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

• ClinicalTrials.gov Identifier: NCT03125616
• Recruitment Status: Completed
• First Posted: April 24, 2017
• Last Update Posted: December 1, 2020
• Sponsor: St George's, University of London
• Collaborators: GlaxoSmithKline; MeningitisNow; Public Health England
• Information provided by (Responsible Party): St George's, University of London

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prematurity; Vaccination; Meningococcal Disease	Biological: 4CMenB Vaccine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This will be an open label, phase IV study.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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.
• Actual Study Start Date: August 1, 2017
• Actual Primary Completion Date: September 2, 2019
• Actual Study Completion Date: August 28, 2020

Arms and Interventions

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 Name: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 4 months; Other Name: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 12 months; Other Name: 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 Name: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 3 months; Other Name: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 4 months; Other Name: Bexsero; Biological: 4CMenB Vaccine; The infants will receive an intramuscular injection of the 4CMenB vaccine at 12 months; Other Name: Bexsero

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 7 Weeks to 11 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United Kingdom

St Georges University Hospital NHS Foundation Trust

Tooting, London, United Kingdom, SW17 0QT

Sponsors and Collaborators

St George's, University of London

GlaxoSmithKline

MeningitisNow

Public Health England

Investigators

• Principal Investigator: Paul Heath, MBBS; St George's, University of London

More Information

Additional Information:

Meningococcal: the green book, chapter 22 

• Responsible Party: St George's, University of London
• ClinicalTrials.gov Identifier: NCT03125616
• Other Study ID Numbers: 16.0247; 2017-001487-38 ( EudraCT Number )
• First Posted: April 24, 2017
• Last Update Posted: December 1, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Individual participant data will not be shared with other researchers.

• 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

Keywords provided by St George's, University of London:

Prematurity; Vaccination

Additional relevant MeSH terms:

Meningococcal Infections; Premature Birth; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs