A phase 2a, double-blind, randomised, placebo-controlled trial of the myeloperoxidase inhibitor, mitiperstat, in participants with chronic obstructive pulmonary disease.

BACKGROUND: Neutrophilic inflammation is a common feature of chronic obstructive pulmonary disease (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 daily up to 24 weeks (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 endpoint was time to first composite endpoint for exacerbations in COPD (COPDCompEx) event. Secondary endpoints 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% confidence interval (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.