Efficacy and Safety Evaluation of Bexotegrast in Idiopathic Pulmonary Fibrosis: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study

The primary objective of this study is to evaluate the effect of **bexotegrast** versus placebo on the change in forced vital capacity (FVC) in participants with **idiopathic pulmonary fibrosis (IPF)** at Week 52. This is clinically relevant as FVC is a critical measure of lung function and its preservation is essential in managing IPF, a progressive and debilitating lung disease.

Secondary objectives include:

• Characterizing the effect of bexotegrast versus placebo over 52 weeks on disease progression.
• Assessing the effect on overall symptom and functional improvement associated with IPF after 52 weeks of treatment.
• Evaluating changes in lung fibrosis using high-resolution computed tomography (HRCT) at Week 52.
• Determining the safety and tolerability of bexotegrast versus placebo in participants with IPF over 52 weeks of treatment.

The clinical trial involves a total of **795 participants** diagnosed with **idiopathic pulmonary fibrosis (IPF)**. The study population includes both male and female subjects, aged **40 years and older**, with a confirmed diagnosis of IPF based on established guidelines. Participants are required to have a **force vital capacity (FVC)** percent predicted of at least 45% and a diffusing capacity for carbon monoxide percent predicted between 30% and 90%, both confirmed through central review. The trial includes individuals currently undergoing stable background therapy for IPF. The selection process ensures a diverse representation of the general IPF population, including vulnerable groups. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to assess the effect of bexotegrast compared to placebo on FVC changes over a 52-week period.

The clinical trial is designed to evaluate the efficacy and safety of **bexotegrast** in the treatment of **idiopathic pulmonary fibrosis** (IPF). This study is a randomized, double-blind, dose-ranging, placebo-controlled trial. Participants will be randomly assigned to receive either bexotegrast or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the study's double-blind nature. The trial is expected to last for 52 weeks, with the primary endpoint being the change from baseline in absolute forced vital capacity (FVC) at Week 52. Secondary endpoints include time to disease progression, changes in dyspnea and cough scores, and the incidence of treatment-emergent adverse events.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, IPF diagnosis, and lung function parameters. Following randomization, participants will attend regular follow-up visits to monitor their health status, assess treatment effects, and ensure adherence to the study protocol. The end-of-study visit will occur at Week 52, where final assessments will be conducted to evaluate the primary and secondary endpoints.

The expected length of participant involvement is approximately 52 weeks, aligning with the trial's duration. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial aims to provide valuable insights into the potential benefits and risks of bexotegrast for individuals with IPF, contributing to the understanding and management of this condition.

The clinical trial involves the administration of **Bexotegrast**, an experimental medication, for the treatment of **idiopathic pulmonary fibrosis**. Bexotegrast is provided in the form of a **film-coated tablet** and is administered orally. The maximum daily dose of Bexotegrast is 320 mg, with a total maximum dose of 116,480 mg over the course of the study. The treatment period extends up to 52 weeks. Bexotegrast is a chemical substance developed by Pliant Therapeutics Inc., and it is identified by the sponsor product code PLN-74809. The study aims to evaluate the efficacy and safety of Bexotegrast by assessing changes in forced vital capacity (FVC) in participants.

In addition to the experimental treatment, a **placebo** is used as a comparator in this randomized, double-blind, placebo-controlled study. The placebo is designed to match the appearance of the Bexotegrast film-coated tablet but does not contain any active substance. The placebo serves as a control to help determine the specific effects of Bexotegrast on the participants. The administration of the placebo follows the same oral route and dosing schedule as the experimental medication, ensuring consistency in the study design.

The efficacy of **bexotegrast** in the treatment of idiopathic pulmonary fibrosis (IPF) will be assessed through a randomized, double-blind, dose-ranging, placebo-controlled study. The primary endpoint for evaluating efficacy is the change from baseline in absolute forced vital capacity (FVC) measured in milliliters at Week 52. Secondary endpoints include the time to disease progression, defined as the time to the first occurrence of a ≥10% absolute decline from baseline in forced vital capacity percent predicted (FVCpp), adjudicated respiratory-related hospitalization, adjudicated acute IPF exacerbation, or all-cause mortality through Week 52. Additional secondary endpoints involve the proportion of participants with a ≥10% absolute decline in FVCpp from baseline or all-cause mortality, changes from baseline in L-PF Dyspnoea and Cough Domain scores, changes in the King’s Brief Interstitial Lung Disease (K-BILD) questionnaire Total score, and the absolute change from baseline in quantitative lung fibrosis (QLF) extent (%) at Week 52.

Data collection will occur at specified timepoints, with the primary endpoint being assessed at Week 52. The study will utilize validated scales and questionnaires, such as the K-BILD questionnaire, to measure patient-reported outcomes. The analysis will include the proportion of participants experiencing treatment-emergent adverse events and serious adverse events. The study is designed to provide comprehensive data on the efficacy of bexotegrast in improving lung function and quality of life in patients with IPF over a 52-week treatment period.