{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:17:26Z","timestamp":1791404246862,"version":"4.3.3"},"reference-count":42,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2023,3,28]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:p>New therapies are needed to prevent exacerbations, improve quality of life and slow disease progression in bronchiectasis. Inhibition of cathepsin C (CatC) activity has the potential to decrease activation of neutrophil-derived serine proteases in patients with bronchiectasis, thereby reducing airway inflammation, improving symptoms, reducing exacerbations and preventing further airway damage. Here we present the design of a phase 2 trial (Airleaf\u2122;<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05238675\">NCT05238675<\/jats:ext-link>) assessing the efficacy and safety of a novel CatC inhibitor, BI 1291583, in adult patients with bronchiectasis. This multinational, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study has a screening period of at least 6\u2005weeks, a treatment period of 24\u201348\u2005weeks and a follow-up period of 4\u2005weeks. \u223c240 adults with bronchiectasis of multiple aetiologies will be randomised to placebo once daily, or BI 1291583 1\u2005mg once daily, 2.5\u2005mg once daily or 5\u2005mg once daily in a 2:1:1:2 ratio, stratified by<jats:italic>Pseudomonas aeruginosa<\/jats:italic>infection and maintenance use of macrolides. The primary efficacy objective is to evaluate the dose\u2013response relationship for the three oral doses of BI 1291583<jats:italic>versus<\/jats:italic>placebo on time to first pulmonary exacerbation up to Week 48 (the primary end-point). Efficacy will be assessed using exacerbations, patient-reported outcomes, measures of symptoms, sputum neutrophil elastase activity and pulmonary function testing. Safety assessment will include adverse event reporting, physical examination, monitoring of vital signs, safety laboratory parameters, 12-lead electrocardiogram, and periodontal and dermatological assessments. If efficacy and safety are demonstrated, results will support further investigation of BI 1291583 in phase 3 trials.<\/jats:p>","DOI":"10.1183\/23120541.00633-2022","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T16:25:54Z","timestamp":1683822354000},"page":"00633-2022","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["A Phase 2 randomised study to establish efficacy, safety and dosing of a novel oral cathepsin C inhibitor, BI 1291583, in adults with bronchiectasis: Airleaf"],"prefix":"10.1183","volume":"9","author":[{"given":"James D.","family":"Chalmers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhya","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7607","authenticated-orcid":false,"given":"Sanjay 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emerging role of proteases in alpha1-antitrypsin deficiency and beyond","volume":"7","author":"Fazleen","year":"2021","journal-title":"ERJ Open Res"},{"key":"2024101711573690000_9.3.00633-2022.26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200213462"},{"key":"2024101711573690000_9.3.00633-2022.27","doi-asserted-by":"crossref","unstructured":"Badorrek P , Diefenbach C , Kogler H , et al. 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A study to assess the efficacy, safety, and tolerability of brensocatib in participants with non-cystic fibrosis bronchiectasis (ASPEN). https:\/\/clinicaltrials.gov\/ct2\/show\/record\/NCT04594369 Date last accessed: 8 July 2022."},{"key":"2024101711573690000_9.3.00633-2022.39","doi-asserted-by":"publisher","DOI":"10.1038\/70472"},{"key":"2024101711573690000_9.3.00633-2022.40","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00328-2018"},{"key":"2024101711573690000_9.3.00633-2022.41","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00399-2021"},{"key":"2024101711573690000_9.3.00633-2022.42","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1164\/rccm.202108-1943OC","article-title":"Endotyping chronic obstructive pulmonary disease, bronchiectasis, and the \u201cchronic obstructive pulmonary disease\u2013bronchiectasis association\u201d","volume":"206","author":"Huang","year":"2022","journal-title":"Am J Respir Crit Care Med"}],"container-title":["ERJ Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/23120541.00633-2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T05:25:18Z","timestamp":1740374718000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/23120541.00633-2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,6,26]]},"published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1183\/23120541.00633-2022"],"URL":"https:\/\/doi.org\/10.1183\/23120541.00633-2022","relation":{},"ISSN":["2312-0541"],"issn-type":[{"value":"2312-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5]]}}}