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.
Systemic sclerosis (SSc) is a chronic autoimmune disease that causes widespread microvascular damage and excessive deposition of collagen in the skin and internal organs. Limited cutaneous systemic sclerosis is primarily cutaneous, affecting the hands, arms, and face. Diffuse cutaneous systemic sclerosis (dcSSc) is a more serious manifestation of the disease and is often rapidly progressive, not only involving the skin, but also involving internal organs including kidney, heart, and lungs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
ROCK-2 Inhibitor
Inactive substance
Viable Research Management_Site number 131
Phoenix, Arizona, United States
Mayo Clinic - Scottsdale_Site number 150
Scottsdale, Arizona, United States
University of California, SD_Site number 008
La Jolla, California, United States
Pacific Arthrirtis Care Center_Site number 136
Los Angeles, California, United States
University of California - Los Angeles_Site number 104
Los Angeles, California, United States
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.
Time frame: Week 24
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).
Time frame: Week 24
OLE Period: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis Score at Week 52
CRISS components included following domains: mRSS, percent predicted FVC, physician global assessment, patient global assessment, and SHAQ-DI. An algorithm determines the predicted probability of improvement from Baseline by incorporating change from baseline in the mRSS, FVC percent predicted, physician and patient global assessments, and SHAQ-DI. The outcome was a continuous variable between 0.0 and 1.0 (0 to 100%). Higher score indicated greater probability of improvement. Participants were not considered improved and assigned a probability of improving equal to 0.0 if they developed new onset of renal crisis, new onset or worsening of lung fibrosis, new onset of pulmonary arterial hypertension, new onset of left ventricular failure during the trial. LOCF method was used to handle missing data.
Time frame: Week 52
DB Period: Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. LS mean and 95% CI were calculated using MMRM model.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 24
FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying interstitial lung disease (ILD). LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24
The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24
The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24
SHAQ-DI included the general health assessment questionnaire-disability index (HAD-DI) assessment and 6 scleroderma-specific VAS items to explore impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. For each question, level of difficulty was scored from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale. SHAQ-DI total score was computed as the sum of domain scores divided by the number of domains answered and it ranged from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
DB Period: Percentage Improvement in Modified Rodnan Skin Score at Week 24
The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. Percentage improvement = change from Baseline value divided by Baseline value\*100. LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
DB Period: Percentage Improvement in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24
The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value\*100. LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
DB Period: Percentage Improvement in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24
The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value\*100. LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
DB Period: Percentage Improvement in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24
SHAQ-DI included general HAD-DI assessment and 6 scleroderma-specific VAS items to explore impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. For each question, level of difficulty was scored from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in SHAQ are visual analog scales that are measured first and then changed to 0-3 scale. SHAQ-DI total score was computed as sum of domain scores divided by number of domains answered and it ranged from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. Percentage improvement = change from Baseline value divided by Baseline value\*100. LS mean and 95% CI were obtained from MMRM model.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Modified Rodnan Skin Score at Week 52
The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. In the below data table, 'number analyzed' = participants with available data for each specified category.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Forced Vital Capacity at Week 52
FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying ILD. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 52
The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 52
The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index Total Score at Week 52
SHAQ-DI included general HAD-DI assessment and 6 scleroderma-specific VAS items to explore the impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. For each question, level of difficulty was scored from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale. SHAQ-DI total score was computed as sum of domain scores divided by the number of domains answered and it ranged from 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. In the data table below, 'number analyzed' = participants with available data for each specified category.
Time frame: Baseline, Week 52
OLE Period: Percentage Improvement in Modified Rodnan Skin Score at Week 52
The mRSS is an accepted clinical measure of skin thickness. The investigator assessed the skin thickness using the mRSS through simple palpation on 17 different skin sites in (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet). Each skin site was rated on a 0 to 3 scale; where 0 = normal skin, 1 = mild thickness, 2 = moderate thickness, and 3 = severe thickness and unable to pinch. Individual site skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (normal skin) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. Percentage improvement = change from Baseline value divided by Baseline value\*100. In the data table below, 'overall number of participants analyzed' = participants with available data for this outcome measure.
Time frame: Baseline, Week 52
OLE Period: Percentage Improvement Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 52
The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value\*100. In the data below, 'overall number of participants analyzed' = participants with available data for this outcome measure.
Time frame: Baseline, Week 52
OLE Period: Percentage Improvement in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 52
The Patient Global Assessment (reported by participant) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. Percentage improvement = change from Baseline value divided by Baseline value\*100. In the data table below, 'overall number of participants analyzed' = participants with available data for this outcome measure.
Time frame: Baseline, Week 52
OLE Period: Percentage Improvement in Scleroderma Health Assessment Questionnaire-Disability Index Score at Week 52
SHAQ-DI: general health assessment questionnaire-disability index (HAD-DI) assessment and 6 scleroderma-specific VAS items to explore impact of participant's disease. General HAD-DI assessment included 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and activities addressing scleroderma related manifestations that contribute to disability. For each question, level of difficulty was scored from 0 to 3; 0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do. Some domains in SHAQ are visual analog scales that are measured first and then changed to 0-3 scale. SHAQ-DI total score computed as sum of domain scores divided by number of domains answered ranging 0 (no difficulty) to 3 (maximum difficulty), where higher score indicated greater disability/worse functionality. Percentage improvement = change from Baseline value divided by Baseline value\*100. 'overall number of participants analyzed' = participants with available data for this outcome measure.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Percent Predicted Forced Vital Capacity Level at Week 24-ILD Participants
FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying ILD. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted FVC level at Week 24 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Diffusing Capacity of the Lungs for Carbon Monoxide (DLco) at Week 24-ILD Participants
DLco is a measurement of the ability of the lungs to transfer gases from the air to the blood. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted DLco at Week 24 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Forced Expiratory Volume (FEV1) at Week 24-ILD Participants
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by a spirometer. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted FEV1 at Week 24 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Residual Volume (RV) at Week 24-ILD Participants
RV is the volume of air remaining in the lungs after maximum forceful expiration. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted RV at Week 24 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 24
DB Period: Change From Baseline in Percent Predicted Total Lung Capacity (TLC) at Week 24-ILD Participants
TLC is the volume of air in the lungs upon the maximum effort of inspiration. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Change from Baseline in percent predicted TLC at Week 24 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Percent Predicted Forced Vital Capacity at Week 52-ILD Participants
FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer which assessed the change in lung function related to the disease status of an underlying ILD. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted FVC at Week 52 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Diffusing Capacity of the Lungs for Carbon Monoxide at Week 52-ILD Participants
DLco is a measurement of the ability of the lungs to transfer gases from the air to the blood. Participants breathe in (inhale) air containing a very small, harmless amount of a tracer gas, such as carbon monoxide. Participants hold their breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas was tested to determine amount of the tracer gas absorbed during the breath. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted DLco at Week 52 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Forced Expiratory Volume at Week 52-ILD Participants
FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by a spirometer. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted FEV1 at Week 52 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Residual Volume at Week 52-ILD Participants
RV is the volume of air remaining in the lungs after maximum forceful expiration. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted RV at Week 52 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 52
OLE Period: Change From Baseline in Percent Predicted Total Lung Capacity at Week 52-ILD Participants
TLC is the volume of air in the lungs upon the maximum effort of inspiration. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period. Change from Baseline in percent predicted TLC at Week 52 in participants with ILD is reported in this outcome measure.
Time frame: Baseline, Week 52
DB Period: Number of Participants With Lung Fibrosis at Baseline and Week 24-ILD Participants
Lung fibrosis is a lung disease in which lung tissue becomes damaged and scared. Lung fibrosis was assessed using high-resolution computerized tomography (HRCT). HRCT is a type of computed tomography used to diagnose and stage the severity. Pure ground-class opacity, pulmonary fibrosis and honeycombing were recorded for each lung (right and left) and three lung zones (upper, middle, and lower). They were recorded categorically for the amount detected, ranged as Absent, 1-25%, 26-50%, 51-75% and \>75% for abnormality/lung fibrosis. For participants who received placebo/belumosudil in the DB period, the Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in the DB period. Number of participants with lung fibrosis at Baseline and Week 24 are reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Number of Participants With Lung Fibrosis at Baseline and Week 52-ILD Participants
Lung fibrosis is a lung disease in which lung tissue becomes damaged and scared. Lung fibrosis was assessed using HRCT. HRCT is a type of computed tomography used to diagnose and stage the severity. Pure ground-class opacity, pulmonary fibrosis and honeycombing were recorded for each lung (right and left) and three lung zones (upper, middle, and lower). They were recorded categorically for the amount detected, ranged as Absent, 1-25%, 26-50%, 51-75% and \>75% for abnormality/lung fibrosis. Number of participants with lung fibrosis at Baseline and Week 52 are reported in this outcome measure. In the data table below, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Time frame: Baseline, Week 52
DB Period: Pharmacokinetics: Plasma Concentration of Belumosudil and Its Metabolite (KD025m2)
Plasma concentration of belumosudil and its metabolite (KD025m2) at pre-dose and 3 hours post-dose at Week 4 and 8 is reported in this outcome measure. The Lower Limit of Quantification (LLOQ) was 10 nanograms per milliliter (ng/mL).
Time frame: Pre-dose and 3 hours post-dose at Week 4 and 8
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Adverse event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs: AEs with onset after the first dose of study drug or existing AEs that worsened during TEAE Period (for DB period: From Day 1 (Week 0) up to Week 28; for OLE period: from Week 29 up to 4 weeks post last study drug administration).
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)
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.
Time frame: Baseline, Week 24
OLE: Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure at Week 52
Change from Baseline in systolic and diastolic blood pressure at Week 52 was reported in this outcome measure. Vital signs (systolic and diastolic blood pressure) were measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other schedules assessments. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Vital Signs: Pulse at Week 24
Vital sign (pulse) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: pulse at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Vital Signs: Pulse at Week 52
Vital sign (pulse) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: pulse at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Vital Signs: Respiratory Rate at Week 24
Vital sign (respiratory rate) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: respiratory rate at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Vital Signs: Respiratory Rate at Week 52
Vital sign (respiratory rate) was measured with the participants after having rested in sitting position. Vital signs assessments were performed before ECGs and other scheduled assessments. Change from Baseline in vital signs: respiratory rate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in 12-lead Electrocardiogram (ECG) Values: Heart Rate at Week 24
ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: heart rate at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in 12-lead Electrocardiogram Values: Heart Rate at Week 52
ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: heart rate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in 12-lead Electrocardiogram Values: PR Interval, RR Interval, QRS Interval, QT Interval and QTcF Interval at Week 24
ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: PR interval, RR interval, QRS interval, QT interval and QTcF interval at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in 12-lead Electrocardiogram Values: PR Interval, RR Interval, QRS Interval, QT Interval and QTcF Interval at Week 52
ECGs were recorded after the participant had rested in the supine position for at least 5 minutes and were performed prior to any blood sample collection. Change from Baseline in 12-lead ECG values: PR interval, RR interval, QRS interval, QT interval and QTcF interval at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameters: Percentage of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Week 24
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameters: percentage of basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameters: Percentage of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes and Neutrophils/Leukocytes at Week 52
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameters: percentage of basophils/leukocytes, eosinophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes and neutrophils/leukocytes at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Hematocrit at Week 24
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter (hematocrit, fraction of 1.0) at Week 24 was reported in this outcome measure. The hematocrit is percentage of the volume of whole blood that is made up of red blood cells.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Hematocrit at Week 52
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter (hematocrit, fraction of 1.0) at Week 52 was reported in this outcome measure. The hematocrit is percentage of the volume of whole blood that is made up of red blood cells. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Hemoglobin at Week 24
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: hemoglobin at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Hemoglobin at Week 52
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: hemoglobin at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Erythrocytes Mean Corpuscular Volume at Week 24
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes mean corpuscular volume at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Erythrocytes Mean Corpuscular Volume at Week 52
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes mean corpuscular volume at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Platelets at Week 24
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: platelets at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Platelets at Week 52
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: platelets at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Erythrocytes at Week 24
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Erythrocytes at Week 52
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: erythrocytes at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Hematological Parameter: Leukocytes at Week 24
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: leukocytes at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Hematological Parameter: Leukocytes at Week 52
Blood samples were collected at specified timepoints to assess hematological parameters. Change from Baseline in hematological parameter: leukocytes at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Albumin, Globulin and Protein at Week 24
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: albumin, globulin and protein at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Albumin, Globulin and Protein at Week 52
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: albumin, globulin and protein at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Week 24
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transferase, and lactate dehydrogenase at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Week 52
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, gamma-glutamyl transferase, and lactate dehydrogenase at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Glucose, Potassium, Magnesium, Phosphate and Sodium at Week 24
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: bicarbonate, blood urea nitrogen, calcium, chloride, glucose, potassium, magnesium, phosphate and sodium at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Bicarbonate, Blood Urea Nitrogen, Calcium, Chloride, Glucose, Potassium, Magnesium, Phosphate and Sodium at Week 52
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: bicarbonate, blood urea nitrogen, calcium, chloride, glucose, potassium, magnesium, phosphate and sodium at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine and Urate at Week 24
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: direct bilirubin, bilirubin, creatinine and urate at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Direct Bilirubin, Bilirubin, Creatinine and Urate at Week 52
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: direct bilirubin, bilirubin, creatinine and urate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Calcium Corrected at Week 24
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: calcium corrected at Week 24 was reported in this outcome measure.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Calcium Corrected at Week 52
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: calcium corrected at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
DB Period: Change From Baseline in Clinical Chemistry Parameter: Glomerular Filtration Rate at Week 24
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: glomerular filtration rate at Week 24 was reported in this outcome measure. Expanded unit of measure is milliliter per minute per 1.73 square meters.
Time frame: Baseline, Week 24
OLE Period: Change From Baseline in Clinical Chemistry Parameter: Glomerular Filtration Rate at Week 52
Blood samples were collected at specified timepoints to assess clinical chemistry parameters. Change from Baseline in clinical chemistry parameter: glomerular filtration rate at Week 52 was reported in this outcome measure. Participants who received placebo in DB period and re-randomized into OLE period, OLE period Baseline was defined as valid and last non-missing value obtained prior to participant receiving first dose of belumosudil in OLE period. Participants who received belumosudil in DB period and continued belumosudil in OLE period, Baseline value was defined as valid and last non-missing value obtained within 29 days prior to participant receiving first study medication in DB period.
Time frame: Baseline, Week 52
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Stanford University Medical Center_Site number 143
Palo Alto, California, United States
University of Connecticut_Site number 147
Farmington, Connecticut, United States
Yale University School of Medicine_Site number 140
New Haven, Connecticut, United States
Georgetown University_Site number 035
Washington D.C., District of Columbia, United States
St. Francis Medical_Site number 085
Clearwater, Florida, United States
...and 16 more locations