Chronic Graft-versus-host-disease
Conditions
Brief summary
Extended Treatment and Follow-up of Subjects Treated with Belumosudil in Study KD025-208 or Study KD025-213
Detailed description
This is a Phase 2, open-label, long-term treatment and follow-up study in subjects with cGVHD who have been previously treated with belumosudil in Study KD025-208 or Study KD025-213. Subjects will not be screened. Subjects who have signed the informed consent form will be enrolled in Study KD025-217 if they have met 1 of the following conditions: * Actively receiving belumosudil or in long-term follow-up (LTFU) in Study KD025-208 or Study KD025-213 * Enrolled in the Companion Study as specified in Study KD025-213 Amendment 2 and received at least 6 months of treatment or is in LTFU Approximately 20 Study Centers will participate with approximately 70 subjects participating overall.
Interventions
Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.
DRUGBelumosudil 200 mg BID
Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.
DRUGBelumosudil 400 mg QD
Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.
Sponsors
Kadmon, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must have been treated with belumosudil for at least 1 of the following: * Actively receiving belumosudil on Study KD025-208 or Study KD025-213 * Is in Long-term Follow-up (LTFU) on Study KD025-208 or Study KD025-213. Long-term Follow-up will be defined as the period after ending treatment with belumosudil and until a FFS event occurs. * Adult enrolled in the Companion Study under KD025-213 Amendment 2 (01 June 2020) and has received at least 6 months of treatment of belumosudil or is in LTFU
Exclusion criteria
* Female subject who is pregnant or breastfeeding * Subject considered unlikely to adhere to treatment and/or follow protocol in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months | DOR is defined as time from first documentation of response to time of first documentation of deterioration from best response (e.g., complete response \[CR\] to partial response \[PR\], or PR to Lack of response \[LR\]). As per the 2014 National Institutes of Health (NIH) Consensus Development Project for clinical trials in cGVHD criteria: CR was defined as resolution of all manifestations of cGVHD in each organ or site.PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.LR included response status of mixed, unchanged, or progression.Mixed LR was defined as complete or partial response in at least 1 organ accompanied by progression in another organ. Unchanged LR was defined as outcomes that did not meet criteria for CR, PR, progression or mixed response. Progression LR was defined as progression in at least 1 organ or site without a response in any other organ or site. Confidence interval (CI) is calculated using Kaplan-Meier method. |
| Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS) | Baseline (Day 1) up to 23 months | The questionnaire asked participants to indicate the degree of bother that they experienced due to symptoms in 7 domains potentially affected by cGVHD. It consists of 30 items of 7 domains: skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each question was rated/scored as 0-not at all, 1-slightly, 2-moderately, 3-quite a bit, 4-extremely with lower values representing better outcome. A domain score was calculated for each domain by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A total score was calculated as average of all non-missing domain scores if more than 50% of them were non-missing, ranged from 0-100. A higher score indicated more bothersome symptoms. A 7-point difference on the total score of cGVHD symptom scale was found to be clinically meaningful. |
| Duration of >=7 Point Reduction as Assessed by Lee Symptom Scale | Baseline (Day 1) up to 23 months | The questionnaire asked participants to indicate the degree of bother that they experienced due to symptoms in 7 domains potentially affected by cGVHD. It consisted of 30 items of 7 domains: skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each question was rated/scored as 0-not at all, 1-slightly, 2-moderately, 3-quite a bit, 4-extremely with lower values representing better outcome. A domain score was calculated for each domain by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A total score was calculated as average of all non-missing domain scores if more than 50% of them were non-missing, ranged from 0-100. A higher score indicated more bothersome symptoms. A 7-point difference on the total score of cGVHD symptom scale was found to be clinically meaningful. Mean of duration of \>=7PtR is presented. |
| Time to Next Treatment (TTNT) | At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months | The TTNT was measured as the time from first treatment to the time of new systemic cGVHD treatment, censored by last response assessment or long term follow up assessment, whichever was the latest and available. TTNT was analyzed by the Kaplan-Meier survival method. |
| Failure-Free Survival (FFS) | At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months | FFS was defined as the absence of new cGVHD systemic therapy, non-relapse mortality and recurrent malignancy (i.e. underlying disease) and was censored by last response assessment or long term follow up assessment, whichever was the latest and available. Kaplan-Meier method was used for the analysis. |
| Overall Survival (OS) | From first dose of study drug (Day 1) to the date of death due to any cause, up to approximately 24 months | OS was defined as time from first dose of belumosudil to the date of death due to any cause. CI was calculated using Kaplan-Meier method. |
| Percentage of Participants With Complete Response (CR) and Partial Response (PR) | At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months | As per the 2014 NIH Consensus Development Project for clinical trials in cGVHD criteria: CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site. |
| Number of Participants With Best Response by Organ System | At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months | The best response (CR, PR) for individual organs (skin, eyes, mouth, esophagus, upper gastrointestinal \[GI\], lower GI, liver, lungs, joints and fascia) was summarized. As per the 2014 NIH Consensus Development Project for clinical trials in cGVHD criteria, CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site. |
| Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction | Baseline (Day 1) and Month 23 | Change in corticosteroid doses was analyzed by using prednisone dose equivalents. If participants were not using prednisone as the systemic corticosteroid, then the prednisone dose equivalent would be determined according to following conversion ratios: 1 mg prednisone is equivalent to: 4.0 mg Hydrocortisone; 0.8 mg Methylprednisolone; 0.15 mg Dexamethasone; 1.0 mg Prednisolone and 0.8 mg Triamcinolone. Baseline was defined as the valid and last non-missing value obtained within 28 days prior to participant receiving the first study drug in parent study (KD025-208 \[NCT02841995\] or KD025-213 \[NCT03640481\]). |
| Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | From Baseline (Day 1) up to 23 months | The GSR assessment was performed by asking the participants to rate their disease severity of cGVHD symptoms on a 0 to 10-point numeric rating scale, where score 0 indicated 'not at all severe cGVHD symptoms' and score 10 indicated 'most severe cGVHD symptoms possible'. The response was defined using scores from 9 organs: skin, eyes, mouth, esophagus, upper GI track, lower GI tract, liver, lungs, and joints and fascia plus GSR. Baseline was defined as the valid and last non-missing value obtained within 28 days prior to participant receiving the first study drug in parent study (KD025-208 \[NCT02841995\] or KD025-213 \[NCT03640481\]). Maximal improvement from Baseline was calculated as lowest GSR score on scheduled visits minus GSR score at Baseline with possible ranges from -10 to 10. The lower the number means the better improvement in cGVHD symptoms. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | From the first dose of study drug (Day 1) up to 28 days after the last dose of study drug, approximately 24 months | An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant associated with the use of a study drug, whether or not considered drug-related. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect or was an important medical event. The severity of each AE was graded using the Common Terminology Criteria for Adverse Events version 4.03 scale. TEAEs were defined as AEs that developed, worsened or became serious during the TE period. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 8 sites in the United States from 23-Feb-2022 to 06-Jun-2024.
Pre-assignment details
A total of 23 participants with chronic graft-versus-host-disease (cGVHD) who were previously treated with belumosudil in study KD025-208 (NCT02841995) or study KD025-213 (NCT03640481) were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Belumosudil 200 mg QD Participants received belumosudil 200 mg tablet orally QD until cGVHD progression, unacceptable toxicity or up to 2 years at the discretion of the Investigator. | 13 |
| Belumosudil 200 mg BID Participants received belumosudil 200 mg tablet orally BID until cGVHD progression, unacceptable toxicity or up to 2 years at the discretion of the Investigator. | 9 |
| Belumosudil 400 mg QD Participants received belumosudil 400 mg tablet orally QD until cGVHD progression, unacceptable toxicity or up to 2 years at the discretion of the Investigator. | 1 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Enrolled but never dosed | 3 | 2 | 1 |
| Overall Study | Investigator decision | 1 | 2 | 0 |
| Overall Study | Other | 3 | 2 | 0 |
| Overall Study | Progression of cGVHD (progression requiring addition of new systemic therapy for cGVHD) | 3 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Sponsor decision | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Belumosudil 200 mg QD | Belumosudil 200 mg BID | Belumosudil 400 mg QD | Total |
|---|---|---|---|---|
| Age, Customized 24-74 years | 13 Participants | 9 Participants | 1 Participants | 23 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 12 Participants | 9 Participants | 1 Participants | 22 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 0 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 9 | 0 / 1 |
| other Total, other adverse events | 8 / 13 | 7 / 9 | 0 / 1 |
| serious Total, serious adverse events | 4 / 13 | 2 / 9 | 0 / 1 |
Outcome results
Primary
Duration of >=7 Point Reduction as Assessed by Lee Symptom Scale
The questionnaire asked participants to indicate the degree of bother that they experienced due to symptoms in 7 domains potentially affected by cGVHD. It consisted of 30 items of 7 domains: skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each question was rated/scored as 0-not at all, 1-slightly, 2-moderately, 3-quite a bit, 4-extremely with lower values representing better outcome. A domain score was calculated for each domain by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A total score was calculated as average of all non-missing domain scores if more than 50% of them were non-missing, ranged from 0-100. A higher score indicated more bothersome symptoms. A 7-point difference on the total score of cGVHD symptom scale was found to be clinically meaningful. Mean of duration of \>=7PtR is presented.
Time frame: Baseline (Day 1) up to 23 months
Population: The full analysis set included all participants enrolled in the study. Only those participants with \>=7PtR from Baseline are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belumosudil 200 mg QD | Duration of >=7 Point Reduction as Assessed by Lee Symptom Scale | 67.2 weeks | Standard Deviation 26.8 |
| Belumosudil 200 mg BID | Duration of >=7 Point Reduction as Assessed by Lee Symptom Scale | 49.5 weeks | Standard Deviation 54.2 |
Primary
Duration of Response (DOR)
DOR is defined as time from first documentation of response to time of first documentation of deterioration from best response (e.g., complete response \[CR\] to partial response \[PR\], or PR to Lack of response \[LR\]). As per the 2014 National Institutes of Health (NIH) Consensus Development Project for clinical trials in cGVHD criteria: CR was defined as resolution of all manifestations of cGVHD in each organ or site.PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.LR included response status of mixed, unchanged, or progression.Mixed LR was defined as complete or partial response in at least 1 organ accompanied by progression in another organ. Unchanged LR was defined as outcomes that did not meet criteria for CR, PR, progression or mixed response. Progression LR was defined as progression in at least 1 organ or site without a response in any other organ or site. Confidence interval (CI) is calculated using Kaplan-Meier method.
Time frame: At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
Population: Responder population included participants in the full analysis set that achieved a partial or complete response at any post-baseline response assessment. Only those participants who achieved CR or PR are reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belumosudil 200 mg QD | Duration of Response (DOR) | NA months |
| Belumosudil 200 mg BID | Duration of Response (DOR) | NA months |
Primary
Failure-Free Survival (FFS)
FFS was defined as the absence of new cGVHD systemic therapy, non-relapse mortality and recurrent malignancy (i.e. underlying disease) and was censored by last response assessment or long term follow up assessment, whichever was the latest and available. Kaplan-Meier method was used for the analysis.
Time frame: At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
Population: The full analysis set included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belumosudil 200 mg QD | Failure-Free Survival (FFS) | NA months |
| Belumosudil 200 mg BID | Failure-Free Survival (FFS) | NA months |
| Belumosudil 400 mg QD | Failure-Free Survival (FFS) | NA months |
Primary
Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS)
The questionnaire asked participants to indicate the degree of bother that they experienced due to symptoms in 7 domains potentially affected by cGVHD. It consists of 30 items of 7 domains: skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each question was rated/scored as 0-not at all, 1-slightly, 2-moderately, 3-quite a bit, 4-extremely with lower values representing better outcome. A domain score was calculated for each domain by taking the mean of all items completed if more than 50% were answered and normalizing to a 0 to 100 scale. A total score was calculated as average of all non-missing domain scores if more than 50% of them were non-missing, ranged from 0-100. A higher score indicated more bothersome symptoms. A 7-point difference on the total score of cGVHD symptom scale was found to be clinically meaningful.
Time frame: Baseline (Day 1) up to 23 months
Population: The full analysis set included all participants enrolled in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belumosudil 200 mg QD | Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS) | >=7PtR From Baseline | 8 Participants |
| Belumosudil 200 mg QD | Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS) | >=7PtR From Baseline on 2 Consecutive Post-Baseline Assessment | 8 Participants |
| Belumosudil 200 mg BID | Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS) | >=7PtR From Baseline | 2 Participants |
| Belumosudil 200 mg BID | Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS) | >=7PtR From Baseline on 2 Consecutive Post-Baseline Assessment | 1 Participants |
| Belumosudil 400 mg QD | Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS) | >=7PtR From Baseline | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With a >=7 Point Reduction (7PtR) From Baseline and >=7 Point Reduction From Baseline on 2 Consecutive Post-Baseline Assessments as Assessed by Lee Symptom Scale (LSS) | >=7PtR From Baseline on 2 Consecutive Post-Baseline Assessment | 0 Participants |
Primary
Number of Participants With Best Response by Organ System
The best response (CR, PR) for individual organs (skin, eyes, mouth, esophagus, upper gastrointestinal \[GI\], lower GI, liver, lungs, joints and fascia) was summarized. As per the 2014 NIH Consensus Development Project for clinical trials in cGVHD criteria, CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.
Time frame: At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
Population: The full analysis set included all participants enrolled in the study. Only those participants with data collected for each specified category are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Liver | 1 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Esophagus | 1 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Eyes | 6 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Lower GI | 0 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Upper GI | 0 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Skin | 6 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Lungs | 1 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Mouth | 4 Participants |
| Belumosudil 200 mg QD | Number of Participants With Best Response by Organ System | Joints and Fascia | 5 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Lungs | 3 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Skin | 5 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Eyes | 4 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Mouth | 3 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Esophagus | 2 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Upper GI | 0 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Lower GI | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Liver | 0 Participants |
| Belumosudil 200 mg BID | Number of Participants With Best Response by Organ System | Joints and Fascia | 7 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Lower GI | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Mouth | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Joints and Fascia | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Liver | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Eyes | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Lungs | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Upper GI | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Esophagus | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Best Response by Organ System | Skin | 0 Participants |
Primary
Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment
The GSR assessment was performed by asking the participants to rate their disease severity of cGVHD symptoms on a 0 to 10-point numeric rating scale, where score 0 indicated 'not at all severe cGVHD symptoms' and score 10 indicated 'most severe cGVHD symptoms possible'. The response was defined using scores from 9 organs: skin, eyes, mouth, esophagus, upper GI track, lower GI tract, liver, lungs, and joints and fascia plus GSR. Baseline was defined as the valid and last non-missing value obtained within 28 days prior to participant receiving the first study drug in parent study (KD025-208 \[NCT02841995\] or KD025-213 \[NCT03640481\]). Maximal improvement from Baseline was calculated as lowest GSR score on scheduled visits minus GSR score at Baseline with possible ranges from -10 to 10. The lower the number means the better improvement in cGVHD symptoms.
Time frame: From Baseline (Day 1) up to 23 months
Population: The full analysis set included all participants enrolled in the study. Only those categories in which at least 1 participant had data are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -5 | 2 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | 0 | 1 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -3 | 1 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -4 | 0 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -8 | 1 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -1 | 1 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -6 | 3 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -7 | 0 Participants |
| Belumosudil 200 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -2 | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -4 | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -8 | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -7 | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -6 | 0 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -5 | 2 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -3 | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -2 | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -1 | 1 Participants |
| Belumosudil 200 mg BID | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | 0 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -6 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -8 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -2 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -7 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | 0 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -4 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -5 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -1 | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) Based on Clinician-Reported Chronic Graft-Versus-Host-Disease Assessment | -3 | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant associated with the use of a study drug, whether or not considered drug-related. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect or was an important medical event. The severity of each AE was graded using the Common Terminology Criteria for Adverse Events version 4.03 scale. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.
Time frame: From the first dose of study drug (Day 1) up to 28 days after the last dose of study drug, approximately 24 months
Population: The full analysis set included all participants enrolled in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belumosudil 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | TEAEs | 8 Participants |
| Belumosudil 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | TESAEs | 4 Participants |
| Belumosudil 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | Grade >=3 TEAEs | 3 Participants |
| Belumosudil 200 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | Deaths | 0 Participants |
| Belumosudil 200 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | Deaths | 0 Participants |
| Belumosudil 200 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | TEAEs | 7 Participants |
| Belumosudil 200 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | Grade >=3 TEAEs | 4 Participants |
| Belumosudil 200 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | TESAEs | 2 Participants |
| Belumosudil 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | Deaths | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | TESAEs | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | Grade >=3 TEAEs | 0 Participants |
| Belumosudil 400 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Grade >=3 Treatment-Emergent Adverse Events and Deaths | TEAEs | 0 Participants |
Primary
Overall Survival (OS)
OS was defined as time from first dose of belumosudil to the date of death due to any cause. CI was calculated using Kaplan-Meier method.
Time frame: From first dose of study drug (Day 1) to the date of death due to any cause, up to approximately 24 months
Population: The full analysis set included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belumosudil 200 mg QD | Overall Survival (OS) | NA months |
| Belumosudil 200 mg BID | Overall Survival (OS) | NA months |
| Belumosudil 400 mg QD | Overall Survival (OS) | NA months |
Primary
Percentage of Participants With Complete Response (CR) and Partial Response (PR)
As per the 2014 NIH Consensus Development Project for clinical trials in cGVHD criteria: CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site.
Time frame: At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
Population: The full analysis set included all participants enrolled in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Belumosudil 200 mg QD | Percentage of Participants With Complete Response (CR) and Partial Response (PR) | CR | 30.8 percentage of participants |
| Belumosudil 200 mg QD | Percentage of Participants With Complete Response (CR) and Partial Response (PR) | PR | 30.8 percentage of participants |
| Belumosudil 200 mg BID | Percentage of Participants With Complete Response (CR) and Partial Response (PR) | CR | 11.1 percentage of participants |
| Belumosudil 200 mg BID | Percentage of Participants With Complete Response (CR) and Partial Response (PR) | PR | 77.8 percentage of participants |
| Belumosudil 400 mg QD | Percentage of Participants With Complete Response (CR) and Partial Response (PR) | CR | 0 percentage of participants |
| Belumosudil 400 mg QD | Percentage of Participants With Complete Response (CR) and Partial Response (PR) | PR | 0 percentage of participants |
Primary
Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction
Change in corticosteroid doses was analyzed by using prednisone dose equivalents. If participants were not using prednisone as the systemic corticosteroid, then the prednisone dose equivalent would be determined according to following conversion ratios: 1 mg prednisone is equivalent to: 4.0 mg Hydrocortisone; 0.8 mg Methylprednisolone; 0.15 mg Dexamethasone; 1.0 mg Prednisolone and 0.8 mg Triamcinolone. Baseline was defined as the valid and last non-missing value obtained within 28 days prior to participant receiving the first study drug in parent study (KD025-208 \[NCT02841995\] or KD025-213 \[NCT03640481\]).
Time frame: Baseline (Day 1) and Month 23
Population: The full analysis set included all participants enrolled in the study. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belumosudil 200 mg QD | Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction | -50.00 percent change |
| Belumosudil 200 mg BID | Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction | 0.0 percent change |
Primary
Time to Next Treatment (TTNT)
The TTNT was measured as the time from first treatment to the time of new systemic cGVHD treatment, censored by last response assessment or long term follow up assessment, whichever was the latest and available. TTNT was analyzed by the Kaplan-Meier survival method.
Time frame: At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
Population: The full analysis set included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belumosudil 200 mg QD | Time to Next Treatment (TTNT) | NA months |
| Belumosudil 200 mg BID | Time to Next Treatment (TTNT) | NA months |
| Belumosudil 400 mg QD | Time to Next Treatment (TTNT) | NA months |