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

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

Detailed Description
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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.

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

Conditions
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Chronic Graft-versus-host-disease

Intervention / Treatment
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* Drug: Belumosudil 200 mg QD
* Drug: Belumosudil 200 mg BID
* Drug: Belumosudil 400 mg QD


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Evaluating safety longitudinally | 3 years | 
| Duration of Response | The time from initial response of PR or CR until documents progression of cGVHD; evaluating efficacy longitudinally. | 3 years | 
| Failure Free Survival | FFS is defined as the absence of cGVHD treatment change, non-relapse mortality and recurrent malignancy; evaluating efficacy longitudinally. | 3 years | 

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 |