Rationale and design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction

• Published in: The American heart journal Vol. 231; pp. 121 - 127
• Main Authors: Gibson, C. Michael, Kastelein, John J.P., Phillips, Adam T., Aylward, Philip E., Yee, Megan K., Tendera, Michal, Nicholls, Stephen J., Pocock, Stuart, Goodman, Shaun G., Alexander, John H., Lincoff, A. Michael, Bode, Christoph, Duffy, Danielle, Heise, Mark, Berman, Gail, Mears, Sojaita Jenny, Tricoci, Pierluigi, Deckelbaum, Lawrence I., Steg, P. Gabriel, Ridker, Paul, Mehran, Roxana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021; Elsevier Limited
• Subjects: Acute coronary syndromes; Aged; Apolipoprotein A; Apolipoprotein A-I; Arteriosclerosis; Atherosclerosis; Blood plasma; Brain Ischemia - prevention & control; Cardiac catheterization; Cardiovascular disease; Cerebral infarction; Cholesterol; Cholesterol - metabolism; Clinical Trials, Phase III as Topic; Coronary artery; Coronary artery disease; Coronary Artery Disease - metabolism; Coronary vessels; Creatinine; Diabetes mellitus; Diabetes Mellitus - drug therapy; Double-Blind Method; Double-blind studies; Drug Administration Schedule; Drug therapy; Efflux; Heart attacks; Heart diseases; Heart failure; Hospitalization - statistics & numerical data; Humans; Intravenous administration; Intubation; Ischemia; Ischemia - prevention & control; Kidney diseases; Lipoproteins, HDL - administration & dosage; Lipoproteins, HDL - adverse effects; Lipoproteins, HDL - therapeutic use; Liver - metabolism; Mortality; Multicenter Studies as Topic; Myocardial infarction; Myocardial Infarction - prevention & control; Myocardial Infarction - therapy; Myocardial Ischemia - prevention & control; Peripheral Vascular Diseases - prevention & control; Placebos - therapeutic use; Plaque, Atherosclerotic - metabolism; Randomized Controlled Trials as Topic; Safety; Stroke - prevention & control; Time Factors; Vascular diseases
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2020.10.052

Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age ≥ 18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or ≥2 of the following: age ≥ 65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365 days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.