Background

Uncontrolled neutrophil serine proteases, activated by cathepsin C (CatC), are key drivers of inflammation in bronchiectasis. BI 1291583, a novel CatC inhibitor, will be investigated in two Phase 2 trials in non-cystic fibrosis bronchiectasis (NCFBE; Airleaf?) and cystic fibrosis bronchiectasis (CFBE; Clairafly?). Here, we outline the design of a Phase 2 rollover study (Clairleaf?) assessing long-term safety and efficacy of BI 1291583.

Methods

Clairleaf? will include ~220 patients who have completed the parent trials Airleaf? or Clairafly?. Part A of Clairleaf? is a randomised, double-blind study assessing efficacy and safety of three doses of BI 1291583. Patients treated with BI 1291583 in a parent trial will stay on the same dose. Those who received placebo will be randomised to one of the three BI 1291583 doses (1:1:1). The duration of Part A will depend on completion of the parent trials and will likely be no longer than 1 year for the first patients entering this trial. After Part A, patients may continue to Part B where they will receive the preferred Phase 3 dose of BI 1291583 (open-label) to assess long-term safety. The length of Part B will depend on the occurrence or outcome of Phase 3.

Results

The primary endpoint is the occurrence of treatment-emergent adverse events during Part A and B. Secondary endpoints are time to first pulmonary exacerbation and rate of pulmonary exacerbations. The trial will have been submitted to health authorities by the time of presentation and is expected to begin in the second half of 2023.

Conclusions

This study will help in understanding the long-term safety and efficacy of BI 1291583 in patients with CFBE and NCFBE.