Evidence map›Paper›PMID 39255990›Full record

Trial reportThe European respiratory journal2025

Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study.

James D Chalmers, Michal Shteinberg, Marcus A Mall, Anne E O'Donnell, Henrik Watz, Abhya Gupta, Edith Frahm, Anastasia Eleftheraki, Johanna Rauch, Sanjay H Chotirmall and 5 more

Abstract readClinical Trial, Phase IIRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in The European respiratory journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Guideline
  2. Pooled it
  3. Endotypes ofAmerican journal of respiratory and critical care medicine · 2025
    Trial
  4. Article
  5. Review
  6. The frequent exacerbator phenotype in bronchiectasis revisited: data from EMBARC registry.American journal of respiratory and critical care medicine · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. The importance of symptoms in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

James D ChalmersDivision of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK j.chalmers@dundee.ac.uk.
Michal ShteinbergCarmel Medical Center, Haifa, Israel.ORCID https://orcid.org/0000-0002-0432-3398
Marcus A MallDepartment of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID https://orcid.org/0000-0002-4057-2199
Anne E O'DonnellGeorgetown University Medical Center, Washington, DC, USA.
Henrik WatzVelocity Clinical Research Grosshansdorf GmbH, formerly Pulmonary Research Institute, LungenClinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
Abhya GuptaBoehringer Ingelheim International GmbH, Biberach an der Riss, Germany.
Edith FrahmBoehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
Anastasia EleftherakiBoehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
Johanna RauchBoehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
Sanjay H ChotirmallLee Kong Chian School of Medicine, Nanyang Technological University, Singapore.ORCID https://orcid.org/0000-0003-0417-7607
April W ArmstrongDivision of Dermatology, University of California Los Angeles, Los Angeles, CA, USA.
Peter EickholzGoethe-University Frankfurt am Main, Department of Periodontology, Frankfurt am Main, Germany.
Naoki HasegawaDepartment of Infectious Diseases, Keio University, Tokyo, Japan.
Wiebke SauterBoehringer Ingelheim International GmbH, Biberach an der Riss, Germany.
Pamela J McShaneUniversity of Texas Health Science Center at Tyler, Tyler, TX, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBronchiectasis 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

methodsIn total, 322 participants were randomised (2:1:1:2) to receive one of three oral doses of BI 1291583 (1 mg/2.5 mg/5 mg) or placebo for 24-48 weeks. A multiple comparison procedure and modelling approach was used to demonstrate a nonflat 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.

resultsA significant dose-dependent benefit of BI 1291583 over placebo was established based on time to first exacerbation (shape: maximum effect curve 1; adjusted p=0.0448). Treatment with BI 1291583 5 mg and 2.5 mg numerically reduced the risk of an exacerbation compared with placebo (hazard ratio (95% CI) 0.71 (0.48 to 1.05) and 0.66 (0.40 to 1.08), respectively; both p>0.05). BI 1291583 2.5 mg showed numerically better efficacy compared with 5 mg across several end-points; 1 mg was similar to placebo. The safety profile of BI 1291583 was similar to placebo.

conclusionTreatment with BI 1291583 resulted in a reduction in the risk of experiencing an exacerbation in adults with bronchiectasis.

Indexed as

BronchiectasisCathepsin CDose-Response Relationship, DrugAdultAgedDisease ProgressionDouble-Blind MethodFemaleHumansMaleMiddle AgedNeutrophilsQuality of LifeTreatment OutcomeCathepsin CCTSC protein, human

Identifiers

PMID39255990
PMCPMC11694546

What Socratic holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.