The Safety and Immunogenicity of a TB Vaccine; MVA85A, in Healthy Volunteers Who Are Infected With HIV - Full Text View

Sponsor:	University of Oxford
Information provided by:	University of Oxford
ClinicalTrials.gov Identifier:	NCT00395720

Purpose

This study is designed to evaluate the safety of MVA85A in healthy volunteers in the UK who are infected with HIV. In phase I studies, a single vaccination with MVA85A, when administered at a dose of 5 x 10^7pfu intradermally, has been shown to be safe in both mycobacterially naïve individuals, those previously vaccinated with BCG and latently infected individuals. Additionally, 5 x 10^7 pfu MVA containing HIV antigens administered twice, 4 weeks apart, in HIV positive individuals, is safe. We will use 5 x 107 pfu MVA85A intradermally in this study. Subjects will be identified from HIV clinics in the Oxford Radcliffe Hospitals NHS Trust and also from Swindon and Marlborough NHS Trust and St. Mary's Hospital NHS Trust if our recruitment targets are not met.

Condition	Intervention	Phase
Tuberculosis HIV Infections	Biological: MVA85A (TB vaccine) Biological: MVA 85A	Phase I

Study Type:	Interventional
Study Design:	Prevention, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety Study
Official Title:	A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine, MVA85A, in Healthy Volunteers Who Are Infected With HIV

Resource links provided by NLM:

MedlinePlus related topics: AIDS Tuberculosis

U.S. FDA Resources

Further study details as provided by University of Oxford:

Primary Outcome Measures:

Data on adverse events [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Immune responses [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	November 2006
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Group 1 (10 volunteers): 5 x 10^7 pfu	Biological: MVA85A (TB vaccine) Intradermal vaccine Biological: MVA 85A Intradermal vaccine
2: Active Comparator Group 2 (10 volunteers): 1 x 10^8 pfu	Biological: MVA85A (TB vaccine) Intradermal vaccine Biological: MVA 85A Intradermal vaccine

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Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy adults aged 18 to 50 years
Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's HIV lead physician (and GP, if appropriate)
BCG vaccinated
HIV antibody positive; diagnosed at least 6 months previously
CD4 count >350; nadir CD4 not < 300
HIV viral load not > 100,000 copies per millilitre
Written informed consent

Exclusion Criteria:

Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or on urinalysis
Any ARV therapy within the past 6 months
Any AIDS defining illness
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 (as defined by an alcohol intake of >42 units a week)
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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00395720

Locations

United Kingdom, Oxfordshire
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, United Kingdom, OX3 7LJ

Sponsors and Collaborators

University of Oxford

Investigators

Principal Investigator:

Helen McShane, Dr

University of Oxford

More Information

Publications:

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.

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.

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.

Cosma A, Nagaraj R, Buhler S, Hinkula J, Busch DH, Sutter G, Goebel FD, Erfle V. Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals. Vaccine. 2003 Dec 8;22(1):21-9.

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.

Goonetilleke NP, McShane H, Hannan CM, Anderson RJ, Brookes RH, Hill AV. Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guerin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J Immunol. 2003 Aug 1;171(3):1602-9.

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.

Responsible Party:	University of Oxford ( Dr Helen McShane )
Study ID Numbers:	TB010
Study First Received:	November 2, 2006
Last Updated:	February 8, 2010
ClinicalTrials.gov Identifier:	NCT00395720 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:

TB
Tuberculosis
HIV
Vaccine

MVA85A
HIV
HIV Therapeutic Vaccine

Additional relevant MeSH terms:

Bacterial Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Immune System Diseases
Acquired Immunodeficiency Syndrome
Infection
Actinomycetales Infections
Immunologic Deficiency Syndromes

Virus Diseases
Gram-Positive Bacterial Infections
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
Mycobacterium Infections
Tuberculosis
Retroviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010