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Original Investigation
September 2018

Effect of Serial Infusions of CER-001, a Pre-β High-Density Lipoprotein Mimetic, on Coronary Atherosclerosis in Patients Following Acute Coronary Syndromes in the CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial: A Randomized Clinical Trial

Author Affiliations
  • 1South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia
  • 2Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  • 3Heart and Vascular Center, Semmelweis University, Budapest, Hungary
  • 4Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
  • 5School of Public Health, Imperial College London, London, England
  • 6University of Colorado School of Medicine, Aurora
  • 7Genesis Healthcare, Sydney, Alexandria, Australia
  • 8Cerenis Pharmaceuticals, Toulouse, France
JAMA Cardiol. 2018;3(9):815-822. doi:10.1001/jamacardio.2018.2121
Key Points

Question  Would infusing low doses of the high-density lipoprotein mimetic, CER-001, modify coronary atherosclerosis disease progression?

Findings  In this randomized clinical trial, 272 patients with an acute coronary syndrome were treated with weekly intravenous infusions of low doses of CER-001 or placebo for 10 weeks and underwent serial intravascular ultrasonography determination of coronary atheroma volume. Infusing CER-001 did not promote regression of coronary atherosclerosis compared with placebo in statin-treated patients.

Meaning  Addition of low doses of the high-density lipoprotein mimetic, CER-001, did not produce plaque regression in statin-treated patients following acute coronary syndrome.

Abstract

Importance  CER-001 is a negatively charged, engineered pre-β high-density lipoprotein (HDL) mimetic containing apolipoprotein A-I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER-001 on cholesterol efflux and vascular inflammation. A post hoc reanalysis of a previously completed study of intravenous infusion of CER-001, 3 mg/k, showed that the intravenous infusion in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasonography.

Objective  To determine the effect of infusing CER-001 on coronary atherosclerosis progression in statin-treated patients.

Design, Setting, and Participants  A double-blind, randomized, multicenter trial evaluating the effect of 10 weekly intravenous infusions of CER-001, 3 mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) greater than 30% in the proximal segment of an epicardial artery by intravascular ultrasonography. The study included 34 academic and community hospitals in Australia, Hungary, the Netherlands, and the United States in patients with ACS presenting for coronary angiography. Patients were enrolled from August 15, 2015, to November 19, 2016.

Interventions  Participants were randomized to receive weekly CER-001, 3 mg/kg, or placebo for 10 weeks in addition to statins.

Main Outcomes and Measures  The primary efficacy measure was the nominal change in PAV from baseline to day 78 measured by serial intravascular ultrasonography imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated.

Results  Among 293 patients (mean [SD] age, 59.8 [9.4] years; 217 men [79.8%] and 261 white race/ethnicity [96.0%]), 86 (29%) had statin prior use prior to the index ACS and 272 (92.8%) had evaluable imaging at follow-up. The placebo and CER-001 groups had similar posttreatment median levels of low-density lipoprotein cholesterol (74 mg/dL vs 79 mg/dL; P = .15) and high-density lipoprotein cholesterol (43 mg/dL vs 44 mg/dL; P = .66). The primary efficacy measure, PAV, decreased 0.41% with placebo (P = .005 compared with baseline), but not with CER-001 (−0.09%; P = .67 compared with baseline; between group differences, 0.32%; P = .15). Similar percentages of patients in the placebo and CER-001 groups demonstrated regression of PAV (57.7% vs 53.3%; P = .49). Infusions were well tolerated, with no differences in clinical and laboratory adverse events observed between treatment groups.

Conclusions and Relevance  Infusion of CER-001 did not promote regression of coronary atherosclerosis in statin-treated patients with ACS and high plaque burden.

Trial Registration  ClinicalTrials.gov Identifier: NCT2484378

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