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

NCT00395720 | Completed Phase 1 DMC

• 1 other identifier: TB010
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis; HIV Infections

Keywords

TB; Tuberculosis; HIV; Vaccine; MVA85A; HIV Therapeutic Vaccine

Outcome Measures

Primary Outcomes (1)

• Data on adverse events

  1 year

Secondary Outcomes (1)

• Immune responses

  1 year

Study Arms (2)

1

ACTIVE COMPARATOR

Group 1 (10 volunteers): 5 x 10\^7 pfu

Biological: MVA85A (TB vaccine); Biological: MVA 85A

2

ACTIVE COMPARATOR

Group 2 (10 volunteers): 1 x 10\^8 pfu

Biological: MVA85A (TB vaccine); Biological: MVA 85A

Interventions

MVA85A (TB vaccine) BIOLOGICAL

Intradermal vaccine

Also known as: TB vaccine

1; 2

MVA 85A BIOLOGICAL

Intradermal vaccine

Also known as: TB Vaccine, modified vaccinia virus Ankara

1; 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 8309034 BACKGROUND

• 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. doi: 10.1128/IAI.69.2.681-686.2001.

  PMID: 11159955 BACKGROUND

• 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. doi: 10.1038/nm0896-893.

  PMID: 8705859 BACKGROUND

• 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. doi: 10.1016/s0264-410x(03)00538-3.

  PMID: 14604567 BACKGROUND

• 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. doi: 10.1086/501459. Epub 2006 Mar 14.

  PMID: 16575727 BACKGROUND

• 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. doi: 10.4049/jimmunol.171.3.1602.

  PMID: 12874255 BACKGROUND

• 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. doi: 10.1038/nm1128. Epub 2004 Oct 24.

  PMID: 15502839 BACKGROUND

MeSH Terms

Conditions

Tuberculosis; HIV Infections

Interventions

MVA 85A; MVA Pfs25-IMX313 malaria vaccine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Helen McShane, Dr

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 2, 2006
• First Posted: November 3, 2006
• Study Start: November 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: March 28, 2011

Record last verified: 2011-03

Locations

GB (1)