A Study to Test an Oral Medicine, Belumosudil, in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease.

Purpose

This is a parallel, Phase 3, two-arm study for the treatment of newly diagnosed moderate or severe chronic GVHD. The study duration for a participant includes up to 4 weeks for screening; a treatment period until clinically meaningful cGVHD progression (defined as progression requiring addition of new systemic treatment for cGVHD), relapse/recurrence of the underlying disease, participant starts new systemic treatment for cGVHD or experiences an unacceptable toxicity, at the request of the participants or the investigators, or until the end of study is reached, whichever comes first; at least 30 days follow-up of adverse events (AEs) after the last dose until resolution or stabilization, if applicable; and long-term follow-up until death or study close-out, whichever comes first.

Condition

  • Chronic Graft Versus Host Disease

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Patients must be at least 12 years of age inclusive, at the time of signing the informed consent - Participants who have undergone allogenic HCT with newly diagnosed moderate to severe cGVHD according to NIH consensus diagnosis and staging criteria (2014) - Participants who require systemic treatment with corticosteroids for cGVHD - Participants who have not received any prior systemic treatment for cGVHD (including ECP) - If participants are receiving other immunosuppressive agents for the prophylaxis or treatment of acute GVHD, the dose should be under the threshold pre-defined in protocol - Body weight ≥ 40kg - Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - Participants or their legally authorized representative must be capable of giving signed informed consent

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply: Medical conditions - Histological relapse of the underlying disease after most recent allogeneic HCT - Post-transplant lymphoproliferative disease within 4 weeks prior to randomization - Female participants who are pregnant or breastfeeding - Unable to tolerate a prednisone equivalent dose of corticosteroids ≥ 1 mg/kg/day Prior/concomitant therapy - Participant has had previous exposure to belumosudil. - Received any previous systemic treatment for cGVHD with the following exception: Corticosteroids for cGVHD received within 7 days prior to the planned administration of IMP only if in the interest of participant. Prior/concurrent clinical study experience - Received any investigational agents, or any investigational device or procedure, or prohibited therapy for this study within 28 days or 5 elimination half-lives prior to randomization, whichever is longer Diagnostic assessments - Karnofsky (if aged ≥16 years)/Lansky (if aged <16 years) Performance Score of < 60 - Platelets <50 x 109/L. Platelet transfusion is not allowed within 3 days before the screening hematological test - Absolute neutrophil count (ANC) <1.0 x 109/L. The use of granulocyte-colony stimulating factor (G-CSF) is not allowed to reach this level during screening - Estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73 m2 using the MDRD-4 variable formula (if aged ≥18 years) or using the Bedside Schwartz formula (if aged <18 years) - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN without liver cGVHD (or >5 × ULN if due to cGVHD with liver cGVHD) - Total bilirubin >1.5 × (ULN) (>3 × ULN if Gilbert syndrome) - Participant has forced expiratory volume in 1 second (FEV1) of predicted ≤39% or has lung score of 3 according to NIH consensus diagnostic and staging criteria (2014) - 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) - Known history of human immunodeficiency virus (HIV) - Active viral disease including hepatitis B virus (HBV) or hepatitis C virus (HCV) - Active uncontrolled cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection worsening are present according to Investigator's judgement - Diagnosed or treated for another malignancy other than the underlying disease allogeneic HCT was indicated for, within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy - Unable to swallow tablets - Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures - Any active, uncontrolled infections assessed to be clinically significant by the Investigator

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Belumosudil
Participants will receive belumosudil 200 mg tablets Per os(PO) once daily (QD) per 28-day cycles starting on Day 1 until discontinuation criteria are met or until end of study note: 200mg two times a day (BID) is used in some cases, when the subject is taking a proton pump inhibitor or a strong CYP3A4 inducer)
  • Drug: Belumosudil
    Pharmaceutical form:Tablet-Route of administration:oral
    Other names:
    • SAR445761/ KD025
    • REZUROCK
  • Drug: Prednisone
    Pharmaceutical form:Tablet-Route of administration:oral
  • Drug: Prednisolone
    Pharmaceutical form:Tablet-Route of administration:oral
Placebo Comparator
Placebo
Participants will receive matching placebo tablets PO QD per 28-day cycles starting on Day 1 until discontinuation criteria are met or until end of study
  • Drug: Placebo
    Pharmaceutical form:Table-Route of administration:oral
  • Drug: Prednisone
    Pharmaceutical form:Tablet-Route of administration:oral
  • Drug: Prednisolone
    Pharmaceutical form:Tablet-Route of administration:oral

Recruiting Locations

University of Arkansas for Medical Sciences-Site Number : 8400019
Little Rock, Arkansas 72205
Contact:
I-Shin Wen
501-686-8274
IWen@uams.edu

City of Hope Site Number : 8400001
Duarte, California 91010

Florida Hospital Site Number : 8400023
Orlando, Florida 32804

Emory University School of Medicine Site Number : 8400020
Atlanta, Georgia 30322

Robert H. Lurie Comprehensive Cancer Cancer Site Number : 8400017
Chicago, Illinois 60611

University of Kentucky Site Number : 8400024
Lexington, Kentucky 40536

Dana Farber Cancer Institute Site Number : 8400005
Boston, Massachusetts 02115
Contact:
Miguel Aguilar Soto
617-632-5626
Miguel_AguilarSoto@DFCI.Harvard.Edu

Barbara Ann Karmanos Cancer Institute-4100 John R St Site Number : 8400013
Detroit, Michigan 48201

UNC Childrens Research Institute Site Number : 8400025
Chapel Hill, North Carolina 27599

Atrium Health Wake Forest University Health Sciences Site Number : 8400007
Winston-Salem, North Carolina 27157

Oncology Hematology Care Inc Site Number : 8400030
Cincinnati, Ohio 45236

James Cancer Hospital & Wexner Medical Center at the Ohio State University Comprehensive Cancer Center Site Number : 8400026
Columbus, Ohio 43210

Oregon Health & Science University Site Number : 8400027
Portland, Oregon 97239

University of Pittsburgh Medical Center - Hillman Cancer Ctr Site Number : 8400008
Pittsburgh, Pennsylvania 15232

Sarah Cannon Research Institute Site Number : 8400003
Nashville, Tennessee 37203
Contact:
Yesenia Herazo
615-982-4331
Yesenia.RomeroHerazo@scri.com

Sarah Cannon Research Institute Site Number : 8400002
Austin, Texas 78745

Texas Oncology, PA Site Number : 8400010
Dallas, Texas 75246

University of Virginia Comprehensive Cancer Center-Site Number : 8400031
Charlottesville, Virginia 22903
Contact:
Danyelle Coley
434-982-5027
jcs6rz@UVAHealth.org

Fred Hutchinson Cancer Research Center Site Number : 8400004
Seattle, Washington 98109

University of Wisconsin Carbone Cancer Center-Site Number : 8400029
Madison, Wisconsin 53792
Contact:
Cancer Connect
800-622-8922
clinicaltrials@cancer.wisc.edu

More Details

NCT ID
NCT06143891
Status
Recruiting
Sponsor
Sanofi

Study Contact

Trial Transparency email recommended (Toll free for US & Canada)
800-633-1610
contact-us@sanofi.com

Detailed Description

Up to 5 years