Phase 2, Open-label, Study of KD025 in Subjects With Psoriasis Vulgaris Who Failed First-line Therapy
Condition: Psoriasis Vulgaris
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study was performed to evaluate the safety, tolerability, activity, pharmacokinetics
      (PK), and daily dose regimen of KD025 administered orally (PO) for 12 weeks to subjects with
      psoriasis vulgaris who failed at least one line of systemic therapy.
    

Detailed description: 
      Study KD025-206 was a phase 2, open-label, dose-finding, safety, tolerability, activity, and
      PK study of KD025 in subjects with psoriasis who had failed at least 1 line of systemic
      therapy or phototherapy.

      Subjects received KD025 PO for 12 weeks. Planned enrollment was 36 subjects in 3 cohorts, 12
      subjects per cohort:

        -  Cohort 1 (12 subjects): KD025 400 mg once daily (QD) PO for 12 weeks

        -  Cohort 2 (12 subjects): KD025 200 mg PO twice daily (BID) for 12 weeks

        -  Cohort 3 (12 subjects): KD025 400 mg BID PO for 12 weeks

      Subjects were initially enrolled simultaneously in Cohort 1 and Cohort 2 according to a
      randomization schedule, with safety reviewed before any subjects. If safety guidelines were
      met, Cohort 3 was added to explore the efficacy and safety of KD025 at a dose of 400 mg PO
      BID.

      Subjects underwent safety evaluations: medical history evaluations; physical examinations
      (PEs); vital sign measurements; weight measurements; adverse event (AE) assessments;
      concomitant medication assessments; blood sample collection for hematology, chemistry, and
      coagulation; lipid panel; thyroid-stimulating hormone; measurements of antinuclear antibody;
      anti-double-stranded deoxyribonucleic acid; Complement C; antiphospholipid antibody; liver
      ultrasound (US); pregnancy testing for females of childbearing potential; PK sampling (subset
      of subjects only); urinalysis; and electrocardiogram (ECG).

      Subjects underwent efficacy evaluations: Psoriasis Area and Severity Index (PASI) scoring;
      Physicians Global Assessment (PGA) scoring; and Dermatologic Life Quality Index (DLQI)
      scoring.

      Subjects participating in PK sampling were admitted to the clinic on Month 1 Day 1 (M1D1) for
      PK procedures and were discharged on M2D2. Blood samples for PK analyses were collected on
      M2D1 and Month 3 Day 1 (M3D1) on an outpatient basis. Subjects were not to take their morning
      dose until after blood samples were drawn.

      A Follow-Up visit occurred 30 ± 3 days after the last dose of study drug.

      The endpoints for efficacy were PASI, PGA, and DSQI scores.

        1. Psoriasis Area and Severity Index (PASI): The PASI is a measure of the psoriasis disease
           severity using the average redness, thickness, and scaliness of the lesions (each graded
           on a 0 to 4 scale), which is weighted by the area of involvement. The PASI combines the
           assessment of the severity of lesions and the area affected into a single score ranging
           from 0 (no disease) to 72 (maximal disease).

        2. Physicians Global Assessment (PGA): The relative PGA documents the physician's
           assessment of the subject's psoriasis status. Consideration was given to the percent of
           body involvement as well as overall induration, scaling, and erythema. The PGA was
           assessed relative to baseline condition and defined as: (1) clear; (2) excellent; (3)
           good; (4) fair; (5) poor; and (6) worse.

        3. Dermatology Life Quality Index (DLQI): The DLQI is a skin disease-specific instrument
           designed to assess the impact of the disease on a subject's quality of life (QOL). It is
           a 10-item questionnaire that assesses 6 different aspects of quality of life: symptoms
           and feelings, daily activities, leisure, work or school performance, personal
           relationships, and treatment. Possible DLQI scores range from 0 (no detectable
           impairment on a subject's QOL) to 30 (extremely large effect on a subject's QOL).

      Safety was assessed by standard clinical and laboratory tests (hematology, serum chemistry,
      and urinalysis), PEs, and reporting of treatment-emergent adverse events (TEAEs). Toxicity
      grades were defined using the National Cancer Institute (NCI) Common Terminology Criteria for
      Adverse Events (CTCAE) Version 5.0. In addition, subjects had liver ultrasound and liver
      functioning testing assessed for possible steatosis.

      Blood samples for determination of PK plasma concentrations of KD025 and its metabolites were
      collected for maximum concentration (Cmax); time of maximum concentration (Tmax); area under
      the concentration-time curve (AUC) at 0 to 24 hours, 0 to last, and 0 to infinity (0 to 24, 0
      to last, 0 to infinity [inf]); half-life (t1/2); and accumulation ratio (metabolic-to-parent
      drug ratio).
    

Intervention name(s): KD025
Intervention type(s): Drug
Other intervention name(s): SLx-2119; belumosudil
Intervention MeSH terms: Belumosudil
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment