This study aims to find out whether the tablet CHF10196 is safe and effective for people with non-cystic fibrosis bronchiectasis, a long-term lung disease that causes widened airways, mucus buildup, infections, and flare ups of symptoms. The main goal is to see whether CHF10196 can reduce the number of lung flareups each year compared with placebo. The study will also assess whether it can improve lung function, quality of life, and overall safety.
The study has two phases. In the first phase, participants receive either CHF10196 tablets or placebo without knowing which one they are taking. In the second phase, all participants receive CHF10196 so its long-term safety can be further studied. Adults aged 18 to 85 years and adolescents aged 12 to under 18 years can take part, while continuing their usual stable bronchiectasis treatment.
Up to about 2.5 years of participation are planned. Around 904 participants will be enrolled, with regular clinic visits and phone check ins. In the first phase, participants take either CHF10196 or inactive tablets once daily; in the second phase, everyone takes CHF10196 once daily. Temporary treatment interruptions are allowed if needed, and participants who stop treatment early may still continue study visits, depending on the study phase.
Signed and dated informed consent obtained prior to any study-related procedure; Adolescents: Written informed consent obtained from the parent(s)/legally authorised representative(s) (according to the local regulation) and written or verbal assent by the participant (when appropriate), obtained prior to any study-related procedures;
Adults: Male or female participant ≥18 and ≤85 years of age; Adolescents: Male or female participant ≥12 and <18 years of age;
Adults: BMI (body mass index) >18.5 kg/m² at screening; Adolescents: Body weight >30 kg at screening;
Clinical history consistent with bronchiectasis (cough, chronic sputum production, and/or recurrent respiratory infections) confirmed by centralised reading of a chest CT, not more than 5 years old demonstrating bronchiectasis affecting 1 or more lobes; Note: If no recent chest CT is available, or if the records/report is not available, a new CT chest will be performed during the screening period;
Participants who have experienced any degree of pulmonary exacerbation or are experiencing a pulmonary exacerbation within 4 weeks prior to screening or during the screening period; Note: Participants can be rescreened only after recovery and 4 weeks after the last dose of antibiotic treatment;
Current diagnosis of CF (cystic fibrosis) as determined by Investigator;
Known history of invasive opportunistic infections (such as but not limited to histoplasmosis, pneumocystosis, or aspergillosis) and/or abnormally frequent or prolonged infections suggesting an immunocompromised status judged incompatible with the introduction of a DPP1 inhibitor by the Investigator;
Diagnosis of A1ATD -Alpha-1-antitrypsin deficiency- (defined as A1AT serum level <110 mg/dL) currently being treated with augmentation therapy; Note: A prior test result of A1AT serum level to confirm the diagnosis will be acceptable;