safety and immunogenicity of a candidate tuberculosis (tb) vaccine in adults with tb disease

Conditions: Tuberculosis

Summary: this study will assess the safety and immunogenicity of gsk biologicals' investigational tuberculosis (tb) vaccine (gsk 692342) compared to placebo when administered at 0, 1 months to human immunodeficiency virus (hiv) negative adults who have received treatment for tb disease (denoted tb-treated cohort) or are currently receiving treatment for tb disease (denoted tb-treatment cohort). for comparative purposes, subjects who have never had tb disease (denoted tb-naïve cohort) will also be enrolled.

a protocol amendment 1, may 2012, was made following the decision to add a second country in the study (i.e. estonia).

Eligibility criteria:
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.

Keywords: tuberculosis vaccine hiv-negative tuberculosis treatment