Study to Evaluate the Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine in Adults

• Incident cases of definite Xpert MTB/RIF pulmonary TB disease not associated with HIV-infection, meeting the second case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Incident cases of definite pulmonary TB disease meeting the third case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Incident cases of Microbiological Pulmonary TB disease meeting the fourth case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Incident cases of clinical TB disease meeting the fifth case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Occurrence of serious adverse events. [ Time Frame: During the entire study period (Day 0 to Month 36). ]
• Occurrence of unsolicited adverse events. [ Time Frame: During the 30 day follow-up period following vaccination (day of vaccination and 29 subsequent days after each vaccine dose). ]
• Occurrence of solicited local and general adverse events in the safety and immune sub-cohort. [ Time Frame: During the 7 day follow-up period following vaccination (day of vaccination and 6 subsequent days after each vaccine dose). ]
• Occurrence of all potential immune-mediated diseases (pIMDs). [ Time Frame: Over a period starting at Day 0 until 6 months post dose 2 (Month 7). ]
• Evaluation of Cell-mediated Immune (CMI) responses in the safety and immune sub-cohort in terms of frequency of M72-specific CD4+/CD8+ T cells expressing TNF-α and/or IFN-γ and/or IL-2 and/or CD40L per million cells identified after in vitro stimulation. [ Time Frame: Prior to dose 1 (Day 0), 1 month post dose 2 (Day 60) and Years 1, 2 and 3. ]
• Evaluation of humoral responses with respect to components of the study vaccine, in the safety and immune sub-cohort in terms of M72-specific antibody titres and seropositivity rates as measured by ELISA. [ Time Frame: Prior to dose 1 (Day 0), 1 month post dose 2 (Day 60) and Years 1, 2 and 3. ]
• Occurrence of grade ≥ 2 haematological and biochemical levels in the safety and immune sub-cohort. [ Time Frame: Days 0, 7, 30 and 37. ]

• Incident cases of definite Xpert MTB/RIF pulmonary TB disease not associated with HIV-infection, meeting the second case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Incident cases of definite pulmonary TB disease meeting the third case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Incident cases of definite pulmonary TB disease meeting the fourth case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Incident cases of clinical TB disease meeting the fifth case definition. [ Time Frame: Over a period starting 1 month post dose 2 (Month 2) and lasting up to 35 months post last vaccination (Month 36). ]
• Occurrence of serious adverse events. [ Time Frame: During the entire study period (Day 0 to Month 36). ]
• Occurrence of unsolicited adverse events. [ Time Frame: During the 30 day follow-up period following vaccination (day of vaccination and 29 subsequent days after each vaccine dose). ]
• Occurrence of solicited local and general adverse events in the safety and immune sub-cohort. [ Time Frame: During the 7 day follow-up period following vaccination (day of vaccination and 6 subsequent days after each vaccine dose). ]
• Occurrence of all potential immune-mediated diseases (pIMDs). [ Time Frame: Over a period starting at Day 0 until 6 months post dose 2 (Month 7). ]
• Evaluation of Cell-mediated Immune (CMI) responses in the safety and immune sub-cohort in terms of frequency of M72-specific CD4+/CD8+ T cells expressing TNF-α and/or IFN-γ and/or IL-2 and/or CD40L per million cells identified after in vitro stimulation. [ Time Frame: Prior to dose 1 (Day 0), 1 month post dose 2 (Day 60) and Years 1, 2 and 3. ]
• Evaluation of humoral responses with respect to components of the study vaccine, in the safety and immune sub-cohort in terms of M72-specific antibody titres and seropositivity rates as measured by ELISA. [ Time Frame: Prior to dose 1 (Day 0), 1 month post dose 2 (Day 60) and Years 1, 2 and 3. ]

Case Definitions:

• First case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture and confirmed HIV-negative at the time of TB diagnosis.

• Second case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken before initiation of TB treatment, by Xpert MTB/RIF and confirmed HIV-negative at the time of TB diagnosis.

• Third case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken up to four weeks after initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture and confirmed HIV-negative at the time of TB diagnosis.

• Fourth case definition: A subject with clinical suspicion of pulmonary TB disease, with MTB complex identified from a sputum specimen, taken up to four weeks after initiation of TB treatment, by Xpert MTB/RIF and/or microbiological culture.

• Fifth case definition: A subject for whom a clinician has diagnosed TB disease and has decided to treat the patient with TB treatment.

• Biological: GSK Biologicals' investigational TB vaccine (GSK692342)
  2 doses administered intramuscularly in the deltoid region of the arm.
• Biological: Placebo
  2 doses administered intramuscularly in the deltoid region of the arm.

• Experimental: Vaccine group
  Subjects will receive 2 doses of the candidate tuberculosis vaccine (Day 0 and Day 30).
  Intervention: Biological: GSK Biologicals' investigational TB vaccine (GSK692342)
• Placebo Comparator: Control group
  Subjects will receive 2 doses of placebo (Day 0 and Day 30).
  Intervention: Biological: Placebo

Inclusion Criteria:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• A male or female between, and including, 18 and 50 years of age at the time of obtaining informed consent.
• Written (or thumb printed and witnessed) informed consent obtained from the subject.
• Baseline positive IGRA test result.
• Baseline negative HIV screen.
• Baseline negative clinical screening questionnaire and negative sputum sample for Pulmonary TB disease.
• Healthy subjects or those with chronic well-controlled disease as established by medical history and clinical examination.

• Female subjects of non-childbearing potential may be enrolled in the study.

  • Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

• Female subjects of childbearing potential may be enrolled in the study, if the subject:

  • has practiced adequate contraception for 25 days prior to vaccination, and
  • has a negative pregnancy test on the day of screening and the day of first vaccination, and
  • has agreed to continue adequate contraception during the entire vaccination period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Current TB disease or history of TB disease and/or treatment for TB.
• Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after each dose of vaccine.
• History of previous administration of experimental Mtb vaccines.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. 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.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Planned participation or participation in another experimental protocol during the study.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
• History of medically confirmed autoimmune disease.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions during the vaccination period and/or before 2 months after completion of the vaccination series.