Design of placebo-controlled trial of nintedanib in patients with progressive massive fibrosis related to coal mine dust exposure

SESSION TITLE: Presentations and Complications of Diffuse Lung Disease SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 01:30 pm - 02:30 pm PURPOSE: Exposure to coal mine dust can cause interstitial lung disease (ILD), which may lead to fibrosis associated with rapidly declining lung function, as occurs in progressive massive fibrosis (PMF). A single-center placebo-controlled trial has been designed to investigate the effects of nintedanib in patients with PMF. METHODS: The trial is enrolling patients with at least ≥5 years’ work in surface or underground coal mining and PMF observed on CT chest performed ≤24 months prior to screening. For those with PMF and past spirometry data, stable lung function with <5% decline in percent predicted FVC obtained at least 12 months but no more than 5 years prior to screening will be excluded. Patients must have FVC ≥45% predicted and diffusing capacity for carbon monoxide (DLco) ≥30% and <80% predicted. Based on the power calculation, approximately 160 patients will be randomized 1:1 to receive nintedanib 150 mg twice daily or placebo. The study will consist of two parts. Part A will be a 52-week treatment period. Part B will be a variable period beyond 52 weeks, during which patients continue to receive blinded randomized treatment until the last patient completes 52 weeks in the trial. RESULTS: The primary endpoint is the rate of decline in FVC (mL/year) over 52 weeks. Secondary endpoints include the rate of decline in FEV1 (mL/year) over 52 weeks; changes in the Living with Pulmonary Fibrosis (L-PF) questionnaire symptoms dyspnea domain and cough domain scores and King's Brief Interstitial Lung Disease (K-BILD) questionnaire total score at week 52; change in 6-minute walk test distance at week 52; time to death, respiratory-related death and disease progression (absolute decline in FVC ≥10% predicted) or death over 52 weeks; and progression of HRCT findings graded according to the International Classification of High-Resolution Computed Tomography for Occupational and Environmental Respiratory Diseases. Adverse events will be recorded. CONCLUSIONS: This randomized placebo-controlled trial will illuminate the effects of nintedanib on the progression of fibrosing coal mine dust-induc CLINICAL IMPLICATIONS: The INBUILD trial showed the utility of nintedanib as a treatment for chronic fibrosing ILDs with a progressive phenotype, but nintedanib has not been evaluated specifically in patients with PMF. The results of the current study will provide further evidence on the effects of nintedanib in patients with PMF. DISCLOSURES: Employee relationship with Boehringer Ingelheim Please note: >$100000 by Shaun Bender, value=Salary Employee relationship with Boehringer Ingelheim Pharmaceuticals Please note: >$100000 by Craig Conoscenti, value=Salary Speaker/Speaker's Bureau relationship with Boerhinger Ingelheim Please note: $20001 - $100000 by Amy Olson, value=Travel Scientific Medical Advisor relationship with Boerhinger Ingelheim Please note: $1001 - $5000 by Amy Olson, value=Consulting fee Speaker/Speaker's Bureau relationship with Genetech Please note: $5001 - $20000 by Amy Olson, value=Travel Speaker/Speaker's Bureau relationship with PeerView Please note: $5001 - $20000 by Amy Olson, value=Travel Scientific Medical Advisor relationship with MGC Diagnostics Please note: $5001 - $20000 by Amy Olson, value=Travel No relevant relationships by Rahul Sangani No relevant relationships by Sijin Wen