BibTex format
@article{Chalmers:2024:10.1183/13993003.01551-2024,
author = {Chalmers, JD and Shteinberg, M and Mall, MA and O'Donnell, AE and Watz, H and Gupta, A and Frahm, E and Eleftheraki, A and Rauch, J and Chotirmall, SH and Armstrong, AW and Eickholz, P and Hasegawa, N and Sauter, W and McShane, PJ},
doi = {10.1183/13993003.01551-2024},
journal = {Eur Respir J},
title = {Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF®, a Phase II randomised, double-blind, placebo-controlled, dose-finding study.},
url = {http://dx.doi.org/10.1183/13993003.01551-2024},
year = {2024}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Bronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil-mediated lung damage. This Phase II, randomised, double-blind, placebo-controlled trial (AIRLEAF®; NCT05238675) evaluated efficacy, safety and optimal dosing of BI 1291583, a novel, reversible CatC inhibitor, in adults with bronchiectasis.In total, 322 participants were randomised (2:1:1:2) to receive one of three oral doses of BI 1291583 (1mg/2.5mg/5mg) or placebo for 24 to 48weeks. A multiple comparison procedure and modelling approach was used to demonstrate a non-flat dose-response curve based on the time to first pulmonary exacerbation up to Week 48. In addition, efficacy of individual BI 1291583 doses was evaluated based on the frequency of exacerbations, severe exacerbations (fatal or leading to hospitalisation and/or intravenous antibiotic administration), lung function and quality of life.A significant dose-dependent benefit of BI 1291583 over placebo was established based on time to first exacerbation (shape: Emax; adjusted p-value: 0.0448). Treatment with BI 1291583 5mg and 2.5mg numerically reduced the risk of an exacerbation compared with placebo (hazard ratios: 0.71 and 0.66, 95% CIs 0.48-1.05 and 0.40-1.08; both p>0.05). BI 1291583 2.5mg showed numerically better efficacy compared with 5mg across several endpoints; 1mg was similar to placebo. The safety profile of BI 1291583 was similar to placebo.Treatment with BI 1291583 resulted in a reduction in the risk of experiencing an exacerbation in adults with bronchiectasis.
AU - Chalmers,JD
AU - Shteinberg,M
AU - Mall,MA
AU - O'Donnell,AE
AU - Watz,H
AU - Gupta,A
AU - Frahm,E
AU - Eleftheraki,A
AU - Rauch,J
AU - Chotirmall,SH
AU - Armstrong,AW
AU - Eickholz,P
AU - Hasegawa,N
AU - Sauter,W
AU - McShane,PJ
DO - 10.1183/13993003.01551-2024
PY - 2024///
TI - Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF®, a Phase II randomised, double-blind, placebo-controlled, dose-finding study.
T2 - Eur Respir J
UR - http://dx.doi.org/10.1183/13993003.01551-2024
UR - https://www.ncbi.nlm.nih.gov/pubmed/39255990
ER -