Phase III AIRTIVITY study design: verducatib (BI 1291583) in people with bronchiectasis

There is an unmet need for therapies targeting chronic neutrophilic inflammation in bronchiectasis. In the phase II, dose-finding AIRLEAF study, the dipeptidyl peptidase 1 (cathepsin C) inhibitor verducatib (BI 1291583) reduced the pulmonary exacerbation risk in people with bronchiectasis and demonstrated a similar safety profile to placebo; these results support the investigation of verducatib in a phase III study. Here, we describe the design of the randomised, placebo-controlled phase III AIRTIVITY study (ClinicalTrials.gov identifier NCT06872892), assessing the efficacy, safety and tolerability of verducatib in people with bronchiectasis. In AIRTIVITY, approximately 1680 adults and 75 adolescents (aged 12-<18 years) with bronchiectasis with a broad range of aetiologies are randomised 2:1 to receive oral verducatib 2.5 mg or placebo for at least 52 weeks and up to 76 weeks. Unlike previous studies of bronchiectasis, people with cystic fibrosis bronchiectasis are included. The primary objective is to demonstrate the superiority of verducatib compared with placebo on the annualised rate of pulmonary exacerbations up to 76 weeks. The main secondary objective is to demonstrate a reduction in lung function decline, an improvement in respiratory symptoms, a prolongation in time to first pulmonary exacerbation and a reduction in annualised rate of severe pulmonary exacerbations for verducatib versus placebo. All pulmonary exacerbations are adjudicated. If the efficacy of verducatib is demonstrated and there is a favourable benefit-risk ratio, the AIRTIVITY results will provide confirmatory evidence for the use of verducatib 2.5 mg in a large and broad bronchiectasis population, independent of underlying aetiology.