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: Active, not recruiting
• 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 National Medical Center_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 Hillman Cancer Center_Site number 132
  • Texas
    • Austin, Texas, United States, 78704
      • St. David's South Austin Medical Center_Site number 091
    • Houston, Texas, United States, 77030
      • 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
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

Collaborators and Investigators

• Sponsor: Kadmon, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2022
• Primary Completion (Estimated): July 10, 2024
• Study Completion (Estimated): July 10, 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): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

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

Drug and device information, study documents

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