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

• Sponsor: Kadmon Corporation, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02317627
• Collaborator: (none)
• Enrollment: 38
• Locations: 9
• Arms: 3
• Duration (Months): 15
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis Vulgaris	Drug: KD025	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Dose-finding Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Psoriasis Vulgaris Who Failed First-line Therapy
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 KD025 400 mg QD PO for 12 weeks	Drug: KD025; Other Names: SLx-2119 belumosudil
Experimental: Cohort 2 KD025 200 mg BID PO for 12 weeks	Drug: KD025; Other Names: SLx-2119 belumosudil
Experimental: Cohort 3 KD025 400 mg BID PO for 12 weeks	Drug: KD025; Other Names: SLx-2119 belumosudil

Outcome Measures

Primary Outcome Measures

1. 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.]

2. 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.]

3. 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 Outcome Measures

1. 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

2. 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

3. 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.]

4. 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.]

5. 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.]

6. 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.]

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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.

14. 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

15. 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.

16. 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)

17. 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

18. Pharmacokinetics: t(1/2) of KD025 [24 hours]

    Half-life (t[1/2]) of Parent drug (KD025)

19. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arrowhead Health Centers	Glendale	Arizona	United States	85306
2	Southern California Dermatology, Inc.	Santa Ana	California	United States	92701
3	Shondra L. Smith	Lake Charles	Louisiana	United States	70605
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Clinical Studies Group, LLC	Henderson	Nevada	United States	89074
6	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
7	High Point Clinical Trials Center	High Point	North Carolina	United States	27265
8	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
9	Metroplex Clinical Research Center (MCRC)	Dallas	Texas	United States	75231

Sponsors and Collaborators

• Kadmon Corporation, LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

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

• Responsible Party: Kadmon Corporation, LLC
• ClinicalTrials.gov Identifier: NCT02317627
• Other Study ID Numbers: KD025-206
• First Posted: Dec 16, 2014
• Last Update Posted: May 26, 2022
• Last Verified: May 1, 2022

• Additional relevant MeSH terms: Psoriasis; Belumosudil

Study Results

Participant Flow

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID
Arm/Group Description	Belumosudil 400 mg administered orally (PO) once daily (QD) for 12 weeks	Belumosudil 200 mg administered PO twice daily (BID) for 12 weeks	Belumosudil 400 mg administered PO BID for 12 weeks
Period Title: Overall Study
STARTED	13	13	12
COMPLETED	11	8	8
NOT COMPLETED	2	5	4

Baseline Characteristics

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Total
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Total of all reporting groups
Overall Participants	13	13	12	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.6 (10.32)	46.5 (11.92)	50.5 (10.26)	47.1 (10.86)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	46.0	45.0	54.5	47.5
Sex: Female, Male (Count of Participants)
Female	5 38.5%	6 46.2%	4 33.3%	15 39.5%
Male	8 61.5%	7 53.8%	8 66.7%	23 60.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 38.5%	4 30.8%	6 50%	15 39.5%
Not Hispanic or Latino	8 61.5%	9 69.2%	6 50%	23 60.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 7.7%	0 0%	0 0%	1 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 7.7%	1 7.7%	0 0%	2 5.3%
White	11 84.6%	12 92.3%	12 100%	35 92.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
BMI (body mass index)--Mean (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	34.42 (7.132)	32.81 (7.747)	32.65 (10.582)	33.31 (8.362)
BMI--Median (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	35.70	31.40	30.35	31.50
Psoriasis Area and Severity Index (PASI) Score--Mean (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	21.0 (10.85)	18.3 (8.51)	20.3 (7.24)	19.8 (8.87)
PASI--Median (Units on a scale) [Median (Full Range) ]
Median (Full Range) [Units on a scale]	18.0	16.2	18.5	17.3
Physician Global Assessment (PGA) (Count of Participants)
Clear (100%)	0 0%	0 0%	0 0%	0 0%
Excellent (75% to 99%)	0 0%	0 0%	0 0%	0 0%
Good (50% to 74%)	0 0%	0 0%	0 0%	0 0%
Fair (25% to 49%)	1 7.7%	5 38.5%	2 16.7%	8 21.1%
Poor (0% to 24%)	12 92.3%	6 46.2%	7 58.3%	25 65.8%
Worse	0 0%	2 15.4%	3 25%	5 13.2%
Dermatology Quality Life Index (DQLI)--Mean (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	14.6 (6.79)	14.2 (6.39)	10.3 (7.77)	13.1 (7.06)
DLQI--Median (Units on a scale) [Median (Full Range) ]
Median (Full Range) [Units on a scale]	16.0	15.0	10.0	12.5

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All subjects enrolled in study

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	12	11	35
≥ 75% Reduction from Baseline	16.7 128.5%	8.3 63.8%	9.1 75.8%	11.4 30%
≥ 50% Reduction from Baseline	41.7 320.8%	50.0 384.6%	18.2 151.7%	37.1 97.6%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Evaluable Population: Subjects who receive at least 80% of the expected amount of study drug if the subject had completed the study

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	7	7	26
≥ 75% Reduction from Baseline	16.7 128.5%	14.3 110%	14.3 119.2%	15.4 40.5%
≥ 50% Reduction from Baseline	41.7 320.8%	71.4 549.2%	28.6 238.3%	46.2 121.6%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	13	13	12	38
All AEs	12 92.3%	11 84.6%	8 66.7%	31 81.6%
Grade 1 (Mild)	69.2 532.3%	46.2 355.4%	33.3 277.5%	50.0 131.6%
Grade 2 (Moderate)	69.2 532.3%	46.2 355.4%	50.0 416.7%	55.3 145.5%
Grade 3 (Severe)	7.7 59.2%	7.7 59.2%	8.3 69.2%	7.9 20.8%
Grade 4 (Life-threatening)	7.7 59.2%	0 0%	0 0%	2.6 6.8%
Grade 5 (Death)	0 0%	0 0%	0 0%	0 0%
Related to KD025	38.5 296.2%	23.1 177.7%	58.3 485.8%	39.5 103.9%
Grade 3, 4, or 5 Related to KD025	0 0%	7.7 59.2%	0 0%	2.6 6.8%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	12	11	35
End of Treatment (or 12 Weeks)	12.4	10.3	14.4	12.3
Change from Baseline at End of Treatment	-8.8	-6.0	-4.8	-6.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg QD PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	0.0282
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 200 mg BID PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	0.0035
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg BID PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	0.0261
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change for all subjects' PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	7	7	26
12 Weeks	12.4	7.6	15.5	12.0
Change from Baseline at 12 Weeks	-8.8	-7.9	-5.9	-7.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg QD PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	0.0282
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 200 mg BID PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	0.0029
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg BID PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	0.0703
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change of all subjects' PASI from baseline to Week 12.
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	13	12	12	37
Number (95% Confidence Interval) [Percentage of participants (%)]	76.9 591.5%	66.7 513.1%	58.3 485.8%	67.6 177.9%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	9	7	28
Number (95% Confidence Interval) [Percentage of participants (%)]	83.3 640.8%	100 769.2%	85.7 714.2%	89.3 235%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	12	11	35
Number (95% Confidence Interval) [Percentage of participants (%)]	75.0 576.9%	75.0 576.9%	81.8 681.7%	77.1 202.9%

9. Secondary Outcome

Title	Efficacy: Percentage of Subjects With a Decrease in PASI Score After 4 Weeks, 8 Weeks, and 12 Weeks---Evaluable Population
Description	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

Outcome Measure Data

Analysis Population Description

Evaluable Population: Subjects who received at least 80% of the expected amount study drug if the subject had completed the study

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	7	7	26
4 Weeks	75.0 576.9%	85.7 659.2%	71.4 595%	76.9 202.4%
8 Weeks	83.3 640.8%	100 769.2%	85.7 714.2%	88.5 232.9%
12 Weeks	75.0 576.9%	100 769.2%	85.7 714.2%	84.6 222.6%

10. Secondary Outcome

Title	Efficacy: Mean Change in PASI Score After 4 Weeks---ITT Population
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	13	12	12	37
Number (95% Confidence Interval) [Score on a scale]	-4.7	-2.6	-2.3	-3.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg QD from baseline to Week 4.
Statistical Test of Hypothesis	p-Value	0.0064
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 200 mg BID from baseline to Week 4.
Statistical Test of Hypothesis	p-Value	0.0479
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg BID from baseline to Week 4.
Statistical Test of Hypothesis	p-Value	0.1513
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change Overall from baseline to Week 4.
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

11. Secondary Outcome

Title	Efficacy: Mean Change in PASI Score After 8 Weeks---ITT Population
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	9	7	28
Number (95% Confidence Interval) [Score on a scale]	-8.6	-6.4	-4.7	-6.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg QD from baseline to Week 8.
Statistical Test of Hypothesis	p-Value	0.0137
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 200 mg BID from baseline to Week 8.
Statistical Test of Hypothesis	p-Value	0.0017
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg BID from baseline to Week 8.
Statistical Test of Hypothesis	p-Value	0.0743
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change Overall from baseline to Week 8.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

12. Secondary Outcome

Title	Efficacy: Mean Change in PASI Score at 4 and 8 Weeks---Evaluable Population
Description	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

Outcome Measure Data

Analysis Population Description

Evaluable Population: Subjects who received at least 80% of the expected amount of study drug if the subject had completed the study

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	7	7	26
4 Weeks	-4.4	-3.5	-2.7	-3.7
8 Weeks	-8.6	-6.8	-4.7	-7.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg QD from baseline to 4 weeks.
Statistical Test of Hypothesis	p-Value	0.0140
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 200 mg BID from baseline to 4 weeks.
Statistical Test of Hypothesis	p-Value	0.0620
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in 400 mg BID from baseline to 4 weeks.
Statistical Test of Hypothesis	p-Value	0.2620
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change of all subjects from baseline to 4 weeks.
Statistical Test of Hypothesis	p-Value	0.0008
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg QD from baseline to 8 weeks.
Statistical Test of Hypothesis	p-Value	0.0137
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 200 mg BID from baseline to 8 weeks.
Statistical Test of Hypothesis	p-Value	0.0064
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg BID from baseline to 8 weeks.
Statistical Test of Hypothesis	p-Value	0.0743
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change of all subjects from baseline to 8 weeks.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

13. Secondary Outcome

Title	Efficacy: Percentage of Subjects With Improvement in PGA af 4 Weeks---ITT Population
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	13	12	12	37
Clear/Excellent (75% to 100% Improvement)	0 0%	0 0%	0 0%	0 0%
Good (50% to 74% Improvement)	7.7 59.2%	8.3 63.8%	8.3 69.2%	8.1 21.3%
Fair (25% to 49% Improvement)	46.2 355.4%	58.3 448.5%	41.7 347.5%	48.6 127.9%

14. Secondary Outcome

Title	Efficacy: Percentage of Subjects With Improvement in PGA af 8 Weeks---ITT Population
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudl 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	9	7	28
Clear/Excellent (75% to 100% Improvement)	8.3 63.8%	0 0%	0 0%	3.6 9.5%
Good (50% to 74% Improvement)	25.0 192.3%	11.1 85.4%	14.3 119.2%	17.9 47.1%
Fair (25% to 49% Improvement)	25.0 192.3%	88.9 683.8%	42.9 357.5%	50.0 131.6%

15. Secondary Outcome

Title	Efficacy: Percentage of Subjects With Improvement in PGA af EOT--ITT Population
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All enrolled subjects

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg PO QD + 200 mg PO QD + 400 mg PO BID for 12 weeks
Measure Participants	12	12	11	35
Clear/Excellent (75% to 100% Improvement)	0 0%	0 0%	0 0%	0 0%
Good (50% to 74% Improvement)	33.3 256.2%	25.0 192.3%	18.2 151.7%	25.7 67.6%
Fair (25% to 49% Improvement)	33.3 256.2%	50.0 384.6%	36.4 303.3%	40.0 105.3%

16. Secondary Outcome

Title	Efficacy: Percentage of Subjects With Improvement in PGA af 4, 8, and 12 Weeks---Evaluable Population
Description	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

Outcome Measure Data

Analysis Population Description

Evaluable Population: Subjects who received at least 80% of the expected amount of study drug if the subject had completed the study

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	7	7	26
4 Weeks: Clear/Excellent	0 0%	0 0%	0 0%	0 0%
4 Weeks: Good	8.3 63.8%	0 0%	14.3 119.2%	7.7 20.3%
4 Weeks: Fair	41.7 320.8%	85.7 659.2%	42.9 357.5%	53.8 141.6%
8 Weeks: Clear/Excellent	8.3 63.8%	0 0%	0 0%	3.8 10%
8 Weeks: Good	25.0 192.3%	0 0%	14.3 119.2%	15.4 40.5%
8 Weeks: Fair	25.0 192.3%	100 769.2%	42.9 357.5%	50.0 131.6%
12 Weeks: Clear/Excellent	0 0%	0 0%	0 0%	0 0%
12 Weeks: Good	33.3 256.2%	14.3 110%	28.6 238.3%	26.9 70.8%
12 Weeks: Fair	33.3 256.2%	85.7 659.2%	28.6 238.3%	46.2 121.6%

17. Secondary Outcome

Title	Efficacy: Mean Changes in DLQI at EOT--ITT Population
Description	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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All enrolled subjects.

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
Measure Participants	12	12	11	35
Mean (Standard Deviation) [Score on a scale]	-4.9 (4.68)	-5.1 (5.35)	-2.5 (4.50)	-4.2 (4.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg QD from baseline to 12 weeks.
Statistical Test of Hypothesis	p-Value	0.004
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 200 mg BID from baseline to 12 weeks.
Statistical Test of Hypothesis	p-Value	0.007
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change in Cohort 400 mg BID from baseline to 12 weeks.
Statistical Test of Hypothesis	p-Value	0.090
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Other
	Comments	No control group was used. Paired t-testing was used to determine the statistical significance of the mean change Overall from baseline to 12 weeks.
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

18. Secondary Outcome

Title	Efficacy: Mean Changes in DLQI at 12 Weeks--Evaluable Population
Description	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

Outcome Measure Data

Analysis Population Description

Evaluable Population: Subjects who received at least 80% of the expected amount of study drug if the subject had completed the study

Arm/Group Title	400 mg QD	200 mg BID	400 mg BID	Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks	Belumosudil 200 mg PO BID for 12 weeks	Belumosudil 400 mg PO BID for 12 weeks	Belumosudil 400 mg PO QD + 200 mg PO QD + 400 mg PO BID for 12 weeks
Measure Participants	12	7	7	26
Mean (Standard Deviation) [Score on a scale]	-4.9 (4.68)	-6.3 (5.82)	-2.3 (2.93)	-4.6 (4.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	400 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	200 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	400 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.084
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Overall (All Subjects)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Statistical significance was set at p ≤ 0.05. No adjustments for multiplicity were made. Missing data were not imputed.
	Method	t-test, 2 sided
	Comments

19. Secondary Outcome

Title	Pharmacokinetics: Cmax of Parent Drug KD025, KD025m1, and KD025m2
Description	Maximum concentration (Cmax) of Parent drug (KD0250), Metabolite 1 (KD025m1), and Metabolite 2 (KD025m2)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

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/Group Title	400 mg QD	200 mg BID
Arm/Group Description	Belumosudil 400 mg administered QD (once daily)	Belumosudil 200 mg administered PO BID (twice daily)
Measure Participants	7	6
KD025	3140 (1760)	1770 (1190)
KD025m1	23.2 (9.66)	22.8 (15.3)
KD025m2	632 (278)	203 (204)

20. Secondary Outcome

Title	Pharmacokinetics: AUC of Parent Drug KD025, KD025m1, and KD025m2
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	400 mg QD	200 mg BID
Arm/Group Description	Belumosudil 400 mg administered QD (once daily)	Belumosudil 200 mg administered PO BID (twice daily)
Measure Participants	7	6
KD025: AUC(0-12)	16200 (8910)	9150 (5950)
KD025m2: AUC(0-12)	2300 (907)	757 (823)
KD025: AUC(0-24)	18800 (10600)	21800 (13900)
KD025m2: AUC(0-24)	2510 (1180)	1790 (1850)
KD025: AUC(0-t)	18800 (10600)	25100 (14800)
KD025m1: AUC(0-t)	93.4 (18.1)	250 (0)
KD025m2: AUC(0-t)	2550 (1080)	1960 (1950)

21. Secondary Outcome

Title	Pharmacokinetics: t(1/2) of KD025
Description	Half-life (t[1/2]) of Parent drug (KD025)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

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/Group Title	400 mg QD	200 mg BID
Arm/Group Description	Belumosudil 400 mg administered QD (once daily)	Belumosudil 200 mg administered PO BID (twice daily)
Measure Participants	7	5
Mean (Standard Deviation) [Hours]	8.00 (2.47)	5.13 (1.12)

22. Secondary Outcome

Title	Pharmacokinetics: MR C(Max) and MR AUC(0-t) for KD025m1 and KD025m2
Description	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

Outcome Measure Data

Analysis Population Description

The metabolite-to-parent ratio is not applicable to parent drug KD025. Not all subjects had data for all PK parameters.

Arm/Group Title	400 mg QD	200 mg BID
Arm/Group Description	Belumosudil 400 mg administered QD (once daily)	Belumosudil 200 mg administered PO BID (twice daily)
Measure Participants	7	6
KD025m1: MR C(max)	0.00736 (0.00272)	0.00984 (0.00287)
KD025m2: MR C(max)	0.199 (0.0794)	0.101 (0.0469)
KD025m1: MR AUC(0-t)	0.00458 (0.00253)	0.00577 (0)
KD025m2: MR AUC(0-t)	0.133 (0.0449)	0.0719 (0.0336)

Adverse Events

Time Frame	Screening Period ≤ 4 week Screening Period + 12-week Treatment Period + 30-day Follow-up = Up to 20 weeks
Arm/Group Title	400 mg QD		200 mg BID		400 mg BID		Overall (All Subjects)
Arm/Group Description	Belumosudil 400 mg PO QD for 12 weeks		Belumosudil 200 mg PO BID for 12 weeks		Belumosudil 400 mg PO BID for 12 weeks		Belumosudil 400 mg QD + 200 mg QD + 400 mg BID for 12 weeks
All Cause Mortality
	400 mg QD		200 mg BID		400 mg BID		Overall (All Subjects)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)		0/12 (0%)		0/38 (0%)
Serious Adverse Events
	400 mg QD		200 mg BID		400 mg BID		Overall (All Subjects)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)		0/12 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	400 mg QD		200 mg BID		400 mg BID		Overall (All Subjects)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		11/13 (84.6%)		8/12 (66.7%)		31/38 (81.6%)
Endocrine disorders
Hypothyroidism	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Gastrointestinal disorders
Diarrhea	2/13 (15.4%)	2	0/13 (0%)	0	1/12 (8.3%)	1	3/38 (7.9%)	3
Nausea	0/13 (0%)	0	2/13 (15.4%)	2	1/12 (8.3%)	1	3/38 (7.9%)	3
Vomiting	1/13 (7.7%)	1	2/13 (15.4%)	2	0/12 (0%)	0	3/38 (7.9%)	3
Constipation	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Dyspepsia	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Hematochezia	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
General disorders
Fatigue	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/38 (2.6%)	1
Edema peripheral	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Immune system disorders
Seasonal allergy	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Infections and infestations
Upper respiratory tract infection	0/13 (0%)	0	0/13 (0%)	0	2/12 (16.7%)	2	2/38 (5.3%)	2
Oral herpes	1/13 (7.7%)	2	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	2
Gastrointestinal viral infection	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Nasopharyngitis	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/38 (2.6%)	1
Pharyngitis streptococcal	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/38 (2.6%)	1
Sinusitis	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/38 (2.6%)	1
Tonsilitis	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Tooth abscess	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Urinary tract infection	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Viral upper respiratory tract infection	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Injury, poisoning and procedural complications
Hand fracture	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Laceration	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Ligament sprain	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Postoperative wound complication	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Procedural pain	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Investigations
Liver function test abnormal	1/13 (7.7%)	1	1/13 (7.7%)	3	1/12 (8.3%)	2	3/38 (7.9%)	6
Transaminases increased	1/13 (7.7%)	5	1/13 (7.7%)	1	0/12 (0%)	0	2/38 (5.3%)	6
Alanine aminotransaminase (ALT) increased	1/13 (7.7%)	1	0/13 (0%)	0	4/12 (33.3%)	4	5/38 (13.2%)	5
Aspartate aminotransferase (AST) increased	1/13 (7.7%)	1	0/13 (0%)	0	2/12 (16.7%)	2	3/38 (7.9%)	3
Blood bilirubin increased	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/38 (2.6%)	1
Blood pressure increased	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Hepatic enzyme increased	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Metabolism and nutrition disorders
Hypercalcemia	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Hyperglycemia	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Hyperlipidemia	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/13 (7.7%)	1	0/13 (0%)	0	1/12 (8.3%)	1	2/38 (5.3%)	2
Arthralgia	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	2	1/38 (2.6%)	2
Joint stiffness	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Musculoskeletal stiffness	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Neck pain	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Psoriatic arthropathy	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Nervous system disorders
Headache	1/13 (7.7%)	1	0/13 (0%)	0	1/12 (8.3%)	1	2/38 (5.3%)	2
Dizziness	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Sinus headache	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/38 (2.6%)	1
Psychiatric disorders
Anorgasmia	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Depression	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Reproductive system and breast disorders
Vaginal discharge	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/13 (0%)	0	2/13 (15.4%)	2	0/12 (0%)	0	2/38 (5.3%)	2
Cough	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Paransal sinus infection	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Rhinitis allergic	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Upper respiratory tract infection	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Skin and subcutaneous tissue disorders
Pruritus	1/13 (7.7%)	1	0/13 (0%)	0	1/12 (8.3%)	1	2/38 (5.3%)	2
Skin burning sensation	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	1/38 (2.6%)	1
Skin discoloration	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Urticaria	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1
Vascular disorders
Flushing	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	1/38 (2.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.