NCT02688647

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

A Randomized, Phase 2, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, and Activity of Belumosudil in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 76 (actual)
• Sponsor: Kadmon Corporation, LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Detailed description

Study KD025-207 is a Phase 2, randomized, 2-part, open-label, crossover study in subjects with IPF. The purpose of the study is to evaluate the safety, tolerability, and activity of 400 mg of belumosudil administered orally (PO) every day (QD) compared to Best Standard of Care (BSC) in subjects with IPF who have previously been treated with or declined treatment with pirfenidone or nintedanib. The primary objectives are to evaluate the change in Forced Vital Capacity (FVC), and the safety and tolerability from baseline to 24 weeks in subjects with IPF after dosing with belumosudil 400 mg PO QD compared to BSC. Part 1: Randomized, Open-label for 24 Weeks Approximately 81 eligible subjects with IPF are to be enrolled, in 10 to 15 sites, and randomized in a 2:1 ratio (belumosudil:BSC) to 1 of the following 2 groups: * Belumosudil-R (Investigational Group): Belumosudil 400 mg PO QD for 24 weeks * BSC-R (Control Group): BSC for 24 weeks The study plan is for 54 subjects to be entered into the Belumosudil-R Treatment Group and 27 subjects into the BSC-R Treatment Group. This sample size provides over 90% power at the 2-sided 0.05 significance level to detect a 20% difference between treatment groups at 24 weeks in percentage change from baseline in FVC assuming a standard deviation (SD) in percentage change from baseline in FVC of 17%. The sample size of 54 subjects receiving belumosudil provides over 90% probability of ≥ 1 subject in the study experiencing an AE that had an underlying rate of ≥ 5%. Part 2: Continuation of Belumosudil Therapy or Crossover to Belumosudil Therapy Subjects in the Belumosudil-R group who complete 24 weeks of treatment with belumosudil 400 mg PO QD have the option of continuing therapy with belumosudil 400 mg PO QD up to an additional 72 weeks if there are no safety signals and if clinical progress continues. No subject in the Belumosudil-R group is to be permitted to receive therapy with belumosudil greater than a total of 96 weeks. Subjects in control group BSC-R who complete 24 weeks of BSC have the option of crossing over to therapy with belumosudil 400 mg PO QD for up to 96 weeks if there are no safety signals and if clinical progress continues. No subject in control group BSC-R is to be permitted to receive belumosudil 400 mg PO QD therapy greater than 96 weeks. Follow-up Period: Follow-up Visits are to occur 30 days (± 3 days) after the last dose of belumosudil during which subjects are to undergo safety assessments. (A Follow-up Visit is not necessary for subjects receiving BSC.) Duration of Study for Individual Subjects: 1. Subjects randomized to belumosudil: total up to 104 weeks (4-week screening, 96-week treatment with belumosudil, and 4-week follow-up) 2. Subject randomized to BSC: total up to 128 weeks (4-week screening; up to 24-week treatment with BSC, 96-week treatment with belumosudil, and 4-week follow-up) Efficacy Assessments * FVC * FVC% Predicted * 6-minute Walking Distance (6MWD) * Diffusing Capacity of Carbon Monoxide (DLCO) * Lung Fibrosis (by HRCT and Radiologist's Visual Assessments) * Time to Acute Exacerbation * Time to Progression of IPF * Time to Respiratory-related Hospitalization * Time to Respiratory-related Death * St. Georges Respiratory Questionnaire (SGRQ) Biomarker Assessments * Matrix Metalloproteinase-7 (MMP7) * Chemokine Ligand 18 (CCL18) * Surfactant Protein-D (SPD) Safety Assessments * Adverse event (AE) * Serious adverse event (SAE) * Physical examination (PE) * Vital signs (VS) * Clinical laboratory evaluations (hematology, chemistry, and urinalysis) * Electrocardiogram (ECG) * Reason for treatment discontinuation due to toxicity Analyses Efficacy and safety are to be analyzed at the end of Part 1 (Week 24) and for the Entire Treatment Period (Parts 1 and 2). Analyses of study subjects are to be grouped and defined as follows: * Belumosudil-R: subjects randomized to belumosudil * BSC-R: subjects randomized to BSC * Belumosudil-WC: subjects randomized to belumosudil plus subjects randomized to BSC and who cross over to treatment with belumosudil * BSC-NC: subjects randomized to BSC and who cross over to treatment with belumosudil but have data censored by the date of crossover

Conditions

• Idiopathic Pulmonary Fibrosis

Interventions

Type	Name	Description
DRUG	Belumosudil
OTHER	BSC	Treatment/drug as determined by each subject's prescribing physician

Timeline

• Start date: 2016-05-26
• Primary completion: 2021-04-13
• Completion: 2021-04-13
• First posted: 2016-02-23
• Last updated: 2022-09-08
• Results posted: 2022-09-08

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study