Clinical trial NCT03125616: Babies Born Early Antibody Response to Men B Vaccination: BEAR Men B
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prematurity
Vaccination
Meningococcal Disease
Keywords: Prematurity
Vaccination
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: MeningitisNow
name: Public Health England
First posted: 2017-04-24
Enrollment: 136
Sex: ALL
Minimum age (years): 7
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be an open label, phase IV study.
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: hSBA GMT
timeFrame: Tested in each infant at 5 months of age (1 month after completion of primary vaccinations)
measure: hSBA proportions
timeFrame: Tested in each infant at 5 months of age (1 month after completion of primary vaccinations)
Secondary outcomes:
measure: Reactions within 7 days
timeFrame: Assessed in each infant for the 7 days following vaccination
measure: Cardiorespiratory status for 72 hours following vaccination
timeFrame: Assessed in all infants in hospital for 72 hours following vaccination
measure: Suspicion of sepsis in 7 days following vaccination
timeFrame: Assessed in all infants in the 7 days following vaccination
measure: Fever and/or suspicion of sepsis in the 28 days following vaccination
timeFrame: Assessed in all infants in the 28 days following vaccination
measure: Serious adverse events
timeFrame: Assessed in all infants at the conclusion of the study
measure: Persistence of hSBA GMTs
timeFrame: Assessed in all infants at 12 months of age
measure: Persistence of hSBA proportions ≥1:4
timeFrame: Assessed in all infants at 12 months of age
measure: Booster response: hSBA GMTs
timeFrame: Assessed in all infants at 13 months of age
measure: Booster response: hSBA proportions ≥1:4
timeFrame: Assessed in all infants at 13 months of age
Other outcomes:
Locations:
city: Tooting
country: United Kingdom
facility: St Georges University Hospital NHS Foundation Trust
state: London
Study officials:
affiliation: St George's, University of London
name: Paul Heath, MBBS
role: PRINCIPAL_INVESTIGATOR
References: