Efficacy and Safety of KD025 in Subjects With cGVHD After At Least 2 Prior Lines of Systemic Therapy

NCT03640481 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: DRI17633KD025-213U1111-1279-2518
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 35

Brief Summary

This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least 2 prior lines of systemic therapy

Conditions

Chronic Graft-versus-host-disease

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The ORR was defined as the percentage of participants with a best response meeting the overall response criteria assessment of complete response (CR) or partial response (PR) at any post-baseline response assessment. CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least one organ or site without progression in any other organ or site. Responses were assessed by the 2014 National Institutes of Health (NIH) Consensus Development Project on Clinical Trials in cGVHD.

  From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)

Secondary Outcomes (15)

• Duration of Response (DOR)

  From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)

• Number of Participants With Improvement (>=7-Point Reduction [7-PtR] From Baseline) as Assessed by Lee Symptom Scale (LSS) Score

  Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms

• Number of Participants With Best Response by Organ System

  From date of randomization until disease progression or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)

• Percentage of Participants With Best Response of PR and CR

  From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)

• Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction

  Baseline (Day 1) and 40.5 months for adult arms; Baseline (Day 1) and 27.6 months for adolescent arms

Study Arms (4)

Arm A: belumosudil 200 mg, QD, adult arm

EXPERIMENTAL

Eligible subjects randomized to arm A will take belumosudil 200 mg once daily

Drug: Belumosudil (KD025)

Arm B: belumosudil 200 mg, BID, adult arm

EXPERIMENTAL

Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily

Drug: Belumosudil (KD025)

Adolescent arm A: belumosudil 200 mg QD

EXPERIMENTAL

Eligible subjects randomized to arm A will take belumosudil 200 mg once daily

Drug: Belumosudil (KD025)

Adolescent arm B: belumosudil 200 mg BID

EXPERIMENTAL

Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily

Drug: Belumosudil (KD025)

Interventions

Belumosudil (KD025) DRUG

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

Also known as: REZUROCK

Adolescent arm A: belumosudil 200 mg QD; Adolescent arm B: belumosudil 200 mg BID; Arm A: belumosudil 200 mg, QD, adult arm; Arm B: belumosudil 200 mg, BID, adult arm

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects at least 12 years of age who have had allogenic hematopoietic cell transplant (HCT).
• 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 Performance Score of ≥ 60 (if aged 16 years or older); Lansky Performance Score of ≥ 60 (if aged \< 16 years)
• Weight ≥ 40kg

You may not qualify if:

• Subjects has not been on a stable dose / regimen of systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and extracorporeal photophoresis (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. Prior treatment with ibrutinib is allowed with a washout of at least 28 days prior to randomization.

Sponsors & Collaborators

• Kadmon, a Sanofi Company: lead

Study Sites (35)

Phoenix Childrens Hospital Site Number : 154

Phoenix, Arizona, 85016, United States

Location

University of Arizona - Cancer Center Site Number : 122

Tucson, Arizona, 85724, United States

Location

City of Hope Medical Center Site Number : 050

Duarte, California, 91010, United States

Location

University of California, Los Angeles (UCLA) - Medical Center Site Number : 104

Los Angeles, California, 90059, United States

Location

University of California, San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center Site Number : 058

San Francisco, California, 94143, United States

Location

Stanford Cancer Center Site Number : 108

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute Site Number : 098

Denver, Colorado, 80218, United States

Location

University of Miami - Sylvester Cancer Center Site Number : 097

Miami, Florida, 33136, United States

Location

Moffitt Site Number : 102

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine Site Number : 100

Atlanta, Georgia, 30322, United States

Location

Augusta University Medical Center Site Number : 093

Augusta, Georgia, 30912, United States

Location

University of Illinois at Chicago Site Number : 139

Chicago, Illinois, 60612, United States

Location

University of Iowa Site Number : 126

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center Site Number : 105

Fairway, Kansas, 66205, United States

Location

Center for Cancer Research National Cancer Institute Site Number : 107

Bethesda, Maryland, 20892-1203, United States

Location

Massachusetts General Hospital Site Number : 002

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute Site Number : 004

Boston, Massachusetts, 02215, United States

Location

CS Mott Children's Hospital Site Number : 157

Ann Arbor, Michigan, 48109-5718, United States

Location

Barbara Ann Karmanos Cancer Institute-4100 John R St Site Number : 094

Detroit, Michigan, 48201, United States

Location

University of Minnesota Site Number : 051

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine Site Number : 125

St Louis, Missouri, 63110, United States

Location

University of Rochester Site Number : 106

Rochester, New York, 14642, United States

Location

Wake Forest Site Number : 123

Winston-Salem, North Carolina, 27157, United States

Location

The Cleveland Clinic Foundation Site Number : 041

Cleveland, Ohio, 44195, United States

Location

James Cancer Hospital & Wexner Medical Center at the Ohio State University Comprehensive Cancer Center Site Number : 103

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University (OHSU) Site Number : 095

Portland, Oregon, 97239-3098, United States

Location

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

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon and HCA Research Institute Site Number : 007

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center Site Number : 063

Nashville, Tennessee, 37232-6868, 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

University of Wisconsin - Carbone Cancer Center Site Number : 135

Madison, Wisconsin, 53792, United States

Location

Froedtert Hospital and the Medical College of Wisconsin Site Number : 101

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (4)

• Przepiorka D, Le RQ, Ionan A, Li RJ, Wang YH, Gudi R, Mitra S, Vallejo J, Okusanya OO, Ma L, Yang Y, Patel P, Mezaache D, Shah R, Banerjee A, McLamore S, Maung AN, Goldberg KB, Pazdur R, Theoret MR, De Claro RA. FDA Approval Summary: Belumosudil for Adult and Pediatric Patients 12 Years and Older with Chronic GvHD after Two or More Prior Lines of Systemic Therapy. Clin Cancer Res. 2022 Jun 13;28(12):2488-2492. doi: 10.1158/1078-0432.CCR-21-4176.

  PMID: 35135839 BACKGROUND

• Sharma R, Holtzman NG, Pusic I, Cutler C, Treister N, Mehta RS, Alousi AS, Vigneswaran N, Javaid A, Boksa F, Mody DP, Costa-da-Silva AC, Schueller O, Mace S, Yao Y, Ji R, Hu B, Marshall K, Blazar BR, Lee SJ, Pavletic SZ, Mays JW. Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study. Blood Adv. 2025 Jul 22;9(14):3479-3494. doi: 10.1182/bloodadvances.2025016170.

  PMID: 40311075 DERIVED

• Lee SJ, Cutler C, Blazar BR, Tu A, Yang Z, Pavletic SZ. Correlation of Patient-Reported Outcomes with Clinical Organ Responses: Data from the Belumosudil Chronic Graft-versus-Host Disease Studies. Transplant Cell Ther. 2022 Oct;28(10):700.e1-700.e6. doi: 10.1016/j.jtct.2022.06.020. Epub 2022 Jul 1.

  PMID: 35781099 DERIVED

• Cutler C, Lee SJ, Arai S, Rotta M, Zoghi B, Lazaryan A, Ramakrishnan A, DeFilipp Z, Salhotra A, Chai-Ho W, Mehta R, Wang T, Arora M, Pusic I, Saad A, Shah NN, Abhyankar S, Bachier C, Galvin J, Im A, Langston A, Liesveld J, Juckett M, Logan A, Schachter L, Alavi A, Howard D, Waksal HW, Ryan J, Eiznhamer D, Aggarwal SK, Ieyoub J, Schueller O, Green L, Yang Z, Krenz H, Jagasia M, Blazar BR, Pavletic S. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood. 2021 Dec 2;138(22):2278-2289. doi: 10.1182/blood.2021012021. Erratum In: Blood. 2022 Mar 17;139(11):1772. doi: 10.1182/blood.2022015598.

  PMID: 34265047 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

belumosudil; KD025

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

Limitations and Caveats

The sponsor decided to prematurely terminate the study due to the challenges encountered in recruiting adolescent participants. This decision was made without any safety concerns.

Results Point of Contact

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

Contact-US@sanofi.com

800-633-1610 ext 6#

Publication Agreements

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

Study Design

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

Model Details: Phase 2, open label, randomized, multicenter study in subjects with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 21, 2018
• Study Start: October 11, 2018
• Primary Completion: December 11, 2023
• Study Completion: December 11, 2023
• Last Updated: December 12, 2024
• Results First Posted: December 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

US (35)