A Safety and Tolerability Study of Belumosudil (KD025) Treatment in Subjects With Moderately Severe Psoriasis Vulgaris

Study Overview
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Brief Summary
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The primary objective is to assess the safety and tolerability of 200 mg of belumosudil administered orally once daily for 28 days.

Detailed Description
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This will be a Phase 2a, open-label, single-arm, safety and tolerability study of belumosudil given daily for treatment of psoriasis. Eight subjects with moderately severe psoriasis who have failed at least 1 line of systemic therapy will be enrolled. Treatment Period Eligible subjects who have failed at least 1 line of systemic therapy will be entered and treated for 4 weeks (28 days) with 200 mg of belumosudil given orally once daily (QD). Subjects will undergo medical history evaluations, physical examinations, vital sign measurements, weight, adverse event assessments, concomitant medication assessments, and laboratory testing including but not limited to blood sample collection for hematology and chemistry, urinalysis, coagulation, lipid panel, electrocardiogram, pregnancy test for females of childbearing potential, testing with the Psoriasis Area and Severity Index (PASI) scale and Physician Global Assessment (PGA) scale, and pharmacokinetic sampling. Follow-up Period: Visit will occur 4 weeks after the last dose of study drug in the Treatment Period of the study. This visit must be done within ± 3 days of the scheduled visit. The same assessments will be performed as in the Treatment Period. The duration of the study is 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up.

Official Title
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A Phase 2a, Open-label Study to Evaluate the Safety and Tolerability of KD025 [Belumosudil] Treatment in Subjects With Moderately Severe Psoriasis Vulgaris Who Have Failed First-line Therapy

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: Belumosudil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of moderately severe plaque psoriasis that has been stable for 6 months and has failed at least one line of systemic therapy and is a candidate for additional systemic therapy. Had a PASI of ≥12 At least 10% of body surface area that is affected by plaque psoriasis. Willing to avoid tanning devices or sun bathing. Willing to forgo systemic and topical treatments for psoriasis during the course of the study. Adequate bone marrow function Negative urine pregnancy test (for women of childbearing potential) Agree to use a highly effective method of birth control (< 1% per year failure rate) during the study and for 1 month after the termination of the study. Willing to complete all study measurements and assessments in compliance with the protocol. Exclusion Criteria: Non-plaque or drug-induced psoriasis Currently using corticosteroid or immunosuppressive therapy except for Class 5 or weaker topical corticosteroids to the face, groin, or scalp Using any topical therapy except for the following: Class 5 or weaker steroids and phototherapy for 4 weeks prior to study entry Immunosuppressive therapies for 4 weeks prior to study entry Methotrexate, acitretin, or cyclosporine for 4 weeks prior to study entry Biologic therapies for 3 months prior to study entry. Concomitant condition requiring treatment with moderate to high dose steroids in the 12 weeks prior to screening. Viral, fungal, or bacterial skin infection. Pregnant or lactating woman. Currently participating in another study with an investigational drug or within 28 days of study entry History or other evidence of severe illness or any other conditions that would make the subject, in the opinion of the investigator, unsuitable for the study History or presence of any of the following: Hepatic disease and or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × the upper limit of normal (ULN) at screening Renal disease and/or serum creatinine > 1.5xULN at screening Has QTc(f) intervals of > 450 msec at the screening or pre-dose ECG Subject is receiving any drugs known to prolong the QTc interval, including any anti-arrhythmic medications within 2 weeks prior to screening Subject is receiving any drug that is a strong CYP enzyme inhibitor Subject is receiving any concomitant systemic drug that is metabolized by CYP enzyme Previous exposure to KD025 or known allergy/sensitivity to KD025 or any other ROCK-2 inhibitor.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belumosudil 200 mg<br>Belumosudil 200 mg (two 100 mg capsules) orally once daily for 28 days | Drug: Belumosudil<br> <br> * Other names: SLx-2119;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability | To evaluate the safety and tolerability of 200 mg of belumosudil administered PO QD to subjects for treatment of psoriasis | Up to 12 weeks:Up to 4 weeks screening (depending on signed informed consent + 4 weeks treatment + 4 weeks follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Change in Overall PASI (Psoriasis Area and Severity Index) From Baseline to Week 4 and Week 8 | The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. The measures are the changes in PASI score at Week 4 from baseline and Week 8 from baseline. Negative changes are favorable; positive changes are unfavorable. | 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up | 
| Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 | PGA score after treatment with belumosudil 200 mg PO QD at 4 weeks (28 days treatment) and at 8 weeks (additional 4 weeks follow-up). Categories: 100% = clear; 75% to 99% clearing (Excellent) = marked improvement, nearly normal skin texture, some erythema may be present; 50% to 74% clear (Good) = moderate improvement, plaque has cleared to point of small scattered papules with normal intervening epidermis; 25% to 49% clearing (Fair) = slight improvement, decrease in scaling and softening of plaque; 0% to 24% clearing (Poor) = little or no change in scaling, erythema, or plaque elevation; Worse | 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up | 
| PK: Cmax and Cmin | Pharmacokinetic measures: Cmax = maximum observed plasma concentration; Cmin = minimum observed plasma concentration over 1 dosing period; KD025 = Parent Drug KD025; M1 = Metabolite KD025 M1; KD025 M2 = Metabolite M2. Day 1 Cmax: 8 subjects each in KD025 and M2, and 6 subjects in M1. Day 28 Cmax: 4 subjects each in KD025 and M2, and 1 subject in M1. Day 1 Cmin: 8 subjects each in KD025 and M2, and 3 subjects in M1. Day 28 Cmin: 4 subjects each in KD025 and M2, and 1 subject in M1. | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose | 
| PK: AUC(0-24) and AUC(Inf) | Pharmacokinetic measures: AUC(0-24) = area under concentration time-curve from pre-dose (time 0) to 24 hours post-dose; AUC(inf) = area under concentration time-curve extrapolated from Day 1 to infinity; KD025 = Parent Drug KD025; M1 = Metabolite KD025 M1; KD025 M2 = Metabolite M2. | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose | 
| PK: Tmax | Pharmacokinetic measure: Tmax = time of maximum observed plasma concentration. Day 1 Tmax: 7 subjects each in KD025 and M2, and 5 subjects in M1. Day 28 Tmax: 4 subjects each in KD025 and M2, and 1 subject in M1. | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose | 
| PK: t(1/2) | KD025 = Parent Drug KD025; KD025 M2 = Metabolite M2; t(1/2) = apparent terminal elimination half-life | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose |