Extended Treatment and Follow-up of Subjects Treated With Belumosudil in Study KD025-208 or Study KD025-213

Extended Treatment and Follow-up of Subjects Treated with Belumosudil in Study KD025-208 or Study KD025-213

Study Overview

• Status: Completed
• Conditions: Chronic Graft-versus-host-disease
• Intervention / Treatment: Drug: Belumosudil 200 mg QD; Drug: Belumosudil 200 mg BID; Drug: Belumosudil 400 mg QD

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Site Number : 050
    • Stanford, California, United States, 94305
      • Stanford Cancer Center Site Number : 108
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Site Number : 125
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center Site Number : 132
  • Texas
    • Austin, Texas, United States, 78704
      • South Austin Medical Center Site Number : 091
    • Houston, Texas, United States, 77030-4009
      • MD Anderson Cancer Center Site Number : 057
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute Site Number : 079
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center Site Number : 052

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: belumosudil 200 mg QD; The assigned arm is per the previous study KD025-213 or study KD025-208	Drug: Belumosudil 200 mg QD; Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.; Other Names: REZUROCK
Experimental: Arm B: belumosudil 200 mg BID; The assigned arm is per the previous study KD025-213 or study KD025-208	Drug: Belumosudil 200 mg BID; Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.; Other Names: REZUROCK
Experimental: Arm C: belumosudil 400 mg QD; The assigned arm is per the previous study KD025-213 or study KD025-208	Drug: Belumosudil 400 mg QD; Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.; Other Names: REZUROCK

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
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.	Baseline (Day 1) up to 23 months
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.	Baseline (Day 1) up to 23 months
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.	At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
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.	At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
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.	From first dose of study drug (Day 1) to the date of death due to any cause, up to approximately 24 months
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.	At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
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.	At Baseline (Day 1), Month 3 and every 3 months thereafter (+/-14 days), up to 23 months
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]).	Baseline (Day 1) and Month 23
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.	From Baseline (Day 1) up to 23 months
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.	From the first dose of study drug (Day 1) up to 28 days after the last dose of study drug, approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade ≥ 3 Adverse Events		3 years
Serious Adverse Events		3 years
Deaths		3 years
Change in Lee Symptom Scale Score: Number of subjects with a ≥7 point reduction/≥7 point reduction on 2 consecutive assessments	Symptom burden will be assessed on Day 1 of each cycle starting on Cycle 1 Day 1, as well as at the EOT visit. The questionnaire asks subjects to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by chronic GVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician assessment specifically for each of affected organ as a Complete Response, Partial Response or Progression	3 years
Change in Lee Symptom Scale Score: Duration of a ≥7 point reduction	Symptom burden will be assessed on Day 1 of each cycle starting on Cycle 1 Day 1, as well as at the EOT visit. The questionnaire asks subjects to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by chronic GVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician assessment specifically for each of affected organ as a Complete Response, Partial Response or Progression	3 years
Overall Survival	Time from first dose of belumosudil to the date of death due to any cause.	3 years
Percentage of subjects who have a best response of PR or CR		3 years
Response by individual organ based on the Clinician-reported Global cGVHD Activity Assessment	The response assessment for the nine individual organs (Skin, Eyes, Mouth, Esophagus, Upper GI, Lower GI, Liver, Lungs, and Joints and fascia).	3 years
Change in corticosteroid dose		3 years
Change in cGVHD Global Severity Rating using the Clinician-reported Global cGVHD Activity Assessment (Appendix B: Clinician-reported Global cGVHD Activity Assessment)	Physician-reported outcome. The global severity rating has a scale of 0-10, 0 being cGVHD symptoms not at all severe, 10 being most severe cGVHD symptoms possible.	3 years

Collaborators and Investigators

• Sponsor: Kadmon, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2022
• Primary Completion (Actual): June 6, 2024
• Study Completion (Actual): June 6, 2024

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Belumosudil
• Other Study ID Numbers: LTS17660; KD025-217 (Other Identifier: Sanofi Identifier); U1111-1279-2612 (Registry Identifier: ICTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No