Investigating effects of nintedanib on biomarkers of ECM turnover in patients with IPF: the INMARK study

Abstract

Introduction: A hallmark of IPF is the excess accumulation of extracellular matrix (ECM) in the lungs. When ECM is degraded by metalloproteinases (MMPs), free-circulating protein fragments (neoepitopes) are generated. INMARK (NCT02788474) is an ongoing trial assessing the effects of nintedanib on changes in biomarkers of ECM turnover and on the association between changes in such biomarkers and disease progression in patients with IPF and limited FVC impairment (FVC ≥80% predicted). Aim: To summarise the baseline characteristics of patients participating in INMARK. Methods: Patients were randomised 1:2 to receive nintedanib 150 mg bid or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. The primary endpoint is the rate of change in serum c-reactive protein degraded by MMP-1/8 (CRPM) from baseline to week 12. The proportion of patients with disease progression (defined as absolute decline in FVC ≥10% predicted or death) over 52 weeks is a key secondary endpoint. Results: Recruitment for the INMARK trial is complete. A total of 346 patients have been treated. At baseline, mean (SD) age was 70.3 (7.4) years; the majority of patients were white (61.8%), male (75.7%) and former or current smokers (72.8%). Mean (SD) FVC was 97.5 (13.5) % predicted and DLco was 63.8 (19.5) % predicted. Conclusion: The INMARK trial will provide insights into the association between changes in biomarkers of ECM turnover and disease progression, and whether treatment with nintedanib affects the rate of change in such biomarkers, in patients with IPF and limited FVC impairment. Results will be presented in 2019.