A phase 2a, double-blind, randomised, placebo-controlled trial of the myeloperoxidase inhibitor, mitiperstat, in participants with COPD
17 affiliations
- 1National Institute for Health Research Patient Recruitment Centre and Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
- 2Clinical Development, Respiratory and Immunology, AstraZeneca, Cambridge, UK
- 3General Practitioners Research Institute, Groningen, The Netherlands
- 4Observational and Pragmatic Research Institute, Singapore, Singapore
- 5Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- 6Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- 7Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- 8Translational Science and Experimental Medicine, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- 9R&I Biometrics and Statistical Innovation, Late Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
- 10Respiratory Pharmacology Group, National Heart and Lung Institute, Imperial College London, London, UK
- 11Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden
- 12Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
- 13Early Biometrics, Late-Stage Development Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Barcelona, Spain
- 14Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK
- 15King's Centre for Lung Health, Peter Gorer Department of Immunobiology, King's College London, London, UK
- 16UCL Respiratory, University College London, London, UK
- 17Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital – Research Institute, Medical University of Lodz, Łódź, Poland
Abstract
Background: Neutrophilic inflammation is a common feature of COPD. Mitiperstat, an inhibitor of myeloperoxidase expressed in neutrophils, may have potential as a COPD treatment.
Methods: This phase 2a, randomised, placebo-controlled, double-blind, parallel-arm, event-driven trial evaluated the efficacy and safety of mitiperstat 5 mg once daily for up to 24 weeks (CRESCENDO; ClinicalTrials.gov: NCT05492877). Adults (40–80 years) with moderate-to-severe COPD, at high risk of exacerbation and receiving dual or triple inhaled therapy were included. The primary end-point was time to first composite end-point for exacerbations in COPD (COPDCompEx) event. Secondary end-points included time to first moderate-to-severe COPD exacerbation, post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) change at week 12, respiratory symptoms, disease impact and safety.
Results: Overall, 381 participants (mean age 66.0 years; 39.6% female) were randomised to mitiperstat (n=189) or placebo (n=192). In total, 125 (66.1%) mitiperstat-treated versus 125 (65.1%) placebo-treated participants experienced COPDCompEx events over 24 weeks. There was no improvement in time to first COPDCompEx event (hazard ratio (HR) 1.07, 90% CI 0.87–1.32; p=0.599) or time to first moderate-to-severe COPD exacerbation (HR 1.23, 90% CI 0.88–1.73) with mitiperstat versus placebo. Improvements in post-BD FEV1, respiratory symptoms or disease impact were not seen with mitiperstat. A similar proportion of participants in both groups reported adverse events; seven mitiperstat-treated participants and two placebo-treated participants had pneumonia during the study.
Conclusion: These results indicate that the risks outweigh the benefits of mitiperstat as a treatment for COPD.
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BibTeX
@article{saralaya2026phase,
title = {{A phase 2a, double-blind, randomised, placebo-controlled trial of the myeloperoxidase inhibitor, mitiperstat, in participants with COPD}},
author = {Dinesh Saralaya and M. Nubli Mustapa and João Ferreira and Janwillem W.H. Kocks and Wayne Brailsford and Sanna Rosengren and Enti Spata and Maria G. Belvisi and Jacob Leander and Camille Riff and Giovanna De Palo and Daniel Windgassen and James D. Chalmers and Richard E.K. Russell and John R. Hurst and Adam Śmiałowski and Rod Hughes},
journal = {The European Respiratory Journal},
year = {2026},
month = nov,
doi = {10.1183/13993003.02567-2025},
url = {https://doi.org/10.1183/13993003.02567-2025},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - A phase 2a, double-blind, randomised, placebo-controlled trial of the myeloperoxidase inhibitor, mitiperstat, in participants with COPD
AU - Dinesh Saralaya
AU - M. Nubli Mustapa
AU - João Ferreira
AU - Janwillem W.H. Kocks
AU - Wayne Brailsford
AU - Sanna Rosengren
AU - Enti Spata
AU - Maria G. Belvisi
AU - Jacob Leander
AU - Camille Riff
AU - Giovanna De Palo
AU - Daniel Windgassen
AU - James D. Chalmers
AU - Richard E.K. Russell
AU - John R. Hurst
AU - Adam Śmiałowski
AU - Rod Hughes
PY - 2026
DA - 2026/11/05
JO - The European Respiratory Journal
DO - 10.1183/13993003.02567-2025
UR - https://doi.org/10.1183/13993003.02567-2025
AB - Background: Neutrophilic inflammation is a common feature of COPD. Mitiperstat, an inhibitor of myeloperoxidase expressed in neutrophils, may have potential as a COPD treatment. Methods: This phase 2a, randomised, placebo-controlled, double-blind, parallel-arm, event-driven trial evaluated the efficacy and safety of mitiperstat 5 mg once daily for up to 24 weeks (CRESCENDO; ClinicalTrials.gov: NCT05492877). Adults (40–80 years) with moderate-to-severe COPD, at high risk of exacerbation and receiving dual or triple inhaled therapy were included. The primary end-point was time to first composite end-point for exacerbations in COPD (COPDCompEx) event. Secondary end-points included time to first moderate-to-severe COPD exacerbation, post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) change at week 12, respiratory symptoms, disease impact and safety. Results: Overall, 381 participants (mean age 66.0 years; 39.6% female) were randomised to mitiperstat (n=189) or placebo (n=192). In total, 125 (66.1%) mitiperstat-treated versus 125 (65.1%) placebo-treated participants experienced COPDCompEx events over 24 weeks. There was no improvement in time to first COPDCompEx event (hazard ratio (HR) 1.07, 90% CI 0.87–1.32; p=0.599) or time to first moderate-to-severe COPD exacerbation (HR 1.23, 90% CI 0.88–1.73) with mitiperstat versus placebo. Improvements in post-BD FEV1, respiratory symptoms or disease impact were not seen with mitiperstat. A similar proportion of participants in both groups reported adverse events; seven mitiperstat-treated participants and two placebo-treated participants had pneumonia during the study. Conclusion: These results indicate that the risks outweigh the benefits of mitiperstat as a treatment for COPD.
SN - 0903-1936
SN - 1399-3003
ER -