Interleukin-1 blockade with RPH-104 (goflikicept) in patients with ST-segment elevation myocardial infarction (STEMI): secondary endpoints from an international, double blind, randomized, placebo-controlled, phase IIa study.

Abstract

In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an Interleukin-1 (IL-1) blocker, significantly reduced systemic inflammation, measured as the area-under-the-curve (AUC) for high-sensitivity C reactive protein (hsCRP) at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical endpoints at 1 year. Patients received a single administration of goflikicept 80 mg (n=34), goflikicept 160 mg (n=34), or placebo (n=34). Both doses of goflikicept significantly reduced the AUC for hsCRP at 28 days compared with placebo, without statistically significant differences between the doses. There we no statistically significant differences between groups in the AUC for natriuretic peptides at 28 days. There were no significant differences between placebo, goflikicept 80 mg and 160 mg groups in deaths (2.9%, 2.9% and 0%), hospitalization for cardiovascular reasons (9.1%, 5.9%, and 0%), new-onset or progression of heart failure (9.1%, 5.9%, and 5.9%), and new or increased use of loop diuretics (24.2%, 14.7%, and 17.6%), nor in the number of patients with treatment emergent adverse events, with no treatment-related serious adverse events in any group. In conclusion, in patients with STEMI, IL-1 blockade with goflikicept 80 mg or 160 mg was well tolerated and associated with significant reduction of systemic inflammation. Further adequately powered studies are warranted to determine whether the reduction in systemic inflammation with goflikicept translates into a clinical benefit in patients with STEMI.