A Study to Test How Well BI 1291583 is Tolerated by People With Cystic Fibrosis Bronchiectasis (Clairafly™)

Study Overview
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Brief Summary
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This study is open to adults aged 18 years and older with cystic fibrosis bronchiectasis. The purpose of this study is to find out whether a medicine called BI 1291583 is tolerated by people with cystic fibrosis bronchiectasis. Participants are put randomly into 2 groups. One group takes BI 1291583 tablets and the other group takes placebo tablets. Placebo tablets look like BI 1291583 tablets but do not contain any medicine. Participants in both groups take 1 tablet once a day for 12 weeks. Participants have twice the chance of being placed in the BI 1291583 group than in the placebo group. Participants are in the study for about 6 months. During this time, they visit the study site 7 times. At the visits, the doctors check the health of the participants and note any health problems that could have been caused by BI 1291583.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Group Trial Evaluating Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BI 1291583 One Tablet Once Daily Over 12 Weeks Versus Placebo in Adult Patients With Cystic Fibrosis Bronchiectasis (Clairafly™)

Conditions
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Cystic Fibrosis, Bronchiectasis

Intervention / Treatment
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* Drug: BI 1291583
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of patients when signing the informed consent ≥18 years Historical clinical diagnosis of Cystic fibrosis (CF) (symptoms of CF and sweat chloride ≥ 60 mmol/L and/or 2 CF-causing Cystic fibrosis transmembrane conductance regulator (CFTR) mutations) Investigator-confirmed diagnosis of Bronchiectasis (BE) by Computed tomography (CT) scan and clinical history consistent with BE (e.g., cough, chronic sputum production, recurrent respiratory infections). Subjects whose past chest CT records are not available will undergo a chest CT scan during Screening. Historical scans must not be older than 5 years History of pulmonary exacerbations requiring antibiotic treatment. In the 12 months before Visit 1, patients must have had either: at least 2 exacerbations, or at least 1 exacerbation and an St. George's Respiratory Questionnaire (SGRQ) Symptoms score of >40 at screening visit 1 For patients on stable oral or inhaled antibiotics as chronic treatment for BE, at least one exacerbation must have occurred while on stable antibiotics. Patients must be able to provide spontaneous or induced sputum samples. Further inclusion criteria apply. Exclusion Criteria: Moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment) or Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) > 3.0x Upper limit of normal (ULN) at Visit 1 Estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula < 30 mL/min at Visit 1 Absolute blood neutrophil count < 1,000/mm^3 (equivalent to < 1000 cells/μL or < 10^9 cells/L) at Visit 1 Any findings in the medical examination (including blood pressure (BP), pulse rate (PR), or electrocardiogram (ECG)) and/or laboratory value assessed at Visit 1 or during screening period that in the opinion of the investigator may put the patient at risk by participating in the trial Positive serological tests for hepatitis B, hepatitis C (also confirmed with Hepatitis C virus ribonucleic acid (HCV RNA)), or human immunodeficiency virus (HIV) infection, or known infection status. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1291583 group<br> | Drug: BI 1291583<br>* BI 1291583<br>|
| Placebo Comparator: Placebo group<br> | Drug: Placebo<br>* Placebo matching BI 1291583<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Treatment emergent Adverse Events (TEAEs) up to 16 weeks from first drug administration |  | up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change from baseline in neutrophil elastase (NE) activity in sputum at week 8 after first drug administration |  | at week 8 | 
| Area under the concentration-time curve of the analyte in plasma over a uniform dosing interval (AUCτ) for the first dose |  | up to 8 hours | 
| Maximum measured concentration of the analyte in plasma (Cmax) for the first dose |  | up to 8 hours | 
| Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval (AUCτ,ss) |  | up to 12 weeks | 
| Maximum measured concentration of the analyte in plasma (Cmax) at steady state (Cmax,ss) |  | up to 12 weeks |