KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis

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.

Time frame: Week 24

Population: Analysis was performed on mITT population.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data and 'number analyzed' = participants with available data for each specified category. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data and 'number analyzed' = participants with available data for each specified category. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data and 'number analyzed' = participants with available data for each specified category. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. 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.

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).

Time frame: Week 24

Population: Analysis was performed on mITT population. LOCF method was used to handle missing data.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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.

Time frame: Baseline, Week 24

Population: Analysis was performed on mITT population. 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.

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).

Time frame: Pre-dose and 3 hours post-dose at Week 4 and 8

Population: Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.

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).

Time frame: 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)

Population: Analysis was performed on safety population which included all participants who received at least 1 dose of study drug.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analyzed on mITT. 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.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on participants with ILD. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for each specified category.

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.

Time frame: Baseline, Week 52

Population: Analyzed on mITT. 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.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

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.

Time frame: Week 52

Population: Analysis was performed on mITT population.

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.

Time frame: Baseline, Week 52

Population: Analysis was performed on participants with ILD. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline: 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: valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.