Condition category
Infections and Infestations
Date applied
23/04/2018
Date assigned
10/05/2018
Last edited
10/05/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
In 2015 4CMenB Vaccine (Bexsero®) (a vaccine against the bacteria meningococcus B) was added to the UK routine immunisation schedule for infants. The aim of this study is to determine if it is sufficient to give a single booster dose of 4CMenB to 11 year olds who have received a full course of the vaccine in their infancy, in order to ensure that they are protected from meningococcal B disease in adolescence. The reason to consider this is because meningococcus B causes disease in two main waves, the first in infancy and the second in adolescence.

Who can participate?
Children aged about 11 who received 4CMenB as part of studies done at the Oxford Vaccine Group around 11 years ago, and children of the same age who have not previously received 4CMenB

What does the study involve?
Children who received 4CMenB are assessed to determine if they still have immunity against meningococcus B so many years after receiving the vaccine, and are given a booster dose of 4CMenB to see whether their immunity can be sufficiently topped up with just a single dose of the vaccine. Children who have never received a meningococcal B vaccine before usually require two doses to become immune to the disease. These children are randomly allocated to one of two groups. One group receives one dose of 4CMenB at visit 1 (day 0) and a second dose at visit 4 (day 365). The other group receives one dose of 4CMenB at visit 1 (day 0) and a second dose at visit 2 (day 28). All participants are followed up at the same timepoints (Day 0, Day 28, Day 180 and Day 365) with blood samples collected at each visit to compare the immune responses of the different groups of children with different schedules of 4CMenB.

What are the possible benefits and risks of participating?
The study will ultimately inform decisions about whether or not to include an adolescent booster meningococcal B vaccine into the UK routine immunisation schedule. Benefits include receiving a booster dose or a full course of 4CMenB. These children are about to enter into their adolescent years in which the risk of meningococcal disease rises, and they will benefit from the protection provided by this vaccine. As the vaccine used in this study is a licensed product, the risks to participants are the same as if they received any licensed vaccine. There is a very small risk of allergy or anaphylaxis to the vaccine, but the vaccine has undergone stringent safety testing. There is a risk of bruises from the blood tests in this study.

Where is the study run from?
University of Oxford (UK)

When is the study starting and how long is it expected to run for?
January 2018 to July 2019

Who is funding the study?
Meningitis Research Foundation (UK)

Who is the main contact?
Rachel Craik
info@ovg.ox.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Rachel Craik

ORCID ID

Contact details

Oxford Vaccine Group
University of Oxford
CCVTM
Churchill Hospital
Headington
Oxford
OX3 7LE
United Kingdom
+44 (0)1865 611400
info@ovg.ox.ac.uk

Additional identifiers

EudraCT number

2017-004732-11

ClinicalTrials.gov number

Protocol/serial number

37797

Study information

Scientific title

Preventing meningitis in young people after infant immunisation: effect of a single meningococcal 4CMenB vaccine booster over 10 years of age

Acronym

Study hypothesis

In 2015 4CMenB Vaccine (Bexsero®) (a vaccine against the bacteria meningococcus B) was added to the UK routine immunisation schedule for infants. The aim of this study is to determine if it is sufficient to give a single booster dose of 4CMenB to 11 year olds that have received a full course of the vaccine in their infancy, in order to ensure that they are protected from meningococcal B disease in adolescence. The reason to consider this is because meningococcus B causes disease in two main waves, the first in infancy and the second in adolescence. The first children to receive 4CMenB in the UK were a group recruited to studies done at the Oxford Vaccine Group around 11 years ago. The trialists are planning to approach these children to determine if they still have immunity against meningococcus B so many years after receiving the vaccine, and whether their immunity can be sufficiently topped up with just a single dose of the vaccine as a booster, as opposed to the two doses required to protect naïve children.

Ethics approval

South Central - Berkshire, 19/01/2018, ref: 17/EM/0466

Study design

Randomised; Interventional; Design type: Prevention, Vaccine

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Specialty: Infection, Primary sub-specialty: Vaccines; UKCRC code/ Disease: Inflammatory and Immune System/ Certain disorders involving the immune mechanism

Intervention

There are three arms to this study, a group of follow-up participants and two groups of naïve participants. The follow up cohort are a group of children who took part in Meningitis B studies run by the Oxford Vaccine Group as infants (groups 1-6 depending upon the previous study they took part in). These children are now 11 years old so they are invited back to participate in this study to investigate their immune response to the licensed MenB vaccine (4CMenB/Bexsero). These participants will receive a booster dose of 4CMenB and have a blood sample collected at visit 1 (Day 0). They will then be followed up for a year where blood samples will be collected at three follow up visits (Day 28, Day 180 and Day 365).

The naïve participants will be randomly allocated via a computer-generated list into two groups with an allocation ratio of 1:1. All naïve participants will receive 2 doses of vaccine, as opposed to the one dose for follow-up children. Naïve participants in group 7 will receive one dose of 4CMenB at visit 1 (day 0) and a second dose at visit 4 (day 365). Participants in group 8 will receive one dose of 4CMenB at visit 1 (day 0) and a second dose at visit 2 (day 28). The naïve groups will all be followed up at the same timepoints as the follow up children with four blood samples being collected at each visit.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Serum bactericidal assay against N. meningitidis serogroup B indicator strains before and after vaccination

Secondary outcome measures

Serum bactericidal assay (SBA) against vaccine strains of MenB will be measured to indicate the antibody response before vaccination at baseline. The differences in SBA will compared between the different treatment groups to indicate if there is any persistence of immunity in the children who have previously had a MenB vaccine.

Overall trial start date

01/01/2018

Overall trial end date

01/07/2019

Reason abandoned

Eligibility

Participant inclusion criteria

For recruitment to all study groups:
1. Parents/legal guardians are willing and able to comply with the requirements of the trial protocol and have internet access for the duration of the study
2. Parents/legal guardians have given informed consent for their child’s participation in the study
3. Participant is willing and able to give informed assent for participation in the trial
4. In the Investigator’s opinion, participants are able and willing to comply with all trial requirements
5. Parents/legal guardians/participants are willing to allow their General Practitioner and consultant, if appropriate, to be notified of participation in the trial

For recruitment to study groups 1 to 6 only:
Male or female, aged approximately 11 years who have completed a vaccination course of 4CMenB as an infant or toddler in clinical trials V72P6, V72P6E1,V72P9 or V72P9E1

For recruitment to naïve groups 7 and 8 only:
Male or female, born between 25/06/2006 – 17/12/2006 (age range is matched with group 1-6), who have not previously received 4CMenB vaccine. The aim is to recruit approximately 50% female and 50% male participants, in order to match with the previously vaccinated group

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 113; UK Sample Size: 113

Participant exclusion criteria

The participant may not enter the trial if ANY of the following apply:
1. Children of parents/legal guardians who are on the delegation log for this study
2. History of invasive meningococcal B disease
3. History of being a household contact with a case of confirmed bacterial meningitis
4. Confirmed or suspected immunodeficiency
5. A family history of congenital or hereditary immunodeficiency, or maternal HIV
6. History of anaphylactic reaction to any component of the vaccine
7. No internet access for the duration of the study
8. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial
9. Participants who have participated in another research trial involving an investigational product in the past 12 weeks.
10. Prior or planned receipt of any other investigational vaccine or drug
11. Thrombocytopenia or any bleeding disorder
12. Receipt of blood, blood products, or plasma derivatives within the past 3 months

Exclusion to study groups 1 to 6 only:
1. Any previous vaccination with 4CMenB vaccine except as part of V72P6, V72P6E1, V72P9 or V72P9E1 clinical trials
2. Any previous vaccination with another meningococcal B vaccine (such as outer membrane vesicle vaccines)
3. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 1 month or long-term systemic corticosteroid therapy (e.g. oral prednisolone >0.5ml/kg/day or intravenous glucocorticoid steroid). However, this may be discussed on a case by case basis. Nasal, topical or inhaled steroids are allowed

Exclusion to naïve groups 7 and 8 only:
1. Previous vaccination with 4CMenB vaccine or with any other meningococcal B vaccine (such as outer membrane vesicle vaccines)
2. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy
3. Current receipt of long-term systemic corticosteroid therapy (e.g. oral prednisolone >0.5ml/kg/day or intravenous glucocorticoid steroid). Nasal, topical or inhaled steroids are allowed.
4. Long-term prophylactic antibiotic use

Temporary exclusions for all study groups:
To receiving 4CMenB vaccine:
1. Administration of any other vaccine within 14 days before the study vaccines
2. Scheduled elective surgery, planned admission or other procedures requiring general anaesthesia within 7 days of receiving 4CMen B vaccine
3. Febrile illness (axillary temperature ≥38°C)
4. Significant acute or chronic infection within the previous 7 days, or fever (≥38°C) within the previous 3 days

For blood draw to be performed:
1. Receipt of systemic antibiotics within the previous 7 days
2. For participants in groups 1-6 who are unable to cease long-term antibiotics for one week prior to the scheduled study visit, we will not take blood samples for analysis. The trialists will still vaccinate these participants if consent is obtained, and collect data on reactogenicity (temperature monitoring) and side effects (eDiary). They will explore the possibility of pausing a child’s long-term antibiotics
with their GPs prior to making the decision of collecting blood samples.

Recruitment start date

24/03/2018

Recruitment end date

01/07/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Oxford
Oxford Vaccine Group CCVTM Churchill Hospital Headington
Oxford
OX3 7LE
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials Research Governance
Joint Research Office
1st Floor
Boundary Brook House
Churchill Drive
Oxford
-
United Kingdom
OX3 7LQ
ctrg@admin.ox.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Meningitis Research Foundation; Grant Codes: 1702.0

Alternative name(s)

MRF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication of the results in a high impact peer reviewed journal as soon after the completion of the project as possible.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date. There are no additional documents for this study.

Intention to publish date

01/07/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes