Protective Efficacy Against Tuberculosis (TB) Disease, Safety, and Immunogenicity of MVA85A/AERAS-485 in HIV-Infected Adults

This is a phase II, proof of concept, randomized, double-blind, placebo-controlled study to evaluate the protective efficacy against TB disease, safety, and immunogenicity of MVA85A/AERAS-485 in healthy, HIV-infected adults.

This study consists of 1400 adults subjects (ages 18-50 years of age inclusive) who will receive study vaccine or control at Study Day 0.

Further study details as provided by Aeras Global TB Vaccine Foundation.

• Tuberculosis
• HIV Infections

• Biological: MVA85A/AERAS-485
  MVA85A/AERAS-485 is a recombinant modified vaccinia virus Ankara expressing the M. tuberculosis antigen, Ag85A. Dosage of the study vaccine to be administered will be 1x10^8 pfu.
  Other Name: MVA85A/AERAS-485
• Biological: Candida albicans Skin Test Antigen
  Candin® is a licensed product manufactured by Allermed, Inc. and is used for evaluation of delayed-type of hypersensitivity reactions in adults. It is produced from a culture filtrate of two strains of Candida albicans grown on a defined medium of inorganic salts, biotin, and sucrose. Candin® will be administered at the same dose volume as MVA85A/AERAS-485.
  Other Name: Candin®

• Placebo Comparator: Candin®
  A maximum of 700 subjects will receive Candin® as placebo control.
  Intervention: Biological: Candida albicans Skin Test Antigen
• Experimental: MVA85A/AERAS-485
  A maximum of 700 subjects will receive MVA85A/AERAS-485 as active.
  Intervention: Biological: MVA85A/AERAS-485

Inclusion Criteria:

• Has completed the written informed consent process prior to undergoing any screening evaluations.
• Either males or females aged 18-50 years (inclusive) on Study Day 0
• In general good health, confirmed by medical history and physical examination
• Has ability to complete follow-up period as required by the protocol
• Has laboratory evidence of human immunodeficiency virus (HIV) infection, defined as a positive HIV-1 ELISA test plus a positive confirmatory test (e.g., a second HIV-1 ELISA, PCR, or rapid ELISA) diagnosed prior to randomization
• Is willing to allow the investigators to discuss the subject's medical history with the subject's HIV physician
• Has 2 CD4+ lymphocyte count test results >350 cells/mm3, performed at least 4 weeks apart, one performed within 6 months prior to randomization and one within 30 days prior to randomization
• Has either: a) a negative QuantiFERON-TB Gold In-Tube test result and tuberculin PPD skin test ≤5 mm induration within 30 days prior to randomization or; b) a positive QuantiFERON-TB Gold In-Tube test result and/or tuberculin PPD skin test >5 mm and has completed 6 months of isoniazid preventive therapy prior to randomization or; c) a positive QuantiFERON-TB Gold In-Tube test result and/or tuberculin PPD skin test >5 mm and has completed treatment for TB disease within 3 year prior to randomization
• Females: Ability to avoid pregnancy during the trial. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must avoid pregnancy by using an acceptable method of avoiding pregnancy from 28 days prior to administration of the study vaccine through the end of the study. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the use of a condom or a diaphragm combined with spermicide.
• Has completed the written informed consent process for simultaneous enrollment in Aeras Vaccine Development Registry protocol

Exclusion Criteria:

• Acute illness
• Fever (temperature > 37.5°C)
• Significant symptomatic infection
• Any evidence of active tuberculosis (TB) disease, as determined by any clinical, radiological, or microbiology measurements.
• Any AIDS defining illness by WHO criteria
• Has received antiretroviral therapy (ART) in the two months prior to study entry (women who have received ART as part of the PMTCT program and completed this more than 2 months prior to randomization ARE eligible)
• Use of any investigational or non-registered drug, vaccine or medical device other than the study vaccine within 182 days preceding dosing of study vaccine, or planned use during the study period
• Previous receipt of a recombinant MVA or FP vector at any time.
• Is enrolled in any other clinical product trial
• Administration of methotrexate, azathioprine, cyclophosphamide, oral corticosteroids (for corticosteroids, this will mean prednisolone, or equivalent, ≥0.5 mg/kg/day; inhaled and topical steroids are allowed) and other immunosuppressive therapies, or blood products or blood derivatives within the six months prior to randomization
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
• Presence of any history of cancer [except basal cell carcinoma of the skin and cervical carcinoma in situ], or renal failure
• Evidence of severe depression, schizophrenia or mania
• Pregnant females and females who are breast-feeding
• Any history of anaphylaxis in reaction to vaccination
• Principal investigator assessment of lack of willingness to participate and comply with the protocol, or increase in the participant's risk of adverse outcome

• University of Oxford
• European and Developing Countries Clinical Trials Partnership (EDCTP)