Safety and Immunogenicity Study of AERAS-456 Vaccine for Tuberculosis
Condition: Latent Tuberculosis; Latent Tuberculosis Bacteriology and Histology Unknown
MeSH terms: Tuberculosis; Latent Tuberculosis
Intervention: H56:IC31
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) formulated in the Th1-stimulating IC31 adjuvant.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV Negative

Summary:

      This is a Phase I, open-label, dose-escalation study with three study groups. This study will
      be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection
      (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is
      AERAS-456 at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50
      ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by
      intramuscular injection.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Has completed the written informed consent process

          2. Is male or female

          3. Is aged 18 through 50 years on Study Day 0

          4. Females: Ability to avoid pregnancy during the trial: 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 avoid pregnancy with an
             acceptable method of avoiding pregnancy from 28 days prior to administration of the
             study vaccine through the end of the study.

          5. Has general good health, confirmed by medical history and physical examination

          6. Is able and willing to complete the full follow-up period of 210 days as required by
             the protocol

          7. Is able and willing to commit to avoiding elective surgery for the duration of the
             study

          8. Is able and willing to stay in contact with the study site for the duration of the
             study

          9. [Groups 2 & 3] Has latent tuberculosis infection (LTBI), diagnosed by a positive
             Quantiferon (QFT)

         10. Has completed simultaneous enrollment in the Registry Protocol

        Exclusion Criteria:

          1. Axillary temperature 37.5 C

          2. Abnormal laboratory values from blood collected within 7 days prior to Study Day 0
             vaccination as follows:

               -  hemoglobin, hematocrit, platelet count, absolute neutrophil count, or absolute
                  lymphocyte count below lower limit of normal (LLN).

               -  white blood cell count above upper limit of normal (ULN) or below LLN

               -  alanine aminotransferase (ALT), aspartate aminotransferase (AST), total
                  bilirubin, alkaline phosphatase (ALP), or creatinine above ULN.

          3. Abnormal urinalysis that, in the opinion of the investigator, indicates systemic or
             local disease.

          4. History or evidence of tuberculosis disease, including but not limited to pulmonary
             tuberculosis, pleural tuberculosis, lymph node tuberculosis or tuberculosis
             meningitis.

          5. [Group 1] Evidence of latent tuberculosis infection (LTBI), defined as a positive
             screening QFT or a history of a positive TST or QFT.

          6. Received a tuberculin skin test (TST) or bacillus Calmette-Guerin (BCG) within 45 days
             prior to Study Day 0.

          7. Received investigational Mtb vaccine at any time prior to Study Day 0.

          8. History or evidence of autoimmune disease.

          9. History or laboratory evidence of HIV infection.

         10. History or laboratory evidence of Hepatitis B or C.

         11. Used immunosuppressive medication (other than inhaled or topical immunosuppressants)
             within 45 days prior to Study Day 0.

         12. Received immunoglobulin or blood products within 45 days prior to Study Day 0

         13. Received any investigational product within 45 days prior to Study Day 0, or plans to
             participate in any other study involving administration of investigational product
             during the study period.

         14. Inability to discontinue daily medications, except contraceptives, inhaled or topical
             immunosuppressants, or nutritional supplements, during the study period.

         15. Documented history of allergic reaction or hypersensitivity to any component of the
             study vaccine.

         16. Female subjects: currently pregnant or lactating/nursing; or positive serum pregnancy
             test during screening; or positive urine pregnancy test on the day of Study Day 0,
             Study Day 56, or Study Day 112 vaccination.

         17. History or evidence of any systemic disease or any acute or chronic illness that, in
             the opinion of the investigator, may compromise the safety of the subject in the study
             or interfere with the evaluation of the safety or immunogenicity of the vaccine.

         18. History of dermatologic disease or skin features that, in the opinion of the
             investigator, may interfere with the assessment of injection site reactions.

         19. History or evidence of any medical, psychiatric, occupational, or substance abuse
             problems that, in the opinion of the investigator, will make it unlikely that the
             subject will comply with the protocol.