A Phase I Study of Safety & Immunogenicity of AERAS-456 in HIV-Neg. Adults Treated for Drug-susceptible Pulmonary TB
Condition: Tuberculosis
MeSH terms: Tuberculosis
Intervention: H56:IC31; Placebo
Intervention description: H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c).; The placebo consists of 10mM Tris and 169 mM NaCl pH 7.4.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      This is a Phase I, double-blind, randomized, placebo-controlled safety and immunogenicity
      study in adults who have recently been successfully treated for drug-susceptible pulmonary
      Tuberculosis (TB). The safety and immunogenicity profile of escalating doses of AERAS-456 in
      HIV-negative subjects recently treated for drug-susceptible pulmonary TB will be
      investigated. The study will be conducted at three sites in South Africa.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is HIV-negative.

          2. Is male or female aged 18 through 60 years on Study Day 0.

          3. Has completed the written informed consent process.

          4. Has a diagnosis of confirmed pulmonary tuberculosis and is on standard TB treatment.

          5. Is confirmed to be Mtb negative by either 2 GeneXpert tests or 2 cultures from sputum
             samples taken on 2 different days at least 1 week apart, the first after at least 4
             calendar months of TB treatment and the second day not later than after 5 calendar
             months (with a window of plus 1 week) of treatment.

          6. Agrees to complete the prescribed course of TB treatment (completion of TB treatment
             can occur after vaccination on Study Day 0; subject must have completed at least 5
             calendar months of TB treatment on Study Day 0; if TB treatment is completed before
             randomization/vaccination then the time from completion of TB treatment to
             randomization/vaccination should not exceed 28 days).

          7. For female subjects: agrees to avoid pregnancy between screening and up until two
             months after last vaccination. Women physically capable of pregnancy (not sterilized
             and still menstruating or within 1 year of the last menses if menopausal) in sexual
             relationships with men must use an acceptable method of avoiding pregnancy from 28
             days prior to administration of study vaccine up until two months after the last
             vaccination. Acceptable methods of avoiding pregnancy include a sterile sexual
             partner, sexual abstinence (not engaging in sexual intercourse), hormonal
             contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, or
             intrauterine device (IUD).

          8. Agrees to stay in contact with the study site for the full duration of the study,
             providing updated contact information as necessary, and has no current plans to move
             from the study area during the duration of the study.

        Exclusion Criteria:

          1. Evidence of a new acute illness that may compromise the safety of the subject in the
             study on Study Day 0.

          2. History of TB prior to current episode.

          3. TB meningitis or other forms of severe TB with high risk of a poor outcome.

          4. Previous medical history that may compromise the safety of the subject in the study,
             including but not limited to severe impairment of pulmonary function from tuberculosis
             infection or other pulmonary disease; chronic illness with signs of cardiac or renal
             failure; suspected progressive neurological disease; or uncontrolled epilepsy.

          5. Evidence of any systemic disease or any acute or chronic illness that may interfere
             with the evaluation of the safety of the vaccine.

          6. History or laboratory evidence of any possible immunodeficiency state.

          7. History of allergic disease or reactions likely to be exacerbated by any component of
             the study vaccine.

          8. Received any non-BCG TB vaccine previously.

          9. For female subjects: Currently pregnant, lactating/nursing, or a positive urine HCG.

         10. Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30
             percent based on screening hematology obtained within 7 days before randomization on
             Study Day 0.

         11. History of autoimmune disease or immunosuppression.

         12. Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and
             topical corticosteroids are permitted).

         13. Received immunoglobulin or blood products within 42 days before Study Day 0.

         14. Received any investigational drug therapy or investigational vaccine within 6 months
             before Study Day 0, or planned participation in any other investigational study during
             the study period.

         15. Received any licensed vaccine within 28 days before Study Day 0, or receipt of any
             vaccine or immunomodulating agent through Study Day 63.

         16. Is, in the judgment of the principal investigator, not suitable to participate in this
             clinical study.