C Michael Gibson1, Serge Korjian2, Pierluigi Tricoci3, Yazan Daaboul2, John H Alexander3, Philippe G Steg4, A Michael Lincoff5, John J P Kastelein6, Roxana Mehran7, Denise D'Andrea8, Bela Merkely9, Maciej Zarebinski10, Ton Oude Ophius11, Robert A Harrington12. 1. PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA. Electronic address: mgibson@bidmc.harvard.edu. 2. PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA. 3. Duke Clinical Research Institute, Department of Medicine, Duke University, Durhman, NC. 4. INSERM-Unité 1148, France Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, France Université Paris-Diderot, Sorbonne-Paris Cité, France National Heart and Lung Institute, Imperial College London, UK Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, United Kingdom. 5. Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH. 6. Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 7. Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY. 8. CSL Behring, LLC, King of Prussia, PA. 9. Heart and Vascular Center, Semmelweis University, Városmajor str. 68, Budapest, Hungary. 10. Department of Cardiology, Warsaw Medical University, Warsaw, Poland. 11. Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands. 12. Department of Medicine, Stanford University, Stanford, CA.
Abstract
BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease. DESIGN: The AEGIS-I trial (ClinicalTrials.govNCT02108262) is a phase 2b, multicenter, randomized, placebo-controlled, dose-ranging clinical trial to evaluate the hepatic and renal safety of multiple administrations of 2 doses of CSL112 among subjects with acute myocardial infarction (AMI). Approximately 1,200 subjects (400 per treatment group) with either normal renal function or mild renal impairment will be enrolled up to 7 days after an AMI and will be stratified by renal function and randomized in a 1:1:1 ratio to either 1 of 2 doses of CSL112 (either 2 g or 6 g) or placebo as a weekly 2-hour infusion over the course of 4 consecutive weeks. The coprimary safety endpoints will be the incidence of hepatic and renal toxicity, defined as either confirmed ALT >3 × ULN, total bilirubin >2 × ULN, serum creatinine ≥1.5×baseline value, or a new requirement for renal replacement therapy through the end of the active treatment period. SUMMARY: The AEGIS-I trial will characterize the safety profile of CSL112, a reconstituted formulation of apolipoprotein A-I, and will assess if administration to patients with a recent AMI is associated with a clinically significant alteration in either liver or kidney function when compared with placebo.
RCT Entities:
BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible humanapolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease. DESIGN: The AEGIS-I trial (ClinicalTrials.govNCT02108262) is a phase 2b, multicenter, randomized, placebo-controlled, dose-ranging clinical trial to evaluate the hepatic and renal safety of multiple administrations of 2 doses of CSL112 among subjects with acute myocardial infarction (AMI). Approximately 1,200 subjects (400 per treatment group) with either normal renal function or mild renal impairment will be enrolled up to 7 days after an AMI and will be stratified by renal function and randomized in a 1:1:1 ratio to either 1 of 2 doses of CSL112 (either 2 g or 6 g) or placebo as a weekly 2-hour infusion over the course of 4 consecutive weeks. The coprimary safety endpoints will be the incidence of hepatic and renal toxicity, defined as either confirmed ALT >3 × ULN, total bilirubin >2 × ULN, serum creatinine ≥1.5×baseline value, or a new requirement for renal replacement therapy through the end of the active treatment period. SUMMARY: The AEGIS-I trial will characterize the safety profile of CSL112, a reconstituted formulation of apolipoprotein A-I, and will assess if administration to patients with a recent AMI is associated with a clinically significant alteration in either liver or kidney function when compared with placebo.
Authors: Stephen J Nicholls; Jordan Andrews; John J P Kastelein; Bela Merkely; Steven E Nissen; Kausik K Ray; Gregory G Schwartz; Stephen G Worthley; Connie Keyserling; Jean-Louis Dasseux; Liddy Griffith; Susan W Kim; Alex Janssan; Giuseppe Di Giovanni; Anthony D Pisaniello; Daniel J Scherer; Peter J Psaltis; Julie Butters Journal: JAMA Cardiol Date: 2018-09-01 Impact factor: 14.676
Authors: C Michael Gibson; Serge Korjian; Pierluigi Tricoci; Yazan Daaboul; Megan Yee; Purva Jain; John H Alexander; P Gabriel Steg; A Michael Lincoff; John J P Kastelein; Roxana Mehran; Denise M D'Andrea; Lawrence I Deckelbaum; Bela Merkely; Maciej Zarebinski; Ton Oude Ophuis; Robert A Harrington Journal: Circulation Date: 2016-11-15 Impact factor: 29.690