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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.

Publication ,  Journal Article
Gibson, CM; Kerneis, M; Yee, MK; Daaboul, Y; Korjian, S; Mehr, AP; Tricoci, P; Alexander, JH; Kastelein, JJP; Mehran, R; Bode, C; Lewis, BS ...
Published in: Am Heart J
February 2019

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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Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2019

Volume

208

Start / End Page

81 / 90

Location

United States

Related Subject Headings

  • Time Factors
  • Sample Size
  • Renal Insufficiency, Chronic
  • Myocardial Infarction
  • Male
  • Lipoproteins, HDL
  • Intention to Treat Analysis
  • Humans
  • Glomerular Filtration Rate
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Gibson, C. M., Kerneis, M., Yee, M. K., Daaboul, Y., Korjian, S., Mehr, A. P., … 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. Am Heart J, 208, 81–90. https://doi.org/10.1016/j.ahj.2018.11.008
Gibson, C Michael, Mathieu Kerneis, Megan K. Yee, Yazan Daaboul, Serge Korjian, Ali Poyan Mehr, Pierluigi Tricoci, et al. “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.Am Heart J 208 (February 2019): 81–90. https://doi.org/10.1016/j.ahj.2018.11.008.
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. 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. Am Heart J. 2019 Feb;208:81–90.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2019

Volume

208

Start / End Page

81 / 90

Location

United States

Related Subject Headings

  • Time Factors
  • Sample Size
  • Renal Insufficiency, Chronic
  • Myocardial Infarction
  • Male
  • Lipoproteins, HDL
  • Intention to Treat Analysis
  • Humans
  • Glomerular Filtration Rate
  • Female