Interleukin-1 Blockade With RPH-104 (Goflikicept) in Patients With ST-Segment Elevation Myocardial Infarction: Secondary End Points From an International, Double-Blind, Randomized, Placebo-Controlled, Phase 2a Study

Abstract

In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an interleukin-1 blocker, significantly reduced systemic inflammation, measured as the area under the curve (AUC) for high-sensitivity C reactive protein at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical end points 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 high-sensitivity C reactive protein at 28 days compared with placebo, without statistically significant differences between the doses. There were 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, interleukin-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.

FIGURE 1.

hsCRP geometric Mean ± SE from baseline to Day 28. Goflikicept versus placebo. Full analysis set. GMeans ± SE of hsCRP on Day14 were statistically significantly lower for goflikicept 160 mg and 80 mg compared with placebo (P < 0.001) and on Day 28 for goflikicept 160 mg compared with placebo (P < 0.001). **A statistically significant reduction (P-value <0.001) in CRP values on Day 14 between each goflikicept group (160 and 80 mg) compared with placebo. *A statistically significant reduction (P-value <0.001) in CRP values on Day 28 between goflikicept 160 mg) compared with placebo. GMean, geometric mean; hsCRP, high-sensitivity C-reactive protein; SE, standard error.

FIGURE 2.

Geometric Mean ± SE BNP and NT-pro-BNP during the study time. Full analysis set effects of goflikicept on BNP (Left) and NT-pro-BNP (Right). We found no significant difference between each goflikicept group versus placebo, between goflikicept groups combined versus placebo, and between the 80 and 160 mg goflikicept regimens. Groups were analyzed using linear mixed models with the treatment group as a fixed factor, baseline value as a covariate, and the study site as a random effect. Data are presented as geometric mean and standard error. BNP, brain natriuretic peptide; NT-pro-BNP, N-terminal pro–B-type natriuretic peptide; SE, standard error.

FIGURE 3.

Kaplan–Meier plot of secondary and exploratory outcomes. Full analysis set. Effects of goflikicept on clinical events. Left, a secondary outcome of hospitalization for cardiovascular reasons. Middle, an exploratory outcome of new or increased use loop diuretics prescribed for heart failure. Right, an exploratory outcome of new or increased use loop diuretics prescribed for any reason. CV, cardiovascular; HF, heart failure.