Back to resultsEfficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis (dcSSC)
Primary Purpose
Diffuse Cutaneous Systemic Sclerosis
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Belumosudil
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Cutaneous Systemic Sclerosis focused on measuring skin diseases, systemic sclerosis, phase 2, Scleroderma Health Assessment Questionnaire Disability Index, Modified Rodnan Skin Score, Combined Response Index in dcSSc (CRISS), diffuse cutaneous systemic sclerosis
Eligibility Criteria
Inclusion Criteria:
- 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
- Must have disease duration (defined as interval from first non Raynaud disease manifestation) of ≤ 6 years
- Must have mRSS of ≥ 15 but ≤ 40
- Must have active disease as determined by the Principal Investigator within the 6 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) and aspartate aminotransferase (AST), and serum creatinine ≤ 1.5 × ULN.
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.
- 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.
- Sexually active women of childbearing potential enrolled in the study must agree to use two 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 (i) intrauterine device plus 1 barrier method; (ii) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus 1 barrier method; or (iii) 2 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.
- 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 6b above during the treatment period and for at least 3 months after the last dose of study drug.
- Male subjects 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:
- Subject has corrected QT interval using Fridericia's formula (QTcF) > 450 ms
- Ongoing use or current use of concomitant medication known to have the potential for QTc prolongation
- Female subject who is 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 subject, in the opinion of the Investigator, unsuitable for the study.
- Chronic heart failure with New York Heart Association Classes 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 Rho-associated Protein Kinase-2 (ROCK2) inhibitor.
- Scleroderma renal crisis within 4 months prior to enrollment.
- FVC ≤ 50% Predicted.
Sites / Locations
- University of California, Los Angeles Medical Center_Site number 104
- Yale University School of Medicine_Site number 140
- Northwestern University_Site number 124
- Columbia University Medical Center_Site number 086
- University of Utah_Site number 048
- Virginia Mason Medical Center_Site number 145
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Belumosudil
Arm Description
Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Outcomes
Primary Outcome Measures
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Week 24
CRISS components included the following domains: modified Rodnan skin score (mRSS), forced vital capacity (FVC) percent predicted, physician global assessment, patient global assessment, and scleroderma health assessment questionnaire disability-index (SHAQ-DI). An algorithm determines the predicted probability of improvement from Baseline by incorporating change 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 are not considered improved if they develop 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. CRISS score greater than 60% is considered the minimally important difference.
Secondary Outcome Measures
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52
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 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 are not considered improved if they develop 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. CRISS score greater than 60% is considered the minimally important difference.
Modified Rodnan Skin Score (mRSS) at Week 24
The mRSS is an accepted clinical measure of the skin thickness. The investigator assessed the thickening of the skin using the modified Rodnan Skin Score through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). 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 skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.
Forced Vital Capacity (FVC) Level at Week 24
FVC was the total amount of air (in liters) 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.
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 a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome.
Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) 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.
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 the impact of participant's disease. The general HAD-DI assessment included 8 domains 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.
Change From Baseline in Modified Rodnan Skin Thickness Score (mRSS) at Weeks 8, 16, 36, and 52
The mRSS is an accepted clinical measure of the skin thickness. The investigator assessed the thickening of the skin using the modified Rodnan Skin Score through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). 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 skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. A negative change from baseline demonstrates improvement.
Change From Baseline in Forced Vital Capacity (FVC) Level at Weeks 8, 16, 36, and 52
FVC was the total amount of air (in liters) 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. Change from Baseline was calculated by subtracting Baseline value from specified values at each reported week (Week 8, 16, 36 and 52).
Change From Baseline in Physician Global Assessment (Reported by the Physician) Quantified of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Weeks 8, 16, 36, and 52
The Physician Global Assessment (reported by the physician) 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. A positive change from Baseline demonstrated improvement.
Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Weeks 8, 16, 36, and 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. A positive change from Baseline demonstrated improvement.
Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Weeks 8, 16, 36, and 52
SHAQ-DI VAS included the general HAD-DI assessment and 6 scleroderma-specific VAS items to explore the impact of participant's disease. The general HAD-DI assessment included 8 domains addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each activity category consisted of 2 to 3 items. 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.
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 investigational medicinal product (IMP) without regard to possibility of causal relationship with the treatment. TEAEs: AEs that developed/worsened or became serious during treatment-emergent period (time of first dose administration of study medication up to 28 days after last dose). Serious AE (SAE): any untoward medical occurrence resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-patient hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event.
Full Information
NCT ID
NCT04680975
First Posted
December 11, 2020
Last Updated
May 8, 2023
Sponsor
Kadmon, a Sanofi Company
1. Study Identification
Unique Protocol Identification Number
NCT04680975
Brief Title
Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis
Acronym
dcSSC
Official Title
A Phase 2, Open-label Multicenter Study to Evaluate the Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis (dcSSc)
Study Type
Interventional
2. Study Status
Record Verification Date
May 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
March 3, 2021 (Actual)
Primary Completion Date
May 10, 2022 (Actual)
Study Completion Date
December 19, 2022 (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
5. Study Description
Brief Summary
This was a phase 2, open-label, single-cohort, multicenter trial of belumosudil in participants with Diffuse Cutaneous Systemic Sclerosis (dcSSc). An estimated total of 12 to 15 participants would receive belumosudil 200 milligrams (mg) administered orally (PO) twice daily (BID) for 52 weeks. The primary analysis was at 24 weeks.
Detailed Description
The primary objective of this phase 2, open-label, single-cohort, multicenter trial was to evaluate the efficacy of belumosudil 200 mg BID using the Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) after 24 weeks of therapy. The duration of the study was approximately 14 months (4 weeks for screening, 52 weeks of dosing period, and 4 weeks of Follow-up)
Participants who had signed an Institutional Review Board/Independent Ethics Committee-(IRB/IEC)-approved informed consent form (ICF) and met all of the inclusion/exclusion criteria were enrolled. A total of 10 participants at 6 sites received belumosudil 200 mg in tablet form administered PO BID for 52 weeks. The total duration of the study is approximately 14 months: a 4-week screening period, a 52-week treatment period, and a 4-week follow-up.
The primary endpoint was analyzed using Week 24 data.
Efficacy was assessed throughout the 52-week dosing period using:
Composite Response Index in Systemic Sclerosis (CRISS)
Modified Rodnan Skin Score (mRSS)
Pulmonary Function Tests (PFTs)
Physician Global Assessment
Patient Global Assessment
Safety was be assessed throughout the study and will include:.
Physical examinations (PEs)
Vital sign measurements
Weight measurements
Blood sample collection for hematology and chemistry; urinalysis
Electrocardiograms (ECGs)
Adverse event (AE) assessments
Concomitant medication assessments
Pregnancy testing for females of childbearing potential.
Reasons for discontinuation of treatment because of adverse events were documented. Careful monitoring of all adverse events was carried out. Dosing could be reduced 1 dose level. If the dose was not tolerated, then the participant was discontinued from the study. If there is an interruption of dosing, after 14 days the participant was discontinued from the study.
Participants were given a study drug diary to record the details of each dose of belumosudil 200 mg. Diaries were dispense/collected on each visit. Compliance with dosing was confirmed using participant diaries, which was examined at each visit by site staff to determine if dosing was as instructed per protocol and follow-up.
A 4-Week Safety Follow-up Visit occurred 28 days (± 3 days) after the last dose of study drug.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Cutaneous Systemic Sclerosis
Keywords
skin diseases, systemic sclerosis, phase 2, Scleroderma Health Assessment Questionnaire Disability Index, Modified Rodnan Skin Score, Combined Response Index in dcSSc (CRISS), diffuse cutaneous systemic sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Belumosudil 200 mg PO BID
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Belumosudil
Arm Type
Experimental
Arm Description
Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Belumosudil
Other Intervention Name(s)
KD025
Intervention Description
10 participants with dcSSc received belumosudil 200 mg PO BID for 52 weeks
Primary Outcome Measure Information:
Title
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Week 24
Description
CRISS components included the following domains: modified Rodnan skin score (mRSS), forced vital capacity (FVC) percent predicted, physician global assessment, patient global assessment, and scleroderma health assessment questionnaire disability-index (SHAQ-DI). An algorithm determines the predicted probability of improvement from Baseline by incorporating change 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 are not considered improved if they develop 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. CRISS score greater than 60% is considered the minimally important difference.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52
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 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 are not considered improved if they develop 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. CRISS score greater than 60% is considered the minimally important difference.
Time Frame
Week 8, 16, 36 and 52
Title
Modified Rodnan Skin Score (mRSS) at Week 24
Description
The mRSS is an accepted clinical measure of the skin thickness. The investigator assessed the thickening of the skin using the modified Rodnan Skin Score through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). 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 skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome.
Time Frame
Week 24
Title
Forced Vital Capacity (FVC) Level at Week 24
Description
FVC was the total amount of air (in liters) 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.
Time Frame
Week 24
Title
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 a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome.
Time Frame
Week 24
Title
Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) 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.
Time Frame
Week 24
Title
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 the impact of participant's disease. The general HAD-DI assessment included 8 domains 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.
Time Frame
Week 24
Title
Change From Baseline in Modified Rodnan Skin Thickness Score (mRSS) at Weeks 8, 16, 36, and 52
Description
The mRSS is an accepted clinical measure of the skin thickness. The investigator assessed the thickening of the skin using the modified Rodnan Skin Score through simple palpation on 17 different skin sites in the fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). 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 skin scores in the 17 body areas were summed and defined as the total mRSS which ranged from 0 (no thickening) to 51 (severe thickening), where higher score indicated more severity of skin thickening/worst outcome. A negative change from baseline demonstrates improvement.
Time Frame
Baseline, Week 8, 16, 36 and 52
Title
Change From Baseline in Forced Vital Capacity (FVC) Level at Weeks 8, 16, 36, and 52
Description
FVC was the total amount of air (in liters) 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. Change from Baseline was calculated by subtracting Baseline value from specified values at each reported week (Week 8, 16, 36 and 52).
Time Frame
Baseline, Week 8, 16, 36 and 52
Title
Change From Baseline in Physician Global Assessment (Reported by the Physician) Quantified of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Weeks 8, 16, 36, and 52
Description
The Physician Global Assessment (reported by the physician) 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. A positive change from Baseline demonstrated improvement.
Time Frame
Baseline, Week 8, 16, 36 and 52
Title
Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Weeks 8, 16, 36, and 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. A positive change from Baseline demonstrated improvement.
Time Frame
Baseline, Week 8, 16, 36 and 52
Title
Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Weeks 8, 16, 36, and 52
Description
SHAQ-DI VAS included the general HAD-DI assessment and 6 scleroderma-specific VAS items to explore the impact of participant's disease. The general HAD-DI assessment included 8 domains addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each activity category consisted of 2 to 3 items. 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.
Time Frame
Baseline, Week 8, 16, 36 and 52
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 investigational medicinal product (IMP) without regard to possibility of causal relationship with the treatment. TEAEs: AEs that developed/worsened or became serious during treatment-emergent period (time of first dose administration of study medication up to 28 days after last dose). Serious AE (SAE): any untoward medical occurrence resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-patient hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event.
Time Frame
From first dose administration (i.e., Day 1) of study medication up to 28 days after last dose (i.e., up to 57.5 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 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.
Had disease duration (defined as interval from first non Raynaud disease manifestation) of less than or equal to (<=) 6 years.
Had mRSS of >=15 but <=40.
Had active disease as determined by the Principal Investigator within the 6 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) and 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 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) must 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 agreed to use two 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 (i) intrauterine device plus 1 barrier method; (ii) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus 1 barrier method; or (iii) 2 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.
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 6b 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:
Participants had corrected QT interval using Fridericia's formula (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 breastfed.
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 Classes 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.
Had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or any other Rho-associated Protein Kinase-2 (ROCK2) inhibitor.
Scleroderma renal crisis within 4 months prior to enrollment.
Forced vital capacity <= 50% Predicted.
Facility Information:
Facility Name
University of California, Los Angeles Medical Center_Site number 104
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Yale University School of Medicine_Site number 140
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Northwestern University_Site number 124
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
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
University of Utah_Site number 048
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Virginia Mason Medical Center_Site number 145
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
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
Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis
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