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

NCT05305989 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: LTS17660KD025-217U1111-1279-2612
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

Chronic Graft-versus-host-disease

Outcome Measures

Primary Outcomes (11)

• 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

Study Arms (3)

Arm A: belumosudil 200 mg QD

EXPERIMENTAL

The assigned arm is per the previous study KD025-213 or study KD025-208

Drug: Belumosudil 200 mg QD

Arm B: belumosudil 200 mg BID

EXPERIMENTAL

The assigned arm is per the previous study KD025-213 or study KD025-208

Drug: Belumosudil 200 mg BID

Arm C: belumosudil 400 mg QD

EXPERIMENTAL

The assigned arm is per the previous study KD025-213 or study KD025-208

Drug: Belumosudil 400 mg QD

Interventions

Belumosudil 200 mg QD DRUG

Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.

Also known as: REZUROCK

Arm A: belumosudil 200 mg QD

Belumosudil 200 mg BID DRUG

Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.

Also known as: REZUROCK

Arm B: belumosudil 200 mg BID

Belumosudil 400 mg QD DRUG

Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.

Also known as: REZUROCK

Arm C: belumosudil 400 mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Female subject who is pregnant or breastfeeding
• Subject considered unlikely to adhere to treatment and/or follow protocol in the opinion of the Investigator

Sponsors & Collaborators

• Kadmon, a Sanofi Company: lead

Study Sites (8)

City of Hope Site Number : 050

Duarte, California, 91010, United States

Location

Stanford Cancer Center Site Number : 108

Stanford, California, 94305, United States

Location

Washington University School of Medicine Site Number : 125

St Louis, Missouri, 63110, United States

Location

University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center Site Number : 132

Pittsburgh, Pennsylvania, 15232, United States

Location

South Austin Medical Center Site Number : 091

Austin, Texas, 78704, United States

Location

MD Anderson Cancer Center Site Number : 057

Houston, Texas, 77030-4009, United States

Location

Texas Transplant Institute Site Number : 079

San Antonio, Texas, 78229, United States

Location

Fred Hutchinson Cancer Research Center Site Number : 052

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

belumosudil; BID protein, human

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: March 31, 2022
• Study Start: February 23, 2022
• Primary Completion: June 6, 2024
• Study Completion: June 6, 2024
• Last Updated: May 2, 2025
• Results First Posted: May 2, 2025

Record last verified: 2025-04

Locations

US (8)