Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis

NCT04680975 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ACT17634KD025-215
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 6

Brief Summary

This was a phase 2, open-label, single-cohort, multicenter trial of belumosudil in participants with Diffuse Cutaneous Systemic Sclerosis (dcSSc). An estimated total of 12 to 15 participants would receive belumosudil 200 milligrams (mg) administered orally (PO) twice daily (BID) for 52 weeks. The primary analysis was at 24 weeks.

Conditions

Diffuse Cutaneous Systemic Sclerosis

Keywords

skin diseases; systemic sclerosis; phase 2; Scleroderma Health Assessment Questionnaire Disability Index; Modified Rodnan Skin Score; Combined Response Index in dcSSc (CRISS); diffuse cutaneous systemic sclerosis

Outcome Measures

Primary Outcomes (1)

• Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Week 24

  CRISS components included the following domains: modified Rodnan skin score (mRSS), forced vital capacity (FVC) percent predicted, physician global assessment, patient global assessment, and scleroderma health assessment questionnaire disability-index (SHAQ-DI). An algorithm determines the predicted probability of improvement from Baseline by incorporating change 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%). A higher score indicated greater probability of improvement. Participants are not considered improved if they develop new onset of renal crisis, new onset or worsening of lung fibrosis, new onset of pulmonary arterial hypertension, new onset of left ventricular failure during the trial. CRISS score greater than 60% is considered the minimally important difference.

  Week 24

Secondary Outcomes (12)

• Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52

  Week 8, 16, 36 and 52

• Modified Rodnan Skin Score (mRSS) at Week 24

  Week 24

• Forced Vital Capacity (FVC) Level at Week 24

  Week 24

• Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24

  Week 24

• Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24

  Week 24

Study Arms (1)

Belumosudil

EXPERIMENTAL

Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.

Drug: Belumosudil

Interventions

Belumosudil DRUG

10 participants with dcSSc received belumosudil 200 mg PO BID for 52 weeks

Also known as: KD025

Belumosudil

Eligibility Criteria

• Age: 18 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.
• Had disease duration (defined as interval from first non Raynaud disease manifestation) of less than or equal to (\<=) 6 years.
• Had mRSS of \>=15 but \<=40.
• Had active disease as determined by the Principal Investigator within the 6 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) and 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 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 agreed 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 (i) intrauterine device plus 1 barrier method; (ii) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus 1 barrier method; or (iii) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm), or a vasectomized partner.
• For male participants who were sexually active and who were partners of premenopausal women: agreement to use 2 forms of contraception as in criterion number 6b above during the treatment period and for at least 3 months after the last dose of study drug.
• Male participants must not donate sperm for 3 months after last dose of study drug.
• Able to provide written informed consent prior to the performance of any study-specific procedures.

You may not qualify if:

• Participants had corrected QT interval using Fridericia's formula (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 breastfed.
• 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 Classes 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.
• Had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or any other Rho-associated Protein Kinase-2 (ROCK2) inhibitor.
• Scleroderma renal crisis within 4 months prior to enrollment.
• Forced vital capacity \<= 50% Predicted.

Sponsors & Collaborators

• Kadmon, a Sanofi Company: lead

Study Sites (6)

University of California, Los Angeles Medical Center_Site number 104

Los Angeles, California, 90095, United States

Location

Yale University School of Medicine_Site number 140

New Haven, Connecticut, 06519, United States

Location

Northwestern University_Site number 124

Chicago, Illinois, 60611, United States

Location

Columbia University Medical Center_Site number 086

New York, New York, 10032, United States

Location

University of Utah_Site number 048

Salt Lake City, Utah, 84132, United States

Location

Virginia Mason Medical Center_Site number 145

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Scleroderma, Diffuse; Skin Diseases; Scleroderma, Systemic

Interventions

belumosudil; KD025

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Due to slow enrollment and strategic consideration, Sponsor decided to terminate the study and the termination was not driven by any safety concerns.

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Belumosudil 200 mg PO BID

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 23, 2020
• Study Start: March 3, 2021
• Primary Completion: May 10, 2022
• Study Completion: December 19, 2022
• Last Updated: June 5, 2023
• Results First Posted: June 5, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

US (6)