A Phase 2a Trial of Myeloperoxidase Inhibitor Mitiperstat in Non-Cirrhotic Metabolic Dysfunction-Associated Steatohepatitis.

BACKGROUND AND AIMS: Neutrophil myeloperoxidase is involved in different inflammatory diseases, including metabolic dysfunction-associated steatohepatitis (MASH). Mitiperstat is a highly potent myeloperoxidase inhibitor. This phase 2a clinical trial evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of mitiperstat in patients with non-cirrhotic MASH.

METHODS

The study enrolled 112 adult participants with histological MASH F1-3 fibrosis and increased alanine aminotransferase (ALT) levels. Participants were randomised 1:1 to once-daily mitiperstat 5 mg or placebo. Primary and secondary endpoints were absolute and placebo-adjusted changes from baseline to week 12 in ALT and N-terminal type-III collagen propeptide (Pro-C3) levels. Exploratory endpoints included other MASH-related biomarkers.

RESULTS

At week 12, there were no significant changes versus placebo for ALT (+7.5%, p = 0.893) and Pro-C3 (-0.9%, p = 0.396), or any other MASH-related biomarkers. Mitiperstat was safe and well tolerated.

CONCLUSION

This study does not provide proof of concept that mitiperstat 5 mg exerts an anti-inflammatory/anti-fibrotic effect in MASH.

TRIAL REGISTRATION: ClincalTrials.gov identifier: NCT05638737.