POS0005 Inhaled Pirfenidone as an innovative therapeutic approach to treat autoimmune ILD and other forms of Progressive Pulmonary Fibrosis: Phase 2b Study Design

Background: Progressive Pulmonary Fibrosis (PPF) is an increasingly recognized condition, defined in 2022 to address the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). PPF is a characteristic feature of autoimmune ILD. Oral pirfenidone has shown positive signals in some studies without reaching primary endpoint, but treatment with oral pirfenidone is also associated with significant adverse events and a poor tolerability profile. This study aims at exploring the efficacy and safety of inhaled pirfenidone which might be a promising therapeutic approach considering the local drug delivery into the lungs and the subsequent reduced systemic exposure. Objectives: Data from the AP01-002 (ATLAS) Study of inhaled pirfenidone in IPF demonstrated efficacy and improved safety compared to that seen with oral pirfenidone [1]. The AP01-005 long term extension study allowed new patients with PPF to enter the study and showed a trend to FVC stabilization. The AP01-007 (MIST Study) is designed to study the efficacy and safety of AP01 (inhaled pirfenidone) in patients with PPF including autoimmune ILD patients. Patients will remain on stable background immunosuppression and up to 30% of patients will remain on background nintedanib therapy. Methods: MIST is a prospective randomized placebo-controlled trial comparing two doses (100mg BID and 50mg BID) of inhaled pirfenidone with placebo over 52 weeks. The primary endpoint is the change in the annual rate of decline in FVC in the AP01 treatment groups as compared to placebo. In addition, efficacy will be measured in secondary endpoints of time to progression, change in fibrotic scores via quantitative HRCT, and change from baseline QoL. Safety outcomes will be assessed as well. Cough will be analyzed through cough counts and cough questionnaires, which should allow differentiation of cough related to PPF vs. the inhalation procedure. Patients will be eligible if they meet at least one of the following criteria for progression of ILD within the 24 months prior to screening: a relative decline in the FVC of at least 10% of the predicted value, a relative decline in the FVC of ≥5% to less than 10% of the predicted value accompanied by worsening of respiratory symptoms or an increased extent of fibrosis on HRCT; or worsening of respiratory symptoms and an increased extent of fibrosis on HRCT. 300 patients will be recruited in 14 countries, including Europe. Results: Results of this study will not be available at this time. The primary endpoint is the change from baseline in forced vital capacity (FVC) (mL) at Week 52. Secondary endpoints include absolute change from baseline in QoL measurements as assessed by Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) total score at Week 52, time to disease progression (disease progression is defined as absolute FVC percent predicted decline of ≥10% prior to Week 52), and change in lung fibrosis score based on high-resolution computed tomography (HRCT) from Baseline to 52 weeks. Conclusion: MIST is the first study to analyze the novel concept of inhaled medications in autoimmune ILD. Safety and efficacy of AP01 in patients with PPF will be studied. In addition to the safety and efficacy endpoints, MIST will examine the presence of cough in this population of patients. REFERENCES: [1] West A, Chaudhuri N, Barczyk A, et al. Inhaled pirfenidone solution (AP01) for IPF: a randomized, open-label, dose-response trial. Thorax. Sep 2023;78(9):882-889. doi:10.1136/thorax-2022-219391 Acknowledgements: NIL . Disclosure of Interests: Oliver Distler has had consultancy relationship with and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis/fibrosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Acepodia Biotech, Aera, Alcimed, Altavant, Amgen, AnaMar, Anaveon AG, Argenx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Calluna (Arxx), Cantargia AB, Catalyze Capital, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, MSD Merck, Miltenyi Biotec, Mitsubishi Tanabe, Nkarta Inc., Novartis, Orion, Pilan, Prometheus, Quell, Redxpharma, Roivant, EMD Serono, Topadur and UCB, Patent issued "mir-29 for the treatment of systemic sclerosis" (US8247389, EP2331143), is a Co-founder of CITUS AG, Research Grants from BI, Kymera, Mitsubishi Tanabe, UCB, Colin Reisner is an employee of Devpro Biopharma, Sébastien Tilleux is an employee of Avalyn pharma Inc, Allison Trucillo is an employee of Avalyn Pharma Inc, Deepthi Nair is an employee of Avalyn Pharma Inc, Felix Woodhead is an employee of Avalyn Pharma Inc, Howard M. Lazarus is an employee of Avalyn Pharma Inc, Craig Conoscenti is an employee of Avalyn Pharma Inc, Martin Kolb has received fees from Boehringer Ingelheim, Roche, European Respiratory Journal, Fortrea, United Therapeutics, Abbvie, Avalyn, DevPro Biopharma, Horizon/Amgen, CSL Behring, AZ, GSK, Sanofi, Structure Therapeutics and Glenmark, grants from the Canadian Institute for Health Research, Boehringer Ingelheim, United Therapeutics, Structure Therapeutics. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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