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Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: design of a double-blind, randomised, placebo-controlled phase II trial
  1. Toby M Maher1,2,
  2. Tamera J Corte3,4,
  3. Aryeh Fischer5,
  4. Michael Kreuter6,
  5. David J Lederer7,
  6. Maria Molina-Molina8,9,
  7. Judit Axmann10,
  8. Klaus-Uwe Kirchgaessler10 and
  9. Vincent Cottin11,12
  1. 1 NIHR Respiratory Clinical Research Facility, Royal Brompton Hospital, London, UK
  2. 2 Fibrosis Research Group, National Heart and Lung Institute, Imperial College London, London, UK
  3. 3 Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  4. 4 Medical School, University of Sydney, Camperdown, New South Wales, Australia
  5. 5 Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA
  6. 6 Center for Interstitial and Rare Lung Diseases and Department of Pulmonology and Critical Care Medicine, Thoraxklinik, Member of the German Center for Lung Research, University of Heidelberg, Heidelberg, Germany
  7. 7 Divison of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York City, New York, USA
  8. 8 Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), University Hospital of Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
  9. 9 Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Madrid, Spain
  10. 10 F. Hoffmann-La Roche, Ltd., Basel, Switzerland
  11. 11 National Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Lyon, France
  12. 12 Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France
  1. Correspondence to Professor Toby M Maher; t.maher{at}


Introduction Despite extensive multidisciplinary team (MDT) assessment, some patients have interstitial lung disease (ILD) that is considered unclassifiable (uILD), for which there are currently no approved treatments. This study will assess the efficacy and safety of the antifibrotic pirfenidone in treating uILD.

Methods and analysis This double-blind, randomised, placebo-controlled phase II trial is enrolling adults with fibrosing ILD, including uILD that fulfils proposed research criteria for interstitial pneumonia with autoimmune features (IPAF), that cannot be classified with moderate or high confidence to any category of ILD following MDT discussion. Study participants must have >10% fibrosis on high-resolution CT scan within the previous 12 months, forced vital capacity (FVC) ≥45% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised to receive 801 mg pirfenidone or placebo three times daily for 24 weeks. The efficacy of pirfenidone vs placebo will be assessed by daily measurement of FVC using a handheld spirometer over the treatment period. Other functional parameters, patient-reported outcomes, samples for biomarker analysis and safety endpoints will be collected. Additionally, the study will assess the efficacy and safety of pirfenidone with and without concomitant mycophenolate mofetil treatment and in study participants with or without IPAF.

Ethics and dissemination This trial is being conducted in accordance with the International Conference on Harmonisation E6 guideline for Good Clinical Practice, Declaration of Helsinki and local laws for countries in which the research is conducted.

Trial registration number NCT03099187.

  • unclassifiable interstitial lung disease
  • interstitial pneumonia with autoimmune features
  • antifibrotic
  • pirfenidone

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  • Contributors All authors provided substantial contributions to the conception and/or design of the work, revised the manuscript critically for important intellectual content, approved the version to be published and agree to be accountable for all aspects of the work.

  • Funding This study is sponsored by F. Hoffmann-La Roche, Ltd., Basel, Switzerland, which was involved in study design and will be involved in the collection, analysis and interpretation of the data. This trial was initially developed as part of an NIHR-funded Clinician Scientist Fellowship awarded to Toby M Maher (NIHR Ref: CS-2013-13-017) and subsequently adapted following discussions with F. Hoffmann-La Roche, Ltd.

  • Competing interests TMM has received industry-academic research funding from GlaxoSmithKline R&D and UCB, has served on a clinical trial advisory board for GlaxoSmithKline R&D, has received stock options from Apellis and has received consultancy or speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, GlaxoSmithKline R&D, ProMetic, Roche, Sanumed and UCB. TJC has received unrestricted educational grants, travel assistance and speaker fees from and served on an advisory board for Boehringer Ingelheim, has received unrestricted educational grants and speaker fees from and served on an advisory board for Roche, has received unrestricted educational grants from Actelion Ltd., Bayer, BMS and Sanofi and has served on an advisory board for AstraZeneca. AF serves as a consultant and steering committee member for Boehringer Ingelheim and Roche. MK, or his institution, has received unrestricted educational grants, speaker fees and research grants from Boehringer Ingelheim and Roche and has served on advisory boards for Boehringer Ingelheim and Roche. DJL is a steering committee member for this study and has received consulting fees from and has served on advisory boards for Genentech-Roche and Veracyte, has served on advisory boards for Boehringer Ingelheim, has served on an adjudication committee for Degge Group, has received lecture fees and fees for generation of educational content from and served on a steering committee for the France Foundation and has received consulting fees from FibroGen, Global Blood Therapeutics, ImmuneWorks, Patara Pharmaceuticals, Philips Respironics and Sanofi Genzyme. DJL’s institution, Columbia University, has received funding for clinical trials in IPF from Boehringer Ingelheim, FibroGen and Global Blood Therapeutics and has received consulting fees from the Pulmonary Fibrosis Foundation. MM-M, or her institution, has received grants from AstraZeneca, Boehringer Ingelheim, BRN, Chiesi, GlaxoSmithKline, InterMune and Roche. JA is an employee of F. Hoffmann-La Roche, Ltd. K-UK is an employee and shareholder of F. Hoffmann-La Roche, Ltd. VC receives consultancy and lecture fees and support for travel to medical meetings from Actelion and Roche, receives consultancy and lecture fees, support for travel to medical meetings and fees for development of educational presentations from Boehringer Ingelheim, receives consultancy and lecture fees from Novartis and Sanofi, receives consultancy fees from Bayer, Galapagos, GlaxoSmithKline and MSD, is a member of an adjudication committee for Gilead, is a chair of the DSMB for Promedior, is a member of the DSMB for Celgene and receives grants to his institution from Boehringer Ingelheim and Roche.

  • Ethics The Ethics Committees of the local study centres: Australia: Bellberry Human Research Ethics Committee; Belgium: UZ Leuven campus Gasthuisberg Ethische commimissie onderzoek; Canada: UBC-Providence Health Care Research Institut; Czech Republic: Etická komise Všeobecné fakultní nemocnice v Praze; Denmark: Regionshuset, Viborg, Regionssekretariatet, Juridisk kontor De Videnskabsetiske Komiteer, For Region Midtjylland; Germany: Justus-Liebig-Universität Gießen, Ethik-Kommission des FB Medizin; Greece: National Ethics Committee; Ireland: Clinical Research Ethics Committee of the Cork Teaching Hospitals; Israel: Meir Medical Center, Helsinki Committee; Italy: Comitato Etico IRST IRCCS; Poland: Bioethics Committee of Medical University in Łódź; Portugal: CEIC-Comissão de Ética para Investigação Clínica; Spain: CEIC Hospital de Bellvitge; UK: North East-Newcastle & North Tyneside 1 Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data statement Qualified researchers may request access to individualpatient level data through the clinical study data request platform ( details on Roche’s criteria for eligible studies are available here ( further details on Roche’s Global Policy on the Sharing of ClinicalInformation and how to request access to related clinical study documents, seehere (

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