KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis

A Phase 2, Randomized, Placebo-controlled, Double-blind, Open-label Extension Multicenter Study to Evaluate the Efficacy and Safety of Belumosudil (KD025) in Subjects With Diffuse Cutaneous Systemic Sclerosis

This randomized, placebo-controlled phase 2 study was seeking to evaluate the efficacy and safety of belumosudil (KD025) for the treatment of diffuse cutaneous systematic sclerosis. Enrolment was terminated earlier than planned for business reasons unrelated to safety. A total of 36 participants were enrolled and randomized into 3 groups to either receive orally administered belumosudil (200 milligrams [mg] once daily [QD] and 200 mg twice daily [BID]) or matched placebo in 1:1:1 ratio in the double-blind (DB) period of this study. Study drug dosing was for 52 weeks: double-blinded for the first 28 weeks followed by an open-label extension of 24 weeks. After unblinding, the participants on belumosudil continued on the same belumosudil dose whereas the participants in the placebo group were re-randomized to one of the belumosudil doses in a 1:1 ratio.

Study Overview

• Status: Terminated
• Conditions: Diffuse Cutaneous Systemic Sclerosis; System; Sclerosis
• Intervention / Treatment: Drug: Belumosudil (KD025); Drug: Placebo

Detailed Description

Systemic sclerosis (SSc) is a chronic autoimmune disease that causes widespread microvascular damage and excessive deposition of collagen in the skin and internal organs. Limited cutaneous systemic sclerosis is primarily cutaneous, affecting the hands, arms, and face. Diffuse cutaneous systemic sclerosis (dcSSc) is a more serious manifestation of the disease and is often rapidly progressive, not only involving the skin, but also involving internal organs including kidney, heart, and lungs.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Viable Research Management_Site number 131
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic - Scottsdale_Site number 150
  • California
    • La Jolla, California, United States, 92037
      • University of California, SD_Site number 008
    • Los Angeles, California, United States, 90045
      • Pacific Arthrirtis Care Center_Site number 136
    • Los Angeles, California, United States, 90095
      • University of California - Los Angeles_Site number 104
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center_Site number 143
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut_Site number 147
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine_Site number 140
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University_Site number 035
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical_Site number 085
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants_Site number 133
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine_Site number 124
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Research_Site number 159
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School of Medicine_Site number 134
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital_Site number 002
    • Boston, Massachusetts, United States, 02118
      • Boston University_Site number 137
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota_Site number 051
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic_Site number 146
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center_Site number 086
    • New York, New York, United States, 10021
      • Hospital For Special Surgery_Site number 138
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital_Site number 096
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center_Site number 149
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina_Site number 054
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center_Site number 145
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research_Site number 130
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin_Site number 012

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female participants greater than or equal to (>=) 18 years old with the diagnosis of dcSSc according to the 2013 American College of Rheumatology and European League Against Rheumatism criteria.
2. Had disease duration (defined as interval from first non-Raynaud disease manifestation) of less than or equal to (<=) 5 years.
3. Had mRSS of >= 15 but <= 35.

4. Active disease defined as any of the following within the 6 months prior to screening:

   1. Increase in mRSS by >= 3 units.
   2. Increase in mRSS by >= 2 units with involvement of 1 new body area.
   3. Involvement of 2 new body areas.
   4. Symptoms indicative of skin activity such as severe cutaneous itching or burning.
5. Participants who had received concomitant immunosuppression must be on a stable dose for at least 3 months prior to screening.

6. Adequate organ and bone marrow functions evaluated during the 28 days prior to enrollment as follows:

   1. Absolute neutrophil count >= 1.5*10^9/L.
   2. Platelet count >=100*10^9/L.
   3. Total bilirubin <= 1.0*upper limit of normal (ULN).
   4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine <= 1.5*ULN.

7. Female participants of childbearing potential had a negative pregnancy test at screening. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.

   1. Women of childbearing potential (i.e., menstruating women) had a negative urine pregnancy test (positive urine tests were to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug.
   2. Sexually active women of childbearing potential enrolled in the study must agree to use 2 forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes (1) intrauterine device plus 1 barrier method; (2) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus 1 barrier method; or (3) two barrier methods. Effective barrier methods were male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm), or a vasectomized partner.
8. For male participants who were sexually active and who were partners of premenopausal women, agreement to use 2 forms of contraception as in Criterion Number 7 above during the treatment period and for at least 3 months after the last dose of study drug.
9. Male participants must not donate sperm for 3 months after last dose of study drug.
10. Able to provide written informed consent prior to the performance of any study-specific procedures.

Exclusion Criteria:

1. Participant had corrected QT interval QTcF greater than (>) 450 milliseconds.
2. Ongoing use or current use of concomitant medication known to have the potential for QTc prolongation.
3. Female participant who was pregnant or breastfeeding.
4. Participated in another study with an investigational drug within 28 days of study entry (for studies involving biologics within 3 half-lives of the biologic).
5. History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
6. Chronic heart failure with New York Heart Association Class II, III, or IV.
7. Acute or chronic liver disease (e.g., cirrhosis).
8. Positive human immunodeficiency virus (HIV) test.
9. Active hepatitis C virus (HCV), hepatitis B virus (HBV), or positive whole blood tuberculin test.
10. Diagnosed with any malignancy within 3 years of enrollment, with the exception of basal cell or completely resected squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection.
11. Has had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or any other ROCK2 inhibitor.
12. Scleroderma renal crisis within 4 months prior to enrollment.
13. FVC <= 50% Predicted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belumosudil QD/Belumosudil QD; Participants received belumosudil 200 mg tablet, QD orally for 28 weeks during the DB period. After completion of DB period, participants entered open-label extension (OLE) period and continued to receive belumosudil 200 mg tablet QD orally for 24 weeks in OLE period (i.e., up to Week 52).	Drug: Belumosudil (KD025); ROCK-2 Inhibitor
Experimental: Belumosudil BID/Belumosudil BID; Participants received belumosudil 200 mg tablet BID orally, for 28 weeks during the DB period. After completion of DB period, participants entered OLE period and continued to receive belumosudil 200 mg tablet BID orally for 24 weeks in OLE period (i.e., up to Week 52).	Drug: Belumosudil (KD025); ROCK-2 Inhibitor
Placebo Comparator: DB Period: Placebo; Participants received placebo (matched to belumosudil) tablet, orally for 28 weeks during the DB period.	Drug: Placebo; Inactive substance
Experimental: OLE Period: Placebo/Belumosudil QD; Participants who had received placebo in the DB period were entered and re-randomized into OLE period and received belumosudil 200 mg tablet QD orally for 24 weeks (i.e., up to Week 52) in the OLE period.	Drug: Belumosudil (KD025); ROCK-2 Inhibitor
Experimental: OLE Period: Placebo/Belumosudil BID; Participants who had received placebo in the DB period were entered and re-randomized into OLE period and received belumosudil 200 mg tablet BID orally for 24 weeks (i.e., up to Week 52) in the OLE period.	Drug: Belumosudil (KD025); ROCK-2 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Number of Participants With Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score Greater Than or Equal to (>=) 60 Percent (%) at Week 24	CRISS components included the following domains: mRSS, FVC percent predicted, physician global assessment, patient global assessment, and SHAQ-DI. An algorithm determines the predicted probability of improvement from Baseline by incorporating change from baseline in the mRSS, FVC percent predicted, physician and patient global assessments, and SHAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 to 100%). Higher score indicated greater probability of improvement. CRISS score >= 60% was considered the minimally important difference. Participants were not considered improved and assigned a probability of improving equal to 0.0 if they developed new onset of renal crisis, new onset or worsening of lung fibrosis, new onset of pulmonary arterial hypertension, or new onset of left ventricular failure during the trial. Last observation carried forward (LOCF) method was used to handle missing data.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis Score at Week 24	CRISS components included the following domains: mRSS, FVC percent predicted, physician global assessment, patient global assessment, and SHAQ-DI. An algorithm determines the predicted probability of improvement from Baseline by incorporating change from baseline in the mRSS, FVC percent predicted, physician and patient global assessments, and SHAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 to 100%). A higher score indicated greater probability of improvement. Participants were not considered improved and assigned a probability of improving equal to 0.0 if they developed new onset of renal crisis, new onset or worsening of lung fibrosis, new onset of pulmonary arterial hypertension, new onset of left ventricular failure during the trial. Least squares (LS) mean and 95% confidence interval (CI) were obtained by mixed-effect model for repeated measures (MMRM).	Week 24
OLE Period: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis Score at Week 52	CRISS components included following domains: mRSS, percent predicted FVC, physician global assessment, patient global assessment, and SHAQ-DI. An algorithm determines the predicted probability of improvement from Baseline by incorporating change from baseline in the mRSS, FVC percent predicted, physician and patient global assessments, and SHAQ-DI. The outcome was a continuous variable between 0.0 and 1.0 (0 to 100%). Higher score indicated greater probability of improvement. Participants were not considered improved and assigned a probability of improving equal to 0.0 if they developed new onset of renal crisis, new onset or worsening of lung fibrosis, new onset of pulmonary arterial hypertension, new onset of left ventricular failure during the trial. LOCF method was used to handle missing data.	Week 52
DB Period: Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24	mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. LS mean and 95% CI were calculated using MMRM model.	Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 24	FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying interstitial lung disease (ILD). LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
DB Period: Change From Baseline in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24	The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
DB Period: Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24	The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
DB Period: Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24	SHAQ-DI included the general health assessment questionnaire-disability index (HAD-DI) assessment and 6 scleroderma-specific VAS items to explore impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. For each question, level of difficulty was scored from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale. SHAQ-DI total score was computed as the sum of domain scores divided by the number of domains answered and it ranged from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
DB Period: Percentage Improvement in Modified Rodnan Skin Score at Week 24	The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. Percentage improvement = change from Baseline value divided by Baseline value*100. LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
DB Period: Percentage Improvement in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24	The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value*100. LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
DB Period: Percentage Improvement in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24	The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value*100. LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
DB Period: Percentage Improvement in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24	SHAQ-DI included general HAD-DI assessment and 6 scleroderma-specific VAS items to explore impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. For each question, level of difficulty was scored from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in SHAQ are visual analog scales that are measured first and then changed to 0-3 scale. SHAQ-DI total score was computed as sum of domain scores divided by number of domains answered and it ranged from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. Percentage improvement = change from Baseline value divided by Baseline value*100. LS mean and 95% CI were obtained from MMRM model.	Baseline, Week 24
OLE Period: Change From Baseline in Modified Rodnan Skin Score at Week 52	The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. In the below data table, 'number analyzed' = participants with available data for each specified category.	Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Forced Vital Capacity at Week 52	FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying ILD. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
OLE Period: Change From Baseline in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 52	The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
OLE Period: Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 52	The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
OLE Period: Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index Total Score at Week 52	SHAQ-DI included general HAD-DI assessment and 6 scleroderma-specific VAS items to explore the impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. For each question, level of difficulty was scored from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale. SHAQ-DI total score was computed as sum of domain scores divided by the number of domains answered and it ranged from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. In the data table below, 'number analyzed' = participants with available data for each specified category.	Baseline, Week 52
OLE Period: Percentage Improvement in Modified Rodnan Skin Score at Week 52	The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites in (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. Percentage improvement = change from Baseline value divided by Baseline value*100. In the data table below, 'overall number of participants analyzed' = participants with available data for this outcome measure.	Baseline, Week 52
OLE Period: Percentage Improvement Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 52	The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value*100. In the data below, 'overall number of participants analyzed' = participants with available data for this outcome measure.	Baseline, Week 52
OLE Period: Percentage Improvement in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 52	The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value*100. In the data table below, 'overall number of participants analyzed' = participants with available data for this outcome measure.	Baseline, Week 52
OLE Period: Percentage Improvement in Scleroderma Health Assessment Questionnaire-Disability Index Score at Week 52	SHAQ-DI: general health assessment questionnaire-disability index (HAD-DI) assessment and 6 scleroderma-specific VAS items to explore impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. For each question, level of difficulty was scored from 0 to 3; 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in SHAQ are visual analog scales that are measured first and then changed to 0-3 scale. SHAQ-DI total score computed as sum of domain scores divided by number of domains answered ranging 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. Percentage improvement = change from Baseline value divided by Baseline value*100. 'overall number of participants analyzed' = participants with available data for this outcome measure.	Baseline, Week 52
DB Period: Change From Baseline in Percent Predicted Forced Vital Capacity Level at Week 24-ILD Participants	FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying ILD. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted FVC level at Week 24 in participants with ILD is reported in this outcome measure.	Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Diffusing Capacity of the Lungs for Carbon Monoxide (DLco) at Week 24-ILD Participants	DLco is a measurement of the ability of the lungs to transfer gases from the air to the blood. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted DLco at Week 24 in participants with ILD is reported in this outcome measure.	Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Forced Expiratory Volume (FEV1) at Week 24-ILD Participants	FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by a spirometer. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted FEV1 at Week 24 in participants with ILD is reported in this outcome measure.	Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Residual Volume (RV) at Week 24-ILD Participants	RV is the volume of air remaining in the lungs after maximum forceful expiration. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted RV at Week 24 in participants with ILD is reported in this outcome measure.	Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Week 24-ILD Participants	TLC is the volume of air in the lungs upon the maximum effort of inspiration. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted TLC at Week 24 in participants with ILD is reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Percent Predicted Forced Vital Capacity at Week 52-ILD Participants	FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying ILD. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted FVC at Week 52 in participants with ILD is reported in this outcome measure.	Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Diffusing Capacity of the Lungs for Carbon Monoxide at Week 52-ILD Participants	DLco is a measurement of the ability of the lungs to transfer gases from the air to the blood. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted DLco at Week 52 in participants with ILD is reported in this outcome measure.	Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Forced Expiratory Volume at Week 52-ILD Participants	FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by a spirometer. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted FEV1 at Week 52 in participants with ILD is reported in this outcome measure.	Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Residual Volume at Week 52-ILD Participants	RV is the volume of air remaining in the lungs after maximum forceful expiration. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted RV at Week 52 in participants with ILD is reported in this outcome measure.	Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Total Lung Capacity at Week 52-ILD Participants	TLC is the volume of air in the lungs upon the maximum effort of inspiration. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted TLC at Week 52 in participants with ILD is reported in this outcome measure.	Baseline, Week 52
DB Period: Number of Participants With Lung Fibrosis at Baseline and Week 24-ILD Participants	Lung fibrosis is a lung disease in which lung tissue becomes damaged and scared. Lung fibrosis was assessed using high-resolution computerized tomography (HRCT). HRCT is a type of computed tomography used to diagnose and stage the severity. Pure ground-class opacity, pulmonary fibrosis and honeycombing were recorded for each lung (right and left) and three lung zones (upper, middle, and lower). They were recorded categorically for the amount detected, ranged as Absent, 1-25%, 26-50%, 51-75% and >75% for abnormality/lung fibrosis. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Number of participants with lung fibrosis at Baseline and Week 24 are reported in this outcome measure.	Baseline, Week 24
OLE Period: Number of Participants With Lung Fibrosis at Baseline and Week 52-ILD Participants	Lung fibrosis is a lung disease in which lung tissue becomes damaged and scared. Lung fibrosis was assessed using HRCT. HRCT is a type of computed tomography used to diagnose and stage the severity. Pure ground-class opacity, pulmonary fibrosis and honeycombing were recorded for each lung (right and left) and three lung zones (upper, middle, and lower). They were recorded categorically for the amount detected, ranged as Absent, 1-25%, 26-50%, 51-75% and >75% for abnormality/lung fibrosis. Number of participants with lung fibrosis at Baseline and Week 52 are reported in this outcome measure. In the data table below, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.	Baseline, Week 52
DB Period: Pharmacokinetics: Plasma Concentration of Belumosudil and Its Metabolite (KD025m2)	Plasma concentration of belumosudil and its metabolite (KD025m2) at pre-dose and 3 hours post-dose at Week 4 and 8 is reported in this outcome measure. The Lower Limit of Quantification (LLOQ) was 10 nanograms per milliliter (ng/mL).	Pre-dose and 3 hours post-dose at Week 4 and 8
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	Adverse event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs: AEs with onset after the first dose of study drug or existing AEs that worsened during TEAE Period (for DB period: From Day 1 (Week 0) up to Week 28; for OLE period: from Week 29 up to 4 weeks post last study drug administration).	For DB period: From Day 1 (Week 0) up to Week 28; for OLE period: from Week 29 up to 4 weeks post last study drug administration (i.e., up to Week 56)
DB Period: Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure at Week 24	Vital signs (systolic and diastolic blood pressure) were measured with the participants after having rested in sitting position. Vital signs assessments were performed before the electrocardiogram (ECG) and other scheduled assessments. Change from Baseline in systolic and diastolic blood pressure at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE: Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure at Week 52	Change from Baseline in systolic and diastolic blood pressure at Week 52 was reported in this outcome measure. Vital signs (systolic and diastolic blood pressure) were measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other schedules assessments. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Vital Signs: Pulse at Week 24	Vital sign (pulse) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: pulse at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Vital Signs: Pulse at Week 52	Vital sign (pulse) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: pulse at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Vital Signs: Respiratory Rate at Week 24	Vital sign (respiratory rate) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: respiratory rate at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Vital Signs: Respiratory Rate at Week 52	Vital sign (respiratory rate) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: respiratory rate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in 12-lead Electrocardiogram (ECG) Values: Heart Rate at Week 24	ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: heart rate at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in 12-lead Electrocardiogram Values: Heart Rate at Week 52	ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: heart rate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in 12-lead Electrocardiogram Values: PR Interval, RR Interval, QRS Interval, QT Interval and QTcF Interval at Week 24	ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: PR interval, RR interval, QRS interval, QT interval and QTcF interval at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in 12-lead Electrocardiogram Values: PR Interval, RR Interval, QRS Interval, QT Interval and QTcF Interval at Week 52	ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: PR interval, RR interval, QRS interval, QT interval and QTcF interval at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameters: Percentage of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Week 24	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameters: percentage of basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameters: Percentage of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Week 52	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameters: percentage of basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Hematocrit at Week 24	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter (hematocrit, fraction of 1.0) at Week 24 was reported in this outcome measure. The hematocrit is percentage of the volume of whole blood that is made up of red blood cells.	Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Hematocrit at Week 52	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter (hematocrit, fraction of 1.0) at Week 52 was reported in this outcome measure. The hematocrit is percentage of the volume of whole blood that is made up of red blood cells. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Hemoglobin at Week 24	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: hemoglobin at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Hemoglobin at Week 52	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: hemoglobin at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Erythrocytes Mean Corpuscular Volume at Week 24	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes mean corpuscular volume at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Erythrocytes Mean Corpuscular Volume at Week 52	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes mean corpuscular volume at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Platelets at Week 24	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: platelets at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Platelets at Week 52	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: platelets at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Erythrocytes at Week 24	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Erythrocytes at Week 52	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Leukocytes at Week 24	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: leukocytes at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Leukocytes at Week 52	Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: leukocytes at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Albumin, Globulin and Protein at Week 24	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: albumin, globulin and protein at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Albumin, Globulin and Protein at Week 52	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: albumin, globulin and protein at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Week 24	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transferase, and lactate dehydrogenase at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Week 52	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transferase, and lactate dehydrogenase at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Glucose, Potassium, Magnesium, Phosphate and Sodium at Week 24	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: bicarbonate, blood urea nitrogen, calcium, chloride, glucose, potassium, magnesium, phosphate and sodium at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Glucose, Potassium, Magnesium, Phosphate and Sodium at Week 52	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: bicarbonate, blood urea nitrogen, calcium, chloride, glucose, potassium, magnesium, phosphate and sodium at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine and Urate at Week 24	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: direct bilirubin, bilirubin, creatinine and urate at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine and Urate at Week 52	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: direct bilirubin, bilirubin, creatinine and urate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Calcium Corrected at Week 24	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: calcium corrected at Week 24 was reported in this outcome measure.	Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Calcium Corrected at Week 52	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: calcium corrected at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Glomerular Filtration Rate at Week 24	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: glomerular filtration rate at Week 24 was reported in this outcome measure. Expanded unit of measure is milliliter per minute per 1.73 square meters.	Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Glomerular Filtration Rate at Week 52	Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: glomerular filtration rate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.	Baseline, Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic (PD): Biomarker Analysis	To evaluate changes in concentration of collagen biomarkers in serum indicative of extracellular matrix turnover from baseline to Week 24 and Week 52.	Baseline, Week 24, and Week 52
PD: Histology of Skin Biopsy Samples	Hematoxylin and eosin stain on skin biopsy samples taken from subjects at baseline, Week 24, and optionally at Week 52.	Up to Week 52
PD: Gene Expression of Skin Biopsy Samples	To assess differential gene expression of markers associated with inflammation and fibrosis from skin biopsies taken from subjects at baseline, Week 24, and optionally at Week 52.	Baseline, Week 24, and Week 52

Collaborators and Investigators

• Sponsor: Kadmon, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2019
• Primary Completion (Actual): August 9, 2022
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: November 21, 2018
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Belumosudil
• Other Study ID Numbers: EFC17665; KD025-209 (Other Identifier: Kadmon)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No