Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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:
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:
Safety is assessed by;
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Belumosudil 200 mg QD + Placebo | Experimental | One belumosudil 200 mg tablet and 1 matching placebo tablet in the morning and 1 matching placebo tablet in the evening |
|
| Belumosudil 200 mg BID (Twice Daily) + Placebo | Experimental | One belumosudil 200 mg tablet and 1 matching placebo tablet in the morning and 1 belumosudil 200 mg tablet in the evening |
|
| Belumosudil 400 mg QD + Placebo | Experimental | Two belumosudil 200 mg tablets in the morning and 1 matching placebo tablet in the evening |
|
| Belumosudil 600 mg/day | Experimental | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening |
|
| Placebo | Placebo Comparator | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Belumosudil | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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.] | 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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.] |
Not provided
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:
Adequate safety laboratory values:
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
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:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alliance Dermatology and Mohs Center | Phoenix | Arizona | 85032 | United States | ||
| University of California, Irvine - Dermatology Clinical Research Center |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Belumosudil 200 mg BID (Twice Daily) + Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 12, 2019 | Aug 12, 2021 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo tablets matching belumosudil |
|
| 48 weeks |
| 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.] | 48 weeks |
| 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.] | 16 weeks |
| 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.] | 16 weeks |
| 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.] | Up to 48 weeks |
| 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.] | Up to 48 weeks |
| 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 | Approximately 52 weeks: up to 48 weeks of treatment and 30-day follow-up |
| Irvine |
| California |
| 92697 |
| United States |
| Dermatology Research Associates | Los Angeles | California | 90045 | United States |
| Renstar Medical Research | Ocala | Florida | 34471 | United States |
| Dawes Fretzin Dermatology Group | Indianapolis | Indiana | 46256 | United States |
| Dermatology Specialists Research | New Albany | Indiana | 40202 | United States |
| Dermatology Specialists Research | Louisville | Kentucky | 40202 | United States |
| Metro Boston Clinical Partners | Brighton | Massachusetts | 02135 | United States |
| Psoriasis Treatment Center of Central New Jersey | East Windsor | New Jersey | 08520 | United States |
| Sadick Research Group | New York | New York | 10075 | United States |
| Oregon Dermatology and Research Center | Portland | Oregon | 97210 | United States |
| Tennessee Clinical Research Center | Nashville | Tennessee | 37215 | United States |
| Suzanne Bruce and Associates | Katy | Texas | 77056 | United States |
| Austin Institute for Clinical Research | Pflugerville | Texas | 78660 | United States |
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 |
| FG002 | 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 |
| FG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| FG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| Completed Period 1: Double-blind |
|
| Completed Period 2: Open-label |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| BG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| BMI (Mean) | Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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.] | PASI 75 determined by Last Observation Carried Forward (LOCF) and Observed at the end of Double-blind Period: 16 weeks | Posted | Number | 95% Confidence Interval | Percentage of participants | 16 weeks |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.] | Not all subjects had PASI performed | Posted | Mean | Standard Deviation | Score on a scale | 48 weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.] | Not all subjects had PASI performed | Posted | Mean | Standard Deviation | Percentage Change in PASI Score | 48 weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.] | Posted | Count of Participants | Participants | 16 weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.] | Not all subjects had a response to treatment | Posted | Number | 95% Confidence Interval | Percentage (%) of subjects | 16 weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.] | Not all subjects could be evaluated at all visits. | Posted | Mean | Standard Deviation | Score on a scale | Up to 48 weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.] | Not all subjects could be evaluated at all visits. Mean decrease in mean DLQI score is favorable; mean increase is not favorable | Posted | Mean | Standard Deviation | Percentage change of DLQI score | Up to 48 weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | Posted | Count of Participants | Participants | Approximately 52 weeks: up to 48 weeks of treatment and 30-day follow-up |
|
Approximately 52 weeks: up to 48 weeks of treatment and 30-day follow-up
Adverse events were categorized as treatment-emergent adverse events (TEAEs). 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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 1 | 23 | 1 | 23 | 14 | 23 |
| EG001 | 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 | 0 | 22 | 0 | 22 | 13 | 22 |
| EG002 | 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 | 0 | 21 | 0 | 21 | 14 | 21 |
| EG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets | 0 | 26 | 3 | 26 | 16 | 26 |
| EG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil | 0 | 18 | 1 | 18 | 11 | 92 |
| EG005 | All Belumosudil | All subjects from all cohorts who received belumosudil | 1 | 92 | 1 | 92 | 57 | 92 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chronic obstructive pulmonary disease (COPD) | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Thalamic infarction | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypercholesterolemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Natural death | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Alanine aminotransaminase (ALT) increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood creatinine phosphokinase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Ligament pain | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Meniscus injry | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Olivier Schueller, Senior Vice President, CMC & Clinical Pharmacology | Kadmon Corporation, LLC | 724-778-6170 | olivier.schueller@kadmon.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 2, 2020 | Aug 12, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012871 | Skin Diseases |
| D058225 | Plaque, Amyloid |
| ID | Term |
|---|---|
| D017437 | Skin and Connective Tissue Diseases |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000718240 | belumosudil |
| C000619755 | KD025 |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Observed (%) |
|
|
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.
| Fisher Exact |
| 0.6419 |
| Superiority |
| 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. | Fisher Exact | > 0.9999 | Superiority |
| 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. | Fisher Exact | 0.3859 | Superiority |
| 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 75 | Fisher Exact | 0.4435 | Superiority |
| 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. | Fisher Exact | 0.2721 | Superiority |
| 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. | Fisher Exact | 0.3577 | Superiority |
| 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. | Fisher Exact | > 0.9999 | Superiority |
| 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. | Fisher Exact | 0.3402 | Superiority |
| 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. | Fisher Exact | 0.3542 | Superiority |
| OG002 | 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 |
| OG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| OG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| OG005 | All Belumosudil | All subjects in the Belumosudil 200 mg QD, 200 mg BID, 400 mg QD, and 600 mg/day cohorts |
|
|
| OG002 | 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 |
| OG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| OG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| OG005 | All Belumosudil | All subjects in the Belumosudil 200 mg QD, 200 mg BID, 400 mg QD, and 600 mg/day cohorts |
|
|
| OG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| OG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| OG005 | All Belumosudil | All subjects in the Belumosudil 200 mg QD, 200 mg BID, 400 mg QD, and 600 mg/day cohorts |
|
|
Two belumosudil 200 mg tablets in the morning and 1 matching placebo tablet in the evening Belumosudil: Belumosudil tablets Placebo: Placebo tablets matching belumosudil |
| OG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| OG004 | All Belumosudil | All subjects in the Belumosudil 200 mg QD, 200 mg BID, 400 mg QD, and 600 mg/day cohorts |
|
|
|
| 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 |
| OG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| OG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| OG005 | All Belumosudil | All subjects in the Belumosudil 200 mg QD, 200 mg BID, 400 mg QD, and 600 mg/day cohorts |
|
|
Two belumosudil 200 mg tablets in the morning and 1 matching placebo tablet in the evening
Belumosudil: Belumosudil tablets
Placebo: Placebo tablets matching belumosudil
| OG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil: Belumosudil tablets |
| OG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| OG005 | All Belumosudil | All subjects in the Belumosudil 200 mg QD, 200 mg BID, 400 mg QD, and 600 mg/day cohorts |
|
|
Two belumosudil 200 mg tablets in the morning and 1 matching placebo tablet in the evening Belumosudil Placebo: Placebo tablets matching belumosudil |
| OG003 | Belumosudil 600 mg/Day | Two belumosudil 200 mg tablets in the morning and 1 belumosudil 200 mg tablet in the evening Belumosudil |
| OG004 | Placebo | Two matching placebo tablets in the morning and 1 matching placebo tablet in the evening Placebo: Placebo tablets matching belumosudil |
| OG005 | All Belumosudile | All subjects from all cohorts who received belumosudil |
|
|
|
|
|
|
|
|
|
|
|
|