Efficacy and Safety of BI 1291583 in Patients with Bronchiectasis: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this Phase III, randomized, double-blind, placebo-controlled study is to demonstrate the **superiority** of BI 1291583 compared to placebo in reducing the annualized rate of adjudicated pulmonary exacerbations in participants with **bronchiectasis**. This is clinically relevant as pulmonary exacerbations significantly impact the quality of life and disease progression in patients with bronchiectasis.

Secondary objectives include: - Demonstrating a reduction in lung function decline as measured by changes from baseline in FEV1 %pred and FVC %pred. - Improving respiratory symptoms as measured by the absolute change from baseline in the QOL-B respiratory symptoms score. - Reducing the risk of pulmonary exacerbations and the annualized rate of severe pulmonary exacerbations for BI 1291583 compared to placebo. - Showing an effect of BI 1291583 on reducing the risk for severe pulmonary exacerbations compared to placebo.

The clinical trial involves a total of **1167 participants** diagnosed with **bronchiectasis**, a chronic condition characterized by cough, chronic sputum production, and recurrent respiratory infections. The study population includes both male and female participants, with an age range starting from 18 years and above, ensuring that all individuals are of legal consenting age. Participants were selected based on a confirmed diagnosis of bronchiectasis via CT scan, and a history of documented pulmonary exacerbations requiring antibiotic treatment. The trial does not include a vulnerable population. Participants are required to have the ability to produce sputum for screening purposes. Lifestyle considerations such as diet and physical activity are not specified, but participants on stable oral or inhaled antibiotics as chronic treatment for bronchiectasis, or those on CFTR-MT, must have experienced at least one exacerbation since the initiation of these treatments. The selection criteria ensure a focus on individuals with a clinical history consistent with bronchiectasis, aiming to evaluate the efficacy of BI 1291583 compared to placebo in reducing the annualized rate of adjudicated pulmonary exacerbations.

The clinical trial is a **Phase III**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of **BI 1291583** administered once daily for up to 76 weeks in patients with **bronchiectasis**. The primary objective is to demonstrate the superiority of BI 1291583 compared to placebo by assessing the annualized rate of adjudicated pulmonary exacerbations. Secondary endpoints include changes in post-bronchodilator FEV1 %pred, QOL-B respiratory symptoms domain score, and FVC %pred at Week 52, as well as the time to first pulmonary exacerbation and the annualized rate of severe pulmonary exacerbations up to Week 76.

The trial will commence with a screening visit to confirm eligibility, which includes a clinical history consistent with bronchiectasis and a CT scan diagnosis. Participants must have a history of documented pulmonary exacerbations requiring antibiotic treatment. The trial will involve multiple follow-up visits to monitor the participants' health and response to the treatment. The end-of-study visit will conclude the trial, assessing the overall outcomes and any adverse events experienced by the participants.

Participant involvement is expected to last up to 76 weeks, with the possibility of early termination if significant adverse effects occur or if the participant withdraws consent. The trial is set to begin recruitment on July 28, 2025, and is estimated to end on October 12, 2028. The study will adhere to Good Clinical Practice (GCP) guidelines, ensuring the safety and rights of the participants throughout the trial duration.

The clinical trial involves the administration of **BI 1291583**, an experimental medication, to evaluate its efficacy, safety, and tolerability in patients with **bronchiectasis**. **BI 1291583** is provided in the form of a **film-coated tablet** and is administered orally. The dosage for this trial is 2.5 mg, taken once daily. The treatment period extends up to 76 weeks. The active substance in this medication is of chemical origin, and the product is developed by Boehringer Ingelheim International. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.

In addition to the experimental medication, a **placebo** matching **BI 1291583** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to mimic the appearance of the **BI 1291583** film-coated tablet but does not contain the active substance. It is also administered orally once daily for up to 76 weeks. The use of a placebo allows for the assessment of the true efficacy and safety of **BI 1291583** by providing a baseline for comparison. The study aims to demonstrate the superiority of **BI 1291583** over the placebo in reducing the annualized rate of adjudicated pulmonary exacerbations in participants with bronchiectasis.

The efficacy of BI 1291583 in the treatment of **bronchiectasis** will be assessed through a Phase III, randomized, double-blind, placebo-controlled study. The primary endpoint for evaluating efficacy is the annualized rate of adjudicated pulmonary exacerbations, measured as the number of events per person-year, up to Week 76. Secondary endpoints include the absolute change from baseline in post-bronchodilator FEV1 %pred and QOL-B respiratory symptoms domain score at Week 52, time to first pulmonary exacerbation up to Week 76, absolute change from baseline in post-bronchodilator FVC %pred at Week 52, annualized rate of severe pulmonary exacerbations up to Week 76, and time to first severe pulmonary exacerbation up to Week 76.

These efficacy parameters will be collected and analyzed at specified timepoints, including Week 52 and Week 76, using validated scales and laboratory tests. The study aims to demonstrate the superiority of BI 1291583 compared to placebo in reducing the rate of pulmonary exacerbations in participants with bronchiectasis. The trial will involve the administration of BI 1291583 at a dose of 2.5 mg once daily for up to 76 weeks. The data collected will be analyzed to determine the efficacy of the treatment in improving respiratory function and quality of life in the study population.