Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine in Adults With TB Disease

Inclusion Criteria:

• Subjects who the investigator believes 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.
• 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, and
  • 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.
• Seronegative for HIV- 1 and -2 antibodies.
• No history of or current extrapulmonary tuberculosis TB. Additionally, based on medical history,

• Subjects in the TB-naive cohort must

  • have no active pulmonary disease as indicated by chest X-ray.
  • have no signs and symptoms of TB.
  • have no history of chemoprophylaxis or treatment for TB.

• Subjects in the TB-treated cohort must

  • have a history of successful treatment for pulmonary TB (completed at least 1 year prior to vaccination).
  • have no active pulmonary disease on chest X-ray.
• Subjects in the TB-treatment cohort must - have documented treatment for pulmonary TB (smear- or culture confirmed) ongoing for 2-4 months prior to vaccination.

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.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Any chronic drug therapy to be continued during the study period, which in the opinion of the investigator could adversely interfere with the vaccine.
• History of previous administration of experimental TB vaccines.
• History of previous exposure to components of the investigational vaccine within 30 days preceding the first dose of study vaccine.
• Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period.
• Planned participation or participation in another experimental protocol during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• History of chronic alcohol and/or drug abuse.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Major congenital defects.
• Pregnant female, lactating female or female planning to become pregnant or discontinue contraceptive precautions during the active phase of the study (from study start till 2 months after dose 2).

• Additionally, for the TB naïve and TB treated cohorts:

  - Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests

• Additionally, for the TB treatment cohort:

  • Acute or chronic clinically relevant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or laboratory screening tests. Individuals with grade 3 levels will be excluded.
  • Failure to convert while on anti-TB treatment at the end of the second month of anti-TB therapy.