Condition category
Infections and Infestations
Date applied
22/01/2018
Date assigned
23/01/2018
Last edited
19/04/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Meningococcus Group B is a bacteria that causes significant morbidity (illness) and mortality (death) by causing meningococcal meningitis or sepsis. A vaccine against the bacteria, Bexsero, does exist, but it has a significant rate of side effects, requires up to four doses to be efficient and is expensive. There has recently been development in vaccine technology using an adenovirus as a vector (as a way to deliver material into cells). Administration of this vaccine will lead to the virus entering human cells and producing the protein, but not replicating itself. The production of this protein produces an immune response to meningococcus group B in mice that is as good as Bexsero and potentially longer lasting. This vaccine candidate is expected to be safe, with previously trials using a similar adenovirus vector proving safe for equivalents vectors for vaccines for malaria, TB, Ebola etc. It is also relatively inexpensive and produces little side-effects. Therefore, we believe this vaccine can improve on the current available vaccine for meningococcus B. We would therefore like to test this vaccine candidate in a Phase 1 trial, primarily to assess the safety of the vaccine in humans. This study also aims to gauge the immunogenicity (the ability to provoke an immune response) as a secondary outcome to inform further potential efficacy trials. In this regard this study is testing combinations of low single dose, high single dose, high single dose with later high booster dose and high booster dose following a primary Bexsero dose. These are compared to Bexsero as a control.

Who can participate?
Adults aged 18 to 50 years old who are in good health.

What does the study involve?
Participants are allocated to one of six sub groups. Those in the first group receive the single low dose of 2.5 x10^10 VP of ChAdOx1 MenB.1. Those in the second group receive a single high dose 5x10^10 VP of ChAdOx1 MenB.1. Those in the third group receive the high dose of ChAdOx1 MenB.1 plus a repeat booster dose at six months. Those in the fourth group receive a dose of Bexsero at baseline with a high dose booster of ChAdOx1 MenB.1 at six months. Those in the fifth group receive two doses of Bexsero at baseline and 28 days later. Those in the last group receive Bexsero at baseline and six months. Symptoms of the shots are recorded in participant diaries.

What are the possible benefits and risks of participating?
Information from this study may help doctors learn more about this study meningitis B vaccine. This information may help us to make a vaccine that can protect babies, children and adults against meningitis B. Participants may experience side effects of the vaccination or blood tests as a part of this study. The team will observe everyone in the study for any side effects, particularly in the first seven days after receiving a vaccine with an eDiary that they fill in. Side effects may be mild or serious. Most effects will stop shortly after receiving the vaccine. In rare cases, side effects can be serious or prolonged, although no serious concerns have been raised in human trials for other similar virus-based vaccines. In general, the known risks following vaccination are minor and brief (lasting a few days). As with any vaccination, the following events could occur: Pain, redness or swelling of your arm around the spot where the vaccine was injecte; General: fatigue, headache, fever, gastrointestinal symptoms such as nausea (feeling sick), vomiting, diarrhoea or abdominal pain. As with all injected vaccines, unexpected, severe allergic reactions may very rarely occur. An allergic reaction can be recognised by itchy skin rash, swelling of the face, difficulties in breathing and swallowing or by a sudden drop in blood pressure. If such reactions occur, they usually start very soon after vaccination. That is why it is important that participants stay at the study site for at least 60 minutes after vaccination, where all medical equipment and personnel are available to treat an allergic reaction. Adenovirus vaccines have previously been trialled in human volunteers, protecting against diseases other than meningitis B. These were not associated with serious side effects. Animal studies conducted to date have shown this vaccine to be capable of stimulating the immune system against meningitis B. There were some minor changes in routine blood results one month after injection, but were not associated with any clinical problems. As it is the first time that the study vaccine will be tested in humans there might be side effects that we don’t yet know about. If any new side effects are identified, from this study or from animal studies, we will tell the participants. Some participants may experience mild pain or discomfort during venepuncture (the blood test) and bruising at the site. In rare cases, participants may feel faint during the blood test. Study staff are trained to deal with these rare occurrences.

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

When is the study starting and how long is it expected to run for?
April 2017 to March 2019

Who is funding the study?
Medical Research Council

Who is the main contact?
Mrs Emma Plested
emma.plested@paediatrics.ox.ac.uk

Trial website

http://trials.ovg.ox.ac.uk/trials/vambox

Contact information

Type

Public

Primary contact

Mrs Emma Plested

ORCID ID

Contact details

University of Oxford
Department of Paediatrics
Level 2
Children's Hospital
John Radcliffe
Headington
Oxford
OX3 9DU
United Kingdom

Additional identifiers

EudraCT number

2017-000965-61

ClinicalTrials.gov number

Protocol/serial number

35928

Study information

Scientific title

A phase I/IIa, single centre, dose-escalation study to assess the safety and immunogenicity of the recombinant adenovirus Meningitis B vaccine candidate ChAdOx1 MenB.1

Acronym

VAMBOX

Study hypothesis

The aim of this study is to investigate safety and tolerability of 2.5 x 10^10 viral particles (VP) or 5x10^10 VP of the proposed ChAdOx1 MenB.1 vaccine against meningococcus serotype B in healthy adults aged 18 to 50 years of age, when given one dose +/- one booster dose; and when given as a booster following primary Bexsero vaccination, in comparison to standard two dose Bexsero vaccination (the current standard of care).

Ethics approval

South Central - Oxford A Research Ethics Committee, 21/12/2017, ref: 17/SC/0470

Study design

Non-randomised; Interventional; Design type: Prevention, Vaccine

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

http://trials.ovg.ox.ac.uk/trials/vambox

Condition

Specialty: Infectious diseases and microbiology, Primary sub-specialty: Infection prevention; UKCRC code/ Disease: Infection/ Sequelae of infectious and parasitic diseases

Intervention

The study is a phase I/IIa, single centre, dose-escalation study to assess the safety and immunogenicity of a single dose +/- booster dose of the recombinant adenovirus Meningitis B vaccine candidate ChAdOx1 MenB.1 in healthy adults. The participants are divided into six subgroups as described below. The total number of participants required to reach the primary endpoint is 47.

Group 1: Low dose arm – This group consists of three-six individuals who receive a single dose of 2.5 x10^10 VP of ChAdOx1 MenB.1 according to a 3+3 study plan. A favourable Data Safety Monitoring Committee review of the safety data from this arm is required before commencement of group 2.

Group 2: High dose arm – This group will only proceed after DSMC review of Group 1 and approval. This group consists of 10 participants assigned to receive a single dose of the higher dose 5x10^10 VP of ChAdOx1 MenB.1. A favourable DSMC review of the safety data from this arm is required before the commencement of group 3.

Group 3: High dose ChAdOx1 MenB.1 plus booster arm – this group consists of eight participants who receive the high dose 5x10^10 VP of ChAdOx1 MenB.1, with a repeat booster dose at six months. Administration of the booster dose are subject to favourable interim review of the safety data of group 2 by the DSMC.

Group 4: Bexsero with high dose ChAdOx1 MenB.1 booster arm – this group consists of eight participants who receives a dose of Bexsero at baseline with a booster high dose of ChAdOx1 MenB.1 at six months.

Group 5: Bexsero Control arm – This group consists of 10 individuals who receive two doses of Bexsero at Day 0 and Day 28 as per adult licensing. This group acts as a control to groups 1 and 2.

Group 6: Bexsero 6 month boost control arm – This group consist of 8 individuals who receive Bexsero doses at Day 0 and 6 months. This group acts as a control for groups 3 and 4.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measures

1. Solicited symptoms the participants record following each vaccination in a diary records from Day 0 (day of vaccination) to Day 7 (plus later if any persisting symptoms). The recording and assessment of local and systemic adverse events following administration of each vaccine dose:
1.1. Tenderness and pain at the injection site
1.2. Induration
1.3. Redness
1.4. Swelling
1.5. Headache
1.6. Malaise
1.7. Myalgia
1.8. Nausea and/or vomiting
1.9. Anorexia
1.10. Fever
1.11. Arthralgia
1.12. Blood parameters
2. Unsolicited adverse events up until and including 28 days following the last vaccine
3. Serious adverse events (SAEs) during the entire study
4. Safety is measured using blood tests at all study visits

Secondary outcome measures

The immunogenicity of 2.5 x 10^10 VP or 5x10^10 VP of the proposed ChAdOx1 MenB.1 vaccine against meningococcus serotype B in healthy adults aged 18 to 50 years of age when given one dose +/- one booster dose; and when given as a booster following primary Bexsero vaccination in comparison to standard two dose Bexsero vaccination (the current standard of care) is measured using of the Serum bactericidal antibody (SBA) assay against homologous strains from D0, D14 and D28 time points.

Overall trial start date

01/04/2017

Overall trial end date

31/03/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Willing and able to give written informed consent for participation in the study
2. Aged between 18 and 50 years inclusive at the time of first vaccination
3. In good health as determined by
3.1. Medical history
3.2. Physical examination
3.3. Clinical judgment of the investigators
4. (Females of childbearing potential) Willing to use effective contraception (such as the oral contraceptive pill, contraceptive implant, barrier methods or complete abstinence from heterosexual sexual intercourse) from one month prior to first vaccination and for three months following last vaccine
5. Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of diary cards
6. Willing to allow his or her General Practitioner to be notified of participation in the study
7. Confirmation from the participants GP that they are satisfied from their knowledge of the volunteer that they are suitable to enrol and/or the provision of a detailed medical summary is provided to the study team to assess participant eligibility
8. Agrees to refrain from donating blood for the duration of the trial
9. Agree to be registered on the Trial Over-Volunteering Prevention Service (TOPS) and agree to provide their National Insurance number or passport number (if not a British citizen) for the purposes of registration
10. Agree to provide National Insurance number and Bank details for reimbursement purposes

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 50; UK Sample Size: 50

Participant exclusion criteria

1. History of significant organ/system disease that could interfere with trial conduct or completion. This includes any history of significant disease in the following;
1.1. Cardiovascular disease including congenital heart disease, previous myocardial infarction, valvular heart disease (or history of rheumatic fever), previous bacterial endocarditis, history of cardiac surgery (including pacemaker insertion), personal or family history of cardiomyopathy or sudden adult death
1.2. Respiratory disease such as uncontrolled asthma and chronic obstructive pulmonary disease
1.3. Endocrine disorders such as diabetes mellitus and Addison’s disease
1.4. Significant renal or bladder disease, including history of renal calculi
1.5. Biliary tract disease
1.6. Gastro-intestinal disease such as inflammatory bowel disease, abdominal surgery within the last two years, coeliac disease and liver disease (including hepatitis B or C infection)
1.7. Neurological disease such as seizures and myasthenia gravis
1.8. Haematological problems such as anaemia or coagulation problems
1.9. Metabolic disease such as glucose-6-phosphate dehydrogenase deficiency
1.10. Psychiatric illness requiring hospitalisation or depression whose severity is deemed clinically significant by the study Investigators and/or GP
1.11. Known or suspected drug and/or alcohol misuse (alcohol misuse defined as an intake exceeding 42 units per week)
1.12. Non-benign cancer, except squamous cell or basal cell carcinoma of the skin and cervical carcinoma in situ
2. History of allergy or anaphylaxis to a vaccine or any component within the vaccines used in this study
3. Have any known or suspected impairment or alteration of immune function, resulting from, for example:
3.1. Congenital or acquired immunodeficiency
3.2. Human Immunodeficiency Virus infection or symptoms/signs suggestive of an HIV-associated condition
3.3. Autoimmune disease
3.4. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid therapy
4. Study significant abnormalities on screening investigations at the discretion of an Investigator
5. Weight < 50 kg
6. Donation of blood within the last 3 (male) or 4 (female) months) or plans on giving blood within the next year
7. Receipt of a live vaccine within 4 weeks prior to vaccination, an inactivated influenza vaccine within 14 days of vaccination or another inactivated vaccine within 7 days prior to vaccination
8. Plan to receive any vaccine other than the study vaccine within 4 weeks following vaccination
9. Scheduled procedures requiring general anaesthesia during the study
10. Receipt of immunoglobulin or any blood product transfusion within 3 months of study start
11. Current active participation in another research study involving an investigational product or where involvement in this study could impact the results
12. Donation of blood in the past 12 weeks (if male) or 16 weeks (if female), or are planning to do so within the 52 weeks of vaccination in this study
13. Previously having received a meningococcal B vaccine of any kind
14. Previously received any adenovirus based vaccine of any kind (usually as part of a trial)
15. Previous occurrence of disease caused by N. meningitidis
16. Inability, in the opinion of the Investigator, to comply with all study requirements
17. Female participants who are pregnant, lactating or planning pregnancy during the course of the study
18. Participant unwilling to allow contact with their GP, is not registered with a GP; or if GP is not contactable.
19. Any other significant disease or disorder which, in the opinion of the Investigator, may
19.1. Put the participants at risk because of participation in the study;
19.2. Influence the result of the study; and/or
19.3. Impair the participant’s ability to participate in the study

Recruitment start date

05/02/2018

Recruitment end date

30/04/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Oxford Vaccine Group, University of Oxford
Centre for Clinical Vaccinology and Tropical Medicine Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials and Research Governance
Oxford
OX1 2JD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Medical Research Council

Alternative name(s)

Medical Research Council of Canada, Medical Research Council, Canada, Medical Research Council, MRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Canada

Results and Publications

Publication and dissemination plan

The Investigator will co-ordinate dissemination of data from this study. All publications (e.g., manuscripts, abstracts, oral/slide presentations, book chapters) based on this study will be reviewed by each sub-investigator prior to submission. The intent is to publish in a scientific peer-reviewed, open access journal. The link to the publication and a synopsis will be available to participants and public on the Oxford Vaccine Group website.

Participants will receive a letter containing these results. The individual participant results would not be identifiable nor would they be identified in any report or publication.

The results of the research will also potentially be used for future academic research within the Oxford Vaccine Group.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/05/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

19/04/2018: Internal review.