C Michael Gibson1, Mathieu Kerneis2, Megan K Yee2, Yazan Daaboul2, Serge Korjian2, Ali Poyan Mehr3, Pierluigi Tricoci4, John H Alexander4, John J P Kastelein5, Roxana Mehran6, Christoph Bode7, Basil S Lewis8, Ravindra Mehta9, Danielle Duffy10, John Feaster10, Majdi Halabi11, Dominick J Angiolillo12, Daniel Duerschmied7, Ton Oude Ophuis13, Bela Merkely14. 1. From the PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA. Electronic address: mgibson@bidmc.harvard.edu. 2. From the PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA. 3. Nephrology Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA. 4. Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke Health, Durham, NC. 5. Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 6. Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, NY. 7. Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 8. Lady Davis Carmel Medical Center and Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 9. Division of Nephrology-Hypertension, University of California San Diego School of Medicine, San Diego, CA. 10. CSL Behring, King of Prussia, PA. 11. Department of Cardiology, Ziv Medical Center, Derech HaRambam, Tsfat 13100, Israel. 12. Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL. 13. Department of Cardiology, Canisius Wilhelmina Ziekenhuis, Nijmegen, the Netherlands. 14. Heart and Vascular Center, Semmelweis University, H-1122 Városmajor str 68, Budapest, Hungary.
Abstract
BACKGROUND:CSL112 (apolipoprotein A-I [human]) is a plasma-derived apolipoprotein A-I developed for early reduction of cardiovascular risk following an acute myocardial infarction (AMI). The safety of CSL112 among AMI subjects with moderate, stage 3 chronic kidney disease (CKD) is unknown. METHODS:CSL112_2001, a multicenter, placebo-controlled, parallel-group, double-blind, randomized phase 2 trial, enrolled patients with moderate CKD within 7 days following AMI. Enrollment was stratified on the basis of estimated glomerular filtration rate and presence of diabetes requiring treatment. Patients were randomized in a 2:1 ratio to receive 4 weekly infusions of CSL112 6 g or placebo. The co-primary safety end points were renal serious adverse events (SAEs) and acute kidney injury, defined as an increase ≥26.5 μmol/L in baseline serum creatinine for more than 24 hours, during the treatment period. RESULTS: A total of 83 patients were randomized (55 CSL112 vs 28 placebo). No increase in renal SAEs was observed in the CSL112 group compared with placebo (CSL112 = 1 [1.9%], placebo = 4 [14.3%]). Similarly, no increase in acute kidney injury events was observed (CSL112 = 2 [4.0%], placebo = 4 [14.3%]). Rates of other SAEs were similar between groups. CSL112 administration resulted in increases in ApoA-I and cholesterol efflux similar to those observed in patients with AMI and normal renal function or stage 2 CKD enrolled in the ApoA-I Event Reducing in Ischemic Syndromes I trial. CONCLUSIONS: These results demonstrate the acceptable safety of the 6-g dose of CSL112 among AMI subjects with moderate stage 3 CKD and support inclusion of these patients in a phase 3 cardiovascular outcomes trial powered to assess efficacy.
RCT Entities:
BACKGROUND: CSL112 (apolipoprotein A-I [human]) is a plasma-derived apolipoprotein A-I developed for early reduction of cardiovascular risk following an acute myocardial infarction (AMI). The safety of CSL112 among AMI subjects with moderate, stage 3 chronic kidney disease (CKD) is unknown. METHODS: CSL112_2001, a multicenter, placebo-controlled, parallel-group, double-blind, randomized phase 2 trial, enrolled patients with moderate CKD within 7 days following AMI. Enrollment was stratified on the basis of estimated glomerular filtration rate and presence of diabetes requiring treatment. Patients were randomized in a 2:1 ratio to receive 4 weekly infusions of CSL112 6 g or placebo. The co-primary safety end points were renal serious adverse events (SAEs) and acute kidney injury, defined as an increase ≥26.5 μmol/L in baseline serum creatinine for more than 24 hours, during the treatment period. RESULTS: A total of 83 patients were randomized (55 CSL112 vs 28 placebo). No increase in renal SAEs was observed in the CSL112 group compared with placebo (CSL112 = 1 [1.9%], placebo = 4 [14.3%]). Similarly, no increase in acute kidney injury events was observed (CSL112 = 2 [4.0%], placebo = 4 [14.3%]). Rates of other SAEs were similar between groups. CSL112 administration resulted in increases in ApoA-I and cholesterol efflux similar to those observed in patients with AMI and normal renal function or stage 2 CKD enrolled in the ApoA-I Event Reducing in Ischemic Syndromes I trial. CONCLUSIONS: These results demonstrate the acceptable safety of the 6-g dose of CSL112 among AMI subjects with moderate stage 3 CKD and support inclusion of these patients in a phase 3 cardiovascular outcomes trial powered to assess efficacy.
Authors: Bo Zheng; Shinya Goto; Regina Clementi; John Feaster; Danielle Duffy; Penelope Dalitz; Jolanta Airey; Serge Korjian; Michael A Tortorici; John Roberts; C Michael Gibson Journal: Clin Transl Sci Date: 2022-08-07 Impact factor: 4.438
Authors: Bronwyn A Kingwell; Stephen J Nicholls; Elena Velkoska; Svetlana A Didichenko; Danielle Duffy; Serge Korjian; C Michael Gibson Journal: J Am Heart Assoc Date: 2022-04-12 Impact factor: 6.106
Authors: Bo Zheng; Danielle Duffy; Pierluigi Tricoci; Helen Kastrissios; Marc Pfister; Samuel D Wright; Andreas Gille; Michael A Tortorici Journal: Br J Clin Pharmacol Date: 2020-12-23 Impact factor: 4.335