A Phase I Study of a New Tuberculosis (TB) Vaccine, MVA85A, in Healthy Volunteers With HIV

Tracking Information
First Submitted Date ICMJE	August 6, 2008
First Posted Date ICMJE	August 11, 2008
Last Update Posted Date	March 28, 2011
Study Start Date ICMJE	August 2008
Actual Primary Completion Date	January 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 8, 2008)	Safety of MVA85A [ Time Frame: Six months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00731471 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: August 8, 2008)	Immunogenicity of MVA85A [ Time Frame: Six months ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Phase I Study of a New Tuberculosis (TB) Vaccine, MVA85A, in Healthy Volunteers With HIV
Official Title ICMJE	A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine, MVA85A, in Healthy Volunteers Who Are Infected With HIV
Brief Summary	This is an open Phase I study of a candidate TB vaccine, MVA85A, in healthy subjects who are infected with HIV. It is designed to study the safety and immunogenicity of the vaccine.
Detailed Description	This study is designed to evaluate the safety of MVA85A in healthy volunteers in Senegal who are infected with HIV. In phase I studies, a single vaccination with MVA85A, when administered at a dose of 5 x 107pfu intradermally, has been shown to be safe in both mycobacterially naïve individuals, those previously vaccinated with BCG and latently infected individuals. We will use 1 x 10^8 pfu MVA85A intradermally in this study. A trial in BCG vaccinated subjects showed that the higher dose (1 x 10^8 pfu MVA85A) induced a significantly higher immune response but did not have a higher AE profile. In addition, because of a variable immune response, the trial in HIV positive subjects in the UK is split into two groups, the first getting 5 x 10^7 pfu and the second getting 1 x 10^8 pfu MVA85A. It has, therefore, been decided to use the higher dose in order to maximise the immune response whilst maintaining a good safety profile.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Condition ICMJE	Tuberculosis
Intervention ICMJE	Biological: MVA85A; Modified vaccinia virus Ankara expressing antigen 85A from Mycobacterium tuberculosis. Both arms will receive two vaccinations six months apart.
Study Arms	Experimental: 1 12 Healthy adults infected with HIV Intervention: Biological: MVA85A; Experimental: 2 12 HIV+ adults on antiretroviral therapy Intervention: Biological: MVA85A
Publications *	Dieye TN, Ndiaye BP, Dieng AB, Fall M, Brittain N, Vermaak S, Camara M, Diop-Ndiaye H, Ngom-Gueye NF, Diaw PA, Toure-Kane C, Sow PS, Mboup S, McShane H. Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naïve subjects gives comparable immunogenicity to one dose in ART+ subjects. PLoS One. 2013 Jun 28;8(6):e67177. doi: 10.1371/journal.pone.0067177. Print 2013. Erratum in: PLoS One. 2013;8(10). doi:10.1371/annotation/67550546-cacf-4063-8d62-d165da14ca61. Britain, Nathaniel [corrected to Brittain, Nathaniel].
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Estimated Enrollment ICMJE; (submitted: September 3, 2009)	24
Original Estimated Enrollment ICMJE; (submitted: August 8, 2008)	12
Actual Study Completion Date	January 2011
Actual Primary Completion Date	January 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Healthy adults aged 18 to 50 years; Resident in or near Dakar for the duration of the study; Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's HIV lead physician; Willing to use effective contraception throughout duration of study (if female); HIV antibody positive; diagnosed at least 6 months previously; CD4 count >300; Arm 1: HIV viral load not >100,000 copies per millilitre; Arm 2: Undetectable HIV viral load; Written informed consent Exclusion Criteria: Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or on urinalysis; Group 1 only: Any ARV therapy within the past 6 months; Previous history of TB disease and/or treatment; Any AIDS defining illness; Group 1: CD4 count nadir <300; Group 2: CD4 count nadir <100; CXR showing TB or evidence of other active infection; 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, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed.); History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products; 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); History of > 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis); Suspected or known current drug and/or alcohol abuse; Seropositive for hepatitis B surface antigen (HBsAg) and/ or hepatitis C (antibodies to HCV); Evidence of serious psychiatric condition; Any other on-going chronic illness requiring hospital specialist supervision; Any confirmed or suspected immunosuppressive or immunodeficient condition, other than HIV infection, such as asplenia; Evidence of hepatomegaly; Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate; Pregnant/lactating female and any female who is willing or intends to become pregnant during the study; Any history of anaphylaxis in reaction to vaccination; 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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 50 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Senegal
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00731471
Other Study ID Numbers ICMJE	TB019
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Dr Helen McShane, University of Oxford
Study Sponsor ICMJE	University of Oxford
Collaborators ICMJE	Centre Hospitalier Universitaire Le Dantec, Dakar, Senegal
Investigators ICMJE	Principal Investigator: Helen McShane University of Oxford Principal Investigator: Souleymane Mboup Centre Hospitalier Universitaire Le Dantec
PRS Account	University of Oxford
Verification Date	March 2011
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP