A Phase 2, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Belumosudil in Subjects With Moderate/Severe Chronic Plaque Psoriasis
Condition: Chronic Plaque Psoriasis
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a phase 2, randomized, placebo-controlled, 2-period study to evaluate the safety,
      tolerability, and efficacy of belumosudil in adult subjects with moderate to severe chronic
      plaque psoriasis who are candidates for systemic therapy or phototherapy.
    

Detailed description: 
      This phase 2, two-period, dose-finding, placebo-controlled study is performed on adult male
      and female subjects to evaluate the efficacy and safety of subjects with moderate to severe
      chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.

      Period 1: Double-blind, Placebo-controlled Treatment Period

      Approximately 110 subjects are planned to be randomly assigned to each of 5 dose cohorts in a
      1:1:1:1:1 manner. Each cohort is planned to have 22 subjects who meet eligibility criteria.
      Subjects are treated with oral (PO) belumosudil tablets or placebo tablets as follows:

        -  200 mg belumosudil once daily (QD) (Cohort 1) = one 200 mg belumosudil tablet and 1
           matching placebo in the morning and 1 matching placebo in the evening

        -  200 mg belumosudil twice daily (BID) (Cohort 2) = one 200 mg belumosudil tablet in the
           morning and one matching placebo in the morning, and one 200 mg belumosudil tablet in
           the evening

        -  400 mg belumosudil QD (Cohort 3) = two 200 mg belumosudil tablets in the morning and one
           matching placebo in the evening

        -  600 mg/day belumosudil (Cohort 4) = two 200 mg belumosudil tablets in the morning and
           one 200 mg belumosudil tablet in the evening

        -  Matching placebo BID (Cohort 5) = 2 matching placebo tablets in the morning and 1
           matching placebo tablet in the evening

      Subjects in each of the 5 cohorts in Period 1 are treated with study medication for a period
      of 16 weeks.

      Note: Originally, a sample size of 36 subjects per cohort was planned to provide
      approximately 90% probability ≥ 1 subject in the 5 cohorts would experience an adverse event
      (AE) that had an underlying rate of ≥ 6% and approximately an 80% probability of ≥ 1 subject
      in the cohort experiencing an AE that had an underlying rate of ≥ 4%. However, due to a newly
      available plaque psoriasis treatment, the study is terminated early with 110 subjects.

      Period 2: Open-label Treatment Period (with Belumosudil)

      All subjects treated for 16 weeks, regardless of treatment with belumosudil (Cohorts 1
      through 4) or placebo (Cohort 5) are given the option to receive 400 mg belumosudil QD for an
      additional 32 weeks (Week 16 through Week 48).

      Follow-up Period

      All subjects have a safety evaluation 30 days after the last dose of study drug.

      Efficacy is assessed by the following scores at scheduled time points throughout the study:

        -  Psoriasis Area and Severity Index (PASI): Measure of psoriasis disease severity using
           average redness, thickness, and scaliness of lesions (each lesion graded 0 to 4),
           combined into single score ranging on a scale from 0 (no disease) to 72 (maximum
           disease)

        -  Physician's Global Assessment (PGA): Physician's assessment of a subject's psoriasis,
           relative to baseline, ranging on a scale from 1 (100% clearing of psoriasis) to 6 (poor
           to no clearing)

        -  Dermatology Life Quality Index (DLQI): Skin disease-specific instrument for assessing
           impact of disease on subject's quality of life ranging on a scale from 0 (no effect on
           subject's life) to 30 (extremely large effect on subject's life)

      Safety is assessed by;

        -  AEs and serious AE (SAEs)

        -  Physical examination

        -  Vital sign measurements

        -  Clinical laboratory evaluations

        -  Electrocardiogram

        -  Reasons for discontinuation due to toxicity analyses

      The maximum duration for subjects who complete Period 1 (Double-blind, Placebo-controlled) is
      24 weeks (up to 4-week Screening, 16-week Period 1 treatment, and 4-week Follow-up). The
      maximum duration for subjects who complete Period 2 (Open-label) is 56 weeks (up to 4-week
      Screening, 16-week Double-blind Treatment Period, 32-week Open-label Treatment Period, and
      4-week Follow-up).
    

Intervention name(s): Belumosudil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Placebo tablets matching belumosudil
Other intervention name(s): Rezurock (brand name); KD025
Intervention MeSH terms: Belumosudil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Skin Diseases; Auto-Immune Diseases; Plaque; Dermatology