A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
Condition: Mitochondrial Diseases; Mitochondrial Respiratory Chain Deficiencies; MELAS Syndrome; Mitochondrial Myopathies
MeSH terms: Muscular Diseases; Mitochondrial Myopathies; MELAS Syndrome; Mitochondrial Diseases; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      This will be a double blind, randomised, placebo controlled, single and multiple oral dose
      study conducted in 3 parts: Part A, Part B and Part C. Part A and Part B include healthy
      volunteers only and will be completed before Part C including patients with primary
      mitochondrial disease will be initiated. The starting dose in the first cohort of Part A will
      be 25 mg. The dose level in the additional cohorts will be decided following review of data
      of the previous cohorts.
    

Detailed description: 
      Part A: Eight healthy subjects will be studied in a single cohort (Group A1). Potential
      subjects will be screened to assess their eligibility to enter the study within 28 days prior
      to the first dose administration. Subjects will participate in 2 treatment periods, fasting
      or after consuming a standard high-fat breakfast. For each treatment period, subjects will
      reside at the Phase I clinical site from Days 1 to 3 (48 hours postdose). Subjects will
      return to the clinical site for outpatient visits on Days 4 and 5. There will be at least a
      10 day washout between doses Additional single-dose cohorts may be enrolled based on data
      obtained from either Parts A or B.

      Part B: Sixteen healthy subjects will be studied in 2 cohorts (Groups B1 and B2), with each
      cohort consisting of 8 subjects. Following review of safety, tolerability, and PK data, up to
      3 additional dose cohorts of healthy subjects may be added to further explore the PK, safety,
      and tolerability of KL1333. Potential subjects will be screened to assess their eligibility
      to enter the study within 28 days prior to the first dose administration. All subjects will
      participate in 1 treatment period and will reside at the Phase I clinical site from Days -1
      to 12 (48 hours post final dose). Subjects will return to the clinical site for outpatient
      visits on Days 13 and 14. On Day 1, 6 subjects will be randomised to receive KL1333 and 2
      subjects will be randomised to receive placebo. Subjects will return for a Follow-up visit on
      Day 15, 5 days after their final dose.

      Part C: A total of 8 patients diagnosed with any mitochondrial disease will be enrolled in
      this part of the study. Part C may start after the dose selection conference has been
      completed for the final cohort of Part B, at a daily dose no higher than the highest
      well-tolerated dose in Part B. Potential study patients will be screened to assess their
      eligibility to enter the study within 35 days prior to the first dose administration.
      Patients will reside at the clinical site from Days -1 to 2 and Days 10 to 11 and return to
      the clinical site for outpatient visits on Days 4 and 8. It is planned for patients to
      receive study drug once daily on Days 1 to 10. Patients will return for a Follow-up visit on
      Day 15, 5 days after their final dose.
    

Intervention name(s): KL1333; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): 25 and 100 mg KL1333 encapsulated tablets; 25 and 100 mg placebo encapsulated tablets
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Mitochondrial Diseases; Mitochondrial Respiratory Chain Deficiencies; MELAS Syndrome; Mitochondrial Myopathies; Kearns-Sayre Syndrome; Ophthalmoplegia, Chronic Progressive External