The CSL112-2001 trial

Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction

C. Michael Gibson, Mathieu Kerneis, Megan K. Yee, Yazan Daaboul, Serge Korjian, Ali Poyan Mehr, Pierluigi Tricoci, John H. Alexander, John J.P. Kastelein, Roxana Mehran, Christoph Bode, Basil S. Lewis, Ravindra Mehta, Danielle Duffy, John Feaster, Majdi Halabi, Dominick J. Angiolillo, Daniel Duerschmied, Ton Oude Ophuis, B. Merkely

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalAmerican Heart Journal
Volume208
DOIs
Publication statusPublished - Feb 1 2019

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Apolipoprotein A-I
Myocardial Infarction
Kidney
Safety
Placebos
Chronic Renal Insufficiency
Acute Kidney Injury
CSL112
human APOA1 protein
Risk Reduction Behavior
Glomerular Filtration Rate
Creatinine
Cholesterol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The CSL112-2001 trial : Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction. / Gibson, C. Michael; Kerneis, Mathieu; Yee, Megan K.; Daaboul, Yazan; Korjian, Serge; Mehr, Ali Poyan; Tricoci, Pierluigi; Alexander, John H.; Kastelein, John J.P.; Mehran, Roxana; Bode, Christoph; Lewis, Basil S.; Mehta, Ravindra; Duffy, Danielle; Feaster, John; Halabi, Majdi; Angiolillo, Dominick J.; Duerschmied, Daniel; Ophuis, Ton Oude; Merkely, B.

In: American Heart Journal, Vol. 208, 01.02.2019, p. 81-90.

Research output: Contribution to journalArticle

Gibson, CM, Kerneis, M, Yee, MK, Daaboul, Y, Korjian, S, Mehr, AP, Tricoci, P, Alexander, JH, Kastelein, JJP, Mehran, R, Bode, C, Lewis, BS, Mehta, R, Duffy, D, Feaster, J, Halabi, M, Angiolillo, DJ, Duerschmied, D, Ophuis, TO & Merkely, B 2019, 'The CSL112-2001 trial: Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction', American Heart Journal, vol. 208, pp. 81-90. https://doi.org/10.1016/j.ahj.2018.11.008
Gibson, C. Michael ; Kerneis, Mathieu ; Yee, Megan K. ; Daaboul, Yazan ; Korjian, Serge ; Mehr, Ali Poyan ; Tricoci, Pierluigi ; Alexander, John H. ; Kastelein, John J.P. ; Mehran, Roxana ; Bode, Christoph ; Lewis, Basil S. ; Mehta, Ravindra ; Duffy, Danielle ; Feaster, John ; Halabi, Majdi ; Angiolillo, Dominick J. ; Duerschmied, Daniel ; Ophuis, Ton Oude ; Merkely, B. / The CSL112-2001 trial : Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction. In: American Heart Journal. 2019 ; Vol. 208. pp. 81-90.
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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.",
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T2 - Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction

AU - Gibson, C. Michael

AU - Kerneis, Mathieu

AU - Yee, Megan K.

AU - Daaboul, Yazan

AU - Korjian, Serge

AU - Mehr, Ali Poyan

AU - Tricoci, Pierluigi

AU - Alexander, John H.

AU - Kastelein, John J.P.

AU - Mehran, Roxana

AU - Bode, Christoph

AU - Lewis, Basil S.

AU - Mehta, Ravindra

AU - Duffy, Danielle

AU - Feaster, John

AU - Halabi, Majdi

AU - Angiolillo, Dominick J.

AU - Duerschmied, Daniel

AU - Ophuis, Ton Oude

AU - Merkely, B.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

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