Exploring efficacy and safety of oral Pirfenidone for progressive, non-IPF lung fibrosis (RELIEF) - a randomized, double-blind, placebo-controlled, parallel group, multi-center, phase II trial

Jürgen Behr,Jasmin Wagner,Andreas Günther,Petra Neuser,Antje Prasse,Michael Kreuter,Klaus Rabe,Carmen Schade-Brittinger

doi:10.1186/s12890-017-0462-y

Abstract

BackgroundPirfenidone is currently approved in the EU for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) and offers a beneficial risk-benefit profile. However, there are several other, progressive fibrotic lung diseases, in which conventional anti-inflammatory therapy is not sufficiently effective and antifibrotic therapies may offer a novel treatment option.Methods/DesignWe designed a study protocol for inclusion of patients with progressive fibrotic lung disease despite conventional anti-inflammatory therapy (EudraCT 2014–000861-32). The study population comprises patients with collagen-vascular disease-associated lung fibrosis (CVD-LF), fibrotic non-specific interstitial pneumonia (fNSIP), chronic hypersensitivity pneumonitis (cHP), and asbestos-related lung fibrosis (ALF). Disease progression needs to be proven by slope calculation of at least three Forced Vital Capacity (FVC) values obtained within 6–24 months prior to inclusion, documenting an annualized decline in percent predicted FVC of 5% (absolute) or more despite appropriate conventional therapy. Absolute change in percent predicted FVC from baseline - analyzed using a rank analysis of covariance (ANCOVA) model - will serve as efficacy-related primary study endpoint.DiscussionThere is an urgent unmet clinical need for effective therapies for patients with a progressive fibrotic lung disease other than IPF. The current study protocol is unique with respect to selecting patients with different disease entities of lung fibrosis which have, however, essential pathophysiological characteristics in common. Moreover, by selecting patients with evidence of disease progression despite conventional therapy, the protocol ensures that a cohort of interstitial lung disease (ILD) patients with a high unmet medical need is targeted and it may allow a sufficiently high event rate for evaluation of treatment responses.Trial registrationDRKS00009822 (registration date: January 13th 2016).

Highlights

Pirfenidone is currently approved in the EU for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) and offers a beneficial risk-benefit profile
The current study protocol is unique with respect to selecting patients with different disease entities of lung fibrosis which have, essential pathophysiological characteristics in common
By selecting patients with evidence of disease progression despite conventional therapy, the protocol ensures that a cohort of interstitial lung disease (ILD) patients with a high unmet medical need is targeted and it may allow a sufficiently high event rate for evaluation of treatment responses

Summary

Discussion

The study is unique for several reasons. First, it allows to enroll patients with different forms of interstitial lung disease. AP received personal fees for consultation and for lecturing from Roche, InterMune, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Novartis and AstraZenca outside the submitted work She is member and primary investigator (PI) of the German Center for Lung Research. MK or his institution received personal fees for consultation and for lecturing from Roche, InterMune, Boehringer Ingelheim, Bayer, GlaxoSmithKline, and Novartis as well as unrestricted funds for research from Boehringer Ingelheim and Roche/InterMune outside the submitted work He is member and primary investigator (PI) of the German Center for Lung Research. AGr received fees for consulting, lecturing and/or research support from Roche, Boehringer Ingelheim, Sanofi, Teva, Inventiva Novartis outside the submitted work Author details 1Department of Internal Medicine V, Comprehensive Pneumology Center, University of Munich (LMU) and Asklepios Fachkliniken München-Gauting, Marchioninistr. 15, 81377 Munich, Member of the German Center for Lung Research (DZL), Germany. 2Coordinating Center for Clinical Trials, Philipps University of Marburg, Marburg, Germany. 3Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany. 4Department of Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany. 5Lungenclinic Grosshansdorf and University of Kiel, Kiel, Germany. 6Department of Internal Medicine II, University of Giessen-Marburg Lung Center, Justus-Liebig University Giessen, Giessen, Germany. 7AGAPLESION Lung Clinic Waldhof-Elgershausen, Greifenstein, Germany

Background

Findings