Evaluation of Inhaled Pirfenidone (AP01) Efficacy and Safety in Progressive Pulmonary Fibrosis: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Trial

The primary objective of this study is to evaluate the effect of **AP01** compared to placebo on lung function over 52 weeks in subjects with **Progressive Pulmonary Fibrosis** (PPF). This is clinically relevant as maintaining or improving lung function is crucial in managing PPF, a condition characterized by progressive scarring of lung tissue leading to respiratory decline.

Secondary objectives include:

• Evaluating the effect of AP01 compared to placebo on quality of life (QoL) change from baseline over 52 weeks. This is important as QoL is a significant concern for patients with chronic conditions like PPF.
• Assessing the effect of AP01 compared to placebo on disease progression from baseline to week 52, which is vital for understanding the potential of AP01 in slowing the advancement of PPF.
• Investigating the effect of AP01 compared to placebo on radiologic measures of lung fibrosis from baseline to 52 weeks, providing insights into the structural changes in the lungs associated with treatment.

The clinical trial involves a total of **197 participants** diagnosed with **Progressive Pulmonary Fibrosis**. The study population includes both male and female subjects who are at least 18 years of age. Participants were selected based on specific inclusion criteria, including lung function parameters such as forced vital capacity and diffusing capacity of the lung for carbon monoxide. The trial does not involve a vulnerable population. Participants may have been on nintedanib treatment prior to the study, with specific conditions regarding its use. The trial aims to evaluate the effect of AP01 compared to a placebo on lung function over a period of 52 weeks. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized, double-blind, placebo-controlled** study designed to evaluate the safety and efficacy of **Pirfenidone Solution for Inhalation** in subjects with **Progressive Pulmonary Fibrosis** (PPF). The trial is set to last for 52 weeks, with the primary objective being to assess the effect of the investigational product on lung function, specifically the change from baseline in forced vital capacity (FVC) at Week 52. Secondary endpoints include changes in quality of life measurements, time to disease progression, and changes in lung fibrosis score based on high-resolution computed tomography.

Participants will be involved in the study for the entire duration of 52 weeks, with several key visits scheduled throughout the trial. The initial visit, known as the screening visit, will determine eligibility based on criteria such as age, lung function parameters, and prior treatment history. Following successful screening, participants will be randomized to receive either the investigational product or a placebo, both administered via the **eFlow Nebuliser System**. Regular follow-up visits will be conducted to monitor safety, adherence, and efficacy outcomes. The end-of-study visit will occur at the conclusion of the 52-week period, where final assessments will be made.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial is expected to commence recruitment in August 2024, with an estimated completion date in January 2027. The study is not categorized as low intervention and is classified as a Phase II trial, focusing on the investigational product's impact on lung function in a controlled environment.

The clinical trial involves the administration of **Pirfenidone Solution for Inhalation**, an experimental medication developed by Avalyn Pharma, Inc. This medication is provided in the form of an **inhalation solution** and is identified by the sponsor product code AP01. The active substance in this formulation is **pirfenidone**, a chemical compound. The solution is administered via **inhalation use** using the eFlow Nebuliser System (Type 678), a handheld, single-patient, reusable electronic nebulizer. This device is equipped with a fine droplet aerosol generator and a valved aerosol chamber, designed to produce dense aerosols with a high proportion of respirable droplets. The treatment period for this medication is set for a maximum of 52 weeks. The dosing schedule and specific dosage amounts are not explicitly detailed in the provided data.

In addition to the experimental medication, a **placebo** is utilized in this study as a comparator treatment. The placebo is referred to as "Placebo for AP01" and is intended to mimic the administration of the experimental treatment without containing the active substance, pirfenidone. The placebo's pharmaceutical form and route of administration are not specified in the available data. The use of a placebo is integral to maintaining the double-blind nature of the study, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias in the evaluation of the treatment's efficacy and safety.

The efficacy of the investigational product, **Pirfenidone Solution for Inhalation**, will be assessed in a randomized, double-blind, placebo-controlled, Phase 2b clinical trial involving subjects with Progressive Pulmonary Fibrosis (PPF). The primary endpoint for evaluating efficacy is the change from baseline in forced vital capacity (FVC), which is the maximum amount of air that can be exhaled when blowing out as fast as possible, measured in milliliters at Week 52. This measurement will provide a quantitative assessment of lung function improvement or decline over the course of the study.

Secondary endpoints include the absolute change from baseline in quality of life (QoL) measurements as assessed by the Living with Pulmonary Fibrosis Symptoms and Impact Questionnaire (L-PF) total score at Week 52, time to disease progression defined as an 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. These secondary endpoints will offer additional insights into the impact of the treatment on both the physiological and quality of life aspects of the disease.

The efficacy parameters will be collected and analyzed at specified timepoints, with the primary endpoint being evaluated at the end of the 52-week treatment period. The eFlow Nebuliser System (Type 678), a handheld, single-patient use, reusable electronic nebulizer, will be utilized for the administration of the inhalation solution, ensuring precise delivery of the medication. The trial aims to provide comprehensive data on the efficacy of **Pirfenidone Solution for Inhalation** in improving lung function and overall patient outcomes in individuals with PPF.