Early protection against meningococcal disease B in infants
| ISRCTN | ISRCTN52318758 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52318758 |
| EudraCT/CTIS number | 2021-001561-21 |
| IRAS number | 265199 |
| Secondary identifying numbers | CPMS 49304, IRAS 265199 |
- Submission date
- 09/07/2021
- Registration date
- 16/07/2021
- Last edited
- 16/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
In 2015, the United Kingdom became the first country in the world to introduce the meningococcal group B (Men B) vaccine into its routine schedule for infants. This vaccine has proved to be very effective in protecting against meningitis (infection of the lining of the brain) and septicaemia (blood poisoning) caused by a subgroup (group B) of the meningococcus germ. In the United Kingdom, babies are offered this vaccination at 2, 4, and 12 months.
The aim of this study is to compare two different schedules of Men B vaccination, the standard schedule (at 2, 4, and 12 months) and the early schedule (at 2, 3, and 12 months). Receiving the first two doses of Men B vaccine by 3 months could provide infants earlier protection against Men B disease.
Who can participate?
Babies born at term, aged 56 days to 70 days on the day of the first visit
What does the study involve?
Babies are randomly allocated to one of the two study groups: one group will receive all recommended vaccines according to the standard UK schedule and the other will receive the second dose of Men B vaccine at 3 instead of 4 months and the first dose of PCV13 at 4 instead of 3 months. Both groups will receive an additional dose 'booster' dose of Men B and PCV13 vaccine at 12 months. The researchers will take three blood samples over the study period to check the babies’ antibody levels against Meningococcus and Pneumococcus germs, and will ask caregivers to keep a record of any reactions that occur after their vaccinations.
What are the possible benefits and risks of participating?
Participants will have the choice of coming to the study site, or the study team can come to the home of the participants to give the vaccinations and take the blood samples. If participants attend at the local site, reasonable travel expenses will be covered. They will have 24-hour telephone access to a member of the study team if they have any concerns about their baby’s vaccinations.
Because the vaccines used in this study are exactly the same ones being used for routine immunisation of other babies in the UK, the researchers do not expect the risk to be any different than with the routinely given vaccines. As with all vaccinations, however, there may occasionally be some redness and/or swelling at the injection site and fever. Fever is a side effect particularly associated with the Men B vaccination and advice will be given to parents about steps they can take to try to prevent this. Severe allergic reactions, such as anaphylaxis, are extremely rare but can occur with any vaccine. The baby would be observed for 20 minutes following each immunisation and the study staff are specifically trained and equipped to deal with this in the extremely unlikely event that it did occur.
Blood tests may be uncomfortable for infants, but the researchers will try to minimise this by offering a local anaesthetic cream, if appropriate, to numb the skin before taking the blood sample.
It is anticipated that the immune response of the 2-3-month Men B schedule will be similar to that of the 2-4-month schedule, and similarly that the change of timing of the pneumococcal vaccine will have no impact on the protection offered by this vaccine. All participants will have their antibody levels checked following the 12-month vaccinations, which provides an opportunity to identify infants who have a sub-optimal response. If this shows that the baby may have inadequate protection, the research team will contact the participant to discuss the options, including the possibility of a booster dose of vaccine.
Where is the study run from?
St George's, University of London (UK)
When is the study starting and how long is it expected to run for?
April 2021 to October 2024
Who is funding the study?
GlaxoSmithKline (UK)
Who is the main contact?
Dr Natasha Thorn
nthorn@sgul.ac.uk
Contact information
Scientific
St George's University of London
Cranmer Terrace
London
SW17 0RE
United Kingdom
| Phone | +44 (0)208 725 4851 |
|---|---|
| nthorn@sgul.ac.uk |
Scientific
St George's University of London
Cranmer Terrace
London
SW17 0RE
United Kingdom
| Phone | +44 (0)2087254851 |
|---|---|
| pheath@sgul.ac.uk |
Public
-
-
-
United Kingdom
| lionmenb@sgul.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Prevention, Vaccine |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | University/medical school/dental school |
| Study type | Prevention |
| Participant information sheet | 40141_PIS_V2.0_01Jun21.docx |
| Scientific title | Phase IV randomisation study of different Men B vaccine primary immunisation schedules in UK infants |
| Study acronym | LION MenB |
| Study hypothesis | This study is being undertaken to compare the immune responses of UK infants who receive their routine immunisations alongside two different 4CMenB primary immunization schedules. Completing the primary 4CMenB schedule by 3 months could provide infants earlier protection against MenB disease since cases peak at 5 months of age and remain high in the second half of the first year before starting to decline (Ladhani et al., 2012). If this clinical trial shows comparable immunogenicity for the main 4CMenB antigens using the two different schedules, then the results could change UK national immunization policy to offer infants earlier protection against this devastating disease and could potentially be adopted by other countries worldwide. |
| Ethics approval(s) |
Approved 25/06/2021, North East - Newcastle & North Tyneside 1 Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; +44 (0)2071048285; newcastlenorthtyneside1.rec@hra.nhs.uk), ref: 21/NE/0093 |
| Condition | Meningococcal disease B |
| Intervention | This study is an open-label, phase IV study which will recruit 220 infants from suitable participating sites. Recruitment: A variety of recruitment strategies will be used by the different participating centres to recruit eligible participants. Some centres may choose to advertise the study on institutional websites or newsletters, or on posters in the hospital or the community (e.g. in GP practices). Eligible infants may also be identified through the local child health information systems (CHIS) and initially contacted by post. Families expressing an interest in participating in the study by post, email, text, or phone will then be approached by the study team. Consent: Parents will be asked to give their informed consent to their infant's participation in the study when they have had time to consider the study and ask questions. Consent will be taken at the first study visit. Randomisation: Infants will be randomised to a treatment group at the first study visit. Visits will take place either in hospital/university or at home depending on family preference and local strategy. Visit 1: Contact details, demographic information, and medical history, including medication, will be collected at this visit and the appropriate CRFs completed. A brief medical examination at this visit will be performed. The infant's temperature will be taken at this visit (preferred route axillary) to confirm that the infant is well for vaccination. All participants will receive the same vaccinations at this visit: DtaP/IPV/Hib/HepB, 4CMenB, Rotavirus. All infants will be observed for 20 minutes following vaccination to ensure they have no adverse reaction. Parents will have the diary (paper or electronic e-diary) explained to them and information will be given as to how to contact the study team if this is needed. Visit 2 (3 months) The parents will be asked about the health of the child in the period since their previous vaccinations, the diary will be collected and discussed with the parents. Parents will be asked about any concomitant medication. The infant's temperature will be taken at this visit (preferred route axillary) to confirm that the infant is well for vaccination. Infants will receive vaccinations according to their study group: Group 1: DtaP/IPV/Hib/HepB, 4CMenB, Rotavirus. Group 2: DtaP/IPV/Hib/HepB, PCV13, Rotavirus. All infants will be observed for 20 minutes following vaccination to ensure they have no adverse reaction. Diary completion instructions will be confirmed at this visit and study staff will check that parents are aware of how to contact the study team. Visit 3 (4 months) The parents will be asked about the health of the child in the period since their previous vaccinations, the diary will be collected and discussed with the parents. Parents will be asked about any concomitant medication. The infant's temperature will be taken at this visit (preferred route axillary) to confirm that the infant is well for vaccination. Infants in Group 1 will have blood taken at this visit. This will ideally be a venous sample, but if this is not possible blood may be obtained by capillary sampling. Infants will receive vaccinations according to their study group: Group 1: DtaP/IPV/Hib/HepB, PCV13. Group 2: DtaP/IPV/Hib/HepB, 4CMenB. All infants will be observed for 20 minutes following vaccination to ensure they have no adverse reaction. Diary completion instructions will be confirmed at this visit and study staff will check that parents are aware of how to contact the study team. Visit 4 (5 months) – Only Group 2 The parents will be asked about the health of the child in the period since their previous vaccinations, the diary will be collected and discussed with the parents. Parents will be asked about any concomitant medication. Infants in Group 2 will have blood taken at this visit. This will ideally be a venous sample, but if this is not possible blood may be obtained by capillary sampling. Visit 5 (12 months) The parents will be asked about the health of the child in the period since their previous vaccinations. Parents will be asked about any concomitant medication. The infant's temperature will be taken at this visit (preferred route axillary) to confirm that the infant is well for vaccination. All infants will have blood taken at this visit. This will ideally be a venous sample, but if this is not possible blood may be obtained by capillary sampling. All participants will receive the same vaccinations at this visit: MCC-TT/Hib-TT, PCV13, 4CMenB, MMR. All infants will be observed for 20 minutes following vaccination to ensure they have no adverse reaction. Diary completion instructions will be confirmed at this visit and study staff will check that parents are aware of how to contact the study team. Visit 6 (13 months) The parents will be asked about the health of the child in the period since their previous vaccinations, the diary will be collected and discussed with the parents. Parents will be asked about any concomitant medication. All infants will have blood taken at this visit. This will ideally be a venous sample, but if this is not possible blood may be obtained by capillary sampling. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | To compare the immunological responses one month after the 12-month 4CMenB booster in infants who received two different primary immunisation schedules of 4CMenB (2 and 3 versus 2 and 4 months of age). |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 4CMenB, Bexsero and PCV13, Prevenar |
| Primary outcome measure | 1. The immunological responses of UK infants between two different primary immunisation schedules of 4CMenB (2 and 3 versus 2 and 4 months of age): 1.1. Antibody geometric mean titers (GMTs) against relevant 4CMenB antigens (fHbp, NadA and PorA) measured by serum bactericidal assay using human complement (hSBA) 4 weeks after 2nd dose of 4CMenB (at 4 months of age for Group 1 versus 5 months of age for Group 2). 1.2. The proportion of infants with antibody titers ≥ 1:4 against relevant 4CMenB antigens (fHbp, NadA and PorA) measured by hSBA assessed at 4 weeks after 2nd dose of 4CMenB (at 4 months of age for Group 1 versus 5 months of age for Group 2) |
| Secondary outcome measures | 1. To compare the persistence of immunological responses to 4CMenB at 12 months chronological age after two different primary immunisation schedules of 4CMenB (2 and 3 versus 2 and 4 months of age). 1.1. GMTs against relevant 4CMenB antigens (fHbp, NadA and PorA) measured by hSBA at 12 months of chronological age (pre-booster). 1.2. The proportion of infants with antibody titers ≥ 1:4 against relevant 4CMenB antigens (fHbp, NadA and PorA) measured by hSBA at 12 months of chronological age (pre booster). 2. To compare the immunological responses one month after the 12-month 4CMenB booster in infants who received two different primary immunisation schedules of 4CMenB (2 and 3 versus 2 and 4 months of age). 2.1. GMTs against relevant 4CMenB antigens (fHbp, NadA and PorA) measured by hSBA at 13 months of chronological age (4 weeks post-booster). 2.2. The proportion of infants with antibody titers ≥ 1:4 against relevant 4CMenB antigens (fHbp, NadA and PorA) measured by hSBA at 13 months of chronological age (4 weeks post booster). 3. To compare the persistence of immunological responses to PCV13 at 12 months chronological age after two different primary immunisation schedules of PCV13 (3 versus 4 months of age). 3.1. Serotype specific GMCs against PCV13 serotypes at 12 months of age (pre PCV13 booster). 3.2. The proportion of infants with serotype-specific GMCs ≥ 0.35 μg/ml against PCV13 serotypes at 12 months of age (pre PCV13 booster). 4. To compare the immunological responses to the booster dose of PCV13 given at 12 months in infants who received two different primary immunisation schedules of PCV13 (3 versus 4 months of age). 5.1 Serotype specific GMCs against PCV13 serotypes at 13 months of age (4 weeks post PCV13 booster). 5.2. The proportion of infants with serotype-specific GMCs ≥ 0.35 μg/ml against PCV13 serotypes at 13 months of age (4 weeks post PCV13 booster). |
| Overall study start date | 01/04/2021 |
| Overall study end date | 31/10/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Child |
| Lower age limit | 56 Days |
| Upper age limit | 70 Days |
| Sex | Both |
| Target number of participants | Planned Sample Size: 220; UK Sample Size: 220 |
| Total final enrolment | 221 |
| Participant inclusion criteria | 1. Term infants born at ≥37 weeks gestation 2. Aged ≥56 days to ≤70 days on the day of the first visit 3. No contraindications to vaccination according to the ‘Green Book’ 4. Willing and able to comply with study procedures 5. Written informed consent |
| Participant exclusion criteria | 1. Contraindication to vaccination according to the Green Book 2. Life-limiting congenital abnormality or condition 3. Prior diagnosis of an immunodeficiency syndrome 4. Previous vaccination against meningococcal disease 5. History of Neisseria meningitidis infection, confirmed either clinically, serologically, or microbiologically 6. Considered unlikely to complete the expected follow up until the end of the study 7. Child in care |
| Recruitment start date | 01/07/2021 |
| Recruitment end date | 22/11/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
London
SW17 0RE
United Kingdom
Oxford
OX3 9DU
United Kingdom
Treliske
Truro
TR1 3LJ
United Kingdom
Cosham
Portsmouth
PO6 3LY
United Kingdom
Sheffield
S10 2TH
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Sponsor information
University/education
c/o Georgia Bullock
Joint Research and Enterprise Service
London
SW17 0RE
England
United Kingdom
| Phone | +44 (0)2082666397 |
|---|---|
| gbullock@sgul.ac.uk | |
| Website | http://www.sgul.ac.uk/ |
"ROR" |
https://ror.org/040f08y74 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/03/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Up to 180 days after the official completion of the trial: During this period the Chief Investigator shall liaise with all investigators and strive to consolidate data and results and submit a manuscript for peer-review with a view to publication in a reputable academic journal or similar outlet as the main publication. After the main publication or after 180 days from the trial end date any investigator or group of investigators may prepare further publications. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version V2.0 | 01/06/2021 | 15/07/2021 | No | Yes |
| Protocol file | version V2.0 | 02/06/2021 | 15/07/2021 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- 40141_PIS_V2.0_01Jun21.docx
- Uploaded 15/07/2021
- 40141_PROTOCOL_V2.0_02Jun21.docx
- Uploaded 15/07/2021
Editorial Notes
16/12/2024: The intention to publish date was changed from 10/12/2024 to 31/03/2025.
21/11/2024: The overall study end date was changed from 30/09/2024 to 31/10/2024.
02/09/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 30/11/2022 to 22/11/2022.
2. The overall study end date was changed from 31/08/2024 to 30/09/2024.
3. The intention to publish date was changed from 01/10/2024 to 10/12/2024.
4. Total final enrolment added.
24/06/2024: The overall study end date was changed from 01/04/2024 to 31/08/2024.
25/04/2024: Internal review.
05/01/2024: A public contact was removed.
19/12/2023: The following changes were made:
1. The study setting university/medical school/dental school was added.
2. Pharmaceutical study type other was added.
3. Study website added.
4. The participant type healthy volunteer was added and all removed.
5. The recruitment end date was changed from 01/07/2022 to 30/11/2022.
6. The scientific contact was changed.
09/07/2021: Trial's existence confirmed by the NIHR.
