Babies Born Early Antibody Response to Men B Vaccination: BEAR Men B (BEAR Men B)

Babies Born Early Antibody Response to Men B Vaccination: A Phase IV Multicentre Randomised Study to Evaluate the Primary and Booster Immune Responses in UK Preterm Infants Receiving Routine Immunisations and Incorporating a Three Dose Versus a Two Dose Schedule of 4CMenB (Bexsero®) for Primary Immunisation.

In the UK, babies receive their vaccinations according to a standard schedule, irrespective of their gestation at birth. This policy is designed so that all babies are protected as early as possible from vaccine preventable diseases such as polio, diphtheria, tetanus, rotavirus, pertussis (whooping cough), Haemophilus influenzae type B, pneumococcal disease and now meningococcal B disease. The 4CMenB vaccination (Bexsero®) was added to the UK schedule in September 2015 and there has been no research looking at whether the vaccine gives the same protection to babies born early as it does to those born at term. The Investigators want to compare two different schedules of 4CMenB and see if one gives better protection to babies born prematurely. It is possible that an extra 4CMenB dose (i.e. three doses in early infancy instead of two) will offer better protection for premature babies. This is what the Investigators are trying to find out through this study.

Study Overview

• Status: Completed
• Conditions: Prematurity; Meningococcal Disease; Vaccination
• Intervention / Treatment: Biological: 4CMenB Vaccine; Biological: 4CMenB Vaccine; Biological: 4CMenB Vaccine; Biological: 4CMenB Vaccine

Detailed Description

This will be an open label, phase IV study. After appropriate consent, 132 premature infants born at <35 weeks gestation (i.e. up to 34 weeks and 6 days), 50% <30 weeks gestation (i.e. up to 29 weeks and 6 days) will be randomised to 1 of 2 4CMen B schedules either at 2,4 and 12 months or 2,3,4 and 12 months. Babies will remain in the study for around 12 months, from recruitment to 13 months of age. All visits can be performed at the participant's home or in clinic, depending on the preference of the parents and study team.

Blood samples will be obtained at 5 months of age (post primary sample), 12 months (persistence sample) and 13 months (post booster sample). Reactogenicity and safety will be assessed by caregiver completion of a 7-day diary after each vaccine dose. Inpatients will be monitored for cardiorespiratory events for 72 hours after vaccination by healthcare staff and this information will be collected on the CRF. This will include details of oxygen saturations, heart rate, respiratory rate and details of any episodes of desaturation, bradycardia or apnoea. Particular emphasis will be placed on rates, timing and intensity of fever and other adverse reactions in the first 24 hours after vaccination, because this remains a cause of great concern amongst neonatologists.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London
    • Tooting, London, United Kingdom, SW17 0QT
      • St Georges University Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Premature infant born at <35 weeks gestation
• No contraindications to vaccination according to the 'Green Book'
• Willing and able to comply with study procedures
• Written informed consent

Exclusion Criteria:

• Contraindication to vaccination according to the Green Book
• Life-limiting congenital abnormality or condition
• Prior diagnosis of an immunodeficiency syndrome
• Considered unlikely to complete expected follow up until the end of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard UK 4CMenB vaccine; 4CMenB (Bexsero®) vaccination at 2 and 4 months and a booster at 12 months .	Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 2 months; Other Names: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 3 months; Other Names: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 4 months; Other Names: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 12 months; Other Names: Bexsero
Experimental: Additional 4CMenB Vaccine; 4CMenB (Bexsero®) vaccination at 2, 3 and 4 months and a booster at 12 months.	Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 2 months; Other Names: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 3 months; Other Names: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 4 months; Other Names: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 12 months; Other Names: Bexsero

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hSBA GMT	hSBA GMT one month after completing primary immunisations for relevant 4CMenB (Bexsero®) antigens: fHbp, NadA and PorA	Tested in each infant at 5 months of age (1 month after completion of primary vaccinations)
hSBA proportions	hSBA proportions ≥ 1:4, one month after completing primary immunisations for relevant 4CMenB (Bexsero®) antigens: fHbp, NadA and PorA.	Tested in each infant at 5 months of age (1 month after completion of primary vaccinations)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactions within 7 days	The percentage of infants experiencing fever, local reactions and non-febrile systemic reactions within the 7 days following each vaccine dose	Assessed in each infant for the 7 days following vaccination
Cardiorespiratory status for 72 hours following vaccination	The percentage of inpatients experiencing change / deterioration in cardiorespiratory status within the 72 hours following each vaccine dose	Assessed in all infants in hospital for 72 hours following vaccination
Suspicion of sepsis in 7 days following vaccination	The percentage of infants investigated for sepsis and commenced on antibiotics within 7 days of vaccination	Assessed in all infants in the 7 days following vaccination
Fever and/or suspicion of sepsis in the 28 days following vaccination	The percentage of infants who experience fever and/or are investigated for sepsis and commenced on antibiotics within 28 days of vaccination	Assessed in all infants in the 28 days following vaccination
Serious adverse events	The percentage of infants who experience a serious adverse event at any point within the study	Assessed in all infants at the conclusion of the study
Persistence of hSBA GMTs	hSBA GMTs at 12 months of age (pre booster) for relevant 4CMenB (Bexsero®) antigens: fHbp, NadA and PorA	Assessed in all infants at 12 months of age
Persistence of hSBA proportions ≥1:4	hSBA proportions ≥1:4, at 12 months of age (pre booster) for relevant 4CMenB (Bexsero®) antigens: fHbp, NadA and PorA	Assessed in all infants at 12 months of age
Booster response: hSBA GMTs	hSBA GMTs at 13 months of age (post booster) for relevant 4CMenB (Bexsero®) antigens: fHbp, NadA and PorA;	Assessed in all infants at 13 months of age
Booster response: hSBA proportions ≥1:4	hSBA proportions ≥1:4, at 13 months of age (post booster) for relevant 4CMenB (Bexsero®) antigens: fHbp, NadA and PorA.	Assessed in all infants at 13 months of age

Collaborators and Investigators

• Sponsor: St George's, University of London
• Collaborators: GlaxoSmithKline; Public Health England; MeningitisNow
• Investigators: Principal Investigator: Paul Heath, MBBS, St George's, University of London

Publications and helpful links

Helpful Links

• Meningococcal: the green book, chapter 22

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): September 2, 2019
• Study Completion (Actual): August 28, 2020

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 30, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Vaccination; Prematurity
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Neisseriaceae Infections; Premature Birth; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 16.0247; 2017-001487-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Individual participant data will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No