Men B vaccination in preterm infants: a comparison of two schedules

ISRCTN ISRCTN14943533
DOI https://doi.org/10.1186/ISRCTN14943533
EudraCT/CTIS number 2017-001487-38
Secondary identifying numbers CPMS: 34643
Submission date
31/07/2017
Registration date
10/07/2019
Last edited
20/04/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Meningitis (infection of the lining of the brain) and septicaemia (blood poisoning) have many causes; an important cause in the UK is a bacteria called Meningococcus. Vaccination protects against some forms of Meningococcus by encouraging the body to make antibody to the bacteria - a chemical which helps fight the bacteria if it is encountered. In the UK babies are vaccinated according to the same schedule whether they are born early (preterm) or on time, but there are concerns that preterm babies may not respond as strongly to their vaccinations - this may result in less protection. In 2015 a new vaccine, the Men B vaccine, was introduced. There have been no studies done to determine whether this will work as well in preterm babies compared with term babies. This study will compare responses made by babies who are vaccinated according to two different schedules. This could help doctors make decisions about what programme should be followed for preterm babies.

Who can participate?
Premature babies born before 35 weeks of pregnancy

What does the study involve?
Parents are approached about the study and provided with information. If parents wish their baby to take part in the study they are asked to sign a consent form. Babies are randomly allocated to receive their Men B vaccine (Bexsero) according to one of two schedules - they either receive two doses of Men B vaccine at 2 and 4 months or three doses of Men B vaccine at 2, 3 and 4 months alongside their routine vaccinations given according to the UK schedule. Parents are asked to complete a diary card for one week following each set of vaccinations. Blood sampling is performed at 5, 12 and 13 months. These blood samples are to measure the amount of antibody (a protein which fights infection) following Men B vaccination to compare the two schedules to see if one gives better protection to babies born preterm.

What are the possible benefits and risks of participating?
If, after the booster vaccination, the baby is found to have a low response to vaccination they are offered an additional booster vaccine. This study involves the administration of vaccines which are given as part of the routine vaccination schedule. Whilst all vaccinations carry a very small risk of adverse reactions this is not greater for those taking part in the study compared with those receiving the vaccinations as part of routine care and all vaccines given as part of the study are given by members of staff trained in vaccine administration and the management of adverse reactions. The study involves blood samples being obtained which can be associated with discomfort and bruising, but these samples will be collected by staff who are trained in obtaining blood samples from babies and local anaesthetic cream can be used for the blood sampling.

Where is the study run from?
1. St George’s Hospital (UK)
2. John Radcliffe Hospital (UK)
3. Churchill Hospital (UK)
4. Norfolk and Norwich University Hospital (UK)
5. Queen Alexandra Hospital (UK)
6. Southampton General Hospital (UK)
7. Royal Cornwall Hospital (UK)

When is the study starting and how long is it expected to run for?
June 2016 to March 2020

Who is funding the study?
1. GlaxoSmithKline
2. Meningitis Now

Who is the main contact?
1. Dr Anna Calvert
acalvert@sgul.ac.uk
2. Jennifer Stuart
jstuart@sgul.ac.uk

Contact information

Dr Anna Calvert
Scientific

St George’s, University of London
Cranmer Terrace
London
SW17 0RE
United Kingdom

ORCiD logoORCID ID 0000-0002-1922-6208
Phone +44 (0)2087253887
Email acalvert@sgul.ac.uk
Ms Jennifer Stuart
Scientific

Paediatric Infectious Diseases Research Team
St George's, University of London
Cranmer Terrace
Tooting
SW17 0RE
United Kingdom

Phone +44 (0)2087255382
Email jstuart@sgul.ac.uk

Study information

Study designRandomised; Interventional; Design type: Prevention, Vaccine
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typePrevention
Participant information sheet ISRCTN14943533_PIS_v2.0_04Dec2017.docx
Scientific titleBabies born Early Antibody Response to Men B vaccination: BEAR Men B
Study acronymBEAR Men B
Study objectivesTo investigate the antibody response in preterm infants to two different schedules of Men B vaccine.
Ethics approval(s)Approved 17/05/2017, Yorkshire & The Humber- Sheffield Research Ethics Committee (Room 001, Jarrow Business Centre, Rolling Mill Road, Jarrow, Tyne and Wear, NE32 3DT, UK; Tel: +44 (0)207 1048082; Email: nrescommittee.yorkandhumber-sheffield@nhs.net), ref: 17/YH/0150
Health condition(s) or problem(s) studiedMeningitis
InterventionBabies will be randomised in a 1:1 ratio to receive two doses (at 2 and 4 months) or three doses (at 2, 3 and 4 months) of Men B vaccine (Bexsero) in their primary vaccination series. All babies will receive their other routine vaccinations according to the UK schedule which will include a booster dose of Men B vaccine (Bexsero) at the age of 12 months.
Intervention typeBiological/Vaccine
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)
Primary outcome measureAntibody response to Men B vaccination assessed using serum bactericidal antibody (SBA) assays performed on samples collected at 5 months (post primary), 12 months (pre-booster) and 13 months (post booster):
1. hSBA GMTs 1 month after completion of primary immunisations for relevant Bexsero antigens: fHbp, NadA and PorA
2. hSBA proportions ≥1:4, at 1 month after completion of primary immunisations for relevant Bexsero antigens: fHbp, NadA and PorA
Secondary outcome measuresLocal and systemic effects of the vaccine collected using a diary card completed for the 7 days following each set of vaccinations:
1. The percentage of infants presenting with fever, local reactions and non-febrile systemic reactions within the 7 days following each Bexsero® vaccine dose
2. The percentage of inpatients who have a change/deterioration in cardiorespiratory status within the 72 hours following each Bexsero® vaccine dose
3. The percentage of infants investigated for sepsis and commenced on antibiotics within 7 days of Bexsero® vaccination

4. hSBA GMTs at 12 months of chronological age (pre booster) for relevant Bexsero® antigens: fHbp, NadA and PorA
5. hSBA proportions ≥1:4, at 12 months of chronological age (pre booster) for relevant Bexsero® antigens: fHbp, NadA and PorA
6. hSBA GMTs at 13 months of chronological age (4-6 weeks post booster) for relevant Bexsero® antigens: fHbp, NadA and PorA
7. hSBA proportions ≥1:4, at 13 months of age (post booster) for relevant Bexsero® antigens: fHbp, NadA and PorA
Overall study start date01/06/2016
Completion date01/03/2020

Eligibility

Participant type(s)Patient
Age groupNeonate
SexBoth
Target number of participantsPlanned Sample Size: 132; UK Sample Size: 132
Key inclusion criteria1. Premature infant born at <35 weeks gestation
2. No contraindications to vaccination according to the ‘Green Book’
3. Willing and able to comply with study procedures
4. Written informed consent
Key exclusion criteria1. Contraindication to vaccination according to the Green Book
2. Life-limiting congenital abnormality or condition
3. Prior diagnosis of an immunodeficiency syndrome
4. Considered unlikely to complete expected follow up until the end of the study
Date of first enrolment01/08/2017
Date of final enrolment01/10/2018

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centres

St George’s Hospital
Blackshaw Road
Tooting
SW17 0QT
United Kingdom
John Radcliffe Hospital
Headley Way
Headington
OX3 9DU
United Kingdom
Centre for Clinical Vaccinology and Tropical Medicine
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
Norfolk and Norwich University Hospital
Colney Lane
Colney
NR4 7UY
United Kingdom
Queen Alexandra Hospital
Cosham
Portsmouth
PO6 3LY
United Kingdom
Southampton General Hospital
Tremona Rd
Southampton
SO16 6YD
United Kingdom
Royal Cornwall Hospital
Treliske
Truro
TR1 3LQ
United Kingdom

Sponsor information

St George's, University of London
Hospital/treatment centre

c/o Mr Subhir Bedi
Cranmer Terrace
London
SW17 0RE
England
United Kingdom

ROR logo "ROR" https://ror.org/040f08y74

Funders

Funder type

Government

GlaxoSmithKline
Government organisation / For-profit companies (industry)
Alternative name(s)
GlaxoSmithKline plc., GSK plc., GSK
Location
United Kingdom
Meningitis Now
Government organisation / Trusts, charities, foundations (both public and private)
Location
United Kingdom

Results and Publications

Intention to publish date01/06/2021
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planThe researchers intend to publish in a high-impact peer reviewed journal by early 2021.
IPD sharing planThe data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Participant information sheet version v2.0 04/12/2017 10/07/2019 No Yes
Protocol file version V2.1 02/08/2018 10/07/2019 No No
HRA research summary 28/06/2023 No No

Additional files

ISRCTN14943533_PROTOCOL_V2.1_02Aug2018.docx
Uploaded 10/07/2019
ISRCTN14943533_PIS_v2.0_04Dec2017.docx
Uploaded 10/07/2019

Editorial Notes

20/04/2021: The intention to publish date was changed from 01/03/2021 to 01/06/2021.
10/07/2019: Uploaded protocol Version V2.1, 02 August 2018 (not peer reviewed). The participant information sheet has been uploaded.
31/07/2017: Trial's existence confirmed by the NIHR.