Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine Given to PPD-Negative Adults

A Phase I Open Label, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Recombinant Mycobacterium Tuberculosis Vaccine, Mtb72F With AS02A Adjuvant, When Administered Intramuscularly to Healthy PPD-Negative Adults

This Phase I study will evaluate the safety and immunogenicity of two doses GSK Biologicals' candidate TB vaccine (692342) according to a 0, 1, 2 months schedule in PPD-negative adults.

Inclusion Criteria:

• Healthy male or female between 18 and 40 years of age at the time of screening
• Negative PPD skin test at screening.
• Subjects must have chest X-ray showing no evidence of pulmonary pathology.
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening, must not be breast-feeding and are required to use adequate contraception from enrolment till 1 month after dose 3.
• Screening laboratory values must be within the laboratory normal ranges.
• Negative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody.
• Subjects must give written informed consent.
• Subjects must be willing to make all evaluation visits, be readily reachable by telephone or personal contact by the study site personnel and have a permanent address.
• Subjects' resting seated vital signs must be within the protocol-defined ranges.

Exclusion Criteria:

• History of prior Bacillus Calmette-Guérin (BCG) vaccinations.
• History of documented exposure to Mycobacterium tuberculosis.
• History of previous administration of experimental Mycobacterium tuberculosis vaccines or previous exposure to experimental products containing components of the experimental vaccine.
• History of employment in a healthcare facility in a capacity that had direct or indirect contact with TB patients.
• Administration of any immunoglobulins or any immunotherapy within the 3 months preceding the first dose of study vaccination, and/or any blood products within the 4 months preceding HIV screening, or planned administrations during the study period.
• Use of St. John's Wort within six months of the Day 0 visit or planned administrations during the study period.
• Participation in another experimental protocol and/or receipt of any investigational products within 30 days prior to Day 0.
• History of autoimmune disease or causes of immunosuppressive states.
• History of any acute or chronic illness or medication that, in the opinion of the Investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
• History of significant psychiatric illness.
• Current drug or alcohol abuse
• History of previous anaphylaxis or severe allergic reaction to vaccines or any other allergen.
• Subjects who are, in the opinion of the investigator, at significantly increased risk of non-cooperation with requirements of the study protocol.
• Any chronic drug therapy to be continued during the study period, with the exception of vitamins and/or dietary supplements (including mineral preparations such as calcium carbonate), herbal medications except St. John's Wort, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (e.g. aspirin, ibuprofen), and acetominophen.
• Chronic administration (defined as more than 14 days total) of immunosuppressants or other immune modifying drugs within six months prior to the first vaccine dose.
• History of chronic or intermittently recurring illnesses such as migraine headaches, diabetes, heart disease, and asthma.
• Current administration of anti-TB prophylaxis or therapy.
• History of administration of a live attenuated virus vaccine within 30 days of enrollment.
• History of administration of a subunit or killed vaccine within 14 days of enrollment.