects analysed	30	20	17	19	27	17	43	29	28
Units: Number of subjects
Any AEs	8	4	4	7	7	3	11	11	6
SAEs	0	0	0	0	0	0	0	0	0
AEs leading to withdrawal	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: 24) Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Top of page

End point title

24) Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) ^[29]

End point description

The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with Unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to premature withdrawal. Analysis was done on the safety population.

End point type

Secondary

End point timeframe

From day 1 to study termination

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B12 14_48	B18 20_48	B24 26_48
Number of subjects analysed	100	11	12
Units: Number of subjects
Any AE	25	2	4
SAEs	0	0	0
AEs leading to withdrawal	0	0	0

No statistical analyses for this end point

Secondary: 25) Number of Subjects Reporting Unsolicited AEs After Any Vaccination.

Top of page

End point title

25) Number of Subjects Reporting Unsolicited AEs After Any Vaccination. ^[30]

End point description

The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to premature withdrawal. Analysis was done on the safety population.

End point type

Secondary

End point timeframe

From day 1 to study termination

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	B48 50
Number of subjects analysed	206
Units: Number of subjects
Any AE	105
SAEs	3
AEs leading to premature withdrawal	1

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Solicited (systematic) local and systemic adverse events (AEs), unsolicited (non-systematic) AEs and med. attended fever were recorded during the 7 days after study vaccination. Serious adverse events (SAEs) were collected throughout the study period.

Adverse event reporting additional description

560 out of 805 enrolled subjects were exposed to study vaccination. Of these, 558 subjects were included in safety set.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

B+R246_18_48

Reporting group description

Reporting group title

B+R246_12_48

Reporting group description

Reporting group title

B+R246_24_48

Reporting group description

Reporting group title

B246_12_48

Reporting group description

Reporting group title

B246_18_48

Reporting group description

Reporting group title

B246_24_48

Reporting group description

Reporting group title

B+R234_12_48

Reporting group description

Previously received rMenB+OMV NZ vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 12months of age. All subjects received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Reporting group title

B+R234_18_48

Reporting group description

Reporting group title

B+R234_24_48

Reporting group description

Reporting group title

B12 14_48

Reporting group description

Previously received two catch-up doses of rMenB+OMV NZ vaccine at 12 &14 months of age. All subjects received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.

Reporting group title

B18 20_48

Reporting group description

Reporting group title

B24 26_48

Reporting group description

Reporting group title

B48 50

Reporting group description

Newly recruited 4 year old naive subjects who received 2 catch-up doses of rMenB+OMV NZ vaccine, two months apart, in the present study.

B+R246_18_48

B+R246_12_48

B+R246_24_48

B246_12_48

B246_18_48

B246_24_48

B+R234_12_48

B+R234_18_48

B+R234_24_48

B12 14_48

B18 20_48

B24 26_48

B48 50

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 20 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 27 (0.00%)

0 / 17 (0.00%)

0 / 43 (0.00%)

0 / 29 (0.00%)

0 / 28 (0.00%)

0 / 100 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

3 / 206 (1.46%)

number of deaths (all causes)

number of deaths resulting from adverse events

Injury, poisoning and procedural complications

Concussion

subjects affected / exposed

0 / 20 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 27 (0.00%)

0 / 17 (0.00%)

0 / 43 (0.00%)

0 / 29 (0.00%)

0 / 28 (0.00%)

0 / 100 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 206 (0.49%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Contusion

subjects affected / exposed

0 / 20 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 27 (0.00%)

0 / 17 (0.00%)

0 / 43 (0.00%)

0 / 29 (0.00%)

0 / 28 (0.00%)

0 / 100 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 206 (0.49%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Periorbital haematoma

subjects affected / exposed

0 / 20 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 27 (0.00%)

0 / 17 (0.00%)

0 / 43 (0.00%)

0 / 29 (0.00%)

0 / 28 (0.00%)

0 / 100 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 206 (0.49%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Croup infectious

subjects affected / exposed

0 / 20 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 27 (0.00%)

0 / 17 (0.00%)

0 / 43 (0.00%)

0 / 29 (0.00%)

0 / 28 (0.00%)

0 / 100 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 206 (0.49%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 20 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 27 (0.00%)

0 / 17 (0.00%)

0 / 43 (0.00%)

0 / 29 (0.00%)

0 / 28 (0.00%)

0 / 100 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 206 (0.49%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 20 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 27 (0.00%)

0 / 17 (0.00%)

0 / 43 (0.00%)

0 / 29 (0.00%)

0 / 28 (0.00%)

0 / 100 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

1 / 206 (0.49%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	B+R246_18_48	B+R246_12_48	B+R246_24_48	B246_12_48	B246_18_48	B246_24_48	B+R234_12_48	B+R234_18_48	B+R234_24_48	B12 14_48	B18 20_48	B24 26_48	B48 50
Total subjects affected by non serious adverse events
subjects affected / exposed	19 / 20 (95.00%)	29 / 30 (96.67%)	17 / 17 (100.00%)	18 / 19 (94.74%)	25 / 27 (92.59%)	17 / 17 (100.00%)	42 / 43 (97.67%)	28 / 29 (96.55%)	27 / 28 (96.43%)	97 / 100 (97.00%)	10 / 11 (90.91%)	12 / 12 (100.00%)	200 / 206 (97.09%)
Nervous system disorders
Somnolence
subjects affected / exposed	7 / 20 (35.00%)	18 / 30 (60.00%)	8 / 17 (47.06%)	9 / 19 (47.37%)	12 / 27 (44.44%)	6 / 17 (35.29%)	22 / 43 (51.16%)	21 / 29 (72.41%)	14 / 28 (50.00%)	52 / 100 (52.00%)	3 / 11 (27.27%)	3 / 12 (25.00%)	105 / 206 (50.97%)
occurrences all number	7	18	8	11	12	7	25	22	15	56	3	3	150
Headache
subjects affected / exposed	1 / 20 (5.00%)	5 / 30 (16.67%)	6 / 17 (35.29%)	3 / 19 (15.79%)	2 / 27 (7.41%)	3 / 17 (17.65%)	7 / 43 (16.28%)	5 / 29 (17.24%)	8 / 28 (28.57%)	20 / 100 (20.00%)	2 / 11 (18.18%)	4 / 12 (33.33%)	40 / 206 (19.42%)
occurrences all number	1	5	6	3	2	5	9	5	8	22	2	4	58
General disorders and administration site conditions
Injection site erythema
alternative assessment type: Systematic
subjects affected / exposed	13 / 20 (65.00%)	23 / 30 (76.67%)	13 / 17 (76.47%)	16 / 19 (84.21%)	21 / 27 (77.78%)	14 / 17 (82.35%)	38 / 43 (88.37%)	24 / 29 (82.76%)	23 / 28 (82.14%)	73 / 100 (73.00%)	8 / 11 (72.73%)	7 / 12 (58.33%)	166 / 206 (80.58%)
occurrences all number	13	23	13	17	23	15	40	24	23	75	8	7	268
Injection site induration
alternative assessment type: Systematic
subjects affected / exposed	8 / 20 (40.00%)	21 / 30 (70.00%)	11 / 17 (64.71%)	14 / 19 (73.68%)	11 / 27 (40.74%)	12 / 17 (70.59%)	24 / 43 (55.81%)	21 / 29 (72.41%)	19 / 28 (67.86%)	46 / 100 (46.00%)	6 / 11 (54.55%)	4 / 12 (33.33%)	117 / 206 (56.80%)
occurrences all number	8	24	11	16	11	12	25	23	21	48	7	4	185
Injection site pain
alternative assessment type: Systematic
subjects affected / exposed	19 / 20 (95.00%)	27 / 30 (90.00%)	17 / 17 (100.00%)	16 / 19 (84.21%)	23 / 27 (85.19%)	16 / 17 (94.12%)	38 / 43 (88.37%)	28 / 29 (96.55%)	27 / 28 (96.43%)	94 / 100 (94.00%)	9 / 11 (81.82%)	11 / 12 (91.67%)	192 / 206 (93.20%)
occurrences all number	19	29	17	16	26	16	40	30	30	97	9	11	354
Injection site swelling
alternative assessment type: Systematic
subjects affected / exposed	7 / 20 (35.00%)	12 / 30 (40.00%)	10 / 17 (58.82%)	13 / 19 (68.42%)	10 / 27 (37.04%)	11 / 17 (64.71%)	25 / 43 (58.14%)	17 / 29 (58.62%)	14 / 28 (50.00%)	46 / 100 (46.00%)	6 / 11 (54.55%)	7 / 12 (58.33%)	96 / 206 (46.60%)
occurrences all number	8	14	12	13	10	11	25	18	15	48	6	7	134
Pyrexia
alternative assessment type: Systematic
subjects affected / exposed	3 / 20 (15.00%)	7 / 30 (23.33%)	3 / 17 (17.65%)	2 / 19 (10.53%)	1 / 27 (3.70%)	1 / 17 (5.88%)	7 / 43 (16.28%)	4 / 29 (13.79%)	2 / 28 (7.14%)	19 / 100 (19.00%)	5 / 11 (45.45%)	5 / 12 (41.67%)	36 / 206 (17.48%)
occurrences all number	3	7	3	2	1	1	7	4	2	19	5	7	45
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 27 (0.00%)	1 / 17 (5.88%)	0 / 43 (0.00%)	0 / 29 (0.00%)	0 / 28 (0.00%)	1 / 100 (1.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 206 (0.49%)
occurrences all number	0	0	0	1	0	1	0	0	0	1	0	0	1
Diarrhoea
subjects affected / exposed	1 / 20 (5.00%)	4 / 30 (13.33%)	1 / 17 (5.88%)	2 / 19 (10.53%)	4 / 27 (14.81%)	2 / 17 (11.76%)	6 / 43 (13.95%)	4 / 29 (13.79%)	3 / 28 (10.71%)	5 / 100 (5.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	18 / 206 (8.74%)
occurrences all number	1	4	1	2	4	2	6	4	3	5	0	2	21
Vomiting
subjects affected / exposed	1 / 20 (5.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 27 (3.70%)	0 / 17 (0.00%)	5 / 43 (11.63%)	3 / 29 (10.34%)	2 / 28 (7.14%)	6 / 100 (6.00%)	2 / 11 (18.18%)	1 / 12 (8.33%)	15 / 206 (7.28%)
occurrences all number	1	0	0	0	1	0	7	3	2	6	2	1	16
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	2 / 19 (10.53%)	0 / 27 (0.00%)	0 / 17 (0.00%)	1 / 43 (2.33%)	0 / 29 (0.00%)	0 / 28 (0.00%)	1 / 100 (1.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	11 / 206 (5.34%)
occurrences all number	0	0	0	2	0	0	1	0	0	1	0	0	12
Rhinorrhoea
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 27 (0.00%)	0 / 17 (0.00%)	1 / 43 (2.33%)	0 / 29 (0.00%)	0 / 28 (0.00%)	0 / 100 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 206 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	0
Catarrh
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	0 / 29 (0.00%)	0 / 28 (0.00%)	0 / 100 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 206 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	1 / 17 (5.88%)	1 / 19 (5.26%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	0 / 29 (0.00%)	0 / 28 (0.00%)	0 / 100 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 206 (0.49%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	0	1
Pruritus
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	0 / 29 (0.00%)	0 / 28 (0.00%)	0 / 100 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 206 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0
Rash
alternative assessment type: Systematic
subjects affected / exposed	1 / 20 (5.00%)	2 / 30 (6.67%)	0 / 17 (0.00%)	5 / 19 (26.32%)	2 / 27 (7.41%)	4 / 17 (23.53%)	7 / 43 (16.28%)	5 / 29 (17.24%)	2 / 28 (7.14%)	13 / 100 (13.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	24 / 206 (11.65%)
occurrences all number	1	2	0	6	2	4	7	5	2	15	0	0	29
Psychiatric disorders
Eating disorders
subjects affected / exposed	6 / 20 (30.00%)	12 / 30 (40.00%)	6 / 17 (35.29%)	12 / 19 (63.16%)	7 / 27 (25.93%)	8 / 17 (47.06%)	20 / 43 (46.51%)	11 / 29 (37.93%)	13 / 28 (46.43%)	42 / 100 (42.00%)	0 / 11 (0.00%)	3 / 12 (25.00%)	75 / 206 (36.41%)
occurrences all number	7	12	6	12	7	9	23	12	14	43	0	3	97
Irritability
subjects affected / exposed	9 / 20 (45.00%)	18 / 30 (60.00%)	11 / 17 (64.71%)	14 / 19 (73.68%)	13 / 27 (48.15%)	8 / 17 (47.06%)	23 / 43 (53.49%)	20 / 29 (68.97%)	16 / 28 (57.14%)	53 / 100 (53.00%)	4 / 11 (36.36%)	5 / 12 (41.67%)	91 / 206 (44.17%)
occurrences all number	9	18	11	14	13	9	26	21	19	56	4	5	135
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	4 / 20 (20.00%)	12 / 30 (40.00%)	6 / 17 (35.29%)	9 / 19 (47.37%)	8 / 27 (29.63%)	5 / 17 (29.41%)	11 / 43 (25.58%)	8 / 29 (27.59%)	12 / 28 (42.86%)	28 / 100 (28.00%)	1 / 11 (9.09%)	6 / 12 (50.00%)	67 / 206 (32.52%)
occurrences all number	4	12	6	10	8	5	11	8	12	28	1	6	86
Infections and infestations
Acute tonsillitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	2 / 29 (6.90%)	0 / 28 (0.00%)	0 / 100 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 206 (0.49%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0	2
Ear infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 27 (0.00%)	1 / 17 (5.88%)	0 / 43 (0.00%)	0 / 29 (0.00%)	1 / 28 (3.57%)	3 / 100 (3.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	6 / 206 (2.91%)
occurrences all number	0	0	0	0	0	1	0	0	1	3	0	0	7
Erythema infectiosum
alternative assessment type: Systematic
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	0 / 29 (0.00%)	0 / 28 (0.00%)	0 / 100 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 206 (0.49%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	1
Gastroenteritis
subjects affected / exposed	0 / 20 (0.00%)	1 / 30 (3.33%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	0 / 29 (0.00%)	1 / 28 (3.57%)	0 / 100 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	2 / 206 (0.97%)
occurrences all number	0	2	0	0	0	0	0	0	1	0	1	0	2
Influenza
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 27 (0.00%)	1 / 17 (5.88%)	0 / 43 (0.00%)	0 / 29 (0.00%)	0 / 28 (0.00%)	0 / 100 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 206 (0.49%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1
Nasopharyngitis
alternative assessment type: Systematic
subjects affected / exposed	0 / 20 (0.00%)	1 / 30 (3.33%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	0 / 29 (0.00%)	0 / 28 (0.00%)	0 / 100 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	3 / 206 (1.46%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	3
Viral infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 27 (0.00%)	0 / 17 (0.00%)	0 / 43 (0.00%)	0 / 29 (0.00%)	1 / 28 (3.57%)	1 / 100 (1.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	3 / 206 (1.46%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	1	3

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

21 Aug 2012

1 - Modification of the inclusion criteria. 2 - Modification of the exclusion criteria to clarify the difference between exclusionary criteria and criteria that should be considered for delay of enrollment, vaccination, or blood sampling visits. 3 - Addition of missing abbreviations into the list. 4 - Editorial changes between: Exclusion Criteria, Vaccines Preparation and Administration, and Other Concomitant Treatment or Vaccines. Clarification of criteria for delay of subject enrollment, vaccination, and/or blood sampling visits under Exclusion Criteria. 5 - Addition and further clarification of missing collection time for immediate reactions post-vaccination for Group 7: Visit 1 and Visit 3. In addition, clarification of collections times for axillary body temperature, solicited local and systemic reactions. 6 - Correction of timing for reporting SAEs by investigator to the sponsor in compliance with EU directive. 7 - Standardizing visit window and clarification of visit window units as “days”.

12 Nov 2012

1 - Modifying the 4th secondary objective upon introducing criteria for measuring sufficiency of immune response after two-dose series of rMenB+OMV NZ. 2 - Increasing the number of subjects planned for enrollment in group B_48 50 and adjusting total number of subjects planned accordingly. 3 - Introducing an interim analysis for group B_48 50. 4 - Editorial changes in one of the vaccine preparation and administration steps to be in alignment with instructions listed in the Investigator’s Brochure (IB) and Summary of Product Characteristics (SmPC).

13 Mar 2013

1 - Add steps for collecting AEs related to study procedures (i.e. Blood draw) for subjects belonging to the non-vaccination subset#1 of groups 1 and 2, who are assigned to have a single blood draw visit. 2 - Clarify study visit windows.

14 Nov 2013

Definition of the End of Study in relation to the testing of the last biological sample collected from the study subjects.

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 3, Open Label, Multi-Center, Extension Study to Assess Antibody Persistence and Response to a Third or Fifth Dose of Novartis Meningococcal B Recombinant Vaccine in 4-Year-Old Children Who Previously Participated in Study V72P12E1

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1) Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules

Primary: 1) Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules

Primary: 2) Persisting antibody titers in children (at 4 years of age), who had previously received three primary doses and one booster dose of rMenB+OMV NZ vaccine according to different schedules.

Primary: 2) Persisting antibody titers in children (at 4 years of age), who had previously received three primary doses and one booster dose of rMenB+OMV NZ vaccine according to different schedules.

Primary: 3) Geometric mean ratio (GMR) in children (at 4 years of age) who had previously received three primary doses at 2, 4, 6 months of age and one booster dose of rMenB+OMV NZ vaccine according to different schedules

Primary: 3) Geometric mean ratio (GMR) in children (at 4 years of age) who had previously received three primary doses at 2, 4, 6 months of age and one booster dose of rMenB+OMV NZ vaccine according to different schedules

Primary: 26) Geometric Mean Ratios (GMRs) in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses at 2, 3, 4 months of age and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules

Primary: 26) Geometric Mean Ratios (GMRs) in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses at 2, 3, 4 months of age and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules

Secondary: 4) Percentages of subjects with persisting serum bactericidal titers ≥1:5 and ≥1:8 (at 4 years of age), who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

Secondary: 4) Percentages of subjects with persisting serum bactericidal titers ≥1:5 and ≥1:8 (at 4 years of age), who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

Secondary: 5) Persisting antibody titers in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

Secondary: 5) Persisting antibody titers in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

Secondary: 6) GMRs of GMTs in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

Secondary: 6) GMRs of GMTs in children (at 4 years of age) who had previously received two catch up doses of rMenB+OMV NZ vaccine according to different schedules

Secondary: 7) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a 5th dose of rMenB+OMV NZ vaccine (at 4 years of age) administered to children who had previously received 3 primary doses and a booster dose of the same vaccine

Secondary: 7) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a 5th dose of rMenB+OMV NZ vaccine (at 4 years of age) administered to children who had previously received 3 primary doses and a booster dose of the same vaccine

Secondary: 8) GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age) in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules

Secondary: 8) GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age) in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules

Secondary: 9) GMRs of GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules

Secondary: 9) GMRs of GMTs following a fifth dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who had previously received 3 primary doses and a booster dose of the same vaccine according to different schedules

Secondary: 10) Percentages of subjects with fourfold increase in hSBA titers after a 5th dose of rMenB+OMV NZ (at 4 years of age) was administered to children who previously received 3 primary and a booster dose of the same vaccine according to different schedules

Secondary: 10) Percentages of subjects with fourfold increase in hSBA titers after a 5th dose of rMenB+OMV NZ (at 4 years of age) was administered to children who previously received 3 primary and a booster dose of the same vaccine according to different schedules

Secondary: 11) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a third dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who previously received 2 catch up doses of the same vaccine according to different schedules

Secondary: 11) Percentages of subjects with hSBA titers ≥1:5 and ≥1:8 after a third dose of rMenB+OMV NZ vaccine (at 4 years of age), in children who previously received 2 catch up doses of the same vaccine according to different schedules

Secondary: 12) GMTs Following a Third Dose of rMenB+OMV NZ Vaccine in Children (at 4 Years of Age) Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules

Secondary: 12) GMTs Following a Third Dose of rMenB+OMV NZ Vaccine in Children (at 4 Years of Age) Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules

Secondary: 13) GMRs of GMTs in Children Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules.

Secondary: 13) GMRs of GMTs in Children Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules.

Secondary: 14) Percentages of Subjects With a 4-fold Increase in hSBA Titers Following a Third Dose of rMenB+OMV NZ Vaccine Given at 4 Years of Age to Children Who Previously Received 2 Catch up Doses of the Same Vaccine

Secondary: 14) Percentages of Subjects With a 4-fold Increase in hSBA Titers Following a Third Dose of rMenB+OMV NZ Vaccine Given at 4 Years of Age to Children Who Previously Received 2 Catch up Doses of the Same Vaccine

Secondary: 15) Percentages of Subjects With hSBA ≥1:5 and ≥1:8 in Response of Two Catch up Doses of rMenB+OMV NZ Vaccine When Administered to Children at 4 Years of Age

Secondary: 15) Percentages of Subjects With hSBA ≥1:5 and ≥1:8 in Response of Two Catch up Doses of rMenB+OMV NZ Vaccine When Administered to Children at 4 Years of Age

Secondary: 16) GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 16) GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 17) GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 17) GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 18) Percentages of Subjects With 4-fold Increase in Serum Bactericidal Titers, Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 18) Percentages of Subjects With 4-fold Increase in Serum Bactericidal Titers, Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 19) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 19) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 20) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 20) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 21) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the first Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 21) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the first Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 22) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the second Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 22) Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving the second Catch up Dose of rMenB+OMV NZ Vaccine at 4 Years of Age

Secondary: 23) Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 23) Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 24) Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 24) Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)

Secondary: 25) Number of Subjects Reporting Unsolicited AEs After Any Vaccination.

Secondary: 25) Number of Subjects Reporting Unsolicited AEs After Any Vaccination.

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 3, Open Label, Multi-Center, Extension Study to Assess Antibody Persistence and Response to a Third or Fifth Dose of Novartis Meningococcal B Recombinant Vaccine in 4-Year-Old Children Who Previously Participated in Study V72P12E1