Investigating the effects of nintedanib on biomarkers of extracellular matrix turnover in patients with IPF: design of the randomised placebo-controlled INMARK®trial

INTRODUCTION: A feature of the pathogenesis of idiopathic pulmonary fibrosis (IPF) is the excess accumulation of extracellular matrix (ECM) in the lungs. Cleavage of the ECM by metalloproteinases (MMPs) generates free-circulating protein fragments known as neoepitopes. The PROFILE study suggested that changes in ECM turnover proteins may be of value as markers of disease progression in patients with IPF. Nintedanib is an approved treatment for IPF that slows disease progression by reducing decline in forced vital capacity (FVC). METHODS AND ANALYSIS: The INMARK® trial is evaluating the effect of nintedanib on the rates of change of biomarkers of ECM turnover in patients with IPF, the value of changes in these biomarkers as predictors of disease progression and whether nintedanib affects the associations between changes in these biomarkers and disease progression. Following a screening period, 347 patients with IPF and FVC ≥80% predicted were randomised 1:2 to receive nintedanib 150 mg two times a day or placebo for 12 weeks, followed by an open-label period in which all patients will receive nintedanib for 40 weeks. The primary endpoint is the rate of change in C reactive protein degraded by MMP-1/8 from baseline to week 12. ETHICS AND DISSEMINATION: This trial is being conducted in compliance with the protocol, the ethical principles detailed in the Declaration of Helsinki and in accordance with the International Conference on Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02788474.