A Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Chronic Graft Versus Host Disease

NCT02841995 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ACT17631KD025-208
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 7

Brief Summary

This study was been conducted to evaluate the safety, tolerability, and activity of belumosudil (formerly known as KD025) in adult participants with chronic graft versus host disease (cGVHD).

Conditions

Graft vs Host Disease

Keywords

cGVHD; Allogeneic hematopoietic stem cell transplantation; Immune System Diseases; Steroid refractory chronic graft vs host disease (cGVHD); Bone Marrow Transplantation; Anti-Inflammatory Agents; Glucocorticoids; Corticosteroids

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Overall Response (OR)

  OR was defined as the percentage of participants with complete response (CR) or partial response (PR). The OR determination of chronic graft versus host disease (cGVHD) was based on cGVHD response assessment performed by clinicians as per the 2014 National Institutes of Health (NIH) Consensus Development Project for Clinical Trials in cGVHD criteria. CR was defined as the resolution of all manifestations 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; and cGVHD progression was defined as the clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.

  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 64.2 months)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs), and Treatment-emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) 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 disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study drug up to 28 days after the last dose of study drug). TEAEs included both SAEs and non-SAEs.

  From first dose of study drug up to 28 days after the last dose of study drug (maximum duration: up to 64.2 months)

Secondary Outcomes (20)

• Number of Participants With Best Overall Response (BOR)

  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 64.2 months)

• Number of Participants With Maximal Improvement From Baseline in Global Severity Rating (GSR) by Clinician-reported cGVHD Assessment

  From Baseline up to end of treatment (i.e., up to 64.2 months)

• Number of Participants With Maximal Improvement From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report

  From Baseline up to end of treatment (i.e., up to 64.2 months)

• Failure-free Survival (FFS)

  From first dose of study drug to either start of another new systemic treatment for cGVHD, relapse of the underlying disease or death or data cut-off, whichever occurred first (maximum duration: up to 64.2 months)

• Change From Baseline in Corticosteroids Dose

  Baseline up to end of treatment (i.e., anytime up to 64.2 months)

Study Arms (3)

Cohort 1: Belumosudil 200 mg QD

EXPERIMENTAL

Participants received belumosudil 200 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 64.2 months).

Drug: Belumosudil (KD025)

Cohort 2: Belumosudil 200 mg BID

EXPERIMENTAL

Participants received belumosudil 200 mg orally BID in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 45.9 months).

Drug: Belumosudil (KD025)

Cohort 3: Belumosudil 400 mg QD

EXPERIMENTAL

Participants received belumosudil 400 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity, or death whichever occurred first (maximum duration: 49.2 months).

Drug: Belumosudil (KD025)

Interventions

Belumosudil (KD025) DRUG

Pharmaceutical form: Capsules or Tablets Route of administration: Oral

Also known as: SLx-2119, REZUROCK

Cohort 1: Belumosudil 200 mg QD; Cohort 2: Belumosudil 200 mg BID; Cohort 3: 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:

• Adult male and female participants at least 18 years of age who had allogenic bone marrow transplant (BMT) or hematopoietic stem cell transplantation (HSCT).
• Received glucocorticoid therapy and calcineurin therapy or glucocorticoid therapy alone for cGVHD at study entry. Participants on calcineurin therapy only, without glucocorticoid therapy, were not eligible. Participants also received other therapies thought not to be immunosuppressive (such as extracorporeal photopheresis; ECP), were considered for enrollment in this study on a case-by-case basis.
• Had persistent active cGVHD manifestations, as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD, after at least 2 months of steroid therapy.
• No more than 3 prior lines of treatment for cGVHD.
• Karnofsky Performance Scale of greater than (\>) 40.
• Adequate organ and bone marrow functions evaluated during the 14 days prior to enrollment as follows:
• Absolute neutrophil count greater than or equal to (\>=) 1.5\*10\^9/L (without myeloid growth factors within 1 week of study entry)
• Platelet count \>=50\*10\^9/L (without transfusion or thrombopoietin or thrombopoietin analogues within 2 weeks of study entry)
• Adequate safety laboratory values:
• Total bilirubin less than or equal to (\<=) 1.5\*upper limit of normal (ULN)
• Alanine aminotransferase and aspartate aminotransferase \<=3\*ULN
• Glomerular filtration rate (GFR) \>= 30 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) using the 4-Variable Modification of Diet in Renal Disease variable formula
• Female participants of childbearing potential have a negative pregnancy test at screening. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had any evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, anti estrogens, or ovarian suppression.
• Women of childbearing potential (i.e., menstruating women) must had a negative urine pregnancy test (positive urine tests were to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug.
• Sexually active women of childbearing potential enrolled in the study must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes:

You may not qualify if:

• Female participant who was pregnant or breastfeeding.
• Received an investigational GVHD treatment within 28 days of study entry.
• Had acute GVHD.
• Taken any medication known to be a moderate or strong inhibitor of the cytochrome (CY) CYP3A4 isozyme or any drugs that are moderate or strong CYP3A4 inducers.
• 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 poorly controlled psychiatric disease or coronary artery disease).
• Regular and excessive use of alcohol within the 6 months prior to study entry defined as alcohol intake \>14 drinks per week in a man or \>7 drinks per week in a woman. Approximately 10 grams of alcohol equals one "drink" unit. One unit equals 1 ounce of distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine.
• Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of enrollment, with the exception of completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection.
• Relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
• Had previous exposure to belumosudil or known allergy/sensitivity to belumosudil or any other Rho-associated protein kinase-2 inhibitor.
• Taken other immunosuppressant drugs for GVHD, including mammalian target of rapamycin inhibitors (Note: Only steroids, calcineurin inhibitors, and ECP are acceptable).
• Corrected QT interval using Fridericia's formula \>450 milliseconds.
• Female participant who was pregnant or breastfeeding.

Sponsors & Collaborators

• Kadmon, a Sanofi Company: lead

Study Sites (7)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• 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

• Jagasia M, Lazaryan A, Bachier CR, Salhotra A, Weisdorf DJ, Zoghi B, Essell J, Green L, Schueller O, Patel J, Zanin-Zhorov A, Weiss JM, Yang Z, Eiznhamer D, Aggarwal SK, Blazar BR, Lee SJ. ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease. J Clin Oncol. 2021 Jun 10;39(17):1888-1898. doi: 10.1200/JCO.20.02754. Epub 2021 Apr 20.

  PMID: 33877856 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Immune System Diseases

Interventions

belumosudil; KD025

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi ( Kadmon, a Sanofi Company )

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: July 20, 2016
• First Posted: July 22, 2016
• Study Start: September 15, 2016
• Primary Completion: May 12, 2022
• Study Completion: May 12, 2022
• Last Updated: June 28, 2023
• Results First Posted: June 28, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)