Trial Outcomes & Findings for A Safety and Tolerability Study of Belumosudil (KD025) Treatment in Subjects With Moderately Severe Psoriasis Vulgaris (NCT NCT02106195)

NCT ID: NCT02106195

Last Updated: 2022-03-23

Results Overview

To evaluate the safety and tolerability of 200 mg of belumosudil administered PO QD to subjects for treatment of psoriasis

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: Up to 12 weeks:Up to 4 weeks screening (depending on signed informed consent + 4 weeks treatment + 4 weeks follow-up
• Results posted on: 2022-03-23

Participant Flow

Open-label, Phase 2a, single-arm study of subjects with moderately severe plaque psoriasis who had been stable for 6 months and had failed at least 1 line of systemic therapy. Subjects were recruited at 1 site in the U.S.

Screening assessments occurred within 28 days prior to assignment and included informed consent, medical/demographic history, physical exam, vital signs, clinical laboratory tests, ECG, urine pregnancy, skin punch biopsy, PK, Psoriasis Area and Severity Index (PASI) scoring, Physician Global Assessment (PGA) scoring, and concomitant AE assessments.

Participant milestones

Measure	Belumosudil 200 mg PO QD 8 subjects with moderately severe psoriasis who had failed at least 1 line of systemic therapy administered belumosudil 200 mg orally QD for 4 weeks
Overall Study STARTED	8
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Belumosudil 200 mg PO QD 8 subjects with moderately severe psoriasis who had failed at least 1 line of systemic therapy administered belumosudil 200 mg orally QD for 4 weeks
Overall Study Adverse Event	2
Overall Study Protocol Violation	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Belumosudil 200 mg PO QD n=8 Participants Belumosudil 200 mg (two 100 mg capsules) orally once daily for 28 days
Age, Continuous	47.6 years STANDARD_DEVIATION 10.31 • n=8 Participants
Age, Customized	49.5 years n=8 Participants
Sex: Female, Male Female	0 Participants n=8 Participants
Sex: Female, Male Male	8 Participants n=8 Participants
BMI	27.61 kg/m^2 n=8 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks:Up to 4 weeks screening (depending on signed informed consent + 4 weeks treatment + 4 weeks follow-up

Population: Safety Population: All subjects who received at least 1 dose of belumosudil 200 mg

To evaluate the safety and tolerability of 200 mg of belumosudil administered PO QD to subjects for treatment of psoriasis

Outcome measures

Measure	Belumosudil 200 mg PO QD n=8 Participants Subjects who received at least 1 dose of belumosudil 200 mg orally daily	Metabolite M1 Metabolite KD025 M1 of parent drug KD025.	Metabolite M2 Metabolite KD025 M2 of parent drug KD025.
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability All AEs	4 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability Related AEs	1 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability Grade ≥3 AEs	1 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability Grade ≥3 Related AEs	0 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability Grade 4 AEs	0 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability Deaths	0 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability SAEs	1 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability Related SAEs	0 Participants	—	—
Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability AEs leading to discontinuation	2 Participants	—	—

SECONDARY outcome

Timeframe: 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up

Population: All 8 subjects who received belumosudil 200 mg PO QD. 7 subjects available at follow-up visit.

The Psoriasis Area and Severity Index (PASI) is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.

The measures are the changes in PASI score at Week 4 from baseline and Week 8 from baseline. Negative changes are favorable; positive changes are unfavorable.

Outcome measures

Measure	Belumosudil 200 mg PO QD n=8 Participants Subjects who received at least 1 dose of belumosudil 200 mg orally daily	Metabolite M1 Metabolite KD025 M1 of parent drug KD025.	Metabolite M2 Metabolite KD025 M2 of parent drug KD025.
Efficacy: Change in Overall PASI (Psoriasis Area and Severity Index) From Baseline to Week 4 and Week 8 Baseline (Day 1)	17.5 Score on a scale Standard Deviation 8.41	—	—
Efficacy: Change in Overall PASI (Psoriasis Area and Severity Index) From Baseline to Week 4 and Week 8 Week 4 (Day 28)	16.3 Score on a scale Standard Deviation 9.49	—	—
Efficacy: Change in Overall PASI (Psoriasis Area and Severity Index) From Baseline to Week 4 and Week 8 Change from Baseline to Week 4	-1.1 Score on a scale Standard Deviation 3.04	—	—
Efficacy: Change in Overall PASI (Psoriasis Area and Severity Index) From Baseline to Week 4 and Week 8 Week 8 (Day 56)	14.7 Score on a scale Standard Deviation 3.41	—	—
Efficacy: Change in Overall PASI (Psoriasis Area and Severity Index) From Baseline to Week 4 and Week 8 Change from Baseline to Week 8	0.0 Score on a scale Standard Deviation 1.54	—	—

SECONDARY outcome

Timeframe: 8 weeks: 4-week (28-day) treatment + 4-week (28-day) follow-up

Population: All 8 subjects had PGA scoring at Day 29 and at the follow-up visit (30 days after last dose of study drug)

PGA score after treatment with belumosudil 200 mg PO QD at 4 weeks (28 days treatment) and at 8 weeks (additional 4 weeks follow-up).

Categories: 100% = clear; 75% to 99% clearing (Excellent) = marked improvement, nearly normal skin texture, some erythema may be present; 50% to 74% clear (Good) = moderate improvement, plaque has cleared to point of small scattered papules with normal intervening epidermis; 25% to 49% clearing (Fair) = slight improvement, decrease in scaling and softening of plaque; 0% to 24% clearing (Poor) = little or no change in scaling, erythema, or plaque elevation; Worse

Outcome measures

Measure	Belumosudil 200 mg PO QD n=8 Participants Subjects who received at least 1 dose of belumosudil 200 mg orally daily	Metabolite M1 Metabolite KD025 M1 of parent drug KD025.	Metabolite M2 Metabolite KD025 M2 of parent drug KD025.
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 4 weeks: 75% to 100%	0 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 4 weeks: 50% to 74% clearing	1 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 4 weeks: 25% to 49% clearing	1 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 4 weeks: 0 to 24% clearing	4 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 4 weeks: Worse	2 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 8 weeks: 75% to 100%	0 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 8 weeks: 50% to 74% clearing	0 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 8 weeks: 25% to 49% clearing	0 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 8 weeks: 0% to 24% clearing	6 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 8 weeks: Worse	1 Participants	—	—
Efficacy: Physician Global Assessment (PGA) at Week 4 and Week 8 8 weeks: Missing (no data)	1 Participants	—	—

SECONDARY outcome

Timeframe: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose

Population: One subject excluded from all the descriptive statistics due to a mix-up of samples between predose and 4 hours (KD025, M1 and M2); Two subjects had no measurable concentrations observed in their profiles for M1 at Day 1

Pharmacokinetic measures:

Cmax = maximum observed plasma concentration; Cmin = minimum observed plasma concentration over 1 dosing period; KD025 = Parent Drug KD025; M1 = Metabolite KD025 M1; KD025 M2 = Metabolite M2.

Day 1 Cmax: 8 subjects each in KD025 and M2, and 6 subjects in M1. Day 28 Cmax: 4 subjects each in KD025 and M2, and 1 subject in M1.

Day 1 Cmin: 8 subjects each in KD025 and M2, and 3 subjects in M1. Day 28 Cmin: 4 subjects each in KD025 and M2, and 1 subject in M1.

Outcome measures

Measure	Belumosudil 200 mg PO QD n=8 Participants Subjects who received at least 1 dose of belumosudil 200 mg orally daily	Metabolite M1 n=6 Participants Metabolite KD025 M1 of parent drug KD025.	Metabolite M2 n=8 Participants Metabolite KD025 M2 of parent drug KD025.
PK: Cmax and Cmin Cmax: Day 1	1240 ng/mL Standard Deviation 704	21.3 ng/mL Standard Deviation 10.9	221 ng/mL Standard Deviation 165
PK: Cmax and Cmin Cmax: Day 28	810 ng/mL Standard Deviation 475	15.0 ng/mL Standard Deviation NA Standard Deviation is not available since only 1 participant was analyzed for the assessment.	131 ng/mL Standard Deviation 152
PK: Cmax and Cmin Cmin: Day 1	59.6 ng/mL Standard Deviation 29.3	18.7 ng/mL Standard Deviation 9.16	21.1 ng/mL Standard Deviation 6.13
PK: Cmax and Cmin Cmin: Day 28	35.9 ng/mL Standard Deviation 22.9	10.7 ng/mL Standard Deviation NA Standard Deviation is not available since only 1 participant was analyzed for the assessment.	17.6 ng/mL Standard Deviation 7.36

SECONDARY outcome

Timeframe: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose

Population: AUC(0-24) Day 1: 7 subjects in KD025 and 3 subjects in M2. AUC(0-24) Day 28: 4 subjects in KD025 and 2 subjects in M2. AUC(inf): 6 subjects in KD025 and 3 subject in M2. Neither AUC(0-24) nor AUC(inf) were calculated for M1.

Pharmacokinetic measures:

AUC(0-24) = area under concentration time-curve from pre-dose (time 0) to 24 hours post-dose; AUC(inf) = area under concentration time-curve extrapolated from Day 1 to infinity; KD025 = Parent Drug KD025; M1 = Metabolite KD025 M1; KD025 M2 = Metabolite M2.

Outcome measures

Measure	Belumosudil 200 mg PO QD n=7 Participants Subjects who received at least 1 dose of belumosudil 200 mg orally daily	Metabolite M1 n=7 Participants Metabolite KD025 M1 of parent drug KD025.	Metabolite M2 Metabolite KD025 M2 of parent drug KD025.
PK: AUC(0-24) and AUC(Inf) AUC(0-24): Day 1	7360 ng*hr/mL Standard Deviation 3180	1040 ng*hr/mL Standard Deviation 545	—
PK: AUC(0-24) and AUC(Inf) AUC(0-24): Day 28	5500 ng*hr/mL Standard Deviation 3790	162 ng*hr/mL Standard Deviation 2320	—
PK: AUC(0-24) and AUC(Inf) AUC(inf) from Day 1	8230 ng*hr/mL Standard Deviation 3600	1120 ng*hr/mL Standard Deviation 680	—

SECONDARY outcome

Timeframe: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose

Population: Day 1: 7 subjects each in KD025 and M2, and 5 subjects in M1. Day 28: 4 subjects each in KD025 and M2, and 1 subject in M1.

Pharmacokinetic measure:

Tmax = time of maximum observed plasma concentration. Day 1 Tmax: 7 subjects each in KD025 and M2, and 5 subjects in M1. Day 28 Tmax: 4 subjects each in KD025 and M2, and 1 subject in M1.

Outcome measures

Measure	Belumosudil 200 mg PO QD n=7 Participants Subjects who received at least 1 dose of belumosudil 200 mg orally daily	Metabolite M1 n=5 Participants Metabolite KD025 M1 of parent drug KD025.	Metabolite M2 n=7 Participants Metabolite KD025 M2 of parent drug KD025.
PK: Tmax Tmax: Day 1	2.00 hours Interval 1.0 to 7.92	2.00 hours Interval 1.0 to 2.0	2.00 hours Interval 1.0 to 7.92
PK: Tmax Tmax: Day 28	4.00 hours Interval 1.0 to 4.13	4.00 hours Interval 4.0 to 4.0	4.00 hours Interval 1.0 to 4.13

SECONDARY outcome

Timeframe: Measured at Baseline (Day 1) and Week 4 (28 days): predose (0), 1, 2, 4, 8, and 24 hours post-dose

Population: One subject was excluded from all descriptive statistics due to a mix-up of samples between pre-dose and 4 hours on Day 1. Three subjects were excluded from day 28 statistics due to varying protocol deviations. Four additional subjects were excluded from M1 Day 28. No data were collected for Metabolite M1.

KD025 = Parent Drug KD025; KD025 M2 = Metabolite M2; t(1/2) = apparent terminal elimination half-life

Outcome measures

Measure	Belumosudil 200 mg PO QD n=6 Participants Subjects who received at least 1 dose of belumosudil 200 mg orally daily	Metabolite M1 n=3 Participants Metabolite KD025 M1 of parent drug KD025.	Metabolite M2 Metabolite KD025 M2 of parent drug KD025.
PK: t(1/2) t(1/2): Day 1	6.08 hours Standard Deviation 0.681	4.25 hours Standard Deviation 3.95	—
PK: t(1/2) t(1/2): Day 28	5.27 hours Standard Deviation 0.692	2.26 hours Standard Deviation NA Standard Deviation not available since only 1 participant was analyzed for the assessment.	—

Adverse Events

Belumosudil 200 mg PO QD

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Belumosudil 200 mg PO QD n=8 participants at risk Subjects who received belumosudil 200 mg orally daily
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 2 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Injury, poisoning and procedural complications Anastomotic ulcer	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Renal and urinary disorders Nephrolithiasis	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.

Other adverse events

Measure	Belumosudil 200 mg PO QD n=8 participants at risk Subjects who received belumosudil 200 mg orally daily
Investigations Transaminase increased	25.0% 2/8 • Number of events 2 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 2 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 2 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Injury, poisoning and procedural complications Anastomotic ulder	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Renal and urinary disorders Nephrolithiasis	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
General disorders Pyrexia	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Metabolism and nutrition disorders Hypokalemia	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Injury, poisoning and procedural complications Rib Fracture	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Injury, poisoning and procedural complications Fall	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Nervous system disorders Somnolence	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.
Gastrointestinal disorders Tooth ache	12.5% 1/8 • Number of events 1 • 12 weeks: up to 4 weeks for screening, 4 weeks of treatment, and 4 weeks of follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 was used. The Clinical Symptom and Adverse Event Grading scale was used for grading toxicities.

Additional Information

Associate VP, Clinical Operations

Kadmon Corporation, LLC

Phone: 833-900-5366

Email: karin.herrera@kadmon.com

Results disclosure agreements

• Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding results. The sponsor cannot require changes to the study results in the communication except to remove sponsor's confidential information. Sponsor cannot unilaterally extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER