Condition category
Infections and Infestations
Date applied
14/12/2009
Date assigned
18/12/2009
Last edited
31/07/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
MVA85A is a new vaccine being developed against tuberculosis (TB) which is designed to act as a boosting immunisation in people who have already received the Bacillus Calmette-Guerin (BCG) vaccine. In clinical trials so far it has been found to be safe in healthy people previously vaccinated with BCG, and also people with latent TB infection. In this study we wished to assess the safety of MVA85A for the first time in HIV-infected adults. We also wished to study the immune response generated by the vaccine in these volunteers. This is an important group of people to study because in parts of the world where a better TB vaccine is most needed, there is a high incidence of TB, and co-infection with HIV and TB is common and devastating.

Who can participate?
HIV-infected adult volunteers aged 18 to 50 were recruited from four hospitals in southern England.

What does the study involve?
The first group received a single low-dose injection of MVA85A and the second group received a single standard dose of MVA85A. Volunteers were followed up for one year and underwent blood tests at several time-points.

What are the possible benefits and risks of participating?
There are some known side effects of MVA85A. In healthy adults, a standard dose of MVA85A causes a mild local reaction when injected into the skin. This is visible as redness and swelling of the skin at the injection site, which lasts a week or two before healing completely without a scar. Occasionally the site of injection is also tender for a few days. About half of volunteers also get mild flu-like symptoms (headache, tiredness, aches) following vaccination with MVA85A but these are mild. Severe allergic reactions are rare but could potentially occur with any vaccine. Blood tests are performed throughout the trial but are not usually harmful. Having blood taken may cause slight pain and occasionally bruising at the site where the needle enters. Rarely, people feel light-headed or even faint. There are no known benefits of participating in this research.

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

When is the study starting and how long is it expected to run for?
The study ran from October 2006 to August 2010.

Who is funding the study?
The Wellcome Trust (UK).

Who is the main contact?
Professor Helen McShane, Jenner Institute, University of Oxford.

Trial website

Contact information

Type

Scientific

Primary contact

Dr Helen McShane

ORCID ID

Contact details

Jenner Institute
Old Road Campus Research Building
University of Oxford
Oxford
OX3 7DQ
United Kingdom

Additional identifiers

EudraCT number

2006-000076-32

ClinicalTrials.gov number

NCT00395720

Protocol/serial number

076943; TB010

Study information

Scientific title

The safety and immunogenicity of a new tuberculosis (TB) vaccine, MVA85A, in healthy volunteers who are infected with human immunodeficiency virus (HIV): an open label phase I study

Acronym

Study hypothesis

This is an open label phase I study of the safety and immunogenicity of two doses of MVA85A in healthy subjects who are infected with human immunodeficiency virus (HIV). Volunteers will be recruited sequentially into two groups:
Group 1 (10 volunteers): vaccinated with 5 x 10^7 pfu MVA85A
Group 2 (10 volunteers): vaccinated with 1 x 10^8 pfu MVA85A

Ethics approval

Gene Therapy Advisory Committee (GTAC) approved on the 12th May 2006 (ref: GTAC 116; EudraCT No.: 2006-000076-32)

Study design

Open label two arm active-controlled phase I study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Human immunodeficiency virus (HIV), tuberculosis (TB)

Intervention

MVA85A is a modified vaccinia virus Ankara expressing antigen 85A from Mycobacterium tuberculosis. Ten subjects will receive a single intradermal vaccination of 5 x 10^7 pfu (plaque forming units) of MVA85A and ten will receive a single intradermal vaccination of 1 x 10^8 pfu MVA85A. There is no control group.

Follow up is for 12 months.

Intervention type

Drug

Phase

Phase I

Drug names

MVA85A

Primary outcome measures

To assess the safety of a single intradermal injection of MVA85A, when administered to healthy subjects who are infected with HIV. Safety is measured throughout the one year follow up period, but specifically on the following days: 2, 7, 14, 28, 56, 84, 168 and 364. Blood for safety testing is taken at Days 7 and 28.

Secondary outcome measures

To assess the immunogenicity of a single intradermal injection of MVA85A, when administered to healthy subjects who are infected with HIV. Immunogenicity is measured throughout the one year follow up period, but specifically on the following days: 7, 14, 28, 56, 84, 168 and 364.

Overall trial start date

01/10/2006

Overall trial end date

01/08/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy adults aged 18 to 55 years (both male and female)
2. Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's HIV lead physician (and GP, if appropriate)
3. HIV antibody positive; diagnosed at least 6 months previously
4. CD4 count greater than 350; nadir CD4 not less than 300
5. HIV viral load not greater than 100,000 copies per ml
6. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

20

Participant exclusion criteria

1. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or on urinalysis
2. Any anti-retroviral (ARV) therapy within the past 6 months
3. Any acquired immune deficiency syndrome (AIDS) defining illness
4. Chest x-ray (CXR) showing tuberculosis (TB) or evidence of other active infection
5. Prior receipt of a recombinant MVA or Fowlpox vaccine
6. Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
7. Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination. (For corticosteroids, this will mean prednisolone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
8. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
9. Presence of any underlying disease that compromises the diagnosis and evaluation of response to the vaccine (including evidence of cardiovascular disease, history of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ), history of insulin requiring diabetes mellitus, any ongoing chronic illness requiring ongoing specialist supervision (e.g., gastrointestinal), and chronic or active neurological disease)
10. History of greater than two hospitalisations for invasive bacterial infections (pneumonia, meningitis)
11. Suspected or known current drug and/or alcohol abuse (as defined by an alcohol intake of greater than 42 units a week)
12. Seropositive for hepatitis B surface antigen (HBsAg) and/or hepatitis C (antibodies to HCV)
13. Evidence of serious psychiatric condition
14. Any other on-going chronic illness requiring hospital specialist supervision
15. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
16. Pregnant/lactating female and any female who is willing or intends to become pregnant during the study
17. Any history of anaphylaxis in reaction to vaccination
18. PI assessment of lack of willingness to participate and comply with all requirements of the protocol, or identification of any factor felt to significantly increase the participant's risk of suffering an adverse outcome

Recruitment start date

01/10/2006

Recruitment end date

01/08/2010

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Jenner Institute
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Centre of Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Oxford
OX3 7LJ
United Kingdom

Sponsor type

University/education

Website

http://www.ox.ac.uk/

Funders

Funder type

Charity

Funder name

The Wellcome Trust (UK) - Senior Clinical Fellowship Grant (grant ref: 076943)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/22102640

Publication citations

  1. Results

    Minassian AM, Rowland R, Beveridge NE, Poulton ID, Satti I, Harris S, Poyntz H, Hamill M, Griffiths K, Sander CR, Ambrozak DR, Price DA, Hill BJ, Casazza JP, Douek DC, Koup RA, Roederer M, Winston A, Ross J, Sherrard J, Rooney G, Williams N, Lawrie AM, Fletcher HA, Pathan AA, McShane H, A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults., BMJ Open, 2011, 1, 2, e000223, doi: 10.1136/bmjopen-2011-000223.

Additional files

Editorial Notes