Phase 2, Open-label, Study of KD025 in Subjects With Psoriasis Vulgaris Who Failed First-line Therapy

NCT02317627 | Completed Phase 2 Results DMC

• 1 other identifier: KD025-206
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Psoriasis Vulgaris

Outcome Measures

Primary Outcomes (3)

• Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population

  Percentage of available subjects who achieved at least a 75% reduction (PASI 75) or at least a 50% reduction from baseline in Psoriasis Area and Severity Index (PASI) score after 12 weeks of treatment with belumosudil or at the end of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]

  12 weeks

• Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population

  Percentage of available subjects who achieved at least a 75% reduction and a 50% reduction from baseline in Psoriasis Area and Severity Index score at end of treatment with belumosudil in the Evaluable Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]

  12 weeks

• Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population

  Percentage of subjects who had an adverse event by severity in the Intent-to-Treat Population: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Percentage of subjects who had an adverse event by relationship to belumosudil in the Intent-to-Treat Population as assessed by the investigator: definitely related, probably related, possibly related, and not related to belumosudil.

  12 weeks

Secondary Outcomes (19)

• Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population

  12 weeks

• Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population

  12 weeks

• Efficacy: Percentage of Subjects With a Decrease in PASI After 4 Weeks---ITT Population

  4 weeks

• Efficacy: Percentage of Subjects With a Decrease in PASI Score After 8 Weeks---ITT Population

  8 weeks

• Efficacy: Percentage of Subjects With a Decrease in PASI Score at EOT---ITT Population

  12 weeks

Study Arms (3)

Cohort 1

EXPERIMENTAL

KD025 400 mg QD PO for 12 weeks

Drug: KD025

Cohort 2

EXPERIMENTAL

KD025 200 mg BID PO for 12 weeks

Drug: KD025

Cohort 3

EXPERIMENTAL

KD025 400 mg BID PO for 12 weeks

Drug: KD025

Interventions

KD025 DRUG

Also known as: SLx-2119, belumosudil

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent prior to the performance of any study specific procedures
• Diagnosis of moderately severe plaque psoriasis that has been moderately stable for 6 months and failed at least 1 line of systemic or phototherapy and is a candidate for additional systemic therapy
• PASI of ≥ 12 within the 24-hour period prior to the first dose of study drug
• At least 10% of body surface area affected by plaque psoriasis within the 24-hour period prior to the first dose of study drug
• Willing to avoid tanning devices
• Willing to forgo other systemic and topical treatments for psoriasis during the course of the study
• Adequate bone marrow function: absolute neutrophil count \> 1500/mm\^3; hemoglobin \> 9.0 g/dL; platelets \> 100,000/mm\^3
• Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
• 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. Effective birth control included implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or vasectomized partner
• Willing to complete all study measurements and assessments in compliance with the protocol

You may not qualify if:

• Non-plaque or drug-induced (antimalarials, lithium) psoriasis (If subject is taking angiotensin II receptor blockers or beta blockers doses had to be stable for 6 months prior to study entry)
• Use of corticosteroid or immunosuppressive therapy within 4 weeks prior to study entry except for Class 5 or weaker topical corticosteroids or immunosuppressive therapies to the face, groin, or scalp.
• Use of methotrexate, acitretin, or cyclosporine within 4 weeks prior to study entry
• Use of phototherapy within 4 weeks prior to study entry
• Use of biologic therapies, including antibodies to IL-17, within 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
• History of gastrointestinal (GI) surgery including bariatric surgery, or any GI condition that might interfere with drug absorption
• 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 (such as poorly controlled psychiatric disease or coronary artery disease)
• Regular and excessive use of alcohol within the 2 years prior to study entry defined as alcohol intake \> 14 drinks per week in a man or \> 7 drinks per week in a woman. Approximately 10 g of alcohol equals one "drink" unit. One unit equals 1 ounce of distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine
• History or presence of any of the following:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.0 × the upper limit of normal (ULN) at screening. (Subjects with an isolated AST elevation of any magnitude, or a ratio of AST:ALT \> 1.5 interviewed regarding use of alcohol, have levels repeated and participation in the study should be discussed with the medical monitor.)
• Renal disease and/or serum creatinine \> 1.5 × ULN at screening

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead

Study Sites (9)

Arrowhead Health Centers

Glendale, Arizona, 85306, United States

Location

Southern California Dermatology, Inc.

Santa Ana, California, 92701, United States

Location

Shondra L. Smith

Lake Charles, Louisiana, 70605, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Clinical Studies Group, LLC

Henderson, Nevada, 89074, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

High Point Clinical Trials Center

High Point, North Carolina, 27265, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Metroplex Clinical Research Center (MCRC)

Dallas, Texas, 75231, United States

Location

Related Publications (1)

• Zanin-Zhorov A, Weiss JM, Trzeciak A, Chen W, Zhang J, Nyuydzefe MS, Arencibia C, Polimera S, Schueller O, Fuentes-Duculan J, Bonifacio KM, Kunjravia N, Cueto I, Soung J, Fleischmann RM, Kivitz A, Lebwohl M, Nunez M, Woodson J, Smith SL, West RF, Berger M, Krueger JG, Ryan JL, Waksal SD. Cutting Edge: Selective Oral ROCK2 Inhibitor Reduces Clinical Scores in Patients with Psoriasis Vulgaris and Normalizes Skin Pathology via Concurrent Regulation of IL-17 and IL-10. J Immunol. 2017 May 15;198(10):3809-3814. doi: 10.4049/jimmunol.1602142. Epub 2017 Apr 7.

  PMID: 28389592 BACKGROUND

MeSH Terms

Interventions

KD025; belumosudil

Results Point of Contact

• Title: Associate VP, Clinical Operations
• Organization: Kadmon Corporation, LLC

karin.herrera@kadmon.com

833-900-5366

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: December 16, 2014
• Study Start: December 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 26, 2022
• Results First Posted: November 1, 2021

Record last verified: 2022-05

Locations

US (9)