Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Human Immunodeficiency Virus (HIV)-Positive Adults
Condition: Tuberculosis
MeSH terms: Tuberculosis
Intervention: GSK's investigational vaccine 692342; Physiological saline
Intervention description: Intramuscular, 2 doses; Intramuscular, 2 doses
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 240.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Tuberculosis vaccine

Summary:

      The purpose of the study is to assess the safety and immunogenicity of a GlaxoSmithKline
      (GSK) Biologicals' candidate tuberculosis vaccine (692342) administered to Human
      Immunodeficiency Virus (HIV)-positive adults aged 18 to 59 years, living in a tuberculosis
      endemic region.

      Subjects will be followed-up for 3 years.

      Subjects will be enrolled in 3 cohorts:

        -  HIV-positive adults on highly active antiretroviral therapy

        -  HIV-positive adults not on highly active antiretroviral therapy

        -  HIV-negative adults

      Each cohort will have 2 groups.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who the investigator believes that they can and will comply with the
             requirements of the protocol.

          -  A male or female between, and including, 18 and 59 years of age at the time of the
             first vaccination.

          -  Written informed consent obtained from the subject prior to any study procedure.

          -  Female subjects of non-childbearing potential may be enrolled in the study.

          -  Female subjects of childbearing potential may be enrolled in the study, if the
             subject:

               -  has practiced adequate contraception for 30 days prior to vaccination,

               -  has a negative pregnancy test on the day of vaccination, and

               -  has agreed to continue adequate contraception during the entire treatment period
                  and for 2 months after completion of the vaccination series.

          -  Clinically acceptable laboratory values at screening as determined by the
             investigator.

          -  No evidence of tuberculosis disease with no evidence of pulmonary pathology as
             confirmed by chest X-ray.

          -  No history of extra pulmonary tuberculosis.

          -  Based on their medical history, all subjects must have no history of chemotherapy for
             tuberculosis.

        Additional inclusion criteria for subjects to be enrolled in HIV+ on highly active
        antiretroviral therapy cohort:

          -  Subjects must be HIV-positive and under care of a physician for at least 6 months.

          -  Subjects must have a CD4+T cell count >= 250 cells/mm3 at screening.

          -  Subjects must be stable on highly active antiretroviral therapy for at least 6 months,
             with an undetectable HIV viral load level at screening.

        Additional inclusion criteria for subjects to be enrolled in HIV+ treatment naïve cohort:

          -  Subjects must be HIV-positive and under care of a physician for at least 6 months

          -  Subjects must be highly active antiretroviral therapy-naïve (never received
             anti-retroviral therapy after HIV diagnosis)

          -  Subjects must have a CD4 + T cell count above 350 cells/mm3 at screening.

          -  Subjects for whom commencement of highly active antiretroviral therapy is not expected
             based on current assessment within next year.

          -  Subjects must have a viral load between 5000 - 80000 copies/mL at screening.

        Additional inclusion criteria for subjects to be enrolled in HIV-negative cohort

        • Subjects must be negative for HIV-1.

        Exclusion Criteria:

          -  Use of any investigational or non-registered product other than the study vaccine
             within 30 days preceding the first dose of study vaccine, or planned use during the
             study period.

          -  Administration of a registered live vaccine not foreseen by the study within 30 days
             preceding the first dose of study vaccine and administration of a registered
             inactivated vaccine within 14 days preceding the first dose of study vaccine.

          -  History of previous administration of experimental Mtb vaccines.

          -  History of previous exposure to components of the investigational vaccine within 30
             days preceding the first dose of study vaccine

          -  Chronic administration of immunosuppressant or other immune-modifying drugs within six
             months prior to the first vaccine/product dose. For corticosteroids, this will mean
             prednisone >= 20 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed.

          -  Any condition or illness or medication, which in the opinion of the Investigator might
             interfere with the evaluation of the safety or immunogenicity of the vaccine.

          -  Planned participation or participation in another experimental protocol with an
             experimental product during the study period.

          -  Administration of any immunoglobulin, any immunotherapy and/or any blood products
             within the three months preceding the first dose of study vaccination, or planned
             administrations during the study period.

          -  Subjects taking any of the following medication: chronic administration of systemic
             steroids, interleukins, systemic interferon or systemic chemotherapy.

          -  History of allergic reactions or anaphylaxis to any drug or vaccine.

          -  History of allergic disease or reactions likely to be exacerbated by any component of
             the vaccine.

          -  History of chronic alcohol consumption and/or drug abuse which in the Investigator's
             opinion would put the subject at risk.

          -  Pregnant female, lactating female or female planning to become pregnant or stop
             contraception.

          -  Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal
             function abnormality as determined by physical examination or laboratory screening
             tests.

        Additional exclusion criteria for subjects to be enrolled in HIV+ on highly active
        antiretroviral therapy cohort:

          -  Any change in anti-retroviral drug regimen within 12 weeks prior to screening.

          -  Any chronic drug therapy, other than highly active antiretroviral therapy or
             prophylaxis for opportunistic HIV related infections, birth control pills,
             anti-histamines for seasonal allergies and SSRIs.