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KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis

Primary Purpose

System; Sclerosis, Diffuse Cutaneous Systemic Sclerosis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Belumosudil (KD025)
Placebo
Sponsored by
Kadmon, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for System; Sclerosis

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male and female subjects ≥ 18 years old with the diagnosis of dcSSc according to the 2013 American College of Rheumatology and European League Against Rheumatism criteria
  2. Must have disease duration (defined as interval from first non-Raynaud disease manifestation) of ≤ 5 years
  3. Must have 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. Subjects receiving 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 subjects of childbearing potential have a negative pregnancy test at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.

    1. Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are 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 are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm), or a vasectomized partner.
  8. For male patients who are sexually active and who are 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 subjects 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. Subject has corrected QT interval QTcF > 450 ms
  2. Ongoing use or current use of concomitant medication known to have the potential for QTc prolongation
  3. Female subject who is 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 subject, 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.

Sites / Locations

  • Viable Research Management_Site number 131
  • Mayo Clinic - Scottsdale_Site number 150
  • University of California, SD_Site number 008
  • Pacific Arthrirtis Care Center_Site number 136
  • University of California - Los Angeles_Site number 104
  • Stanford University Medical Center_Site number 143
  • University of Connecticut_Site number 147
  • Yale University School of Medicine_Site number 140
  • Georgetown University_Site number 035
  • St. Francis Medical_Site number 085
  • Omega Research Consultants_Site number 133
  • Northwestern Medicine_Site number 124
  • DelRicht Research_Site number 159
  • Johns Hopkins University School of Medicine_Site number 134
  • Massachusetts General Hospital_Site number 002
  • Boston University_Site number 137
  • University of Minnesota_Site number 051
  • Mayo Clinic_Site number 146
  • Hospital For Special Surgery_Site number 138
  • Columbia University Medical Center_Site number 086
  • Thomas Jefferson University Hospital_Site number 096
  • University of Pittsburgh Medical Center_Site number 149
  • Medical University of South Carolina_Site number 054
  • Virginia Mason Medical Center_Site number 145
  • Premier Clinical Research_Site number 130
  • Froedtert Hospital and the Medical College of Wisconsin_Site number 012

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

Belumosudil QD/Belumosudil QD

Belumosudil BID/Belumosudil BID

DB Period: Placebo

OLE Period: Placebo/Belumosudil QD

OLE Period: Placebo/Belumosudil BID

Arm Description

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).

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).

Participants received placebo (matched to belumosudil) tablet, orally for 28 weeks during the DB period.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
November 21, 2018
Last Updated
August 4, 2023
Sponsor
Kadmon, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT03919799
Brief Title
KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision due to slow enrollment and strategic consideration; not driven by any safety concerns.
Study Start Date
June 26, 2019 (Actual)
Primary Completion Date
August 9, 2022 (Actual)
Study Completion Date
February 17, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kadmon, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
System; Sclerosis, Diffuse Cutaneous Systemic Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Three groups (1:1:1) to receive orally administered belumosudil 200 mg QD, belumosudil 200 mg BID, or matched placebo for 28 weeks. The study was double-blinded for the first 28 weeks followed by an open-label extension of 24 weeks. After unblinding, the participants in the belumosudil groups continued on the same belumosudil dose whereas the participants in the placebo group were re-randomized to one of the belumosudil doses (200 mg QD or 200 BID) in 1:1 fashion.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blinded for the first 28 Weeks
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Belumosudil QD/Belumosudil QD
Arm Type
Experimental
Arm Description
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).
Arm Title
Belumosudil BID/Belumosudil BID
Arm Type
Experimental
Arm Description
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).
Arm Title
DB Period: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo (matched to belumosudil) tablet, orally for 28 weeks during the DB period.
Arm Title
OLE Period: Placebo/Belumosudil QD
Arm Type
Experimental
Arm Description
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.
Arm Title
OLE Period: Placebo/Belumosudil BID
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Belumosudil (KD025)
Intervention Description
ROCK-2 Inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inactive substance
Primary Outcome Measure Information:
Title
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
Description
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
Secondary Outcome Measure Information:
Title
DB Period: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis Score at Week 24
Description
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
Title
OLE Period: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis Score at Week 52
Description
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
Title
DB Period: Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
Description
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
Title
DB Period: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 24
Description
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
Title
DB Period: Change From Baseline in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24
Description
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
Title
DB Period: Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24
Description
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
Title
DB Period: Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24
Description
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
Title
DB Period: Percentage Improvement in Modified Rodnan Skin Score at Week 24
Description
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
Title
DB Period: Percentage Improvement in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24
Description
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
Title
DB Period: Percentage Improvement in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24
Description
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
Title
DB Period: Percentage Improvement in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24
Description
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
Title
OLE Period: Change From Baseline in Modified Rodnan Skin Score at Week 52
Description
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
Title
OLE Period: Change From Baseline in Percent Predicted Forced Vital Capacity at Week 52
Description
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
Title
OLE Period: Change From Baseline in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 52
Description
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
Title
OLE Period: Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 52
Description
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
Title
OLE Period: Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index Total Score at Week 52
Description
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
Title
OLE Period: Percentage Improvement in Modified Rodnan Skin Score at Week 52
Description
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.
Time Frame
Baseline, Week 52
Title
OLE Period: Percentage Improvement Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 52
Description
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.
Time Frame
Baseline, Week 52
Title
OLE Period: Percentage Improvement in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 52
Description
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.
Time Frame
Baseline, Week 52
Title
OLE Period: Percentage Improvement in Scleroderma Health Assessment Questionnaire-Disability Index Score at Week 52
Description
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.
Time Frame
Baseline, Week 52
Title
DB Period: Change From Baseline in Percent Predicted Forced Vital Capacity Level at Week 24-ILD Participants
Description
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
Title
DB Period: Change From Baseline in Percent Predicted Diffusing Capacity of the Lungs for Carbon Monoxide (DLco) at Week 24-ILD Participants
Description
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
Title
DB Period: Change From Baseline in Percent Predicted Forced Expiratory Volume (FEV1) at Week 24-ILD Participants
Description
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
Title
DB Period: Change From Baseline in Percent Predicted Residual Volume (RV) at Week 24-ILD Participants
Description
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
Title
DB Period: Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Week 24-ILD Participants
Description
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
Title
OLE Period: Change From Baseline in Percent Predicted Forced Vital Capacity at Week 52-ILD Participants
Description
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
Title
OLE Period: Change From Baseline in Percent Predicted Diffusing Capacity of the Lungs for Carbon Monoxide at Week 52-ILD Participants
Description
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
Title
OLE Period: Change From Baseline in Percent Predicted Forced Expiratory Volume at Week 52-ILD Participants
Description
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
Title
OLE Period: Change From Baseline in Percent Predicted Residual Volume at Week 52-ILD Participants
Description
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
Title
OLE Period: Change From Baseline in Percent Predicted Total Lung Capacity at Week 52-ILD Participants
Description
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
Title
DB Period: Number of Participants With Lung Fibrosis at Baseline and Week 24-ILD Participants
Description
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
Title
OLE Period: Number of Participants With Lung Fibrosis at Baseline and Week 52-ILD Participants
Description
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
Title
DB Period: Pharmacokinetics: Plasma Concentration of Belumosudil and Its Metabolite (KD025m2)
Description
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
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
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)
Title
DB Period: Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure at Week 24
Description
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
Title
OLE: Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure at Week 52
Description
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
Title
DB Period: Change From Baseline in Vital Signs: Pulse at Week 24
Description
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
Title
OLE Period: Change From Baseline in Vital Signs: Pulse at Week 52
Description
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
Title
DB Period: Change From Baseline in Vital Signs: Respiratory Rate at Week 24
Description
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
Title
OLE Period: Change From Baseline in Vital Signs: Respiratory Rate at Week 52
Description
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
Title
DB Period: Change From Baseline in 12-lead Electrocardiogram (ECG) Values: Heart Rate at Week 24
Description
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
Title
OLE Period: Change From Baseline in 12-lead Electrocardiogram Values: Heart Rate at Week 52
Description
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
Title
DB Period: Change From Baseline in 12-lead Electrocardiogram Values: PR Interval, RR Interval, QRS Interval, QT Interval and QTcF Interval at Week 24
Description
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
Title
OLE Period: Change From Baseline in 12-lead Electrocardiogram Values: PR Interval, RR Interval, QRS Interval, QT Interval and QTcF Interval at Week 52
Description
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
Title
DB Period: Change From Baseline in Hematological Parameters: Percentage of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Week 24
Description
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
Title
OLE Period: Change From Baseline in Hematological Parameters: Percentage of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Week 52
Description
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
Title
DB Period: Change From Baseline in Hematological Parameter: Hematocrit at Week 24
Description
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
Title
OLE Period: Change From Baseline in Hematological Parameter: Hematocrit at Week 52
Description
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
Title
DB Period: Change From Baseline in Hematological Parameter: Hemoglobin at Week 24
Description
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
Title
OLE Period: Change From Baseline in Hematological Parameter: Hemoglobin at Week 52
Description
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
Title
DB Period: Change From Baseline in Hematological Parameter: Erythrocytes Mean Corpuscular Volume at Week 24
Description
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
Title
OLE Period: Change From Baseline in Hematological Parameter: Erythrocytes Mean Corpuscular Volume at Week 52
Description
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
Title
DB Period: Change From Baseline in Hematological Parameter: Platelets at Week 24
Description
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
Title
OLE Period: Change From Baseline in Hematological Parameter: Platelets at Week 52
Description
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
Title
DB Period: Change From Baseline in Hematological Parameter: Erythrocytes at Week 24
Description
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
Title
OLE Period: Change From Baseline in Hematological Parameter: Erythrocytes at Week 52
Description
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
Title
DB Period: Change From Baseline in Hematological Parameter: Leukocytes at Week 24
Description
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
Title
OLE Period: Change From Baseline in Hematological Parameter: Leukocytes at Week 52
Description
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
Title
DB Period: Change From Baseline in Clinical Chemistry Parameter: Albumin, Globulin and Protein at Week 24
Description
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
Title
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Albumin, Globulin and Protein at Week 52
Description
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
Title
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
Description
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
Title
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
Description
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
Title
DB Period: Change From Baseline in Clinical Chemistry Parameter: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Glucose, Potassium, Magnesium, Phosphate and Sodium at Week 24
Description
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
Title
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Glucose, Potassium, Magnesium, Phosphate and Sodium at Week 52
Description
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
Title
DB Period: Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine and Urate at Week 24
Description
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
Title
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine and Urate at Week 52
Description
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
Title
DB Period: Change From Baseline in Clinical Chemistry Parameter: Calcium Corrected at Week 24
Description
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
Title
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Calcium Corrected at Week 52
Description
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
Title
DB Period: Change From Baseline in Clinical Chemistry Parameter: Glomerular Filtration Rate at Week 24
Description
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
Title
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Glomerular Filtration Rate at Week 52
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Had disease duration (defined as interval from first non-Raynaud disease manifestation) of less than or equal to (<=) 5 years. Had mRSS of >= 15 but <= 35. Active disease defined as any of the following within the 6 months prior to screening: Increase in mRSS by >= 3 units. Increase in mRSS by >= 2 units with involvement of 1 new body area. Involvement of 2 new body areas. Symptoms indicative of skin activity such as severe cutaneous itching or burning. Participants who had received concomitant immunosuppression must be on a stable dose for at least 3 months prior to screening. Adequate organ and bone marrow functions evaluated during the 28 days prior to enrollment as follows: Absolute neutrophil count >= 1.5*10^9/L. Platelet count >=100*10^9/L. Total bilirubin <= 1.0*upper limit of normal (ULN). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine <= 1.5*ULN. 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. 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. 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. 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. Male participants must not donate sperm for 3 months after last dose of study drug. Able to provide written informed consent prior to the performance of any study-specific procedures. Exclusion Criteria: Participant had corrected QT interval QTcF greater than (>) 450 milliseconds. Ongoing use or current use of concomitant medication known to have the potential for QTc prolongation. Female participant who was pregnant or breastfeeding. 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). 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. Chronic heart failure with New York Heart Association Class II, III, or IV. Acute or chronic liver disease (e.g., cirrhosis). Positive human immunodeficiency virus (HIV) test. Active hepatitis C virus (HCV), hepatitis B virus (HBV), or positive whole blood tuberculin test. 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. Has had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or any other ROCK2 inhibitor. Scleroderma renal crisis within 4 months prior to enrollment. FVC <= 50% Predicted.
Facility Information:
Facility Name
Viable Research Management_Site number 131
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85004
Country
United States
Facility Name
Mayo Clinic - Scottsdale_Site number 150
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of California, SD_Site number 008
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Pacific Arthrirtis Care Center_Site number 136
City
Los Angeles
State/Province
California
ZIP/Postal Code
90045
Country
United States
Facility Name
University of California - Los Angeles_Site number 104
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University Medical Center_Site number 143
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Connecticut_Site number 147
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
Facility Name
Yale University School of Medicine_Site number 140
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Georgetown University_Site number 035
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
St. Francis Medical_Site number 085
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
Omega Research Consultants_Site number 133
City
DeBary
State/Province
Florida
ZIP/Postal Code
32713
Country
United States
Facility Name
Northwestern Medicine_Site number 124
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
DelRicht Research_Site number 159
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
Johns Hopkins University School of Medicine_Site number 134
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Massachusetts General Hospital_Site number 002
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Boston University_Site number 137
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Minnesota_Site number 051
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic_Site number 146
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Hospital For Special Surgery_Site number 138
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia University Medical Center_Site number 086
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Thomas Jefferson University Hospital_Site number 096
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Medical Center_Site number 149
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Medical University of South Carolina_Site number 054
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Virginia Mason Medical Center_Site number 145
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
Premier Clinical Research_Site number 130
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
Froedtert Hospital and the Medical College of Wisconsin_Site number 012
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis

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