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

IMPORTANCE CER-001 is a negatively charged, engineered pre-β high-density lipoprotein (HDL) mimetic containing apolipoproteinA-I and sphingomyelin. Preliminary studies demonstrated favorable effects ofCER-001oncholesterol effluxandvascular inflammation.Aposthocreanalysis of a previously completed study of intravenous infusion of CER-001, 3mg/k, showed that the intravenousinfusioninpatientswithahighcoronaryplaqueburdenpromotedregressionasassessed 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 10weekly intravenous infusions of CER-001, 3mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) greater than30%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. Patientswere enrolled from August 15, 2015, to November 19, 2016. INTERVENTIONS Participants were randomized to receive weekly CER-001, 3mg/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 today 78 measured by serial intravascular ultrasonography imaging. These condary efficacy measureswere nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerabilitywere 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 indexACS and 272 (92.8%)had evaluable imagingat follow-up. The place boand CER-001 groups had similar post treatment median levels of low-density lipoprotein cholesterol (74mg/dL vs 79mg/dL; P = .15) and high-density lipoproteincholesterol(43mg/dLvs44mg/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.