A Randomized, Subject- and Investigator-blinded, Placebo-controlled, Parallel Group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of QBW251 in Patients With Bronchiectasis
The purpose of this study is to determine whether potentiating the cystic fibrosis transmembrane conductance regulator (CFTR) with QBW251 in patients with bronchiectasis will demonstrate clinical safety and efficacy related to improved mucociliary clearance with reduced bacterial colonization as potential drivers of airway obstruction, reduced airway inflammation, exacerbations and mucus load, improved lung function, clinical symptoms and quality of life to support further development in bronchiectasis.
• Male or female patients aged ≥18 years at screening.
• Proven diagnosis of bronchiectasis by chest CT at screening as determined by investigator.
• Evidence of sputum bacterial load of ≥106 CFU/mL with at least one potentially pathogenic microorganism (H. Influenzae, M catarrhalis, S aureus, S pneumoniae, Enterobacteriaceae, P aeruginosa, Stenotrophomonous maltophilia, or any potential pathogenic non-fermenting Gram-negative bacteria measured by dilution/outgrowth).
• Documented history of at least one bronchiectasis exacerbation between January 2019 and study screening.
• Patients with bronchial hypersecretion, defined as productive cough that occurred on most days (defined as \>50% days) for at least three consecutive months within 12 months prior to screening, as assessed by documentation of patient recollection (anamnesis) or documented in patients' record.
• Patients were allowed to stay on fixed or free combinations of LABA/LAMA or LABA/ICS or LABA/LAMA/ICS as maintenance therapy if they were treated with them at a stable dose for the last 3 months prior to screening. Patients were also allowed to stay on macrolides as maintenance therapy if they were treated with them at a stable dose, 3 months before screening. Patients were allowed to use mucolytics or hyperosmolar agents if they were treated with them before study start.
• If prescribed, patients were included in the study with unchanged chest physiotherapy for at least 4 weeks prior to screening.
• Clinically stable pulmonary status in the opinion of the investigator and unlikely to require any change in the standard regimen of care during the course of the study.