Multiple Ascending Dose (MAD) Study of IMT-002 in HLA-DQ8-positive Type 1 Diabetes
Condition: Type1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is designed to characterize the safety, steady-state pharmacokinetics (PK) of
      IMT-002, and will serve as a dose range identification for the pharmacodynamic effect of
      blocking self-antigen presentation in adults with type 1 diabetes (T1D) having the human
      leukocyte antigen (HLA)-DQ8 gene.
    

Detailed description: 
      This is a randomized, single-blind, placebo-controlled study that will include 4 ascending
      dose cohorts: 350 mg twice daily (BID), 1050 mg once daily (QD), 700 mg BID, and 1050 mg BID.
      Subjects will undergo prescreening for genetic typing and then screening procedures up to 28
      days prior to the first dose to determine eligibility. T1D adults between 18 and 45 years of
      age, inclusive, who are positive for at least one gene encoding for HLA-DQ8 (DQA1*0301,
      DQB1*0302) will be enrolled.

      Each cohort will include 6 subjects on active drug, and the study will include 6 subjects
      total on placebo. Each cohort will participate in a 2-week dosing period. Enrollment of the
      cohorts will be sequentially staggered such that initial safety data after the first four
      subjects assigned to active treatment complete one week of treatment in each cohort will be
      reviewed before the next ascending dose cohort is enrolled. The safety reviews will include
      cumulative safety data for all subjects to that point. Subjects will have 5 scheduled clinic
      visits: screening, first day of dosing, 1 week after dosing begins, 2 weeks after dosing
      begins (end of treatment), and 1 week following the final dose. Subjects will self-administer
      study drug on non-clinic treatment days. Safety assessments will be conducted at all study
      visits. Insulin use (dose and frequency) will be monitored.

      Pharmacokinetic (PK) assessments will be evaluated at every visit during the treatment period
      to characterize the following: single dose PK, trough PK and steady PK. Pharmacodynamic (PD)
      and immunological assessments will be evaluated before, during and after treatment.
    

Intervention name(s): 350mg BID (700mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule; 700mg BID (1400mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule; 1050mg QD (1050mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule; 1050mg BID (2100mg total daily) IMT-002, D-methyldopa, active formulation in capsule or Placebo, microcrystalline cellulose in capsule
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily; Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily; Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily; Oral drug or placebo self-administered by subject as a capsule by mouth once-daily or twice-daily
Other intervention name(s): 350mg BID; 700mg BID; 1050mg QD; 1050mg BID
Intervention MeSH terms: Methyldopa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: diabetes; prescreening; autoimmunity; HLA