KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis

NCT03919799 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: EFC17665KD025-209
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 26

Brief Summary

This randomized, placebo-controlled phase 2 study was seeking to evaluate the efficacy and safety of belumosudil (KD025) for the treatment of diffuse cutaneous systematic sclerosis. Enrolment was terminated earlier than planned for business reasons unrelated to safety. A total of 36 participants were enrolled and randomized into 3 groups to either receive orally administered belumosudil (200 milligrams \[mg\] once daily \[QD\] and 200 mg twice daily \[BID\]) or matched placebo in 1:1:1 ratio in the double-blind (DB) period of this study. Study drug dosing was for 52 weeks: double-blinded for the first 28 weeks followed by an open-label extension of 24 weeks. After unblinding, the participants on belumosudil continued on the same belumosudil dose whereas the participants in the placebo group were re-randomized to one of the belumosudil doses in a 1:1 ratio.

Conditions

System; Sclerosis; Diffuse Cutaneous Systemic Sclerosis

Outcome Measures

Primary Outcomes (1)

• DB Period: Number of Participants With Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score Greater Than or Equal to (>=) 60 Percent (%) at Week 24

  CRISS components included the following domains: mRSS, FVC percent predicted, physician global assessment, patient global assessment, and SHAQ-DI. An algorithm determines the predicted probability of improvement from Baseline by incorporating change from baseline in the mRSS, FVC percent predicted, physician and patient global assessments, and SHAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 to 100%). Higher score indicated greater probability of improvement. CRISS score \>= 60% was considered the minimally important difference. Participants were not considered improved and assigned a probability of improving equal to 0.0 if they developed new onset of renal crisis, new onset or worsening of lung fibrosis, new onset of pulmonary arterial hypertension, or new onset of left ventricular failure during the trial. Last observation carried forward (LOCF) method was used to handle missing data.

  Week 24

Secondary Outcomes (70)

• DB Period: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis Score at Week 24

  Week 24

• OLE Period: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis Score at Week 52

  Week 52

• DB Period: Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24

  Baseline, Week 24

• DB Period: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 24

  Baseline, Week 24

• DB Period: Change From Baseline in Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale Score at Week 24

  Baseline, Week 24

Study Arms (5)

Belumosudil QD/Belumosudil QD

EXPERIMENTAL

Participants received belumosudil 200 mg tablet, QD orally for 28 weeks during the DB period. After completion of DB period, participants entered open-label extension (OLE) period and continued to receive belumosudil 200 mg tablet QD orally for 24 weeks in OLE period (i.e., up to Week 52).

Drug: Belumosudil (KD025)

Belumosudil BID/Belumosudil BID

EXPERIMENTAL

Participants received belumosudil 200 mg tablet BID orally, for 28 weeks during the DB period. After completion of DB period, participants entered OLE period and continued to receive belumosudil 200 mg tablet BID orally for 24 weeks in OLE period (i.e., up to Week 52).

Drug: Belumosudil (KD025)

DB Period: Placebo

PLACEBO COMPARATOR

Participants received placebo (matched to belumosudil) tablet, orally for 28 weeks during the DB period.

Drug: Placebo

OLE Period: Placebo/Belumosudil QD

EXPERIMENTAL

Participants who had received placebo in the DB period were entered and re-randomized into OLE period and received belumosudil 200 mg tablet QD orally for 24 weeks (i.e., up to Week 52) in the OLE period.

Drug: Belumosudil (KD025)

OLE Period: Placebo/Belumosudil BID

EXPERIMENTAL

Participants who had received placebo in the DB period were entered and re-randomized into OLE period and received belumosudil 200 mg tablet BID orally for 24 weeks (i.e., up to Week 52) in the OLE period.

Drug: Belumosudil (KD025)

Interventions

Belumosudil (KD025) DRUG

ROCK-2 Inhibitor

Belumosudil BID/Belumosudil BID; Belumosudil QD/Belumosudil QD; OLE Period: Placebo/Belumosudil BID; OLE Period: Placebo/Belumosudil QD

Placebo DRUG

Inactive substance

DB Period: Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants greater than or equal to (\>=) 18 years old with the diagnosis of dcSSc according to the 2013 American College of Rheumatology and European League Against Rheumatism criteria.
• Had disease duration (defined as interval from first non-Raynaud disease manifestation) of less than or equal to (\<=) 5 years.
• Had mRSS of \>= 15 but \<= 35.
• Active disease defined as any of the following within the 6 months prior to screening:
• Increase in mRSS by \>= 3 units.
• Increase in mRSS by \>= 2 units with involvement of 1 new body area.
• Involvement of 2 new body areas.
• Symptoms indicative of skin activity such as severe cutaneous itching or burning.
• Participants who had received concomitant immunosuppression must be on a stable dose for at least 3 months prior to screening.
• Adequate organ and bone marrow functions evaluated during the 28 days prior to enrollment as follows:
• Absolute neutrophil count \>= 1.5\*10\^9/L.
• Platelet count \>=100\*10\^9/L.
• Total bilirubin \<= 1.0\*upper limit of normal (ULN).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine \<= 1.5\*ULN.
• Female participants of childbearing potential had a negative pregnancy test at screening. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who have 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.

You may not qualify if:

• Participant had corrected QT interval QTcF greater than (\>) 450 milliseconds.
• Ongoing use or current use of concomitant medication known to have the potential for QTc prolongation.
• Female participant who was pregnant or breastfeeding.
• Participated in another study with an investigational drug within 28 days of study entry (for studies involving biologics within 3 half-lives of the biologic).
• 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.
• Chronic heart failure with New York Heart Association Class II, III, or IV.
• Acute or chronic liver disease (e.g., cirrhosis).
• Positive human immunodeficiency virus (HIV) test.
• Active hepatitis C virus (HCV), hepatitis B virus (HBV), or positive whole blood tuberculin test.
• Diagnosed with any malignancy within 3 years of enrollment, with the exception of basal cell or completely resected 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.
• Has had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or any other ROCK2 inhibitor.
• Scleroderma renal crisis within 4 months prior to enrollment.
• FVC \<= 50% Predicted.

Sponsors & Collaborators

• Kadmon, a Sanofi Company: lead

Study Sites (26)

Viable Research Management_Site number 131

Phoenix, Arizona, 85004, United States

Location

Mayo Clinic - Scottsdale_Site number 150

Scottsdale, Arizona, 85259, United States

Location

University of California, SD_Site number 008

La Jolla, California, 92037, United States

Location

Pacific Arthrirtis Care Center_Site number 136

Los Angeles, California, 90045, United States

Location

University of California - Los Angeles_Site number 104

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center_Site number 143

Palo Alto, California, 94304, United States

Location

University of Connecticut_Site number 147

Farmington, Connecticut, 06030, United States

Location

Yale University School of Medicine_Site number 140

New Haven, Connecticut, 06520, United States

Location

Georgetown University_Site number 035

Washington D.C., District of Columbia, 20007, United States

Location

St. Francis Medical_Site number 085

Clearwater, Florida, 33765, United States

Location

Omega Research Consultants_Site number 133

DeBary, Florida, 32713, United States

Location

Northwestern Medicine_Site number 124

Chicago, Illinois, 60611, United States

Location

DelRicht Research_Site number 159

New Orleans, Louisiana, 70115, United States

Location

Johns Hopkins University School of Medicine_Site number 134

Baltimore, Maryland, 21224, United States

Location

Massachusetts General Hospital_Site number 002

Boston, Massachusetts, 02114, United States

Location

Boston University_Site number 137

Boston, Massachusetts, 02118, United States

Location

University of Minnesota_Site number 051

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic_Site number 146

Rochester, Minnesota, 55905, United States

Location

Hospital For Special Surgery_Site number 138

New York, New York, 10021, United States

Location

Columbia University Medical Center_Site number 086

New York, New York, 10032, United States

Location

Thomas Jefferson University Hospital_Site number 096

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center_Site number 149

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina_Site number 054

Charleston, South Carolina, 29425, United States

Location

Virginia Mason Medical Center_Site number 145

Seattle, Washington, 98101, United States

Location

Premier Clinical Research_Site number 130

Spokane, Washington, 99202, United States

Location

Froedtert Hospital and the Medical College of Wisconsin_Site number 012

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Chung L, Silver RM, Steen V, Furst DE, Castelino FV, Trojanowski M, Spiera R, Domsic R, Rodriguez-Pla A, Katsumoto TR, Goulaouic H, Wang H, Espinasse M, El-Chemaly S, Wang R. Belumosudil in diffuse cutaneous systemic sclerosis: a randomized, double-blind, open-label extension, placebo-controlled, phase 2 study. Rheumatology (Oxford). 2025 Jul 1;64(7):4299-4308. doi: 10.1093/rheumatology/keaf062.

  PMID: 40088930 DERIVED

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

belumosudil; KD025

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Limitations and Caveats

The study was terminated early by the Sponsor due to slow enrollment and strategic consideration and was not driven due to any safety concerns.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: 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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded for the first 28 Weeks
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Three groups (1:1:1) to receive orally administered belumosudil 200 mg QD, belumosudil 200 mg BID, or matched placebo for 28 weeks. The study was double-blinded for the first 28 weeks followed by an open-label extension of 24 weeks. After unblinding, the participants in the belumosudil groups continued on the same belumosudil dose whereas the participants in the placebo group were re-randomized to one of the belumosudil doses (200 mg QD or 200 BID) in 1:1 fashion.

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: April 18, 2019
• Study Start: June 26, 2019
• Primary Completion: August 9, 2022
• Study Completion: February 17, 2023
• Last Updated: August 30, 2023
• Results First Posted: August 30, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

US (26)