Challenge Model for Assessment of Human TB Immunity
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase I open-label, dose escalation trial to evaluate the use of Tice® BCG as a
      challenge for future assessment of in vivo TB immunity. Subjects will be recruited from the
      target population reflecting the community at 2 VTEU sites. Enrollment will occur over 14
      months. Subjects who provide informed consent will be screened, and up to 120 eligible, HIV
      and TB uninfected subjects, 18-45 years, inclusive, will be enrolled for study interventions
      and sequentially assigned to 1 of 4 dose groups. Doses of Tice BCG from 2 to 16x10^6 cfu will
      be delivered ID in a dose escalation format to 4 groups of 30 subjects per dose group.
      Primary Objectives: 1) Evaluate the safety of different doses of ID Tice BCG for use as a
      human challenge model for TB infection. 2) Examine shedding from ID challenge sites after
      administration of different doses of Tice BCG in TB naive healthy subjects. 3) Evaluate the
      reproducibility of BCG shedding over time with both quantitative PCR and culture.
    

Detailed description: 
      This is a Phase I open-label, dose escalation trial to evaluate the use of Tice® BCG as a
      challenge for future assessment of in vivo TB immunity. Subjects will be recruited from the
      target population reflecting the community at large at 2 VTEU sites. It is anticipated that
      enrollment will occur over a 14-month period. Subjects who provide informed consent will be
      considered for eligibility (screened), and up to 120 eligible, willing, healthy, HIV and TB
      uninfected subjects aged 18 to 45 years, inclusive, will be enrolled for study interventions
      and sequentially assigned to 1 of 4 dose groups. Dose titrations of Tice® BCG from 2x10^6 cfu
      to 16x10^6 cfu will be delivered intradermally in a dose escalation format to 4 groups of 30
      subjects per dose group. In the first dose group, subjects will be immunized intradermally
      with a single dose of 2x10^6 cfu Tice® BCG. The Tice® BCG doses will be increased
      sequentially from 2x10^6 cfu to 4x10^6 cfu to 8x10^6 cfu to a maximum dose of 16x10^6 cfu
      following assessment of safety and reactogenicity data from previous dose groups and sentinel
      subjects. Following administration of Tice® BCG, intradermal (ID) site reactions will be
      assessed for at least 30 minutes as well as by memory aid on a daily basis throughout the
      first 15 days. Subjects will also return to the clinic on Days 22, 25, 29, 32, 36, 39, 43,
      46, 50, 53, and 57 to evaluate the ID challenge site, assess for lymphadenopathy if indicated
      based on review of interim medical history and clinical assessment, and review AEs/SAEs,
      concomitant medications and health status, and collect and dispose of returned biohazard
      materials. A final clinic visit will be performed at approximately 3 months (Day 99)
      following administration of Tice® BCG to evaluate the ID challenge site, assess for
      lymphadenopathy if indicated based on review of interim medical history and clinical
      assessment, and review SAEs and health status. At approximately 6 months (Day 181) following
      administration of Tice® BCG a telephone call will be performed to query for any SAEs that may
      have occurred since the last visit. Based on this information, subjects may be asked to
      return to the clinic to be evaluated. The duration of the study for each subject will be up
      to approximately 7 to 8 months. Primary Objectives: 1) Evaluate the safety of different doses
      of intradermal Tice® BCG for use as a human challenge model for Mycobacterium tuberculosis
      infection. 2) Examine BCG shedding from intradermal challenge sites after administration of
      different doses of Tice® BCG in TB naive healthy subjects. 3) Evaluate the reproducibility of
      BCG shedding over time with both quantitative PCR and culture techniques. Secondary
      objectives: 1) Determine a tolerable dose of intradermal Tice® BCG that will induce optimal
      reproducibility of BCG shedding. 2) Determine the method of mycobacterial quantitation that
      will result in the least variable results. 3) Characterize the magnitude and kinetics of BCG
      shedding after intradermal Tice® BCG administration at 4 different doses. Parent protocol to
      sub-study 12-0096.
    

Intervention name(s): BCG TICE strain
Intervention type(s): Biological
Intervention description(s): All doses: Tice Bacillus Calmette-Guerin (BCG) will be administered as a single 0.1 ml ID injection over the deltoid muscle of the preferred arm. Groups 1 - 4 will receive one dose of Tice BCG intradermally at 2x10^6 cfu, 4x10^6 cfu, 8x10^6 cfu and 16x10^6 cfu, respectively.
Intervention MeSH terms: BCG Vaccine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: challenge; Mycobacterium tuberculosis; parent protocol; TB; Tice BCG; tuberculosis