Design of the MIST study: a double-blind, randomised, placebo-controlled phase 2b trial of pirfenidone solution for inhalation in patients with progressive pulmonary fibrosis

INTRODUCTION: Progressive pulmonary fibrosis (PPF) is a debilitating 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 in smaller academic studies, it did not achieve a statistically significant change in the primary endpoint. Increased systemic exposure with oral administration may lead to substantial adverse events and limit its utility. Clinical data support inhaled pirfenidone for the treatment of PPF with improved tolerability compared with orally administered pirfenidone. METHODS AND ANALYSIS: Approximately 300 patients with PPF will be randomised 2:1:2 to one of three treatment arms: AP01 100 mg two times per day, AP01 50 mg two times per day or placebo two times per day by oral inhalation using the investigational eFlow Nebuliser System (PARI Pharma GmbH, Germany). The primary endpoint is the change from baseline in forced vital capacity at week 52. The main secondary endpoints are change in quality of life measurements from baseline to 52 weeks, time to disease progression and change in lung fibrosis scores based on high-resolution CT from baseline to 52 weeks. TRIAL REGISTRATION NUMBER: NCT06329401.