A phase I study evaluating the safety and immunogenicity of a new tuberculosis (TB) vaccine, MVA85A, in healthy volunteers who are infected with human immunodeficiency virus (HIV)
| ISRCTN | ISRCTN34189114 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN34189114 |
| EudraCT/CTIS number | 2006-000076-32 |
| ClinicalTrials.gov number | NCT00395720 |
| Secondary identifying numbers | 076943; TB010 |
- Submission date
- 14/12/2009
- Registration date
- 18/12/2009
- Last edited
- 31/07/2013
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
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.
Contact information
Scientific
Jenner Institute
Old Road Campus Research Building
University of Oxford
Oxford
OX3 7DQ
United Kingdom
Study information
| Study design | Open label two arm active-controlled phase I study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study objectives | 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(s) | Gene Therapy Advisory Committee (GTAC) approved on the 12th May 2006 (ref: GTAC 116; EudraCT No.: 2006-000076-32) |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | MVA85A |
| Primary outcome measure | 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 study start date | 01/10/2006 |
| Completion date | 01/08/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 20 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/10/2006 |
| Date of final enrolment | 01/08/2010 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
OX3 7DQ
United Kingdom
Sponsor information
University/education
Centre of Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Oxford
OX3 7LJ
England
United Kingdom
| Website | http://www.ox.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 14/11/2011 | Yes | No |
