Psoriasis Vulgaris
Conditions
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.
Detailed description
Study KD025-206 was a phase 2, open-label, dose-finding, safety, tolerability, activity, and PK study of KD025 in subjects with psoriasis who had failed at least 1 line of systemic therapy or phototherapy. Subjects received KD025 PO for 12 weeks. Planned enrollment was 36 subjects in 3 cohorts, 12 subjects per cohort: * Cohort 1 (12 subjects): KD025 400 mg once daily (QD) PO for 12 weeks * Cohort 2 (12 subjects): KD025 200 mg PO twice daily (BID) for 12 weeks * Cohort 3 (12 subjects): KD025 400 mg BID PO for 12 weeks Subjects were initially enrolled simultaneously in Cohort 1 and Cohort 2 according to a randomization schedule, with safety reviewed before any subjects. If safety guidelines were met, Cohort 3 was added to explore the efficacy and safety of KD025 at a dose of 400 mg PO BID. Subjects underwent safety evaluations: medical history evaluations; physical examinations (PEs); vital sign measurements; weight measurements; adverse event (AE) assessments; concomitant medication assessments; blood sample collection for hematology, chemistry, and coagulation; lipid panel; thyroid-stimulating hormone; measurements of antinuclear antibody; anti-double-stranded deoxyribonucleic acid; Complement C; antiphospholipid antibody; liver ultrasound (US); pregnancy testing for females of childbearing potential; PK sampling (subset of subjects only); urinalysis; and electrocardiogram (ECG). Subjects underwent efficacy evaluations: Psoriasis Area and Severity Index (PASI) scoring; Physicians Global Assessment (PGA) scoring; and Dermatologic Life Quality Index (DLQI) scoring. Subjects participating in PK sampling were admitted to the clinic on Month 1 Day 1 (M1D1) for PK procedures and were discharged on M2D2. Blood samples for PK analyses were collected on M2D1 and Month 3 Day 1 (M3D1) on an outpatient basis. Subjects were not to take their morning dose until after blood samples were drawn. A Follow-Up visit occurred 30 ± 3 days after the last dose of study drug. The endpoints for efficacy were PASI, PGA, and DSQI scores. 1. Psoriasis Area and Severity Index (PASI): The PASI is a measure of the psoriasis disease severity using the average redness, thickness, and scaliness of the lesions (each graded on a 0 to 4 scale), which is weighted by the area of involvement. The PASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 (no disease) to 72 (maximal disease). 2. Physicians Global Assessment (PGA): The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse. 3. Dermatology Life Quality Index (DLQI): The DLQI is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life (QOL). It is a 10-item questionnaire that assesses 6 different aspects of quality of life: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. Possible DLQI scores range from 0 (no detectable impairment on a subject's QOL) to 30 (extremely large effect on a subject's QOL). Safety was assessed by standard clinical and laboratory tests (hematology, serum chemistry, and urinalysis), PEs, and reporting of treatment-emergent adverse events (TEAEs). Toxicity grades were defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. In addition, subjects had liver ultrasound and liver functioning testing assessed for possible steatosis. Blood samples for determination of PK plasma concentrations of KD025 and its metabolites were collected for maximum concentration (Cmax); time of maximum concentration (Tmax); area under the concentration-time curve (AUC) at 0 to 24 hours, 0 to last, and 0 to infinity (0 to 24, 0 to last, 0 to infinity \[inf\]); half-life (t1/2); and accumulation ratio (metabolic-to-parent drug ratio).
Interventions
DRUGKD025
Sponsors
Kadmon Corporation, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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: 1. 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.) 2. Renal disease and/or serum creatinine \> 1.5 × ULN at screening * QTc(F) interval (QT interval data corrected using Fridericia's formula) \> 450 msec at the screening or predose ECG * Previous exposure to KD025 or known allergy/sensitivity to KD025 or any other ROCK-2 inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | 12 weeks | 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. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
| Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | 12 weeks | 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. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
| Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Percentage of Subjects With a Decrease in PASI Score After 8 Weeks---ITT Population | 8 weeks | The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline after 8 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
| Efficacy: Percentage of Subjects With a Decrease in PASI Score at EOT---ITT Population | 12 weeks | The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline at the end of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
| Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 12 weeks | The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline after 4 weeks, 8 weeks, and 12 weeks of treatment with belumosudil in the Evaluable Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
| Efficacy: Mean Change in PASI Score After 4 Weeks---ITT Population | 4 weeks | Mean change in the Psoriasis Area and Severity Index score from baseline after 4 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable |
| Efficacy: Mean Change in PASI Score After 8 Weeks---ITT Population | 8 weeks | Mean change in the Psoriasis Area and Severity Index score from baseline after 8 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable |
| Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 8 weeks | Mean change in the Psoriasis Area and Severity Index score from baseline after 4 and 8 weeks of treatment with belumosudil in the Evaluable Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable |
| Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | 4 weeks | Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 4 weeks of treatment with belumosudil in the Intent-to-Treat Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement |
| Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | 8 weeks | Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 8 weeks of treatment with belumosudil in the Intent-to-Treat Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse. PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement |
| Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | 12 weeks | Mean change in Psoriasis Area and Severity Index score after 12 weeks of treatment or End of Treatment with KD025 from baseline in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable |
| Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 weeks | Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 4 weeks, after 8 weeks, and after 12 week of treatment with belumosudil in the Evaluable Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse. PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement. |
| Efficacy: Mean Changes in DLQI at EOT--ITT Population | 12 weeks | Mean changes in the Dermatology Life Quality Index from baseline after 12 weeks of treatment with belumosudil or end of treatment with KD025 in the Intent-to-Treat Population \[The Dermatology Life Quality Index (DLQI) is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. The scale range is 0 to 30: 0-1=no effect on subject's quality of life; 2-5=small effect; 6-10= moderate effect; 11-20=very large effect; 21-30=extremely large effect.\] Negative mean change is favorable; positive mean change is unfavorable |
| Efficacy: Mean Changes in DLQI at 12 Weeks--Evaluable Population | 12 weeks | Mean changes in the Dermatology Life Quality Index (DLQI) score from baseline after 12 weeks of treatment with belumosudil in the Evaluable Population. \[The Dermatology Life Quality Index (DLQI) is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. The scale range is 0 to 30: 0-1=no effect on subject's quality of life; 2-5=small effect; 6-10= moderate effect; 11-20=very large effect; 21-30=extremely large effect.\] Negative mean change is favorable; positive mean change is unfavorable. |
| Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2 | 24 hours | Maximum concentration (Cmax) of Parent drug (KD0250), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2) |
| Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | 24 hours | Area Under Concentration Time Curve (AUC) for Parent Drug KD025, Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2): AUC(0-12) = AUC from predose to 12 hours post-dose AUC(0-24) = AUC from predose to 24 hours post-dose AUC(0-t) = AUC from predose to a given time t post-dose |
| Pharmacokinetics: t(1/2) of KD025 | 24 hours | Half-life (t\[1/2\]) of Parent drug (KD025) |
| Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | 24 hours | Metabolite-to-parent ratio of maximum concentration (MR C\[max\]) and metabolite-to-parent ratio of the area under concentration time curve from pre-dose to a given time t for Metabolite 1 (KD025m1) and Metabolite 2 (KD025m2) |
| Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | 12 weeks | Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 12 weeks of treatment with belumosudil or at the end of treatment (EOT) in the Intent-to-Treat Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse. PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement |
| Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | 12 weeks | Mean change in Psoriasis Area and Severity Index score after 12 weeks of treatment or end of treatment with belumosudil from baseline in the Evaluable Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable |
| Efficacy: Percentage of Subjects With a Decrease in PASI After 4 Weeks---ITT Population | 4 weeks | The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline after 4 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 400 mg QD Belumosudil 400 mg PO QD for 12 weeks | 13 |
| 200 mg BID Belumosudil 200 mg PO BID for 12 weeks | 13 |
| 400 mg BID Belumosudil 400 mg PO BID for 12 weeks | 12 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 3 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 |
| Overall Study | Non-compliance with study drug | 0 | 1 | 0 |
| Overall Study | Stopped by Investigator | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | 400 mg QD | 200 mg BID | 400 mg BID | Total |
|---|---|---|---|---|
| Age, Continuous | 46.0 years | 45.0 years | 54.5 years | 47.5 years |
| BMI (body mass index)--Mean | 34.42 kg/m^2 STANDARD_DEVIATION 7.132 | 32.81 kg/m^2 STANDARD_DEVIATION 7.747 | 32.65 kg/m^2 STANDARD_DEVIATION 10.582 | 33.31 kg/m^2 STANDARD_DEVIATION 8.362 |
| BMI--Median | 35.70 kg/m^2 | 31.40 kg/m^2 | 30.35 kg/m^2 | 31.50 kg/m^2 |
| Dermatology Quality Life Index (DQLI)--Mean | 14.6 Units on a scale STANDARD_DEVIATION 6.79 | 14.2 Units on a scale STANDARD_DEVIATION 6.39 | 10.3 Units on a scale STANDARD_DEVIATION 7.77 | 13.1 Units on a scale STANDARD_DEVIATION 7.06 |
| DLQI--Median | 16.0 Units on a scale | 15.0 Units on a scale | 10.0 Units on a scale | 12.5 Units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 6 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 9 Participants | 6 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| PASI--Median | 18.0 Units on a scale | 16.2 Units on a scale | 18.5 Units on a scale | 17.3 Units on a scale |
| Physician Global Assessment (PGA) Clear (100%) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Physician Global Assessment (PGA) Excellent (75% to 99%) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Physician Global Assessment (PGA) Fair (25% to 49%) | 1 Participants | 5 Participants | 2 Participants | 8 Participants |
| Physician Global Assessment (PGA) Good (50% to 74%) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Physician Global Assessment (PGA) Poor (0% to 24%) | 12 Participants | 6 Participants | 7 Participants | 25 Participants |
| Physician Global Assessment (PGA) Worse | 0 Participants | 2 Participants | 3 Participants | 5 Participants |
| Psoriasis Area and Severity Index (PASI) Score--Mean | 21.0 Units on a scale STANDARD_DEVIATION 10.85 | 18.3 Units on a scale STANDARD_DEVIATION 8.51 | 20.3 Units on a scale STANDARD_DEVIATION 7.24 | 19.8 Units on a scale STANDARD_DEVIATION 8.87 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 12 Participants | 12 Participants | 35 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 4 Participants | 15 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 8 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 38 |
| other Total, other adverse events | 12 / 13 | 11 / 13 | 8 / 12 | 31 / 38 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 38 |
Outcome results
Primary
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. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 12 weeks
Population: Intent-to-Treat (ITT) Population: All subjects enrolled in study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 75% Reduction from Baseline | 16.7 Percentage of participants (%) |
| 400 mg QD | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 50% Reduction from Baseline | 41.7 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 50% Reduction from Baseline | 50.0 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 75% Reduction from Baseline | 8.3 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 75% Reduction from Baseline | 9.1 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 50% Reduction from Baseline | 18.2 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 75% Reduction from Baseline | 11.4 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease in PASI Score at EOT---ITT Population | ≥ 50% Reduction from Baseline | 37.1 Percentage of participants (%) |
Primary
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. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 12 weeks
Population: Evaluable Population: Subjects who receive at least 80% of the expected amount of study drug if the subject had completed the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 75% Reduction from Baseline | 16.7 Percentage of participants (%) |
| 400 mg QD | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 50% Reduction from Baseline | 41.7 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 50% Reduction from Baseline | 71.4 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 75% Reduction from Baseline | 14.3 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 75% Reduction from Baseline | 14.3 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 50% Reduction from Baseline | 28.6 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 75% Reduction from Baseline | 15.4 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With ≥ 75% Decrease or ≥ 50% Decrease With PASI Score at EOT---Evaluable Population | ≥ 50% Reduction from Baseline | 46.2 Percentage of participants (%) |
Primary
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.
Time frame: 12 weeks
Population: ITT Population: All enrolled subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | All AEs | 12 Percentage of participants (%) |
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 1 (Mild) | 69.2 Percentage of participants (%) |
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 2 (Moderate) | 69.2 Percentage of participants (%) |
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3 (Severe) | 7.7 Percentage of participants (%) |
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 4 (Life-threatening) | 7.7 Percentage of participants (%) |
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 5 (Death) | 0 Percentage of participants (%) |
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Related to KD025 | 38.5 Percentage of participants (%) |
| 400 mg QD | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3, 4, or 5 Related to KD025 | 0 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 5 (Death) | 0 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 4 (Life-threatening) | 0 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 1 (Mild) | 46.2 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3, 4, or 5 Related to KD025 | 7.7 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Related to KD025 | 23.1 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3 (Severe) | 7.7 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 2 (Moderate) | 46.2 Percentage of participants (%) |
| 200 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | All AEs | 11 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Related to KD025 | 58.3 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 2 (Moderate) | 50.0 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3 (Severe) | 8.3 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 4 (Life-threatening) | 0 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 5 (Death) | 0 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3, 4, or 5 Related to KD025 | 0 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | All AEs | 8 Percentage of participants (%) |
| 400 mg BID | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 1 (Mild) | 33.3 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 2 (Moderate) | 55.3 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3 (Severe) | 7.9 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 1 (Mild) | 50.0 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | All AEs | 31 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 4 (Life-threatening) | 2.6 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 3, 4, or 5 Related to KD025 | 2.6 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Related to KD025 | 39.5 Percentage of participants (%) |
| Overall (All Subjects) | Safety: Percentage of Subjects With AEs by Severity and Relationship to Belumosudil--ITT Population | Grade 5 (Death) | 0 Percentage of participants (%) |
Secondary
Efficacy: Mean Change in PASI Score After 4 Weeks---ITT Population
Mean change in the Psoriasis Area and Severity Index score from baseline after 4 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable
Time frame: 4 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 400 mg QD | Efficacy: Mean Change in PASI Score After 4 Weeks---ITT Population | -4.7 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score After 4 Weeks---ITT Population | -2.6 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score After 4 Weeks---ITT Population | -2.3 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score After 4 Weeks---ITT Population | -3.2 Score on a scale |
p-value: 0.0064t-test, 2 sided
p-value: 0.0479t-test, 2 sided
p-value: 0.1513t-test, 2 sided
p-value: 0.0002t-test, 2 sided
Secondary
Efficacy: Mean Change in PASI Score After 8 Weeks---ITT Population
Mean change in the Psoriasis Area and Severity Index score from baseline after 8 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable
Time frame: 8 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 400 mg QD | Efficacy: Mean Change in PASI Score After 8 Weeks---ITT Population | -8.6 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score After 8 Weeks---ITT Population | -6.4 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score After 8 Weeks---ITT Population | -4.7 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score After 8 Weeks---ITT Population | -6.9 Score on a scale |
p-value: 0.0137t-test, 2 sided
p-value: 0.0017t-test, 2 sided
p-value: 0.0743t-test, 2 sided
p-value: <0.0001t-test, 2 sided
Secondary
Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population
Mean change in Psoriasis Area and Severity Index score after 12 weeks of treatment or end of treatment with belumosudil from baseline in the Evaluable Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable
Time frame: 12 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 400 mg QD | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | 12 Weeks | 12.4 Score on a scale |
| 400 mg QD | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | Change from Baseline at 12 Weeks | -8.8 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | Change from Baseline at 12 Weeks | -7.9 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | 12 Weeks | 7.6 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | 12 Weeks | 15.5 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | Change from Baseline at 12 Weeks | -5.9 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | 12 Weeks | 12.0 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--Evaluable Population | Change from Baseline at 12 Weeks | -7.8 Score on a scale |
p-value: 0.0282t-test, 2 sided
p-value: 0.0029t-test, 2 sided
p-value: 0.0703t-test, 2 sided
p-value: 0.0002t-test, 2 sided
Secondary
Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population
Mean change in Psoriasis Area and Severity Index score after 12 weeks of treatment or End of Treatment with KD025 from baseline in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable
Time frame: 12 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 400 mg QD | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | End of Treatment (or 12 Weeks) | 12.4 Score on a scale |
| 400 mg QD | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | Change from Baseline at End of Treatment | -8.8 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | Change from Baseline at End of Treatment | -6.0 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | End of Treatment (or 12 Weeks) | 10.3 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | End of Treatment (or 12 Weeks) | 14.4 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | Change from Baseline at End of Treatment | -4.8 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | End of Treatment (or 12 Weeks) | 12.3 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score at 12 Weeks From Baseline--ITT Population | Change from Baseline at End of Treatment | -6.6 Score on a scale |
p-value: 0.0282t-test, 2 sided
p-value: 0.0035t-test, 2 sided
p-value: 0.0261t-test, 2 sided
p-value: <0.0001t-test, 2 sided
Secondary
Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population
Mean change in the Psoriasis Area and Severity Index score from baseline after 4 and 8 weeks of treatment with belumosudil in the Evaluable Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] Negative mean change is favorable; positive mean change is unfavorable
Time frame: 8 weeks
Population: Evaluable Population: Subjects who received at least 80% of the expected amount of study drug if the subject had completed the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 4 Weeks | -4.4 Score on a scale |
| 400 mg QD | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 8 Weeks | -8.6 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 8 Weeks | -6.8 Score on a scale |
| 200 mg BID | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 4 Weeks | -3.5 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 4 Weeks | -2.7 Score on a scale |
| 400 mg BID | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 8 Weeks | -4.7 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 4 Weeks | -3.7 Score on a scale |
| Overall (All Subjects) | Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population | 8 Weeks | -7.1 Score on a scale |
p-value: 0.014t-test, 2 sided
p-value: 0.062t-test, 2 sided
p-value: 0.262t-test, 2 sided
p-value: 0.0008t-test, 2 sided
p-value: 0.0137t-test, 2 sided
p-value: 0.0064t-test, 2 sided
p-value: 0.0743t-test, 2 sided
p-value: <0.0001t-test, 2 sided
Secondary
Efficacy: Mean Changes in DLQI at 12 Weeks--Evaluable Population
Mean changes in the Dermatology Life Quality Index (DLQI) score from baseline after 12 weeks of treatment with belumosudil in the Evaluable Population. \[The Dermatology Life Quality Index (DLQI) is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. The scale range is 0 to 30: 0-1=no effect on subject's quality of life; 2-5=small effect; 6-10= moderate effect; 11-20=very large effect; 21-30=extremely large effect.\] Negative mean change is favorable; positive mean change is unfavorable.
Time frame: 12 weeks
Population: Evaluable Population: Subjects who received at least 80% of the expected amount of study drug if the subject had completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 mg QD | Efficacy: Mean Changes in DLQI at 12 Weeks--Evaluable Population | -4.9 Score on a scale | Standard Deviation 4.68 |
| 200 mg BID | Efficacy: Mean Changes in DLQI at 12 Weeks--Evaluable Population | -6.3 Score on a scale | Standard Deviation 5.82 |
| 400 mg BID | Efficacy: Mean Changes in DLQI at 12 Weeks--Evaluable Population | -2.3 Score on a scale | Standard Deviation 2.93 |
| Overall (All Subjects) | Efficacy: Mean Changes in DLQI at 12 Weeks--Evaluable Population | -4.6 Score on a scale | Standard Deviation 4.71 |
p-value: 0.004t-test, 2 sided
p-value: 0.029t-test, 2 sided
p-value: 0.084t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Efficacy: Mean Changes in DLQI at EOT--ITT Population
Mean changes in the Dermatology Life Quality Index from baseline after 12 weeks of treatment with belumosudil or end of treatment with KD025 in the Intent-to-Treat Population \[The Dermatology Life Quality Index (DLQI) is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. The scale range is 0 to 30: 0-1=no effect on subject's quality of life; 2-5=small effect; 6-10= moderate effect; 11-20=very large effect; 21-30=extremely large effect.\] Negative mean change is favorable; positive mean change is unfavorable
Time frame: 12 weeks
Population: Intent-to-Treat: All enrolled subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 mg QD | Efficacy: Mean Changes in DLQI at EOT--ITT Population | -4.9 Score on a scale | Standard Deviation 4.68 |
| 200 mg BID | Efficacy: Mean Changes in DLQI at EOT--ITT Population | -5.1 Score on a scale | Standard Deviation 5.35 |
| 400 mg BID | Efficacy: Mean Changes in DLQI at EOT--ITT Population | -2.5 Score on a scale | Standard Deviation 4.5 |
| Overall (All Subjects) | Efficacy: Mean Changes in DLQI at EOT--ITT Population | -4.2 Score on a scale | Standard Deviation 4.86 |
p-value: 0.004t-test, 2 sided
p-value: 0.007t-test, 2 sided
p-value: 0.09t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Efficacy: Percentage of Subjects With a Decrease in PASI After 4 Weeks---ITT Population
The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline after 4 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 4 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With a Decrease in PASI After 4 Weeks---ITT Population | 76.9 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI After 4 Weeks---ITT Population | 66.7 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI After 4 Weeks---ITT Population | 58.3 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With a Decrease in PASI After 4 Weeks---ITT Population | 67.6 Percentage of participants (%) |
Secondary
Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population
The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline after 4 weeks, 8 weeks, and 12 weeks of treatment with belumosudil in the Evaluable Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 12 weeks
Population: Evaluable Population: Subjects who received at least 80% of the expected amount study drug if the subject had completed the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 4 Weeks | 75.0 Percentage of participants (%) |
| 400 mg QD | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 12 Weeks | 75.0 Percentage of participants (%) |
| 400 mg QD | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 8 Weeks | 83.3 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 4 Weeks | 85.7 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 12 Weeks | 100 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 8 Weeks | 100 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 8 Weeks | 85.7 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 4 Weeks | 71.4 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 12 Weeks | 85.7 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 4 Weeks | 76.9 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 12 Weeks | 84.6 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population | 8 Weeks | 88.5 Percentage of participants (%) |
Secondary
Efficacy: Percentage of Subjects With a Decrease in PASI Score After 8 Weeks---ITT Population
The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline after 8 weeks of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 8 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 8 Weeks---ITT Population | 83.3 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 8 Weeks---ITT Population | 100 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 8 Weeks---ITT Population | 85.7 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With a Decrease in PASI Score After 8 Weeks---ITT Population | 89.3 Percentage of participants (%) |
Secondary
Efficacy: Percentage of Subjects With a Decrease in PASI Score at EOT---ITT Population
The percentage of subjects who exhibit any decrease in the Psoriasis Area and Severity Index score from baseline at the end of treatment with belumosudil in the Intent-to-Treat Population. \[The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 12 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With a Decrease in PASI Score at EOT---ITT Population | 75.0 Percentage of participants (%) |
| 200 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score at EOT---ITT Population | 75.0 Percentage of participants (%) |
| 400 mg BID | Efficacy: Percentage of Subjects With a Decrease in PASI Score at EOT---ITT Population | 81.8 Percentage of participants (%) |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With a Decrease in PASI Score at EOT---ITT Population | 77.1 Percentage of participants (%) |
Secondary
Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population
Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 4 weeks, after 8 weeks, and after 12 week of treatment with belumosudil in the Evaluable Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse. PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement.
Time frame: 12 weeks
Population: Evaluable Population: Subjects who received at least 80% of the expected amount of study drug if the subject had completed the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Clear/Excellent | 0 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Good | 33.3 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Clear/Excellent | 0 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Fair | 41.7 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Clear/Excellent | 8.3 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Fair | 25.0 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Good | 25.0 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Fair | 33.3 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Good | 8.3 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Fair | 85.7 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Fair | 100 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Good | 0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Fair | 85.7 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Good | 0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Clear/Excellent | 0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Good | 14.3 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Clear/Excellent | 0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Clear/Excellent | 0 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Fair | 28.6 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Clear/Excellent | 0 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Good | 14.3 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Fair | 42.9 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Clear/Excellent | 0 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Good | 14.3 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Clear/Excellent | 0 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Good | 28.6 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Fair | 42.9 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Fair | 53.8 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Good | 7.7 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Good | 15.4 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 4 Weeks: Clear/Excellent | 0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Fair | 46.2 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Good | 26.9 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 12 Weeks: Clear/Excellent | 0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Fair | 50.0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population | 8 Weeks: Clear/Excellent | 3.8 Percentage of participants |
Secondary
Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population
Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 4 weeks of treatment with belumosudil in the Intent-to-Treat Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement
Time frame: 4 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Fair (25% to 49% Improvement) | 46.2 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Good (50% to 74% Improvement) | 7.7 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Fair (25% to 49% Improvement) | 58.3 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Good (50% to 74% Improvement) | 8.3 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Fair (25% to 49% Improvement) | 41.7 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Good (50% to 74% Improvement) | 8.3 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Fair (25% to 49% Improvement) | 48.6 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Good (50% to 74% Improvement) | 8.1 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
Secondary
Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population
Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 8 weeks of treatment with belumosudil in the Intent-to-Treat Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse. PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement
Time frame: 8 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 8.3 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Good (50% to 74% Improvement) | 25.0 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Fair (25% to 49% Improvement) | 25.0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Fair (25% to 49% Improvement) | 88.9 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Good (50% to 74% Improvement) | 11.1 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Good (50% to 74% Improvement) | 14.3 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Fair (25% to 49% Improvement) | 42.9 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Clear/Excellent (75% to 100% Improvement) | 3.6 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Fair (25% to 49% Improvement) | 50.0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population | Good (50% to 74% Improvement) | 17.9 Percentage of participants |
Secondary
Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population
Percentage of subjects evaluated by the Physician Global Assessment who improve (excellent, good, or fair) from baseline after 12 weeks of treatment with belumosudil or at the end of treatment (EOT) in the Intent-to-Treat Population. The relative PGA documents the physician's assessment of the subject's psoriasis status. Consideration was given to the percent of body involvement as well as overall induration, scaling, and erythema. The PGA was assessed relative to baseline condition and was defined as: (1) clear; (2) excellent; (3) good; (4) fair; (5) poor; and (6) worse. PGA improvement is defined as the categorical change from baseline: Clear = 100% improvement; Excellent = 75% to 99% improvement; Good = 50% to 74% improvement; Fair = 25% to 49% improvement
Time frame: 12 weeks
Population: Intent-to-Treat (ITT) Population: All enrolled subjects
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Good (50% to 74% Improvement) | 33.3 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| 400 mg QD | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Fair (25% to 49% Improvement) | 33.3 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Fair (25% to 49% Improvement) | 50.0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| 200 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Good (50% to 74% Improvement) | 25.0 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Good (50% to 74% Improvement) | 18.2 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Fair (25% to 49% Improvement) | 36.4 Percentage of participants |
| 400 mg BID | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Fair (25% to 49% Improvement) | 40.0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Clear/Excellent (75% to 100% Improvement) | 0 Percentage of participants |
| Overall (All Subjects) | Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population | Good (50% to 74% Improvement) | 25.7 Percentage of participants |
Secondary
Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2
Area Under Concentration Time Curve (AUC) for Parent Drug KD025, Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2): AUC(0-12) = AUC from predose to 12 hours post-dose AUC(0-24) = AUC from predose to 24 hours post-dose AUC(0-t) = AUC from predose to a given time t post-dose
Time frame: 24 hours
Population: PK Population: Subjects received at least 1 dose of study drug and had at least 1 post-dose PK sample drawn.~Note: KD025m2 did not have AUC(0-12) or AUC(0-24) available. Not all subjects had all PK measurements. AUC(0-12) and AUC(0-24) for KD025m1 were not calculable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg QD | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025: AUC(0-24) | 18800 hour*ng/mL | Standard Deviation 10600 |
| 400 mg QD | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025: AUC(0-t) | 18800 hour*ng/mL | Standard Deviation 10600 |
| 400 mg QD | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2: AUC(0-12) | 2300 hour*ng/mL | Standard Deviation 907 |
| 400 mg QD | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m1: AUC(0-t) | 93.4 hour*ng/mL | Standard Deviation 18.1 |
| 400 mg QD | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2: AUC(0-24) | 2510 hour*ng/mL | Standard Deviation 1180 |
| 400 mg QD | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2: AUC(0-t) | 2550 hour*ng/mL | Standard Deviation 1080 |
| 400 mg QD | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025: AUC(0-12) | 16200 hour*ng/mL | Standard Deviation 8910 |
| 200 mg BID | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2: AUC(0-t) | 1960 hour*ng/mL | Standard Deviation 1950 |
| 200 mg BID | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025: AUC(0-12) | 9150 hour*ng/mL | Standard Deviation 5950 |
| 200 mg BID | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2: AUC(0-12) | 757 hour*ng/mL | Standard Deviation 823 |
| 200 mg BID | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025: AUC(0-24) | 21800 hour*ng/mL | Standard Deviation 13900 |
| 200 mg BID | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2: AUC(0-24) | 1790 hour*ng/mL | Standard Deviation 1850 |
| 200 mg BID | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025: AUC(0-t) | 25100 hour*ng/mL | Standard Deviation 14800 |
| 200 mg BID | Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2 | KD025m1: AUC(0-t) | 250 hour*ng/mL | Standard Deviation 0 |
Secondary
Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2
Maximum concentration (Cmax) of Parent drug (KD0250), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2)
Time frame: 24 hours
Population: PK Population: Subjects received at least 1 dose of study drug and had at least 1 post-dose PK sample drawn.~Note: Not all subjects had all data available for PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg QD | Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2 | KD025 | 3140 ng/mL | Standard Deviation 1760 |
| 400 mg QD | Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2 | KD025m1 | 23.2 ng/mL | Standard Deviation 9.66 |
| 400 mg QD | Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2 | 632 ng/mL | Standard Deviation 278 |
| 200 mg BID | Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2 | KD025 | 1770 ng/mL | Standard Deviation 1190 |
| 200 mg BID | Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2 | KD025m1 | 22.8 ng/mL | Standard Deviation 15.3 |
| 200 mg BID | Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2 | KD025m2 | 203 ng/mL | Standard Deviation 204 |
Secondary
Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2
Metabolite-to-parent ratio of maximum concentration (MR C\[max\]) and metabolite-to-parent ratio of the area under concentration time curve from pre-dose to a given time t for Metabolite 1 (KD025m1) and Metabolite 2 (KD025m2)
Time frame: 24 hours
Population: The metabolite-to-parent ratio is not applicable to parent drug KD025. Not all subjects had data for all PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg QD | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m1: MR AUC(0-t) | 0.00458 Number (ratio) | Standard Deviation 0.00253 |
| 400 mg QD | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m1: MR C(max) | 0.00736 Number (ratio) | Standard Deviation 0.00272 |
| 400 mg QD | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m2: MR C(max) | 0.199 Number (ratio) | Standard Deviation 0.0794 |
| 400 mg QD | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m2: MR AUC(0-t) | 0.133 Number (ratio) | Standard Deviation 0.0449 |
| 200 mg BID | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m2: MR AUC(0-t) | 0.0719 Number (ratio) | Standard Deviation 0.0336 |
| 200 mg BID | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m1: MR AUC(0-t) | 0.00577 Number (ratio) | Standard Deviation 0 |
| 200 mg BID | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m2: MR C(max) | 0.101 Number (ratio) | Standard Deviation 0.0469 |
| 200 mg BID | Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2 | KD025m1: MR C(max) | 0.00984 Number (ratio) | Standard Deviation 0.00287 |
Secondary
Pharmacokinetics: t(1/2) of KD025
Half-life (t\[1/2\]) of Parent drug (KD025)
Time frame: 24 hours
Population: Subjects received at least 1 dose of study drug and had at least 1 post-dose PK sample drawn.~One subject in 200 mg BID cohort did not have t(1/2) data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 400 mg QD | Pharmacokinetics: t(1/2) of KD025 | 8.00 Hours | Standard Deviation 2.47 |
| 200 mg BID | Pharmacokinetics: t(1/2) of KD025 | 5.13 Hours | Standard Deviation 1.12 |