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A Phase 2 Study of the Efficacy and Safety of Belumosudil in Subjects With Moderate/Severe Chronic Plaque Psoriasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02852967
Recruitment Status : Completed
First Posted : August 2, 2016
Last Update Posted : April 6, 2021
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Chronic Plaque Psoriasis Drug: Belumosudil Drug: Placebo Phase 2

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Study, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Belumosudil in Subjects With Moderate/Severe Chronic Plaque Psoriasis Who Are Candidates for Systemic Therapy or Phototherapy
Actual Study Start Date : August 2016
Actual Primary Completion Date : July 2018
Actual Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Experimental: Belumosudil 200 mg QD + Placebo
One belumosudil 200 mg tablet and 1 matching placebo tablet in the morning and 1 matching placebo tablet in the evening
Drug: Belumosudil
Belumosudil tablets
Other Name: KD025

Drug: Placebo
Placebo tablets matching belumosudil

Experimental: Belumosudil 200 mg BID (Twice Daily) + Placebo
One belumosudil 200 mg tablet and 1 matching placebo tablet in the morning and 1 belumosudil 200 mg tablet in the evening
Drug: Belumosudil
Belumosudil tablets
Other Name: KD025

Drug: Placebo
Placebo tablets matching belumosudil

Experimental: Belumosudil 400 mg QD + Placebo
Two belumosudil 200 mg tablets in the morning and 1 matching placebo tablet in the evening
Drug: Belumosudil
Belumosudil tablets
Other Name: KD025

Drug: Placebo
Placebo tablets matching belumosudil

Experimental: Belumosudil 600 mg/day
Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening
Drug: Belumosudil
Belumosudil tablets
Other Name: KD025

Placebo Comparator: Placebo
Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening
Drug: Placebo
Placebo tablets matching belumosudil




Primary Outcome Measures :
  1. Efficacy: Proportion (%) of Subjects with a ≥ 75% Decrease in PASI (PASI 75) at Week 16--Observed and LOCF [ Time Frame: 16 weeks ]
    The proportion (%) of subjects who exhibit a 75% decrease or greater in the Psoriasis Area and Severity Index Score (PASI 75) for subjects who complete 16 weeks of treatment (observed) and the proportion of subjects who do not complete 16 weeks of treatment (last observation carried forward [LOCF]). PASI scale: 0 (no disease) to 72 (maximal disease)

  2. Efficacy: Difference in Proportion (%) of Subjects with PASI 75 Between Belumosudil Cohorts and Placebo Cohort from Baseline at Week 16--Observed and LOCF [ Time Frame: 16 weeks ]
    Change in the proportion of of subjects who have at least 75% reduction in PASI score (PASI 75) from baseline to Week 16 for treatment with belumosudil compared to treatment with placebo for subjects who complete 16 weeks of treatment (observed) and for subjects who do not complete 16 weeks of treatment (last observation carried forward [LOCF]). Negative difference in PASI 75: decrease from baseline (improvement). Positive difference in PASI 75: increase from baseline (worsening)


Secondary Outcome Measures :
  1. Efficacy: Proportion (%) of Subjects with PASI 75 at Week 48--Observed and LOCF [ Time Frame: Up to 48 weeks ]
    The proportion (%) of subjects who exhibit a 75% decrease or greater in PASI score for subjects who complete 48 weeks of treatment (observed) and for subjects who do not complete 48 weeks of treatment (last observation carried forward [LOCF]). PASI scale: 0 (no disease) to 72 (maximal disease)

  2. Efficacy: Difference in Proportion (%) of Subjects with PASI 75 Between Belumosudil Cohorts and Placebo Cohort from Baseline to Week 48--Observed and LOCF [ Time Frame: 48 weeks ]
    Change in the proportion of PASI scores with 75% or greater decrease (PASI 75) from baseline at Week 48 for subjects treated with KD025 compared to subjects treated with placebo for those who complete 48 weeks of treatment (observed) and for those who do not complete 48 weeks of treatment (last observation carried forward [LOCF]). Negative difference in PASI 75: decrease from baseline (improvement). Positive difference in PASI 75: increase from baseline (worsening)

  3. Efficacy: Change in Mean PASI Score and Percent Change in Mean PASI Score from Baseline at Week 16 and at Week 48--Observed and LOCF [ Time Frame: Up to 48 weeks ]
    Change in mean PASI score from baseline at Week 16 and at Week 48 for subjects who complete 16 and 48 weeks of treatment, respectively (observed), and for subjects who do and do not complete 16 and 48 weeks of treatment, respectively (last observation carried forward [LOCF]). Negative difference: decrease in mean PASI from baseline (improvement). Positive difference from baseline in mean PASI from baseline (worsening)

  4. Efficacy: Proportion (%) of Subjects with Physician Global Assessment (PGA) Score of Clear/Almost Clear at Week 16 and at Week 48--Observed and LOCF [ Time Frame: Up to 48 weeks ]
    Proportion of subjects who have a Physician Global Assessment (PGA) of Clear or Almost Clear at Week 16 and at Week 48 for subjects who complete treatment (observed) and for subjects and do not complete treatment (last observation carried forward [LOCF])

  5. Efficacy: Difference in Proportion (%) of Subjects with a PGA of Clear/Almost Clear Between Belumosudil Cohorts and Placebo at Week 16 and at Week 48--LOCF [ Time Frame: Up to 48 weeks ]
    Difference between the proportion of subjects with belumosudil who have a Physician Global Assessment (PGA) of Clear or Almost Clear compared to placebo at Week 16 and at Week 48 for subjects who do and subjects who do not complete treatment (last observation carried forward [LOCF]). Negative difference in PGA: KD025 cohort superior. Positive difference in PGA: placebo cohort superior

  6. Efficacy: Change and Percent Change in Dermatology Life Quality Index (DLQI) Score at Week 16 and at Week 48 [ Time Frame: Up to 48 weeks ]
    Changes in Dermatology Life Quality Index (DLQI) from baseline at Week 16 and at Week 48. Negative difference in DLQI score: improvement. Positive difference in DLQI score: worsening

  7. Pharmacodynamics: IL-17 Concentration Change from Baseline at Week 16 [ Time Frame: Subjects who had IL-17 concentrations measured at baseline and Week 16 ]
    Changes in the concentration of interluekin (IL-)17 at Week 16 and the percent change from baseline

  8. Safety: Proportion (%) of Subjects with AEs [ Time Frame: Up to 48 weeks ]
    The proportion (%) of subjects who experience any adverse events, any AE of severity Grade >= 3, related to study drug, and Grade >= 3 severity related to study drug

  9. Safety: Proportion (%) of Subjects with SAEs [ Time Frame: Up to 48 weeks ]
    The proportion (%) of subjects who experience any serious adverse event and any SAE related to study drug

  10. Safety: Proportion of Subjects Discontinued from the Study Due to AE [ Time Frame: Up to 48 weeks ]
    The proportion (%) of subjects for whom study drug had to be discontinued due to an AE which was not related to study drug and which was related to study drug.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult subjects between the ages of 18 and 65 years
  • Able to provide written Informed Consent Form prior to the performance of any study-specific procedures
  • Diagnosis of moderate to severe chronic plaque psoriasis and a candidate for systemic therapy or phototherapy
  • PASI of ≥ 12 at screening and prior to the first dose of study drug, confirmed at Week 1 Day 1 (Baseline)
  • ≥ 10% PASI body surface area involvement at screening and prior to the first dose of study drug, confirmed at Baseline
  • Willing to avoid tanning devices
  • Adequate bone marrow function:

    • Absolute neutrophil count > 1500/mm^3
    • Hemoglobin > 9.0 g/dL
    • Platelets > 100,000/mm^3
  • Adequate safety laboratory values:

    • Serum total bilirubin within normal limits (WNL)
    • Aspartate aminotransferase (AST) and alalnine aminotransferase (ALT) < 2 × upper limit of normal (ULN)
    • Serum creatinine < 1.5 × ULN
  • Female subjects of childbearing potential with a negative pregnancy test at screening. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had any evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, antiestrogens, or ovarian suppression

    • Women of childbearing potential (i.e., menstruating women) had to have a negative urine pregnancy test (positive urine tests were to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug
    • Sexually active women of childbearing potential enrolled in the study had to agree to use 2 forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control included: (a) intrauterine device plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; and (c) 2 barrier methods. Effective barrier methods were male or female condoms, diaphragms, and spermicides (creams or gels that contained a chemical to kill sperm); or (d) a vasectomized partner
  • For male patients who were sexually active and who were partners of premenopausal women: agreed to use 2 forms of contraception as defined above during the treatment period and for at least 3 months after the last dose of study drug
  • Willing to complete all study measurements and assessments in compliance with the protocol

Exclusion Criteria:

  • Non-plaque or drug-induced (antimalarials, lithium) psoriasis (If subject was taking angiotensin II receptor blockers or beta blockers doses must have been stable for 6 months prior to study entry)
  • Used systemic corticosteroids within 12 weeks prior to study entry
  • Used topical corticosteroids except to the face, groin, or scalp
  • Used methotrexate, retinoids (such as acitretin), or calcineurin inhibitors (such as cyclosporine) within 4 weeks prior to study entry
  • Phototherapy within 4 weeks prior to study entry
  • Biologic therapies, including antibodies to IL-17; anti-tumor necrosis factor-alpha; and anti-IL-12 & IL-23 within 3 months prior to study entry
  • Current use of an inhibitor or inducer of CYP3A4
  • Active viral, fungal, or bacterial skin infection (other than nail fungal infection).
  • Pregnant or lactating woman
  • History of gastrointestinal (GI) surgery including any bariatric surgery, or any GI condition that might interfere with drug absorption
  • Participating in another study with an investigational drug or within 28 days or 5 half-lives of the investigational drug (whichever was longer) 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
  • Regular and/or excessive use of alcohol within 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 equaled one "drink" unit. One unit equaled 1 ounce of distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine
  • QT interval data corrected using Fridericia's formula (QTcF) > 450 msec (average of 3 readings) during screening
  • Exposure to belumosudil or known allergy/sensitivity to belumosudil within the last 6 months prior to study entry or any other ROCK-2 inhibitor
  • History or presence of any of the following:

    • ALT or AST > 2.0 × ULN at screening
    • Renal disease and/or serum creatinine > 1.5 × ULN at screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02852967


Locations
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United States, Arizona
Alliance Dermatology and Mohs Center
Phoenix, Arizona, United States, 85032
United States, California
University of California, Irvine - Dermatology Clinical Research Center
Irvine, California, United States, 92697
Dermatology Research Associates
Los Angeles, California, United States, 90045
United States, Florida
Renstar Medical Research
Ocala, Florida, United States, 34471
United States, Indiana
Dawes Fretzin Dermatology Group
Indianapolis, Indiana, United States, 46256
Dermatology Specialists Research
New Albany, Indiana, United States, 40202
United States, Kentucky
Dermatology Specialists Research
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Metro Boston Clinical Partners
Brighton, Massachusetts, United States, 02135
United States, New Jersey
Psoriasis Treatment Center of Central New Jersey
East Windsor, New Jersey, United States, 08520
United States, New York
Sadick Research Group
New York, New York, United States, 10075
United States, Oregon
Oregon Dermatology and Research Center
Portland, Oregon, United States, 97210
United States, Tennessee
Tennessee Clinical Research Center
Nashville, Tennessee, United States, 37215
United States, Texas
Suzanne Bruce and Associates
Katy, Texas, United States, 77056
Austin Institute for Clinical Research
Pflugerville, Texas, United States, 78660
Sponsors and Collaborators
Kadmon Corporation, LLC
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Responsible Party: Kadmon Corporation, LLC
ClinicalTrials.gov Identifier: NCT02852967    
Other Study ID Numbers: KD025-211
First Posted: August 2, 2016    Key Record Dates
Last Update Posted: April 6, 2021
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Kadmon Corporation, LLC:
Skin Diseases
Auto-Immune Diseases
Plaque
Dermatology
Additional relevant MeSH terms:
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Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases