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.

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.

• Authors: 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, Bela Merkely
• Journal: American heart journal (Am Heart J) Vol. 208 Pg. 81-90 (02 2019) ISSN: 1097-6744 [Electronic] United States
• PMID: 30580130 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Apolipoprotein A-I
• Biomarkers
• CSL112
• Lipoproteins, HDL
• Cholesterol
• Creatinine

Topics

• Acute Kidney Injury (blood, chemically induced)
• Aged
• Apolipoprotein A-I (blood)
• Biomarkers (blood)
• Cholesterol (blood)
• Creatinine (blood)
• Female
• Glomerular Filtration Rate
• Humans
• Intention to Treat Analysis
• Lipoproteins, HDL (administration & dosage, adverse effects)
• Male
• Myocardial Infarction (blood, complications, drug therapy)
• Renal Insufficiency, Chronic (blood, complications)
• Sample Size
• Time Factors