Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Human Immunodeficiency Virus (HIV)-Positive Adults

• Occurrence of grade 3 solicited local and general adverse events [ Time Frame: During the 7-day follow-up period following vaccination. ] [ Designated as safety issue: No ]
• Occurrence of grade 3 unsolicited adverse events [ Time Frame: During the 30-day follow-up period following vaccination. ] [ Designated as safety issue: No ]
• Occurrence of serious adverse events [ Time Frame: From screening up to one month post dose 2. ] [ Designated as safety issue: No ]
• Grade 3 haematological and biochemical levels at baseline [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
• Grade 3 haematological and biochemical levels post dose 1 (Day 7) [ Time Frame: post dose 1 (Day 7) ] [ Designated as safety issue: No ]
• Grade 3 haematological and biochemical levels post dose 1 (Day 30) [ Time Frame: post dose 1 (Day 30) ] [ Designated as safety issue: No ]
• Grade 3 haematological and biochemical levels post dose 2 (Day 37) [ Time Frame: post dose 2 (Day 37) ] [ Designated as safety issue: No ]
• Grade 3 haematological and biochemical levels post dose 2 (Day 60) [ Time Frame: post dose 2 (Day 60) ] [ Designated as safety issue: No ]

• Humoral immunogenicity [ Time Frame: At Day 0, post dose 1 (day 30) and post dose 2 (Days 60, 210 and years 1, 2 and 3) ] [ Designated as safety issue: No ]
• Cell-mediated immunogenicity [ Time Frame: At Day 0, post dose 1 (Days 7 and 30) and post dose 2 (Days 37, 60, 210 and years 1, 2 and 3) ] [ Designated as safety issue: No ]
• Occurrence of any solicited local and general adverse events [ Time Frame: During the 7-day follow-up period following vaccination ] [ Designated as safety issue: No ]
• Occurrence of any unsolicited adverse events [ Time Frame: During the 30-day follow-up period following vaccination ] [ Designated as safety issue: No ]
• Occurrence of serious adverse events [ Time Frame: From 1 month post dose 2 up to study end ] [ Designated as safety issue: No ]
• Haematological and biochemical levels [ Time Frame: Day 0, post dose 1 (Days 7 and 30) and post dose 2 (Days 37 and 60) ] [ Designated as safety issue: No ]

• Humoral immunogenicity [ Time Frame: At Day 0, one month post dose 1 and post dose 2 and 6 months post dose 2 ] [ Designated as safety issue: No ]
• Cell-mediated immunogenicity [ Time Frame: At Day 0, 7 days and one month post dose 1 and post dose 2 and 6 months post dose 2 ] [ Designated as safety issue: No ]
• Occurrence of any solicited local and general adverse events [ Time Frame: During the 7-day follow-up period following vaccination ] [ Designated as safety issue: No ]
• Occurrence of any unsolicited adverse events [ Time Frame: During the 30-day follow-up period following vaccination ] [ Designated as safety issue: No ]
• Occurrence of serious adverse events [ Time Frame: From 1 month post dose 2 up to study end ] [ Designated as safety issue: No ]
• Haematological and biochemical levels [ Time Frame: Day 0, post dose 1 (Days 7 and 30) and post dose 2 (Days 37 and 60) ] [ Designated as safety issue: No ]

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.

This Protocol Posting has been updated following Protocol Amendment 1, February 2011, leading to the update of the outcome measures and the inclusion and exclusion criteria.

• Biological: GSK's investigational vaccine 692342
  Intramuscular, 2 doses
• Biological: Physiological saline
  Intramuscular, 2 doses

• Experimental: Group A
  HIV-positive subjects on highly active anti retroviral therapy will receive GlaxoSmithKline's (GSK's) investigational vaccine 692342.
  Intervention: Biological: GSK's investigational vaccine 692342
• Placebo Comparator: Group B
  HIV-positive subjects on highly active anti retroviral therapy will receive physiological saline.
  Intervention: Biological: Physiological saline
• Experimental: Group C
  Treatment naïve HIV-positive subjects will receive GSK's investigational vaccine 692342.
  Intervention: Biological: GSK's investigational vaccine 692342
• Placebo Comparator: Group D
  Treatment naïve HIV-positive subjects will receive physiological saline.
  Intervention: Biological: Physiological saline
• Experimental: Group E
  HIV negative subjects will receive GSK's investigational vaccine 692342.
  Intervention: Biological: GSK's investigational vaccine 692342
• Placebo Comparator: Group F
  HIV negative subjects will receive physiological saline.
  Intervention: Biological: Physiological saline

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.