Abstract 15525: CER-001, a Synthetic HDL-Mimetic, Safely Mobilizes Cholesterol in Healthy Dyslipidemic Volunteers
Background: CER-001 is a synthetic HDL, comprised of recombinant human ApoA-I complexed with phospholipids and designed to mimic the beneficial properties of natural, nascent pre-ß HDL. These benefits include an increase in cholesterol efflux and its subsequent esterification and elimination by reverse cholesterol transport. Previous human studies with synthetic HDLs have demonstrated acute changes in femoral plaque morphology in patients with claudication, and reduction in coronary artery plaque in patients with acute coronary syndromes.
Methods: Healthy male and female volunteers, 18 to 55 years old with an LDL:HDL ratio of ≥3.0, received single intravenous doses of placebo and CER-001, in a double-blind, randomized, cross-over fashion. Subjects remained in-clinic for 72 hours post-dose and were followed on an outpatient basis for 3 weeks post-dose in each dosing period. Study assessments included adverse event (AE) monitoring, clinical laboratory measurements, serial blood sampling for determination of PK/PD parameters, ECGs, physical exams, vital signs and telemetry.
Results and Conclusions: The study enrolled 32 subjects and evaluated dose levels from 0.25 to 45 mg/kg of CER-001. All doses of CER-001 were safe and well tolerated, with an AE profile similar to that observed with placebo. Effects on clinical chemistry, hematology and coagulation parameters were comparable to placebo. No adverse effects of CER-001 on ECGs were observed. No antibodies to ApoA-I were detected following single dose administration of CER-001. Plasma ApoA-I levels increased in a dose-related manner and returned to baseline by 24 hours post-dose for doses up to 10 mg/kg but remained in circulation longer than 72 hours post-dose for doses ≥10 mg/kg, suggesting longer residence time of CER-001 in plasma. Administration of CER-001 caused elevations in plasma cholesterol, as well as, total and free cholesterol in HDL fraction suggesting increased reverse cholesterol transport. Mobilization of free cholesterol in the HDL fraction was seen with CER-001 doses as low as 2.0 mg/kg indicating efficacy at very low doses and supporting the further evaluation of a wide range of doses as potential therapy for patients with atherosclerotic disease.
- © 2011 by American Heart Association, Inc.