A Study in Patients With Non-cystic Fibrosis Bronchiectasis to Test How Well Different Doses of BI 1323495 Are Tolerated and How BI 1323495 Affects Biomarkers of Inflammation

Exclusion Criteria

• •Vaccination against Streptococcus pneumoniae in accordance with national vaccination recommendations
• •Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation.
• •FEV1 ≥ 30 % predicted (post-bronchodilator) at Screening Visit 1.
• •Stable (i.e., no dose change) regimen of standard nCFB treatment (including - but not limited to - hypertonic inhalation solutions, mucolytics, Long Acting Muscarinic Agonists (LAMA)/ Long Acting Beta Agonists (LABA) / inhaled corticosteriods (iCS), oral antibiotic maintenance regimen, and physiotherapy), if applicable, administered at least for 4 weeks prior to Screening Visit 1 and throughout the run-in period.
• •Regular daily sputum producers with a history of chronic expectoration who are able to provide a typical bronchiectasis sputum sample at Screening Visit 1.
• •Sputum neutrophil elastase positive based on point of care test (NEATstik® score ≥ 6) assessment at Visit 2a and Visit 2b.
• •Subjects genotyped as UDP-Glucuronosyltransferase-2B17 (UGT2B17) extensive metabolizers prior to randomisation, i.e., carrying at least one functional allele of the UGT2B17 gene (\*1/\*1 or \*1/\*2)
• •Any finding in the medical examination (including BP, pulse rate (PR), or ECG) and/or laboratory value and/or any evidence of a concomitant disease assessed as clinically relevant by the investigator.
• •Concomitant diagnosis of pulmonary disease other than bronchiectasis, chronic obstructive pulmonary disease (COPD), or asthma.
• •A current diagnosis of cystic fibrosis (CF), primary immunodeficiency, active Allergic Bronchopulmonary Aspergillosis (ABPA) (defined by receipt of corticosteroids, anti-fungal treatment or monoclonal antibody treatment), or alpha-1 antitrypsin (A1AT) deficiency as underlying disease.
• •A history or current immunodeficiency or are currently being treated (or are planned to be treated) with immunomodulatory drugs (except for iCS or low-dose oral corticosteroids), including disease-modifying anti-rheumatic drugs (DMARDs), and/or Immunglobulin G (IgG) treatments. Other medication that is excluded will be provided in the investigator site file (ISF). On the day of the site visit with lung function measurement, no bronchodilators should be used until after completion of lung function assessment
• •Any acute infections defined as infections requiring antibiotic therapy, or Upper Respiratory Tract Infection (URTI). Are currently being treated (or are planned to be treated) for a nontuberculous mycobacterial (NTM) lung infection or tuberculosis.
• •A history of invasive pneumococcal disease.
• •Inhaled antibiotic treatment or cycling oral antibiotic treatment with changed dose regimen 4 weeks prior to Screening Visit 1.
• •A treatment for a pulmonary exacerbation 4 weeks prior to Screening Visit 1.
• •Laboratory confirmed severe acute respiratory syndrome (SARS)-coronavisurs (CoV)-2 infection (PCR positive) within 4 weeks prior to Screening Visit 1.
• •Household contact with an individual with confirmed SARS-CoV-2 infection within 4 weeks prior to Screening Visit 1.