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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Belumosudil 200 mg | Experimental | Belumosudil 200 mg (two 100 mg capsules) orally once daily for 28 days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belumosudil | Drug |
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| 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 |
| 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. |
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Inclusion Criteria:
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:
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:
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.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Irvine Health, Dept of Dermatology | Irvine | California | 92697 | United States |
Screening assessments occurred within 28 days prior to assignment and included informed consent, medical/demographic history, physical exam, vital signs, clinical laboratory tests, ECG, urine pregnancy, skin punch biopsy, PK, Psoriasis Area and Severity Index (PASI) scoring, Physician Global Assessment (PGA) scoring, and concomitant AE assessments.
Open-label, Phase 2a, single-arm study of subjects with moderately severe plaque psoriasis who had been stable for 6 months and had failed at least 1 line of systemic therapy. Subjects were recruited at 1 site in the U.S.
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| ID | Title | Description |
|---|---|---|
| FG000 | Belumosudil 200 mg PO QD | 8 subjects with moderately severe psoriasis who had failed at least 1 line of systemic therapy administered belumosudil 200 mg orally QD for 4 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Belumosudil 200 mg PO QD | Belumosudil 200 mg (two 100 mg capsules) orally once daily for 28 days |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Safety Population: All subjects who received at least 1 dose of belumosudil 200 mg | Posted | Count of Participants | Participants | Up to 12 weeks:Up to 4 weeks screening (depending on signed informed consent + 4 weeks treatment + 4 weeks follow-up |
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12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up.
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Belumosudil 200 mg PO QD | Subjects who received belumosudil 200 mg orally daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA Version 16.0 | Systematic Assessment | Same subject had SAE |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Transaminase increased | Investigations | MedDRA Version 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Associate VP, Clinical Operations | Kadmon Corporation, LLC | 833-900-5366 | karin.herrera@kadmon.com |
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| ID | Term |
|---|---|
| C000718240 | belumosudil |
| C000619755 | KD025 |
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| 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 |
| years |
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| Age, Customized | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| BMI | Body mass index (kg/m^2) | Mean | Standard Deviation | kg/m^2 |
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| BMI | Body mass index (kg/m^2) | Median | Full Range | kg/m^2 |
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| Participants |
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| Secondary | 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. | All 8 subjects who received belumosudil 200 mg PO QD. 7 subjects available at follow-up visit. | Posted | Mean | Standard Deviation | Score on a scale | 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up |
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| Secondary | 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 | All 8 subjects had PGA scoring at Day 29 and at the follow-up visit (30 days after last dose of study drug) | Posted | Count of Participants | Participants | 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up |
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| Secondary | 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. | One subject excluded from all the descriptive statistics due to a mix-up of samples between predose and 4 hours (KD025, M1 and M2); Two subjects had no measurable concentrations observed in their profiles for M1 at Day 1 | Posted | Mean | Standard Deviation | ng/mL | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose |
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| Secondary | 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. | AUC(0-24) Day 1: 7 subjects in KD025 and 3 subjects in M2. AUC(0-24) Day 28: 4 subjects in KD025 and 2 subjects in M2. AUC(inf): 6 subjects in KD025 and 3 subject in M2. Neither AUC(0-24) nor AUC(inf) were calculated for M1. | Posted | Mean | Standard Deviation | ng*hr/mL | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose |
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| Secondary | 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. | Day 1: 7 subjects each in KD025 and M2, and 5 subjects in M1. Day 28: 4 subjects each in KD025 and M2, and 1 subject in M1. | Posted | Median | Full Range | hours | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose |
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| Secondary | PK: t(1/2) | KD025 = Parent Drug KD025; KD025 M2 = Metabolite M2; t(1/2) = apparent terminal elimination half-life | One subject was excluded from all descriptive statistics due to a mix-up of samples between pre-dose and 4 hours on Day 1. Three subjects were excluded from day 28 statistics due to varying protocol deviations. Four additional subjects were excluded from M1 Day 28. No data were collected for Metabolite M1. | Posted | Mean | Standard Deviation | hours | Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose |
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| 0 |
| 8 |
| 1 |
| 8 |
| 4 |
| 8 |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 16.0 | Systematic Assessment | Same subject had SAE |
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| Anastomotic ulcer | Injury, poisoning and procedural complications | MedDRA Version 16.0 | Systematic Assessment | Same subject had SAE |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA Version 16.0 | Systematic Assessment | Same subject had SAE |
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| Nausea | Gastrointestinal disorders | MedDRA Version 16.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 16.0 | Systematic Assessment |
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| Anastomotic ulder | Injury, poisoning and procedural complications | MedDRA Version 16.0 | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA Version 16.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 16.0 | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | MedDRA Version 16.0 | Systematic Assessment |
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| Rib Fracture | Injury, poisoning and procedural complications | MedDRA Version 16.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA Version 16.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA Version 16.0 | Systematic Assessment |
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| Tooth ache | Gastrointestinal disorders | MedDRA Version 16.0 | Systematic Assessment |
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The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding results. The sponsor cannot require changes to the study results in the communication except to remove sponsor's confidential information. Sponsor cannot unilaterally extend the embargo.
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| Change from Baseline to Week 4 |
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| Week 8 (Day 56) |
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| Change from Baseline to Week 8 |
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| Title | Measurements |
|---|---|
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| 4 weeks: 0 to 24% clearing |
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| 4 weeks: Worse |
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| 8 weeks: 75% to 100% |
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| 8 weeks: 50% to 74% clearing |
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| 8 weeks: 25% to 49% clearing |
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| 8 weeks: 0% to 24% clearing |
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| 8 weeks: Worse |
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| 8 weeks: Missing (no data) |
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| Cmax: Day 28 |
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| Cmin: Day 1 |
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| Cmin: Day 28 |
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| AUC(0-24): Day 28 |
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| AUC(inf) from Day 1 |
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| Tmax: Day 28 |
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| t(1/2): Day 28 |
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