A randomized double-blind, placebo-controlled clinical phase IIa trial on safety, immunomodulatory effects and pharmacokinetics of EA-230 during experimental human endotoxaemia

Abstract

Aims: EA-230 is a human chorionic gonadotropin hormone-derived linear tetrapeptide, developed for the treatment of systemic inflammation-related disorders. EA-230 has shown promising immunomodulatory and tissue-protective effects in animals and an excellent safety profile in human phase I studies that we performed. The present phase IIa study follows-up on these results by investigating the safety, efficacy and pharmacokinetics of EA-230 under systemic inflammatory conditions induced by experimental human endotoxaemia. Methods: In this randomized, double blind, placebo-controlled phase IIa study, systemic inflammation was induced by intravenous administration of Escherichia coli-derived lipopolysaccharide (LPS). At t = 0 hours, 36 healthy male volunteers received 2 ng/kg LPS, followed by a 2-hour continuous infusion of EA-230 (15, 45 and 90 mg/kg/h, n = 8 per group) or placebo (n = 12). Results: EA-230 was well tolerated and showed a favourable safety profile. Treatment with the highest dose of EA-230 resulted in a significant attenuation of the LPS-induced increase in plasma levels of inflammatory mediators interleukin (IL)-6, IL-8, IL-1 receptor antagonist, monocyte chemoattractant protein-1, macrophage inflammatory proteins-1α and -1β, and vascular cell adhesion protein-1 (% reduction of 48, 28, 33, 28, 14, 16 and 19 respectively, p