Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease

Kevin R Flaherty, Kevin K Brown, Athol U Wells, Emmanuelle Clerisme-Beaty, Harold R Collard, Vincent Cottin, Anand Devaraj, Yoshikazu Inoue, Florence Le Maulf, Luca Richeldi, Hendrik Schmidt, Simon Walsh, William Mezzanotte, Rozsa Schlenker-Herceg, Kevin R Flaherty, Kevin K Brown, Athol U Wells, Emmanuelle Clerisme-Beaty, Harold R Collard, Vincent Cottin, Anand Devaraj, Yoshikazu Inoue, Florence Le Maulf, Luca Richeldi, Hendrik Schmidt, Simon Walsh, William Mezzanotte, Rozsa Schlenker-Herceg

Abstract

600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks.

Ethics and dissemination: The trial is conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) and Japanese GCP regulations.

Trial registration number: NCT02999178.

Keywords: interstitial fibrosis; rare lung diseases.

Conflict of interest statement

Competing interests: KRF reports grants and personal fees from Genentech, grants from Afferent, and personal fees from Boehringer Ingelheim, Veracyte, Roche, Biogen, Aeolus and Pharmakea. KKB reports grants from NHLBI, grants and personal fees from Actelion, Amgen, Gilead, and personal fees from Almiral, Altitude Pharma, Astra Zeneca, Byer, Biogen/Stromedix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Fibrogen, Galecto, GlaxoSmithKline, MedImmune, Novartis, Pfizer, Promedior, Roche/Genentech, Sanofi/Genzyme, Veracyte, Aeolus and ProMetic. AUW reports lecturing and consultancy fees from Boehringer Ingelheim, Roche, InterMune, Actelion and Bayer. HRC reports personal fees from MedImmune, Bayer, Biogen, Boehringer Ingelheim, Xfibra, Genoa, Gilead, GlaxoSmithKline, Mesoblast, Moerae Matrix, PharmAkea, Promedior, Prometic, Pulmatrix, Pulmonary Fibrosis Foundation (senior medical advisor), Unity, Aeolus, aTyr Pharmaceuticals, Pfizer, UCB Celltech, GBT, Veracyte, Patara, Samumed, Alkermes, Five Prime and Takeda. VC reports personal fees from Actelion, Bayer, Biogen Idec, Boehringer Ingelheim, Gilead, GSK, Intermune, MSD, Novartis, Pfizer, Roche and Sanofi, grants from Actelion, Boehringer Ingelheim, GSK, Pfizer and Roche, and personal fees from Boehringer Ingelheim. YI reports lecture and advisory fees from Boehringer Ingelheim, Shionogi & Co., Ltd., Takeda, Nobel Pharma, Novartis, Serendex, Bayer, Chugai and Daiichi Sankyo. LR reports grants and personal fees from InterMune, and personal fees from MedImmune, Biogen, SanofiAventis, Roche, Takeda, ImmuneWorks, Shionogi, Boehringer Ingelheim and Pliant Therapeutics. ECB, HS, WM and RSH are full-time employees of Boehringer Ingelheim. FLM was a full-time employee of Boehringer Ingelheim at the time of manuscript development. SW and AD report no competing interests.

Figures

Figure 1
Figure 1
Trial design. Study design schematic of the PF-ILD trial followed by a separate open-label trial (optional): part A (visits 1 through 9 over 52 weeks) and part B (visit 10 through EOT visit over variable period for each patient). EOT, end of treatment; PF-ILD, progressive fibrosing interstitial lung disease; R, randomisation (1:1 ratio for nintedanib:placebo).

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Source: PubMed

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