Meningococcal Disease, Prematurity, Vaccination
Conditions
Keywords
Prematurity, Vaccination
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.
Interventions
BIOLOGICAL4CMenB Vaccine
The infants will receive an intramuscular injection of the 4CMenB vaccine at 2 months
Sponsors
GlaxoSmithKline
MeningitisNow
Public Health England
St George's, University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This will be an open label, phase IV study.
Eligibility
Sex/Gender
ALL
Age
7 Weeks to 11 Weeks
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| hSBA GMT | 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 |
| hSBA proportions | 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
| Measure | Time frame | Description |
|---|---|---|
| Suspicion of sepsis in 7 days following vaccination | 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 |
| Fever and/or suspicion of sepsis in the 28 days following vaccination | 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 |
| Serious adverse events | 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 |
| Reactions within 7 days | 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 |
| Persistence of hSBA proportions ≥1:4 | 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 |
| Booster response: hSBA GMTs | 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; |
| Booster response: hSBA proportions ≥1:4 | 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. |
| Persistence of hSBA GMTs | 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 |
| Cardiorespiratory status for 72 hours following vaccination | 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 |
Countries
United Kingdom
Outcome results
None listed