Abstract 14664: Safety, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of Recombinant Human Lecithin-Cholesterol Acyltransferase (MEDI6012) in Subjects With Stable Coronary Heart Disease

Introduction: MEDI6012 is recombinant human lecithin-cholesterol acyltransferase (LCAT), the rate-limiting enzyme in reverse cholesterol transport (RCT) that facilitates the esterification of cholesterol in high-density lipoprotein (HDL-C) and the maturation of HDL particles. Increases in esterified cholesterol via an LCAT infusion have the potential to enhance RCT and benefit patients with coronary heart disease (CHD). Hypotheses: Co-primary hypotheses: 1) MEDI6012 exhibits an acceptable safety profile and 2) MEDI6012 results in dose-dependent responses for HDL-C as a result of increased cholesteryl ester on HDL (HDL-CE). Secondary and exploratory hypotheses examined changes in apolipoprotein A1 (ApoA1) and lipoprotein particle number. Methods: This phase 2a, double-blind study randomized 48 subjects with stable CHD on statin to a single dose of MEDI6012 or placebo (6:2). Four cohorts were dosed intravenously over 1 h (doses A, B, C, and D) and two cohorts were dosed subcutaneously (doses X and Y) and fo...