Condition category
Infections and Infestations
Date applied
08/11/2013
Date assigned
08/11/2013
Last edited
22/01/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Tuberculosis (TB) remains an important global health problem. There is an urgent need for a better vaccine as the only licensed vaccine, BCG, protects against severe TB in infancy but less well against lung disease, which is how TB spreads. MVA85A is a new vaccine that improves the effect of BCG in animals. MVA85A is a viral vector vaccine, i.e. made from a weakened virus (vector, MVA) that has been altered to contain pieces of DNA from M.tb, the bacterium which causes TB (insert, 85A). To date MVA85A has been given by an injection into the skin but it is likely that giving MVA85A directly into the lungs by a mist of air (aerosol) would be better, as the route of vaccination then matches the route by which TB is caught. A problem with virally-vectored vaccines is that individuals build up immunity to the virus base (anti-vector immunity), which makes the vaccine less efficient and also not suitable for re-use (boosting). Non-human primate data has suggested that aerosolised vaccination avoids anti-vector immunity. This proposed study aims to study the effect of aerosol vaccination of MVA85A on anti-vector and insert (85A) immunity in humans.

Who can participate?
Healthy adults aged 18-65 who live near Oxford can take part in the study.

What does the study involve?
Participants are invited for a screening visit first where the study is explained in detail and a medical review undertaken to ensure volunteers are suitable to take part. Volunteers who are enrolled will be randomly allocated to one of three groups: the first group receives the vaccine through an aerosol followed by a vaccine by injection in the skin a month later. The second group gets the vaccine by injection in the skin first followed by the vaccine by aerosol a month later. The third group receives the vaccine by a skin injection twice spaced apart by a month. Regular blood tests are performed throughout the trial and a bronchoscopy is performed 1 week after each vaccination.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
University of Oxford, UK.

When is the study starting and how long is it expected to run for?
The study starts in November 2013 and runs until February 2015.

Who is funding the study?
National Institute for Health Research (NIHR), UK.

Who is the main contact?
Dr Zita-Rose Manjaly Thomas
zita-rose.manjaly@ndm.ox.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Zita-Rose Manjaly Thomas

ORCID ID

Contact details

Old Road Campus
Roosevelt Drive Headington
Oxford
OX3 7DQ
United Kingdom
zita-rose.manjaly@ndm.ox.ac.uk

Additional identifiers

EudraCT number

2013-002020-16

ClinicalTrials.gov number

NCT01954563

Protocol/serial number

15209

Study information

Scientific title

A Phase I trial evaluating mucosal administration of a candidate TB vaccine, MVA85A, as a way to induce potent local cellular immune responses and avoid anti-vector immunity

Acronym

TB035

Study hypothesis

TB remains a significant global health problem. There is an urgent need for a better vaccine as the only licensed vaccine, BCG, protects against severe TB in infancy but less well against lung disease, which is how TB spreads. MVA85A is a new vaccine that improves the effect of BCG in animals. MVA85A is a viral vector vaccine, i.e. made from a weakened virus (vector, MVA) that has been altered to contain pieces of DNA from M.tb, the pathogen which causes TB (insert, 85A). To date MVA85A has been given by an injection into the skin but it is likely that delivering MVA85A directly into the lungs by a mist of air (aerosol) would be better, as the route of vaccination then matches the route by which TB is caught.

A problem with virally-vectored vaccines is that individuals build up immunity to the virus base (anti-vector immunity) which makes the vaccine less efficient and also not suitable for reuse (boosting).

Non-human primate data has suggested that aerosolised vaccination avoids anti-vector immunity. This proposed study aims to study the effect of aerosol vaccination of MVA85A on anti-vector and insert (85A) immunity in humans in a clinical trial.

Ethics approval

13/SC/0329; First MREC approval date 29/07/2013

Study design

Randomised; Interventional; Design type: Not specified

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Prevention

Patient information sheet

http://www.jenner.ac.uk/tuberculosis-vaccine-trial-tb035

Condition

Topic: Infection; Subtopic: Infection (all Subtopics); Disease: Infectious diseases and microbiology

Intervention

36 volunteers are randomised into 3 groups of 12 volunteers.

1. The first group will receive 5 x 10^7 pfu dose of MVA85A administered by aerosol followed by the same dose of the same vaccine administered by intradermal injection 1 month later.
2. The second group will receive 5 x 10^7 pfu dose of MVA85A administered by intradermal injection followed by the same dose of the same vaccine administered by aerosol 1 month later.
3. The third group will receive 5 x 10^7 pfu dose of MVA85A administered by intradermal injection followed by the same dose of the same vaccine administered by intradermal injection again 1 month later

Vaccines are administered together with a paired placebo, allowing that volunteers are blinded to route and group.

Intervention type

Biological/Vaccine

Phase

Phase I

Drug names

Primary outcome measures

Safety of 5 x 10^7 pfu dose of MVA85A administered by aerosol and compared to the same dose administered intradermally

Secondary outcome measures

1. Characterise mucosal and systemic immunogenicity of viral vector (MVA) and insert (Ag85A) by comprehensive characterisation of humoral and cellular immune responses
2. Evaluate functional relevance of anti-vector immunity induced by aerosol and systemic immunisation in MVA85A-prime followed

Outcomes will be measured on blood tests and bronchoalveolar lavage samples (lung washings).

There is a blood test at screening, day 0, day 2, day 7, day 14, day 28, day 30, day 35, day 42, day 84 and day 168, and bronchoscopies are done on day 7 and day 35. Vaccinations are on day 0 and day 28.

Overall trial start date

12/11/2013

Overall trial end date

02/02/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy adult aged 18-55 years
2. Resident in or near Oxford for the duration of the trial period
3. No relevant findings in medical history or on physical examination
4. Confirmation of prior vaccination with BCG not less than 6 months prior to projected trial vaccination date (by visible BCG scar on examination or written documentation)
5. Allow the investigators to discuss the individual’s medical history with their GP
6. Use effective contraception for the duration of the trial period (females only)
7. Refrain from blood donation during the trial
8. Give written informed consent
9. Allow the Investigator to register subject details with a confidential database to prevent concurrent entry into clinical trials
10. Able and willing (in the investigator’s opinion) to comply with all the trial requirements

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 36; UK Sample Size: 36; Description: Healthy BCG vaccinated Volunteers in 3 groups of 12

Participant exclusion criteria

1. Any respiratory disease, including asthma
2. Current smoker
3. Clinically significant abnormality on screening chest X-ray
4. Clinically significant abnormality of pulmonary function tests
5. Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy
6. Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs
7. Laboratory evidence at screening of latent M. tuberculosis infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
8. Clinical, radiological, or laboratory evidence of current active TB disease
9. Previous vaccination with candidate vaccine MVA85A or candidate vaccine FP85A or any other recombinant MVA vaccine
10. Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse
11. History of serious psychiatric condition
12. Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents
13. History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccine, sedative drugs, or any local or general anaesthetic agents
14. Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the subject in the trial
15. Positive HBsAg, HCV or HIV antibodies
16. Female currently lactating, confirmed pregnancy or intention to become pregnant during trial period
17. Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the trial vaccine for 30 days prior to dosing with the trial vaccine, or planned use during the trial period
18. Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date
19. Any other significant disease, disorder or finding, which, in the opinion of the investigator, may either put the subject at risk or may influence the result of the trial or may affect the subject’s ability to participate in the trial

Recruitment start date

12/11/2013

Recruitment end date

02/02/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Old Road Campus
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

CTRG
Joint Research Office
Block 60 Churchill Hospital
Headington
OX3 7LJ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research (NIHR)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Wellcome Trust (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes