Inhalation innovation: phase 2b study design of inhaled pirfenidone in the treatment of progressive pulmonary fibrosis

<bold>Introduction:</bold> 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). Oral pirfenidone has been studied in non-IPF ILDs but never achieved a statistically significant change in primary endpoint. Trends seen in secondary endpoints support efficacy in PPF. <bold>Objective:</bold> Data from the AP01-002 (ATLAS) Study of inhaled pirfenidone in IPF demonstrated efficacy and improved safety compared to that seen with oral pirfenidone. The AP01-007 (MIST Study) is designed to study the efficacy and safety of AP01 (aerosolized pirfenidone) in patients with PPF. Patients will remain on background immunosuppression and up to 30% of patients will remain on background nintedanib therapy. <bold>Methods:</bold> The primary objective is to observe 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 6MWT difference, 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 nebulization procedure. <bold>Conclusion:</bold> MIST will study the safety and efficacy of AP01 (aerosolized pirfenidone) in patients with PPF. In addition to the safety and efficacy endpoints, MIST will carefully examine the presence of cough in this population of patients.