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Clinical Trial Results:
Babies born Early Antibody Response to Men B vaccination: BEAR Men B

Summary
EudraCT number	2017-001487-38
Trial protocol	GB
Global end of trial date	28 Aug 2020

Results information
Results version number	v1(current)
This version publication date	24 Feb 2023
First version publication date	24 Feb 2023
Other versions
Summary report(s)	Final report Bear Men B

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

16.0247

ISRCTN number

US NCT number

NCT03125616

WHO universal trial number (UTN)

Sponsor organisation name

St George's University of London

Sponsor organisation address

Cranmer Terrace , London, United Kingdom,

Public contact

Paul Heath , St George's, University of London, pheath@sgul.ac.uk

Scientific contact

Paul Heath, St George's, University of London, pheath@sgul.ac.uk

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?

Analysis stage

Final

Date of interim/final analysis

26 Aug 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

28 Aug 2020

Global end of trial reached?

Yes

Global end of trial date

28 Aug 2020

Was the trial ended prematurely?

Main objective of the trial

To compare the immune responses of infants born prematurely to Men B vaccination after two primary doses at 2 and 4 months of age compared with three primary doses at 2, 3 and 4 months of age.

Protection of trial subjects

Anaesthetic instructions given to participants for the injection site to minimise distress.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Jul 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 136

Worldwide total number of subjects

136

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

136

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 145 babies were recruited into the study

Screening details

Screening identified 392 potentially eligible participants, of whom 247 were excluded. A total of 145 babies were recruited into the study

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Control

Arm description

Arm type

Control

Investigational medicinal product name

Bexsero

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Injection

Dosage and administration details

One dose (0.5 ml) given at 2,4 and 12 months of age

Trial arm

Arm description

Arm type

Experimental

Investigational medicinal product name

Bexsero

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Injection

Dosage and administration details

One dose (0.5 ml) given at 2, 3, 4 and 12 months of age

Number of subjects in period 1	Control	Trial arm
Started	67	69
Completed	64	68
Not completed	3	1
Adverse event, serious fatal	2	-
Consent withdrawn by subject	1	1

Baseline characteristics

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End points

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Reporting group title

Control

Reporting group description

Reporting group title

Trial arm

Reporting group description

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

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End point title

hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

End point description

End point type

Primary

End point timeframe

1 month

End point values	Control	Trial arm
Number of subjects analysed	64	68
Units: Geometric Mean Titre (GMT)
geometric mean (confidence interval 95%)	40.5 (31.2 to 52.6)	27.7 (20.4 to 37.7)

Attachments

All results

fHbp

Comparison groups

Control v Trial arm

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.13

Method

Kruskal-wallis

Confidence interval

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Top of page

End point title

hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: NadA

End point description

End point type

Primary

End point timeframe

1 month

End point values	Control	Trial arm
Number of subjects analysed	64	68
Units: Geometric Mean Titre (GMT)
geometric mean (confidence interval 95%)	481.1 (387.6 to 597.6)	603.7 (509.8 to 715.5)

NadA

Comparison groups

Trial arm v Control

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.19

Method

Kruskal-wallis

Confidence interval

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Top of page

End point title

hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: PorA

End point description

End point type

Primary

End point timeframe

1 month

End point values	Control	Trial arm
Number of subjects analysed	64	68
Units: Geometric Mean Titre (GMT)
geometric mean (confidence interval 95%)	8.7 (5.9 to 12.9)	11.1 (8.4 to 14.8)

PorA

Comparison groups

Control v Trial arm

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4

Method

Kruskal-wallis

Confidence interval

Primary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Top of page

End point title

hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

End point description

End point type

Primary

End point timeframe

1 month

End point values	Control	Trial arm
Number of subjects analysed	64	68
Units: Percentage
geometric mean (confidence interval 95%)	98 (90 to 100)	94 (85 to 98)

fHbp

Comparison groups

Control v Trial arm

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.37

Method

Fisher exact

Confidence interval

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: NadA

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End point title

hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: NadA

End point description

End point type

Secondary

End point timeframe

1 month

End point values	Control	Trial arm
Number of subjects analysed	64	68
Units: percentage
geometric mean (confidence interval 95%)	100 (94 to 100)	100 (94 to 100)

No statistical analyses for this end point

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Top of page

End point title

hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: PorA

End point description

End point type

Secondary

End point timeframe

1 month

End point values	Control	Trial arm
Number of subjects analysed	64	68
Units: Percentage
geometric mean (confidence interval 95%)	70 (70 to 70)	87 (87 to 87)

PorA

Comparison groups

Control v Trial arm

Number of subjects included in analysis

132

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Fisher exact

Confidence interval

Adverse events

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Timeframe for reporting adverse events

28 days

Assessment type

Systematic

Dictionary name

DAIDS

Dictionary version

2.1

Reporting group title

Control

Reporting group description

Reporting group title

Trial arm

Reporting group description

Serious adverse events	Control	Trial arm
Total subjects affected by serious adverse events
subjects affected / exposed	49 / 67 (73.13%)	51 / 69 (73.91%)
number of deaths (all causes)	2	1
number of deaths resulting from adverse events	1	0
Cardiac disorders
Hypertension
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Patent Ductus Arteriosus ligation
subjects affected / exposed	0 / 67 (0.00%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 67 (0.00%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Collapse
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
post haemorrhagic hydrocephalus
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infantile spasms
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sleepy
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Elective admission for vaccination following previous instability
subjects affected / exposed	1 / 67 (1.49%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Retinopathy of Prematurity
subjects affected / exposed	1 / 67 (1.49%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	2 / 67 (2.99%)	3 / 69 (4.35%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 67 (2.99%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Choking
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 67 (1.49%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastro-oesophageal reflux disease
subjects affected / exposed	0 / 67 (0.00%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 67 (0.00%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Poor feeding infant
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileostomy
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Bronchiolitis
subjects affected / exposed	14 / 67 (20.90%)	5 / 69 (7.25%)
occurrences causally related to treatment / all	0 / 14	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 1
Respiratory distress
subjects affected / exposed	5 / 67 (7.46%)	6 / 69 (8.70%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	2 / 67 (2.99%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Refractory respiratory failure
subjects affected / exposed	1 / 67 (1.49%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Apnoea
subjects affected / exposed	4 / 67 (5.97%)	3 / 69 (4.35%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Increased work of breathing
subjects affected / exposed	1 / 67 (1.49%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Stridor
subjects affected / exposed	1 / 67 (1.49%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cough
subjects affected / exposed	0 / 67 (0.00%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheostomy formation
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Increased oxygen requirements
subjects affected / exposed	0 / 67 (0.00%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 67 (0.00%)	2 / 69 (2.90%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Neuromuscular weakness
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
coryzal
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	2 / 67 (2.99%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vaccination reaction causing fever
subjects affected / exposed	1 / 67 (1.49%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Groin swelling
subjects affected / exposed	0 / 67 (0.00%)	1 / 69 (1.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
cow milk intolerancia
subjects affected / exposed	1 / 67 (1.49%)	0 / 69 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Control	Trial arm
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 67 (1.49%)	9 / 69 (13.04%)
Infections and infestations
Fever
subjects affected / exposed	1 / 67 (1.49%)	9 / 69 (13.04%)
occurrences all number	1	9

More information

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Were there any global substantial amendments to the protocol? Yes

15 Aug 2019

Respective SmPC for NIMPs updates: Prevenar 13 suspension for injection updated 01-May-2019; Rotarix Oral Applicator updated 03-Apr-2019; Priorix updated 24-Jan-2019; Menitorix updated 08-Mar-2016 Respective SmPC for NIMPs addition of Infanrix hexa, Powder and suspension for suspension for injection 15-Feb-2019 to substitute INFANRIX-IPV+Hib 25-Apr-2017 Protocol changes: primarily the study completion date for March 2020 BearMenB Protocol version 2.1, 2nd Aug 2018 TC BearMenB Protocol version 2.1, 2nd Aug 2018 Sponsor Contact Details: Change Debbie Rolfe [Regulatory Assurance Manager] to Subhir Bedi [Head of Research Governance and Delivery] We would like to inform the removal of the non-IMP Pediacel syringe 19th Feb 2017 from the study.

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.

N/A

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Clinical trials

Clinical Trial Results:
Babies born Early Antibody Response to Men B vaccination: BEAR Men B

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Primary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Primary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Babies born Early Antibody Response to Men B vaccination: BEAR Men B

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Primary: hSBA GMTs one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Primary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Primary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: fHbp

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: NadA

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Secondary: hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB antigens: PorA

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Babies born Early Antibody Response to Men B vaccination: BEAR Men B