Efficacy Against TB Disease, Safety, and Immunogenicity of MVA85A/AERAS-485 in HIV-Infected Adults (C-030-485)
Condition: Tuberculosis; HIV Infections
MeSH terms: Tuberculosis
Intervention: MVA85A/AERAS-485; Placebo
Intervention description: Subjects received intradermal injection of MVA85A/AERAS-485 on Study Day 0, followed 6-9 months later by a booster injection of MVA85A/AERAS-485.; Subjects received an intradermal injection placebo on Study Day 0, followed 6-9 months later by a booster injection of placebo.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 650.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: HIV; Tuberculosis; Vaccine

Summary:

      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 650 adults subjects (ages 18-50 years of age inclusive) who will
      receive study vaccine or placebo at Study Day 0 and again 6-9 months later. Samples for
      real-time evaluation of immunogenicity were to be collected from 70 subjects (immunogenicity
      analysis set).
    

Eligibility criteria:

        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, polymerase chain reaction (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
             purified protein derivative (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 Prevention of Mother-to-Child Transmission
             [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 modified vaccinia Ankara (MVA) or fusion protein
             (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