A 2-Part, Phase 2 Open-label and Crossover Study of Belumosudil for Treatment of Idiopathic Pulmonary Fibrosis

NCT02688647 | Completed Phase 2 Results FDA Drug

• 1 other identifier: KD025-207
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 10

Brief Summary

This Phase 2 study is to be conducted to evaluate the safety, tolerability, and activity of 400 mg of belumosudil orally (PO) once-daily (QD) compared to Best Supportive Care (BSC) in male and postmenopausal/surgically sterilized female subjects with Idiopathic Pulmonary Fibrosis (IPF). The primary objectives are to evaluate the:

• Change in Forced Vital Capacity (FVC) from baseline to 24 weeks after dosing with belumosudil 400 mg PO QD in subjects with IPF compared to BSC
• Safety and tolerability of belumosudil 400 mg PO QD when administered for 24 weeks to subjects with IPF compared to BSC

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Pulmonary Fibrosis; Fibrosis; Idiopathic Interstitial Pneumonias; Lung Diseases

Outcome Measures

Primary Outcomes (6)

• Efficacy: Mean Changes in FVC From Baseline to Week 24

  Changes in the mean Forced Vital Capacity (FVC) from baseline at Week 24. Normal FVC-- Healthy males 20 to 60 years: 4.75 to 5.5 L; healthy females 20 to 60 years: 3.25 to 3.75 L

  24 weeks

• Efficacy: Mean Changes in FVC% Predicted From Baseline at Week 24

  Changes in the mean Forced Vital Capacity (FVC)% Predicted from baseline at Week 24. Normal FVC%: 80% to 120%

  24 weeks

• Safety: Percentages of Subjects With Non-serious TEAEs and Relationship to Study Treatment

  Percentage of subjects with non-serious TEAEs by relationship to treatment with belumosudil, BSC, or belumosudil and BSC. Severity of TEAEs were measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 22.1 (Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = fatal).

  Up to 96 weeks (Weeks 24, 48, and 96) of treatment with belumosudil. Subjects randomized to BSC had the option of crossing over at 24 weeks.

• Safety: Percentages of Subjects With SAEs Related to Study Treatment

  Percentage of subjects with serious TEAEs by relationship to treatment with belumosudil and/or BSC. Investigators assessed whether events were related to treatment as possibly, probably, or definitely related.

  Up to 96 weeks (Weeks 24, 48, and 96) of treatment with belumosudil. Subjects randomized to BSC and crossing over also up to 24 weeks of BSC.

• Safety: Percentages of Subjects With TEAEs Leading to Discontinuation of Treatment With Belumosudil

  Percentage of subjects with treatment-emergent adverse events (TEAEs) leading to subjects discontinuing from treatment. Investigators assessed whether TEAEs leading to discontinuation were related to study drug (possibly, probably, or definitely), belumosudil 400 mg PO QD.

  Up to 96 weeks (Weeks 24, 48, and 96) of treatment with belumosudil

• Safety: Percentages of Subjects With Deaths Related to Study Treatment

  Percentage of subjects with deaths by relationship to treatment with belumosudil, BSC, or belumosudil and BSC. Investigators assessed whether events were related to treatment as possibly, probably, or definitely related.

  Up to 96 weeks (Weeks 24, 8, and 96) of treatment with belumosudil. Subjects randomized to BSC also had the option of crossing over to treatment with belumosudil at 24 weeks.

Secondary Outcomes (18)

• Efficacy: Mean Changes in FVC From Baseline at Week 24 by GAP Stage and by Use of Pirfenidone or Nintedanib--

  24 weeks

• Efficacy: Mean Changes in FVC From Baseline at Week 48, Week 96, and EOT

  Up to 96 weeks (Weeks 24, 48, and 96)

• Efficacy: Mean Change in Mean FEV1/FVC Ratio From Baseline at Weeks 24, 48, and 96 and EOT

  Up to 96 weeks (Weeks 24, 48, and 96)

• Efficacy: Mean Changes in FVC% Predicted at Week 24 by GAP Stage and by Use of Pirfenidone or Nintedanib--

  24 weeks

• Efficacy: Percentages of Subjects With Decrease ≥ 5% in FVC% Predicted From Baseline at Weeks 24, 48, and 96

  Up to 96 weeks (Weeks 24, 48, and 96)

Study Arms (2)

Belumosudil-R

EXPERIMENTAL

Subjects receive two 200 mg tablets of belumosudil (400 mg) PO QD for 24 weeks. Subjects may also continue treatment with belumosudil 400 mg PO QD after 24 weeks. No subject may receive more than 96 weeks of treatment with belumosudil

Drug: Belumosudil

BSC-R

ACTIVE COMPARATOR

Subjects receive best supportive care as determined by the physician. Subjects may later crossover to treatment with belumosudil 400 mg PO QD. No subject may receive more than 96 weeks of treatment with belumosudil.

Other: BSC

Interventions

Belumosudil DRUG

Also known as: KD025, SLx-2119

Belumosudil-R

BSC OTHER

Treatment/drug as determined by each subject's prescribing physician

Also known as: Best standard of care

BSC-R

Eligibility Criteria

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

You may qualify if:

• A subject had to meet all of the following criteria to be eligible for the study:
• Adult male and postmenopausal/surgically sterilized female subjects at least 18 years of age (if female, was surgically sterilized \[i.e., total hysterectomy, or bilateral salpingo-oophorectomy\]).
• Able to provide written informed consent before the performance of any study specific procedures.
• IPF diagnosis within 5 years before study entry, proven according to the American Thoracic Society/European Respiratory Society consensus conference criteria, with surgical lung biopsy. In the absence of a surgical lung biopsy, high-resolution computerized tomography (HRCT) consistent with usual interstitial pneumonitis.
• Resting state pulse oximeter oxygen saturation (SpO2) ≥ 88% with or without supplemental oxygen, Forced Vital Capacity % (FVC%) ≥ 50% normal predicted value, and diffusing capcity (in the lung) of carbon monoxide (DLCO) ≥ 30% normal predicted value at baseline.
• Men with partners of childbearing potential willing to use 2 medically acceptable methods of contraception during the trial and for 3 months after the last dose of study drug. Effective birth control includes:
• Intrauterine device plus 1 barrier method
• Stable doses of hormonal contraception for ≥ 3 months (e.g., oral, injectible, implant, transdermal) plus 1 barrier method
• barrier methods. Effective barrier methods were male or female condoms, diaphragms, and spermicides (creams or gels containing a chemical to kill sperm)
• Vasectomy.
• Have adequate bone marrow function:
• Absolute neutrophil count \> 1500/mm\^3
• Hemoglobin (Hb) \> 9.0 g/L
• Platelets \> 100,000/mm\^3
• Willing to complete all study measurements and assessments in compliance with protocol

You may not qualify if:

• A subject who met any of the following criteria was ineligible for the study:
• Interstitial lung disease caused by conditions other than IPF
• Severe concomitant illness limiting life expectancy (\< 1 year)
• DLCO \< 30% predicted
• Residual volume (RV) ≥ 120% predicted
• Obstructive lung disease: Forced Expiratory Volume in 1 Second (FEV1/FVC ratio \< 0.70)
• Documented sustained improvement of the subject's IPF condition up to 12 months before study entry with or without IPF-specific therapy
• Pulmonary infection or upper respiratory tract infection (URTI) within 4 weeks before study entry
• Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (e.g., pulmonary function tests \[PFTs\])
• Chronic heart failure with New York Heart Association Class III/IV or known left ventricular ejection fraction \< 25%
• Moderate to severe hepatic impairment (i.e., Child-Pugh Class B or C)
• Estimated creatinine clearance \< 30 mL/min
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2.0 \* upper limit of normal (ULN)
• Hb \< 75% of the lower limit of normal
• Systolic blood pressure \< 100 mmHg

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead

Study Sites (10)

Pulmonary Associates, PA

Phoenix, Arizona, 85006, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

UC Davis Medical Center, Division of Pulmonary/CC/SM

Sacramento, California, 95817, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

Pulmonary Disease Specialists, PA, d/b/a PDS Research

Kissimmee, Florida, 34741, United States

Location

Central Florida Pulmonary Group, PA

Orlando, Florida, 32803, United States

Location

Piedmont Healthcare Pulmonary and Critical Care Research

Austell, Georgia, 30106, United States

Location

Pulmonix, LLC

Greensboro, North Carolina, 27403, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis; Fibrosis; Idiopathic Interstitial Pneumonias; Lung Diseases

Interventions

belumosudil; KD025

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Karin Herrera, Vice President, Clinical Operations
• Organization: Kadmon Corporation

karin.herrera@kadmon.com

1-724-778-6134

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: In Part 1: Subjects are randomized to treatment with either Belumosudil 400 mg PO QD (Belumosudil-R) or to BSC (BSC-R). In Part 2: Subjects who are randomized and receive Belumosudil 400 mg PO QD during Part 1 have the option to continue treatment with Belumosudil 400 mg PO QD and subjects randomized to BSC have the option to cross over to treatment with Belumosudil 400 mg PO QD. No subject is permitted \> 96 weeks of treatment with belumosudil

Study Record Dates

• First Submitted: February 18, 2016
• First Posted: February 23, 2016
• Study Start: May 26, 2016
• Primary Completion: April 13, 2021
• Study Completion: April 13, 2021
• Last Updated: September 8, 2022
• Results First Posted: September 8, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)