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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Prematurity, Vaccination, Meningococcal Disease

Intervention / Treatment
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* Biological: 4CMenB Vaccine
* Biological: 4CMenB Vaccine
* Biological: 4CMenB Vaccine
* Biological: 4CMenB Vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 7 Weeks
Maximum Age: 11 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be an open label, phase IV study.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prematurity, Vaccination