Chronic Plaque Psoriasis
Conditions
Keywords
Skin Diseases, Auto-Immune Diseases, Plaque, Dermatology
Brief summary
This is a phase 2, randomized, placebo-controlled, 2-period study to evaluate the safety, tolerability, and efficacy of belumosudil in adult subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
Detailed description
This phase 2, two-period, dose-finding, placebo-controlled study is performed on adult male and female subjects to evaluate the efficacy and safety of subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. Period 1: Double-blind, Placebo-controlled Treatment Period Approximately 110 subjects are planned to be randomly assigned to each of 5 dose cohorts in a 1:1:1:1:1 manner. Each cohort is planned to have 22 subjects who meet eligibility criteria. Subjects are treated with oral (PO) belumosudil tablets or placebo tablets as follows: * 200 mg belumosudil once daily (QD) (Cohort 1) = one 200 mg belumosudil tablet and 1 matching placebo in the morning and 1 matching placebo in the evening * 200 mg belumosudil twice daily (BID) (Cohort 2) = one 200 mg belumosudil tablet in the morning and one matching placebo in the morning, and one 200 mg belumosudil tablet in the evening * 400 mg belumosudil QD (Cohort 3) = two 200 mg belumosudil tablets in the morning and one matching placebo in the evening * 600 mg/day belumosudil (Cohort 4) = two 200 mg belumosudil tablets in the morning and one 200 mg belumosudil tablet in the evening * Matching placebo BID (Cohort 5) = 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening Subjects in each of the 5 cohorts in Period 1 are treated with study medication for a period of 16 weeks. Note: Originally, a sample size of 36 subjects per cohort was planned to provide approximately 90% probability ≥ 1 subject in the 5 cohorts would experience an adverse event (AE) that had an underlying rate of ≥ 6% and approximately an 80% probability of ≥ 1 subject in the cohort experiencing an AE that had an underlying rate of ≥ 4%. However, due to a newly available plaque psoriasis treatment, the study is terminated early with 110 subjects. Period 2: Open-label Treatment Period (with Belumosudil) All subjects treated for 16 weeks, regardless of treatment with belumosudil (Cohorts 1 through 4) or placebo (Cohort 5) are given the option to receive 400 mg belumosudil QD for an additional 32 weeks (Week 16 through Week 48). Follow-up Period All subjects have a safety evaluation 30 days after the last dose of study drug. Efficacy is assessed by the following scores at scheduled time points throughout the study: * Psoriasis Area and Severity Index (PASI): Measure of psoriasis disease severity using average redness, thickness, and scaliness of lesions (each lesion graded 0 to 4), combined into single score ranging on a scale from 0 (no disease) to 72 (maximum disease) * Physician's Global Assessment (PGA): Physician's assessment of a subject's psoriasis, relative to baseline, ranging on a scale from 1 (100% clearing of psoriasis) to 6 (poor to no clearing) * Dermatology Life Quality Index (DLQI): Skin disease-specific instrument for assessing impact of disease on subject's quality of life ranging on a scale from 0 (no effect on subject's life) to 30 (extremely large effect on subject's life) Safety is assessed by; * AEs and serious AE (SAEs) * Physical examination * Vital sign measurements * Clinical laboratory evaluations * Electrocardiogram * Reasons for discontinuation due to toxicity analyses The maximum duration for subjects who complete Period 1 (Double-blind, Placebo-controlled) is 24 weeks (up to 4-week Screening, 16-week Period 1 treatment, and 4-week Follow-up). The maximum duration for subjects who complete Period 2 (Open-label) is 56 weeks (up to 4-week Screening, 16-week Double-blind Treatment Period, 32-week Open-label Treatment Period, and 4-week Follow-up).
Interventions
DRUGBelumosudil
DRUGPlacebo
Placebo tablets matching belumosudil
Sponsors
Kadmon Corporation, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adult subjects between the ages of 18 and 65 years * Able to provide written Informed Consent Form prior to the performance of any study-specific procedures * Diagnosis of moderate to severe chronic plaque psoriasis and a candidate for systemic therapy or phototherapy * PASI of ≥ 12 at screening and prior to the first dose of study drug, confirmed at Week 1 Day 1 (Baseline) * ≥ 10% PASI body surface area involvement at screening and prior to the first dose of study drug, confirmed at Baseline * Willing to avoid tanning devices * Adequate bone marrow function: * Absolute neutrophil count \> 1500/mm\^3 * Hemoglobin \> 9.0 g/dL * Platelets \> 100,000/mm\^3 * Adequate safety laboratory values: * Serum total bilirubin within normal limits (WNL) * Aspartate aminotransferase (AST) and alalnine aminotransferase (ALT) \< 2 × upper limit of normal (ULN) * Serum creatinine \< 1.5 × ULN * Female subjects of childbearing potential with 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, antiestrogens, or ovarian suppression * Women of childbearing potential (i.e., menstruating women) had to have 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 had to agree to use 2 forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control included: (a) intrauterine device plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; and (c) 2 barrier methods. Effective barrier methods were male or female condoms, diaphragms, and spermicides (creams or gels that contained a chemical to kill sperm); or (d) a vasectomized partner * For male patients who were sexually active and who were partners of premenopausal women: agreed to use 2 forms of contraception as defined above during the treatment period and for at least 3 months after the last dose of study drug * Willing to complete all study measurements and assessments in compliance with the protocol
Exclusion criteria
* Non-plaque or drug-induced (antimalarials, lithium) psoriasis (If subject was taking angiotensin II receptor blockers or beta blockers doses must have been stable for 6 months prior to study entry) * Used systemic corticosteroids within 12 weeks prior to study entry * Used topical corticosteroids except to the face, groin, or scalp * Used methotrexate, retinoids (such as acitretin), or calcineurin inhibitors (such as cyclosporine) within 4 weeks prior to study entry * Phototherapy within 4 weeks prior to study entry * Biologic therapies, including antibodies to IL-17; anti-tumor necrosis factor-alpha; and anti-IL-12 & IL-23 within 3 months prior to study entry * Current use of an inhibitor or inducer of CYP3A4 * Active viral, fungal, or bacterial skin infection (other than nail fungal infection). * Pregnant or lactating woman * History of gastrointestinal (GI) surgery including any bariatric surgery, or any GI condition that might interfere with drug absorption * Participating in another study with an investigational drug or within 28 days or 5 half-lives of the investigational drug (whichever was longer) of study entry * 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 * Regular and/or excessive use of alcohol within 2 years prior to study entry defined as alcohol intake \> 14 drinks per week in a man or \> 7 drinks per week in a woman. Approximately 10 g of alcohol equaled one drink unit. One unit equaled 1 ounce of distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine * QT interval data corrected using Fridericia's formula (QTcF) \> 450 msec (average of 3 readings) during screening * Exposure to belumosudil or known allergy/sensitivity to belumosudil within the last 6 months prior to study entry or any other ROCK-2 inhibitor * History or presence of any of the following: * ALT or AST \> 2.0 × ULN at screening * Renal disease and/or serum creatinine \> 1.5 × ULN at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | 16 weeks | The percentage of subjects who exhibited a 75% decrease or greater in the Psoriasis Area and Severity Index Score (PASI 75) whether they completed 16 weeks of treatment or not (last observation carried forward \[LOCF\]) and those who did complete 16 weeks of treatment (observed). \[PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | 48 weeks | The percentage (%) change in the mean Psoriasis Area and Severity Index (PASI) score from baseline ore to Week 16 and to Week 48 whether the subject completed 16 and 48 weeks, respectively (last observation carried forward \[LOCF\]) or for only those subjects who completed 16 and 48 weeks (observed), respectively. \[The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
| Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF | 16 weeks | The number of subjects who had a Clear or Almost Clear assessment, using the Physician Global Assessment Scale (PGA), at Week 16 of all subjects whether they completed 16 weeks or not (last observation carried forward \[LOCF\]) \[The PGA documents the physician's assessment of the subject's psoriasis and was assessed relative to baseline conditions. The PGA rating is from 1-6, where 1 = 100% clearing of psoriasis (clear), 5 = 0 to 24% clearing (little or no change), and 6 = worse.\] |
| Efficacy: Percentage of Subjects With Clear or Almost Clear PGA Comparing Belumosudil to Placebo at Week 16--LOCF | 16 weeks | The percentage (%) of subjects who had a Clear or Almost Clear assessment using the Physician Global Assessment Scale at Week 16 of belumosudil vs. placebo for all subjects whether they completed 16 weeks or not (last observation carried forward \[LOCF\]). \[The PGA documents the physician's assessment of the subject's psoriasis and was assessed relative to baseline conditions. The PGA rating is from 1-6, where 1 = 100% clearing of psoriasis (clear), 5 = 0 to 24% clearing (little or no change), and 6 = worse.\] |
| Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | 48 weeks | The mean change in the raw Psoriasis Area and Severity Index (PASI) score from baseline score to Week 16 and to Week 48 whether the subject completed 16 and 48 weeks, respectively (last observation carried forward \[LOCF\]), or for only those subjects who completed 16 and 48 weeks (observed), respectively. Negative values represent favorable results; positive values represent unfavorable results. \[The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\] |
| Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Up to 48 weeks | Mean percentage changes in Dermatology Life Quality Index (DLQI) from baseline at Week 16 (End of Double-blind Period) and at Week 48 (End of Study Treatment). \[The DLQI is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. The rating ranges from 0 (no effect on a subject's life) to 30 (extremely large effect on a subject's life.\] |
| Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Approximately 52 weeks: up to 48 weeks of treatment and 30-day follow-up | The number of subjects who had treatment-emergent adverse events (TEAEs), severity of TEAEs, relationship of TEAEs to study medication, serious TEAEs (SAEs), dose interruption, discontinuations, and deaths. Treatment-emergent adverse events (TEAEs) are AEs that are not present before the first dose of IMP or that are present before the first dose of IMP but worsen in intensity during exposure to IMP. Severity: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = Death. Related to study medication is defined as possible related, probable related, and related |
| Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Up to 48 weeks | Changes in mean Dermatology Life Quality Index (DLQI) score from baseline at Week 16 (End of Double-blind Period) and at Week 48 (End of Study Treatment). \[The DLQI is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. DLQI scoring as measured on subject's life: 0-1 = no effect; 2-5 = small effect; 6-10 = moderate effect; 11 to 20 = very large effect; 21 to 30 = extremely large effect. Change \< 0% is improvement; \> 0% is worsening. The total rating ranges from 0 (no effect on a subject's life) to 30 (extremely large effect on a subject's life.\] |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Belumosudil 200 mg QD + Placebo One belumosudil 200 mg tablet and 1 matching placebo tablet in the morning and 1 matching placebo tablet in the evening
Belumosudil: Belumosudil tablets
Placebo: Placebo tablets matching belumosudil | 23 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo One belumosudil 200 mg tablet and 1 matching placebo tablet in the morning and 1 belumosudil 200 mg tablet in the evening
Belumosudil: Belumosudil tablets
Placebo: Placebo tablets matching belumosudil | 22 |
| Belumosudil 400 mg QD + Placebo Two belumosudil 200 mg tablets in the morning and 1 matching placebo tablet in the evening
Belumosudil: Belumosudil tablets
Placebo: Placebo tablets matching belumosudil | 21 |
| Belumosudil 600 mg/Day Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening
Belumosudil: Belumosudil tablets | 26 |
| Placebo Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening
Placebo: Placebo tablets matching belumosudil | 18 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 0 | 1 | 0 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Dispensing Drug Violation | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Elevated Liver Enzymes | 2 | 0 | 0 | 2 | 2 |
| Overall Study | Inclusion/Exclusion Violation | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 3 | 4 | 4 |
| Overall Study | Non-compliance | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 |
| Overall Study | SAE | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 12 | 7 | 10 | 10 |
Baseline characteristics
| Characteristic | Belumosudil 200 mg QD + Placebo | Belumosudil 200 mg BID (Twice Daily) + Placebo | Belumosudil 400 mg QD + Placebo | Belumosudil 600 mg/Day | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 49.3 Years STANDARD_DEVIATION 8.9 | 46.2 Years STANDARD_DEVIATION 9.6 | 43.0 Years STANDARD_DEVIATION 11.4 | 43.5 Years STANDARD_DEVIATION 11.5 | 45.7 Years STANDARD_DEVIATION 14.2 | 45.5 Years STANDARD_DEVIATION 11.2 |
| BMI (Mean) | 33.8 kg/m^2 STANDARD_DEVIATION 9.9 | 30.7 kg/m^2 STANDARD_DEVIATION 7 | 29.9 kg/m^2 STANDARD_DEVIATION 7.4 | 33.1 kg/m^2 STANDARD_DEVIATION 10.7 | 32 kg/m^2 STANDARD_DEVIATION 6.7 | 32.0 kg/m^2 STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 4 Participants | 8 Participants | 2 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 18 Participants | 16 Participants | 18 Participants | 15 Participants | 85 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 20 Participants | 19 Participants | 17 Participants | 24 Participants | 14 Participants | 94 Participants |
| Sex: Female, Male Female | 16 Participants | 13 Participants | 14 Participants | 15 Participants | 11 Participants | 69 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 7 Participants | 11 Participants | 7 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 23 | 0 / 22 | 0 / 21 | 0 / 26 | 0 / 18 | 1 / 92 |
| other Total, other adverse events | 14 / 23 | 13 / 22 | 14 / 21 | 16 / 26 | 11 / 92 | 57 / 92 |
| serious Total, serious adverse events | 1 / 23 | 0 / 22 | 0 / 21 | 3 / 26 | 1 / 18 | 1 / 92 |
Outcome results
Primary
Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed
The percentage of subjects who exhibited a 75% decrease or greater in the Psoriasis Area and Severity Index Score (PASI 75) whether they completed 16 weeks of treatment or not (last observation carried forward \[LOCF\]) and those who did complete 16 weeks of treatment (observed). \[PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 16 weeks
Population: PASI 75 determined by Last Observation Carried Forward (LOCF) and Observed at the end of Double-blind Period: 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | LOCF (%) | 8.7 Percentage of participants |
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | Observed (%) | 7.1 Percentage of participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | LOCF (%) | 9.1 Percentage of participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | Observed (%) | 13.3 Percentage of participants |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | LOCF (%) | 19.0 Percentage of participants |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | Observed (%) | 23.5 Percentage of participants |
| Belumosudil 600 mg/Day | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | LOCF (%) | 7.7 Percentage of participants |
| Belumosudil 600 mg/Day | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | Observed (%) | 12.5 Percentage of participants |
| Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | LOCF (%) | 16.7 Percentage of participants |
| Placebo | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | Observed (%) | 30.0 Percentage of participants |
| All Belumosudil | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | LOCF (%) | 10.9 Percentage of participants |
| All Belumosudil | Efficacy: Percentage of Subjects With a ≥ 75% Decrease in PASI (PASI 75) at Week 16 (Double-blind Period)--LOCF and Observed | Observed (%) | 14.5 Percentage of participants |
Comparison: LOCF at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 200 mg QD + placebo (n = 23) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 18) who achieved PASI 75.p-value: 0.6384Fisher Exact
Comparison: LOCF at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 200 mg BID + placebo (n = 22) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 18) who achieved PASI 75.p-value: 0.6419Fisher Exact
Comparison: LOCF at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 400 mg QD + placebo (n = 21) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 18) who achieved PASI 75.p-value: >0.9999Fisher Exact
Comparison: LOCF at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 600 mg (n = 26) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 18) who achieved PASI 75.p-value: 0.3859Fisher Exact
Comparison: LOCF at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of all subjects treated with belumosudil (n = 92) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 18) who achieved PASI 75p-value: 0.4435Fisher Exact
Comparison: Observed at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 200 mg QD + placebo (n = 14) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 10) who achieved PASI 75.p-value: 0.2721Fisher Exact
Comparison: Observed at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 200 mg BID+ Placebo (n = 15) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 10) who achieved PASI 75.p-value: 0.3577Fisher Exact
Comparison: Observed at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 500 mg QD + Placebo (n = 17) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 10) who achieved PASI 75.p-value: >0.9999Fisher Exact
Comparison: Observed at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of subjects treated with belumosudil 600 mg/day (n = 16) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 10) who achieved PASI 75.p-value: 0.3402Fisher Exact
Comparison: Observed at 16 weeks (Double-blind Treatment Period): Fisher's Exact Method analysis of the percentage of all subjects treated with belumosudil 200 mg QD + Placebo (n = 62) who achieved PASI 75 compared to the percentage of subjects treated with placebo (n = 10) who achieved PASI 75.p-value: 0.3542Fisher Exact
Secondary
Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48
Changes in mean Dermatology Life Quality Index (DLQI) score from baseline at Week 16 (End of Double-blind Period) and at Week 48 (End of Study Treatment). \[The DLQI is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. DLQI scoring as measured on subject's life: 0-1 = no effect; 2-5 = small effect; 6-10 = moderate effect; 11 to 20 = very large effect; 21 to 30 = extremely large effect. Change \< 0% is improvement; \> 0% is worsening. The total rating ranges from 0 (no effect on a subject's life) to 30 (extremely large effect on a subject's life.\]
Time frame: Up to 48 weeks
Population: Not all subjects could be evaluated at all visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Belumosudil 200 mg QD + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Baseline | 10.6 Score on a scale | Standard Deviation 6.3 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 16 | -2.2 Score on a scale | Standard Deviation 5.6 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 48 | -6.5 Score on a scale | Standard Deviation 5.1 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Baseline | 16.5 Score on a scale | Standard Deviation 9.4 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 48 | -1.0 Score on a scale | Standard Deviation 8.6 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 16 | -3.4 Score on a scale | Standard Deviation 4 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 48 | -5.2 Score on a scale | Standard Deviation 6.9 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Baseline | 12.2 Score on a scale | Standard Deviation 6.5 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 16 | -2.5 Score on a scale | Standard Deviation 6 |
| Belumosudil 600 mg/Day | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 48 | -3.7 Score on a scale | Standard Deviation 3.2 |
| Belumosudil 600 mg/Day | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 16 | -2.3 Score on a scale | Standard Deviation 7 |
| Belumosudil 600 mg/Day | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Baseline | 11.0 Score on a scale | Standard Deviation 7.1 |
| Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 16 | -4.0 Score on a scale | Standard Deviation 6.7 |
| Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 48 | -3.0 Score on a scale | Standard Deviation 2.8 |
| Placebo | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Baseline | 10.3 Score on a scale | Standard Deviation 6.4 |
| All Belumosudil | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 48 | -4.7 Score on a scale | Standard Deviation 6.3 |
| All Belumosudil | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Baseline | 12.5 Score on a scale | Standard Deviation 7.7 |
| All Belumosudil | Efficacy: Change in Mean DLQI Raw Score at Week 16 and at Week 48 | Change at Week 16 | -2.6 Score on a scale | Standard Deviation 5.7 |
Secondary
Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed
The mean change in the raw Psoriasis Area and Severity Index (PASI) score from baseline score to Week 16 and to Week 48 whether the subject completed 16 and 48 weeks, respectively (last observation carried forward \[LOCF\]), or for only those subjects who completed 16 and 48 weeks (observed), respectively. Negative values represent favorable results; positive values represent unfavorable results. \[The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 48 weeks
Population: Not all subjects had PASI performed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Belumosudil 200 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--LOCF | -3.85 Score on a scale | Standard Deviation 10.53 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--LOCF | -5.69 Score on a scale | Standard Deviation 8.59 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Baseline | 18.93 Score on a scale | Standard Deviation 8.31 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--Observed | -5.93 Score on a scale | Standard Deviation 11.26 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--Observed | -3.75 Score on a scale | Standard Deviation 8.62 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--LOCF | -4.49 Score on a scale | Standard Deviation 7.44 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--LOCF | -6.38 Score on a scale | Standard Deviation 5.16 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Baseline | 20.60 Score on a scale | Standard Deviation 8.27 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--Observed | -5.30 Score on a scale | Standard Deviation 5.88 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--Observed | -6.29 Score on a scale | Standard Deviation 6.45 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--LOCF | -5.0 Score on a scale | Standard Deviation 8.31 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--LOCF | -9.01 Score on a scale | Standard Deviation 7.63 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--Observed | -12.99 Score on a scale | Standard Deviation 6.71 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--Observed | -4.96 Score on a scale | Standard Deviation 8.72 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Baseline | 18.82 Score on a scale | Standard Deviation 6.08 |
| Belumosudil 600 mg/Day | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--Observed | -3.81 Score on a scale | Standard Deviation 5.37 |
| Belumosudil 600 mg/Day | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Baseline | 19.80 Score on a scale | Standard Deviation 9.03 |
| Belumosudil 600 mg/Day | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--LOCF | -4.63 Score on a scale | Standard Deviation 8.04 |
| Belumosudil 600 mg/Day | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--LOCF | -0.83 Score on a scale | Standard Deviation 7.73 |
| Belumosudil 600 mg/Day | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--Observed | -4.27 Score on a scale | Standard Deviation 2.16 |
| Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--LOCF | -9.56 Score on a scale | Standard Deviation 18.98 |
| Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Baseline | 20.72 Score on a scale | Standard Deviation 8.08 |
| Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--Observed | 9.45 Score on a scale | Standard Deviation 21 |
| Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--LOCF | -5.68 Score on a scale | Standard Deviation 12.31 |
| Placebo | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--Observed | -8.44 Score on a scale | Standard Deviation 15.36 |
| All Belumosudil | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Baseline | 19.55 Score on a scale | Standard Deviation 7.97 |
| All Belumosudil | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--LOCF | -5.11 Score on a scale | Standard Deviation 8.45 |
| All Belumosudil | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--LOCF | -4.96 Score on a scale | Standard Deviation 7.98 |
| All Belumosudil | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 48--Observed | -7.98 Score on a scale | Standard Deviation 8.76 |
| All Belumosudil | Efficacy: Mean Change of Raw PASI Score From Baseline to Week 16 and Week 48--LOCF and Observed | Change at Week 16--Observed | -4.71 Score on a scale | Standard Deviation 7.31 |
Secondary
Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF
The number of subjects who had a Clear or Almost Clear assessment, using the Physician Global Assessment Scale (PGA), at Week 16 of all subjects whether they completed 16 weeks or not (last observation carried forward \[LOCF\]) \[The PGA documents the physician's assessment of the subject's psoriasis and was assessed relative to baseline conditions. The PGA rating is from 1-6, where 1 = 100% clearing of psoriasis (clear), 5 = 0 to 24% clearing (little or no change), and 6 = worse.\]
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belumosudil 200 mg QD + Placebo | Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF | 1 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF | 0 Participants |
| Belumosudil 400 mg QD + Placebo | Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF | 2 Participants |
| Belumosudil 600 mg/Day | Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF | 1 Participants |
| Placebo | Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF | 2 Participants |
| All Belumosudil | Efficacy: Number of Subjects With Clear or Almost Clear PGA at Week 16--LOCF | 4 Participants |
Secondary
Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed
The percentage (%) change in the mean Psoriasis Area and Severity Index (PASI) score from baseline ore to Week 16 and to Week 48 whether the subject completed 16 and 48 weeks, respectively (last observation carried forward \[LOCF\]) or for only those subjects who completed 16 and 48 weeks (observed), respectively. \[The PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign is assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis.\]
Time frame: 48 weeks
Population: Not all subjects had PASI performed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--LOCF | -27.17 Percentage Change in PASI Score | Standard Deviation 37.6 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--Observed | -15.21 Percentage Change in PASI Score | Standard Deviation 36.9 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--LOCF | -12.82 Percentage Change in PASI Score | Standard Deviation 40.33 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--Observed | -21.81 Percentage Change in PASI Score | Standard Deviation 38.75 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--LOCF | -30.75 Percentage Change in PASI Score | Standard Deviation 24.51 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--Observed | -29.70 Percentage Change in PASI Score | Standard Deviation 30.72 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--LOCF | -19.61 Percentage Change in PASI Score | Standard Deviation 35.6 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--Observed | -30.02 Percentage Change in PASI Score | Standard Deviation 34.39 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--Observed | -63.04 Percentage Change in PASI Score | Standard Deviation 29.04 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--LOCF | -46.97 Percentage Change in PASI Score | Standard Deviation 39.9 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--Observed | -24.17 Percentage Change in PASI Score | Standard Deviation 44.61 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--LOCF | -24.31 Percentage Change in PASI Score | Standard Deviation 42.74 |
| Belumosudil 600 mg/Day | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--LOCF | -20.07 Percentage Change in PASI Score | Standard Deviation 31.2 |
| Belumosudil 600 mg/Day | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--Observed | -33.16 Percentage Change in PASI Score | Standard Deviation 15.48 |
| Belumosudil 600 mg/Day | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--Observed | -20.22 Percentage Change in PASI Score | Standard Deviation 30.16 |
| Belumosudil 600 mg/Day | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--LOCF | -9.31 Percentage Change in PASI Score | Standard Deviation 41.28 |
| Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--LOCF | -19.89 Percentage Change in PASI Score | Standard Deviation 90.61 |
| Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--Observed | 84.98 Percentage Change in PASI Score | Standard Deviation 166.19 |
| Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--Observed | -25.09 Percentage Change in PASI Score | Standard Deviation 54.31 |
| Placebo | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--LOCF | -18.23 Percentage Change in PASI Score | Standard Deviation 43.93 |
| All Belumosudil | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--Observed | -22.46 Percentage Change in PASI Score | Standard Deviation 35.77 |
| All Belumosudil | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--LOCF | -25.54 Percentage Change in PASI Score | Standard Deviation 39.87 |
| All Belumosudil | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 48--Observed | -38.33 Percentage Change in PASI Score | Standard Deviation 36.22 |
| All Belumosudil | Efficacy: Percentage Change in Mean PASI Score From Baseline to Week 16 and to Week 48--LOCF and Observed | Change (%) at Week 16--LOCF | -22.78 Percentage Change in PASI Score | Standard Deviation 36.27 |
Secondary
Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48
Mean percentage changes in Dermatology Life Quality Index (DLQI) from baseline at Week 16 (End of Double-blind Period) and at Week 48 (End of Study Treatment). \[The DLQI is a skin disease-specific instrument designed to assess the impact of the disease on a subject's quality of life. The rating ranges from 0 (no effect on a subject's life) to 30 (extremely large effect on a subject's life.\]
Time frame: Up to 48 weeks
Population: Not all subjects could be evaluated at all visits. Mean decrease in mean DLQI score is favorable; mean increase is not favorable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 16 | -5.73 Percentage change of DLQI score | Standard Deviation 60.75 |
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 48 | -32.41 Percentage change of DLQI score | Standard Deviation 86.97 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 16 | -14.8 Percentage change of DLQI score | Standard Deviation 28.78 |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 48 | 3.54 Percentage change of DLQI score | Standard Deviation 54.32 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 16 | -22.22 Percentage change of DLQI score | Standard Deviation 48.6 |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 48 | -45.60 Percentage change of DLQI score | Standard Deviation 45.84 |
| Belumosudil 600 mg/Day | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 16 | -6.4 Percentage change of DLQI score | Standard Deviation 79.95 |
| Belumosudil 600 mg/Day | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 48 | -53.73 Percentage change of DLQI score | Standard Deviation 45.24 |
| Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 16 | -40.30 Percentage change of DLQI score | Standard Deviation 47.83 |
| Placebo | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 48 | -54.17 Percentage change of DLQI score | Standard Deviation 41.25 |
| All Belumosudil | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 16 | -12.55 Percentage change of DLQI score | Standard Deviation 56.58 |
| All Belumosudil | Efficacy: Percentage Change of Mean DLQI Score From Baseline to Week 16 and Week 48 | Percentage Change at Week 48 | -33.11 Percentage change of DLQI score | Standard Deviation 65.64 |
Secondary
Efficacy: Percentage of Subjects With Clear or Almost Clear PGA Comparing Belumosudil to Placebo at Week 16--LOCF
The percentage (%) of subjects who had a Clear or Almost Clear assessment using the Physician Global Assessment Scale at Week 16 of belumosudil vs. placebo for all subjects whether they completed 16 weeks or not (last observation carried forward \[LOCF\]). \[The PGA documents the physician's assessment of the subject's psoriasis and was assessed relative to baseline conditions. The PGA rating is from 1-6, where 1 = 100% clearing of psoriasis (clear), 5 = 0 to 24% clearing (little or no change), and 6 = worse.\]
Time frame: 16 weeks
Population: Not all subjects had a response to treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Belumosudil 200 mg QD + Placebo | Efficacy: Percentage of Subjects With Clear or Almost Clear PGA Comparing Belumosudil to Placebo at Week 16--LOCF | -6.8 Percentage (%) of subjects |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Efficacy: Percentage of Subjects With Clear or Almost Clear PGA Comparing Belumosudil to Placebo at Week 16--LOCF | -11.1 Percentage (%) of subjects |
| Belumosudil 400 mg QD + Placebo | Efficacy: Percentage of Subjects With Clear or Almost Clear PGA Comparing Belumosudil to Placebo at Week 16--LOCF | -1.6 Percentage (%) of subjects |
| Belumosudil 600 mg/Day | Efficacy: Percentage of Subjects With Clear or Almost Clear PGA Comparing Belumosudil to Placebo at Week 16--LOCF | -7.3 Percentage (%) of subjects |
| Placebo | Efficacy: Percentage of Subjects With Clear or Almost Clear PGA Comparing Belumosudil to Placebo at Week 16--LOCF | -6.8 Percentage (%) of subjects |
Comparison: Percentage of subjects treated with belumosudil compared to placebo who had a PGA rating of clear or almost clearp-value: 0.5728Fisher Exact
Comparison: Percentage of subjects treated with belumosudil compared to placebo who had a PGA rating of clear or almost clearp-value: 0.1962Fisher Exact
p-value: >0.9999Fisher Exact
Comparison: Percentage of subjects treated with belumosudil compared to placebo who had a PGA rating of clear or almost clearp-value: 0.5583Fisher Exact
Comparison: Percentage of subjects treated with belumosudil compared to placebo who had a PGA rating of clear or almost clearp-value: 0.2538Fisher Exact
Secondary
Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study
The number of subjects who had treatment-emergent adverse events (TEAEs), severity of TEAEs, relationship of TEAEs to study medication, serious TEAEs (SAEs), dose interruption, discontinuations, and deaths. Treatment-emergent adverse events (TEAEs) are AEs that are not present before the first dose of IMP or that are present before the first dose of IMP but worsen in intensity during exposure to IMP. Severity: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = Death. Related to study medication is defined as possible related, probable related, and related
Time frame: Approximately 52 weeks: up to 48 weeks of treatment and 30-day follow-up
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related SAE | 0 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Discontinuation | 6 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Grade 3 or Greater TEAE | 2 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related TEAE | 8 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related Grade 3 or Greater TEAE | 1 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Deaths | 1 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Dose Interruption | 1 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | SAE | 1 Participants |
| Belumosudil 200 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | At least 1 TEAE | 14 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | SAE | 0 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related Grade 3 or Greater TEAE | 1 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related TEAE | 6 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related SAE | 0 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Grade 3 or Greater TEAE | 3 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Discontinuation | 1 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Dose Interruption | 1 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | At least 1 TEAE | 13 Participants |
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Deaths | 0 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | At least 1 TEAE | 14 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Deaths | 0 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Discontinuation | 1 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related TEAE | 5 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related Grade 3 or Greater TEAE | 0 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Grade 3 or Greater TEAE | 0 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | SAE | 0 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Dose Interruption | 1 Participants |
| Belumosudil 400 mg QD + Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related SAE | 0 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Dose Interruption | 4 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related Grade 3 or Greater TEAE | 3 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Grade 3 or Greater TEAE | 5 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related SAE | 0 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Deaths | 0 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related TEAE | 9 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | At least 1 TEAE | 16 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | SAE | 3 Participants |
| Belumosudil 600 mg/Day | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Discontinuation | 7 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Grade 3 or Greater TEAE | 2 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | At least 1 TEAE | 11 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related TEAE | 6 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related Grade 3 or Greater TEAE | 1 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Dose Interruption | 0 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | SAE | 1 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related SAE | 0 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Discontinuation | 3 Participants |
| Placebo | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Deaths | 0 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Dose Interruption | 7 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Deaths | 1 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Leading to Discontinuation | 15 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related Grade 3 or Greater TEAE | 5 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related TEAE | 28 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Grade 3 or Greater TEAE | 10 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | At least 1 TEAE | 57 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | Related SAE | 0 Participants |
| All Belumosudil | Safety: Number of Subjects With TEAEs, SAEs, and Deaths Throughout the Study | SAE | 4 Participants |