Clinical trial NCT02106195: A Safety and Tolerability Study of Belumosudil (KD025) Treatment in Subjects With Moderately Severe Psoriasis Vulgaris
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis Vulgaris
Lead sponsor: Kadmon Corporation, LLC
Sponsor class: INDUSTRY
First posted: 2014-04-08
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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:

  1. Class 5 or weaker steroids and phototherapy for 4 weeks prior to study entry
  2. Immunosuppressive therapies for 4 weeks prior to study entry
  3. Methotrexate, acitretin, or cyclosporine for 4 weeks prior to study entry
  4. 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:

  1. Hepatic disease and or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 × the upper limit of normal (ULN) at screening
  2. 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.

Primary outcomes:
measure: Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 12 weeks:Up to 4 weeks screening (depending on signed informed consent + 4 weeks treatment + 4 weeks follow-up
Secondary outcomes:
measure: Efficacy: Change in Overall PASI (Psoriasis Area and Severity Index) From Baseline to Week 4 and Week 8
timeFrame: 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up
measure: Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8
timeFrame: 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up
measure: PK: Cmax and Cmin
timeFrame: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose
measure: PK: AUC(0-24) and AUC(Inf)
timeFrame: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose
measure: PK: Tmax
timeFrame: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose
measure: PK: t(1/2)
timeFrame: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose
Other outcomes:
Locations:
city: Irvine
country: United States
facility: UC Irvine Health, Dept of Dermatology
state: California
Study officials:
References: