Safety and Efficacy of Oral Belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander Male and Female Participants Aged 12 Years and Above With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy

A Phase 2, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander Participants With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy

The purpose of this study is to measure safety and efficacy of oral belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander male and female participants with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy aged 12 years and above.

The duration of participants participation will be up to 4 weeks for screening, treatment until clinically significant progression of disease, and 4 weeks of safety follow-up, and then long-term follow-up every 12 weeks.1 Cycle = 28 days.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Graft Versus Host Disease
• Intervention / Treatment: Drug: Belumosudil

Detailed Description

Up to 4 weeks for screening, treatment until clinically significant progression of disease, 4 weeks of safety follow-up and then long-term follow-up every 12 weeks.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33155
      • Recruiting
      • Nicklaus Children's Hospital - Miami - Southwest 62nd Avenue- Site Number : 129
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland School of Medicine - Baltimore- Site Number : 128
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • Westchester Medical Center- Site Number : 130

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants are included in the study if any of the following criteria apply:
• Participant is Black or African American, or American Indian or Alaska Native, or Native Hawaiian or Other Pacific Islander by self-identification.
• Previously received at least 2 and not more than 5 lines of systemic therapy for cGVHD.
• Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening.
• Have persistent cGVHD manifestations and systemic therapy is indicated.
• Karnofsky (if aged ≥ 16 years) / Lansky (if aged < 16 years) Performance Score of ≥ 60.
• At least 12 years of age; weight ≥ 40 kilograms (kg).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 x ULN.
• Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants
• Capable of giving signed informed consent.

Exclusion Criteria:

• Participants are excluded from the study if any of the following criteria apply:
• Participant has not been on a stable dose/regimen of systemic cGVHD treatment(s) for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and ECP are acceptable. Systemic investigational GVHD treatments are not permitted).
• Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
• Current treatment with ibrutinib or ruxolitinib. Prior treatment with ibrutinib or ruxolitinib is allowed with a washout of at least 28 days prior to enrollment.
• History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study (such as malabsorption syndromes, poorly controlled psychiatric disease, or coronary artery disease).
• Corrected QT interval using Fridericia's formula (QTc[F]) > 480 ms.
• Forced expiratory volume (in the first second; FEV1) ≤ 39% The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belumosudil; Participants will receive belumosudil orally, once daily (QD) or twice daily (BID) if they are taking strong CYP3A4 inducers or proton pump inhibitors.	Drug: Belumosudil; Pharmaceutical form: Tablet; Route of administration: Oral; Other Names: KD025; SAR445761; Rezurock

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with clinically significant laboratory abnormalities		Up to approximately 12 months
Change from baseline in systolic and diastolic blood pressure		Baseline; up to approximately 12 months
Change from baseline in heart rate		Baseline; up to approximately 12 months
Change from baseline in corrected QT interval using Fridericia's formula (QTc[F])		Baseline; up to approximately 12 months
Overall Response Rate (ORR)	The ORR is defined as the proportion of participants meeting the overall response criteria assessment of Complete Response (CR) or Partial Response (PR) as defined by the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD at any post-baseline response assessment.	Up to approximately 12 months
Number of participants with treatment emergent adverse events and serious adverse events	Safety will be assessed by monitoring adverse events, physical Examinations, clinical laboratory evaluations, vital sign measurements, and ECG parameters.	Up to approximately 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	Assessments of DOR includes; The time from first response to progression, death, or new systemic therapy for cGVHD; Time from initial response to start of additional systemic cGVHD therapy or death	Up to approximately 12 months
Response rate by organ system	The response rate for the nine individual organs (skin, eyes, mouth, esophagus, upper GI, lower GI, liver, lungs, and joints and fascia) will be assessed by the clinician.	Up to approximately 12 months
Time to Response (TTR)	TTR defined as the time from the first dose of belumosudil to the first documented cGVHD response.	Up to approximately 12 months
Time to Next Treatment (TTNT)	TTNT defined as the time from the first dose of belumosudil to the start of additional systemic cGVHD therapy.	Up to approximately 12 months
Number of participants who have a best response of PR and CR	CR is defined as resolution of all manifestations of cGVHD in each organ or site. PR is defined as Improvement in at least 1 organ or site without progression in any other organ or site.	Up to approximately 12 months
Change from baseline in corticosteroid dose	The prednisone equivalent dose of corticosteroids (mg/kg/day) during the study will be analyzed. The change in systemic corticosteroid dose over time will be determined.	Baseline; up to approximately 12 months
Change from baseline in calcineurin inhibitor dose	The change in calcineurin inhibitor dose over time will be determined.	Baseline; up to approximately 12 months
Failure-free survival (FFS)	FFS defined as the absence of new cGVHD systemic therapy, non-relapse mortality and recurrent malignancy. Median FFS (from first dose of belumosudil) will be analyzed.	Up to approximately 12 months
Overall survival (OS)	OS defined as time from first dose of belumosudil to the date of death due to any cause.	Up to approximately 12 months
Change from baseline in cGVHD global severity rating using the Clinician-Reported Global cGVHD Activity Assessment	Patient-reported outcome	Baseline; up to approximately 12 months
Change from baseline in symptom activity as based on cGVHD Activity Assessment Patient Self-Report	Patient-reported outcome	Baseline; up to approximately 12 months
Plasma belumosudil concentrations		Day 1 of Cycles 2, 3, 5, and 7 (1 Cycle = 28 days)
Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction	Changes in symptom burden/bother will be assessed using the Lee Symptom Scale, a symptom scale designed for individuals with chronic Graft Versus Host Disease (cGVHD). The questionnaire asks participants to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by cGVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician's assessment.	Baseline; up to approximately 12 months
Change from baseline in the Lee Symptom Scale Score: Number of participants with a ≥ 7-point reduction on 2 consecutive assessments	Changes in symptom burden/bother will be assessed using the Lee Symptom Scale, a symptom scale designed for individuals with chronic Graft Versus Host Disease (cGVHD). The questionnaire asks participants to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by cGVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician's assessment.	Baseline; up to approximately 12 months
Change from baseline in the Lee Symptom Scale Score: Duration of a ≥ 7 point reduction	Changes in symptom burden/bother will be assessed using the Lee Symptom Scale, a symptom scale designed for individuals with chronic Graft Versus Host Disease (cGVHD). The questionnaire asks participants to indicate the degree of bother that they experienced due to symptoms in seven domains potentially affected by cGVHD (skin, eyes, mouth, breathing, eating and digestion, energy, and emotional distress). The response will be determined based on clinician's assessment.	Baseline; up to approximately 12 months

Collaborators and Investigators

• Sponsor: Kadmon, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Estimated): June 16, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

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; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; belumosudil; KD025
• Other Study ID Numbers: SFY17661; U1111-1277-6715 (Registry Identifier: ICTRP); KD025-218 (Other Identifier: Sanofi Identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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