Tuberculosis Clinical Trial
Official title:
A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine, MVA85A, in Healthy Volunteers Who Are Latently Infected With Mycobacterium Tuberculosis.
This study is designed to evaluate the safety of MVA85A in healthy volunteers in the UK who are latently infected with M.tb. A single vaccination with MVA85A, when administeredat a dose of 5 x 107pfu intradermally, is safe in both mycobacterially naïve individuals and those previously vaccinated with BCG. We will use the same vaccination regime in this study. Subjects will be defined as being latently infected if they have a positive elispot response to ESAT6 or CFP10. Subjects will be identified from TB contact clinics.
Status | Completed |
Enrollment | 12 |
Est. completion date | April 2007 |
Est. primary completion date | |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 18 Years to 50 Years |
Eligibility |
Inclusion Criteria - Healthy adults aged 18 to 50 years - Resident in or near Oxford for the duration of the vaccination study - Willingness to allow the investigators to discuss the volunteer’s medical history with the volunteer’s GP - Screening Elispot positive (more than 50 spots/million PBMC) for at least any 1 of the 3 ESAT6 peptide pools or any one of the 3 CFP10 pools ; and screening Elispot positive for PPD. - Heaf test grade II-IV or positive Mantoux test. - CXR normal; or abnormal but not clinically significant CXR findings with no evidence of past/present TB infection or disease on the CXR. - For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day of vaccination - Agreement to refrain from blood donation during the course of the study - Written informed consent - Willingness to undergo an HIV Exclusion Criteria - Any deviation from the normal range in biochemistry or haematology blood tests or in urine analysis - Heaf grade IV - Prior receipt of a recombinant MVA or Fowlpox vaccine - 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 - 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, e 0.5 mg/kg/day. Inhaled and topical steroids are allowed.) - Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection and asplenia - History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products - 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 - Chronic or active neurological disease requiring ongoing specialist supervision |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Country | Name | City | State |
---|---|---|---|
United Kingdom | Centre for Clinical Vaccinology and Tropical Medicine | Oxford | Oxfordshire |
Lead Sponsor | Collaborator |
---|---|
University of Oxford |
United Kingdom,
Bejon P, Peshu N, Gilbert SC, Lowe BS, Molyneux CS, Forsdyke J, Lang T, Hill AV, Marsh K. Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria antigens, ME-TRAP or the circumsporozoite protein, in children and adults in Kenya. Clin Infect Dis. 2006 Apr 15;42(8):1102-10. Epub 2006 Mar 14. — View Citation
Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994 Mar 2;271(9):698-702. — View Citation
Goonetilleke NP, McShane H, Hannan CM, Anderson RJ, Brookes RH, Hill AV. Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guérin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J Immunol. 2003 Aug 1;171(3):1602-9. — View Citation
Huygen K, Content J, Denis O, Montgomery DL, Yawman AM, Deck RR, DeWitt CM, Orme IM, Baldwin S, D'Souza C, Drowart A, Lozes E, Vandenbussche P, Van Vooren JP, Liu MA, Ulmer JB. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med. 1996 Aug;2(8):893-8. — View Citation
McShane H, Brookes R, Gilbert SC, Hill AV. Enhanced immunogenicity of CD4(+) t-cell responses and protective efficacy of a DNA-modified vaccinia virus Ankara prime-boost vaccination regimen for murine tuberculosis. Infect Immun. 2001 Feb;69(2):681-6. — View Citation
McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, Hill AV. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med. 2004 Nov;10(11):1240-4. Epub 2004 Oct 24. Erratum in: Nat Med. 2004 Dec;10(12):1397. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety of a single intradermal injection of 5 x 107pfu MVA85A | One year | ||
Secondary | Efficacy | One year | ||
Secondary | latently infected with MVA85A on the immune response, both to antigen 85A (the antigen in | |||
Secondary | the vaccine) and to ESAT6/CFP10 antigens (M.tb specific). | |||
Secondary | Endpoints: | |||
Secondary | The specific endpoints for safety and reactogenicity will be actively and passively collected | |||
Secondary | data on adverse events (AEs). The specific endpoints for immunogenicity will be markers of | |||
Secondary | cell-mediated immunity as described below. |
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