Trial Outcomes & Findings for Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis (NCT NCT04680975)

NCT ID: NCT04680975

Last Updated: 2023-06-05

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2023-06-05

Participant Flow

The study was conducted at 6 active sites. A total of 11 participants were screened between 03 Mar 2021 and 23 Nov 2021, of which 1 participant was screen failure due to not meeting eligibility criteria.

A total of 10 participants were enrolled and treated with belumosudil in the study.

Participant milestones

Measure	Belumosudil Participants received belumosudil 200 milligrams (mg) tablet orally (PO), twice a day (BID) for 52 weeks.
Overall Study STARTED	10
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Belumosudil Participants received belumosudil 200 milligrams (mg) tablet orally (PO), twice a day (BID) for 52 weeks.
Overall Study Adverse Event	3
Overall Study Death	1
Overall Study Progressive Disease	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis

Baseline characteristics by cohort

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet PO, BID for 52 weeks.
Age, Continuous	46.9 years STANDARD_DEVIATION 7.31 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

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

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.

Outcome measures

Measure	Belumosudil n=4 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Week 24	6.65 score on a scale Standard Deviation 12.926

SECONDARY outcome

Timeframe: Week 8, 16, 36 and 52

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

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.

Outcome measures

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52 Week 8	13.97 score on a scale Standard Deviation 24.657
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52 Week 16	20.48 score on a scale Standard Deviation 41.654
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52 Week 36	22.38 score on a scale Standard Deviation 44.715
Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52 Week 52	25.49 score on a scale Standard Deviation 49.674

SECONDARY outcome

Timeframe: Week 24

Population: Analysis was performed on mITT population. Here," overall number of participants analyzed" signifies participants with available data for this outcome measure.

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.

Outcome measures

Measure	Belumosudil n=6 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Modified Rodnan Skin Score (mRSS) at Week 24	24.2 score on a scale Standard Deviation 11.16

SECONDARY outcome

Timeframe: Week 24

Population: Analysis was performed on mITT population. Here," overall number of participants analyzed" signifies participants with available data for this outcome measure.

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.

Outcome measures

Measure	Belumosudil n=6 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Forced Vital Capacity (FVC) Level at Week 24	85.7 liters Standard Deviation 25.28

SECONDARY outcome

Timeframe: Week 24

Population: Analysis was performed on mITT population. Here," overall number of participants analyzed" signifies participants with available data for this outcome measure.

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.

Outcome measures

Measure	Belumosudil n=6 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24	61.2 score on a scale Standard Deviation 30.32

SECONDARY outcome

Timeframe: Week 24

Population: Analysis was performed on mITT population. Here," overall number of participants analyzed" signifies participants with available data for this outcome measure.

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.

Outcome measures

Measure	Belumosudil n=6 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24	51.3 score on a scale Standard Deviation 34.54

SECONDARY outcome

Timeframe: Week 24

Population: Analysis was performed on mITT population. Here," overall number of participants analyzed" signifies participants with available data for this outcome measure.

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.

Outcome measures

Measure	Belumosudil n=5 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24	1.750 score on a scale Standard Deviation 1.072

SECONDARY outcome

Timeframe: Baseline, Week 8, 16, 36 and 52

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

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.

Outcome measures

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Change From Baseline in Modified Rodnan Skin Thickness Score (mRSS) at Weeks 8, 16, 36, and 52 Week 8	-1.2 score on a scale Standard Deviation 2.82
Change From Baseline in Modified Rodnan Skin Thickness Score (mRSS) at Weeks 8, 16, 36, and 52 Week 16	-1.0 score on a scale Standard Deviation 4.86
Change From Baseline in Modified Rodnan Skin Thickness Score (mRSS) at Weeks 8, 16, 36, and 52 Week 36	0.2 score on a scale Standard Deviation 6.57
Change From Baseline in Modified Rodnan Skin Thickness Score (mRSS) at Weeks 8, 16, 36, and 52 Week 52	-1.0 score on a scale Standard Deviation 8.98

SECONDARY outcome

Timeframe: Baseline, Week 8, 16, 36 and 52

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

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).

Outcome measures

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Change From Baseline in Forced Vital Capacity (FVC) Level at Weeks 8, 16, 36, and 52 Week 8	0.8 liters Standard Deviation 4.15
Change From Baseline in Forced Vital Capacity (FVC) Level at Weeks 8, 16, 36, and 52 Week 16	2.9 liters Standard Deviation 4.85
Change From Baseline in Forced Vital Capacity (FVC) Level at Weeks 8, 16, 36, and 52 Week 36	3.3 liters Standard Deviation 9.32
Change From Baseline in Forced Vital Capacity (FVC) Level at Weeks 8, 16, 36, and 52 Week 52	0.8 liters Standard Deviation 15.52

SECONDARY outcome

Timeframe: Baseline, Week 8, 16, 36 and 52

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

The Physician Global Assessment (reported by the physician) quantified the participant's overall health during the last week based on a VAS which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicated better outcome. A positive change from Baseline demonstrated improvement.

Outcome measures

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
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 Week 8	0.1 score on a scale Standard Deviation 19.04
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 Week 16	3.5 score on a scale Standard Deviation 19.72
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 Week 36	7.6 score on a scale Standard Deviation 29.23
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 Week 52	12.0 score on a scale Standard Deviation 32.22

SECONDARY outcome

Timeframe: Baseline, Week 8, 16, 36 and 52

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

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.

Outcome measures

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
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 Week 8	-5.6 score on a scale Standard Deviation 27.68
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 Week 16	-7.2 score on a scale Standard Deviation 17.38
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 Week 36	-3.0 score on a scale Standard Deviation 45.54
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 Week 52	-20.0 score on a scale Standard Deviation 22.82

SECONDARY outcome

Timeframe: Baseline, Week 8, 16, 36 and 52

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

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.

Outcome measures

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Weeks 8, 16, 36, and 52 Week 8	-0.069 score on a scale Standard Deviation 0.208
Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Weeks 8, 16, 36, and 52 Week 16	-0.036 score on a scale Standard Deviation 0.312
Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Weeks 8, 16, 36, and 52 Week 36	-0.075 score on a scale Standard Deviation 0.244
Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Weeks 8, 16, 36, and 52 Week 52	0.031 score on a scale Standard Deviation 0.483

SECONDARY outcome

Timeframe: 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)

Population: Analysis was performed on safety population which included all participants who received at least 1 dose of belumosudil 200 mg.

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.

Outcome measures

Measure	Belumosudil n=10 Participants Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TEAEs	10 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TESAEs	4 Participants

Adverse Events

Belumosudil

Serious events: 4 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Measure	Belumosudil n=10 participants at risk Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal Proliferative Breast Lesion	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Nervous system disorders Syncope	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Renal and urinary disorders Acute Kidney Injury	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Vascular disorders Hypotension	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Vascular disorders Shock	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.

Other adverse events

Measure	Belumosudil n=10 participants at risk Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.
Cardiac disorders Sinus Bradycardia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Cardiac disorders Tachycardia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Ear and labyrinth disorders Ear Pain	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Eye disorders Dry Eye	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Eye disorders Photophobia	20.0% 2/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Eye disorders Vision Blurred	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Abdominal Discomfort	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Abdominal Distension	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Abdominal Pain	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Diarrhoea	60.0% 6/10 • Number of events 7 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Dysphagia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	20.0% 2/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Nausea	60.0% 6/10 • Number of events 9 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Oral Pain	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Stomatitis	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Tooth Discolouration	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Gastrointestinal disorders Vomiting	60.0% 6/10 • Number of events 8 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
General disorders Fatigue	50.0% 5/10 • Number of events 7 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
General disorders Pyrexia	10.0% 1/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Covid-19	20.0% 2/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Coronavirus Infection	20.0% 2/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Gastrointestinal Bacterial Overgrowth	10.0% 1/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Helicobacter Gastritis	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Helicobacter Infection	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	20.0% 2/10 • Number of events 6 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Oral Candidiasis	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Postoperative Wound Infection	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Rash Pustular	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Infections and infestations Urinary Tract Infection	10.0% 1/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Injury, poisoning and procedural complications Procedural Pain	20.0% 2/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Injury, poisoning and procedural complications Road Traffic Accident	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Investigations Urine Analysis Abnormal	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Investigations Weight Decreased	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Metabolism and nutrition disorders Decreased Appetite	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Metabolism and nutrition disorders Hyperkalaemia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Metabolism and nutrition disorders Hypoglycaemia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Metabolism and nutrition disorders Hypomagnesaemia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • Number of events 3 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Muscular Weakness	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Pain In Extremity	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Systemic Scleroderma	10.0% 1/10 • Number of events 3 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Temporomandibular Joint Syndrome	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Nervous system disorders Dizziness	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Nervous system disorders Headache	40.0% 4/10 • Number of events 4 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Nervous system disorders Memory Impairment	20.0% 2/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Nervous system disorders Peripheral Sensory Neuropathy	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Psychiatric disorders Abnormal Dreams	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Psychiatric disorders Insomnia	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Psychiatric disorders Irritability	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Reproductive system and breast disorders Breast Mass	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Reproductive system and breast disorders Vaginal Haemorrhage	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Angioedema	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Hypertrichosis	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Pruritus	30.0% 3/10 • Number of events 3 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Skin Tightness	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Skin Ulcer	10.0% 1/10 • Number of events 1 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Vascular disorders Hypertension	10.0% 1/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.
Vascular disorders Raynaud's Phenomenon	20.0% 2/10 • Number of events 2 • 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) Reported AEs and deaths were treatment emergent AEs that developed, worsened, or became serious during treatment emergent period (time from first dose of study drug up to 28 days after the last dose of study drug). Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Sanofi (Kadmon, a Sanofi Company)

Phone: 800-633-1610

Email: Contact-US@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
• Publication restrictions are in place

Restriction type: OTHER