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
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 airwa...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/173554 |
| _version_ | 1811680604381511680 |
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| author | Chalmers, James D. Gupta, Abhya Chotirmall, Sanjay Haresh Armstrong, April Eickholz, Peter Hasegawa, Naoki McShane, Pamela J. O'Donnell, Anne E. Shteinberg, Michal Watz, Henrik Eleftheraki, Anastasia Diefenbach, Claudia Sauter, Wiebke |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Chalmers, James D. Gupta, Abhya Chotirmall, Sanjay Haresh Armstrong, April Eickholz, Peter Hasegawa, Naoki McShane, Pamela J. O'Donnell, Anne E. Shteinberg, Michal Watz, Henrik Eleftheraki, Anastasia Diefenbach, Claudia Sauter, Wiebke |
| author_sort | Chalmers, James D. |
| collection | NTU |
| description | 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™; NCT05238675) 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 weeks, a treatment period of 24-48 weeks and a follow-up period of 4 weeks. ∼240 adults with bronchiectasis of multiple aetiologies will be randomised to placebo once daily, or BI 1291583 1 mg once daily, 2.5 mg once daily or 5 mg once daily in a 2:1:1:2 ratio, stratified by Pseudomonas aeruginosa infection and maintenance use of macrolides. The primary efficacy objective is to evaluate the dose-response relationship for the three oral doses of BI 1291583 versus 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. |
| first_indexed | 2024-10-01T03:27:41Z |
| format | Journal Article |
| id | ntu-10356/173554 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:27:41Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1735542024-02-18T15:37:57Z 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 Chalmers, James D. Gupta, Abhya Chotirmall, Sanjay Haresh Armstrong, April Eickholz, Peter Hasegawa, Naoki McShane, Pamela J. O'Donnell, Anne E. Shteinberg, Michal Watz, Henrik Eleftheraki, Anastasia Diefenbach, Claudia Sauter, Wiebke Lee Kong Chian School of Medicine (LKCMedicine) Tan Tock Seng Hospital Medicine, Health and Life Sciences Cathepsin C Inhibitor Asthma 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™; NCT05238675) 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 weeks, a treatment period of 24-48 weeks and a follow-up period of 4 weeks. ∼240 adults with bronchiectasis of multiple aetiologies will be randomised to placebo once daily, or BI 1291583 1 mg once daily, 2.5 mg once daily or 5 mg once daily in a 2:1:1:2 ratio, stratified by Pseudomonas aeruginosa infection and maintenance use of macrolides. The primary efficacy objective is to evaluate the dose-response relationship for the three oral doses of BI 1291583 versus 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. Published version This study is being funded by Boehringer Ingelheim. The authors did not receive payment related to the development of the manuscript. Funding information for this article has been deposited with the Crossref Funder Registry. 2024-02-14T01:08:06Z 2024-02-14T01:08:06Z 2023 Journal Article Chalmers, J. D., Gupta, A., Chotirmall, S. H., Armstrong, A., Eickholz, P., Hasegawa, N., McShane, P. J., O'Donnell, A. E., Shteinberg, M., Watz, H., Eleftheraki, A., Diefenbach, C. & Sauter, W. (2023). 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. ERJ Open Research, 9(3). https://dx.doi.org/10.1183/23120541.00633-2022 2312-0541 https://hdl.handle.net/10356/173554 10.1183/23120541.00633-2022 37465817 2-s2.0-85163829731 3 9 en ERJ Open Research © The authors 2023. This version is distributed under the terms of the Creative Commons Attribution Licence 4.0. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Cathepsin C Inhibitor Asthma Chalmers, James D. Gupta, Abhya Chotirmall, Sanjay Haresh Armstrong, April Eickholz, Peter Hasegawa, Naoki McShane, Pamela J. O'Donnell, Anne E. Shteinberg, Michal Watz, Henrik Eleftheraki, Anastasia Diefenbach, Claudia Sauter, Wiebke 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 |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | phase 2 randomised study to establish efficacy safety and dosing of a novel oral cathepsin c inhibitor bi 1291583 in adults with bronchiectasis airleaf |
| topic | Medicine, Health and Life Sciences Cathepsin C Inhibitor Asthma |
| url | https://hdl.handle.net/10356/173554 |
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