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.

Acute Kidney Injury / blood Aged Apolipoprotein A-I / blood Biomarkers / blood Cholesterol / blood Creatinine / blood Female Glomerular Filtration Rate Humans Intention to Treat Analysis Lipoproteins, HDL / administration & dosage Male Myocardial Infarction / blood Renal Insufficiency, Chronic / blood Sample Size Time Factors

Journal

American heart journal

ISSN: 1097-6744

Titre abrégé: Am Heart J

Pays: United States

ID NLM: 0370465

Informations de publication

Date de publication:
02 2019

Historique:

received: 01 05 2018

accepted: 14 11 2018

pubmed: 24 12 2018

medline: 17 10 2019

entrez: 24 12 2018

Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND

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.

Identifiants

DOI: 10.1016/j.ahj.2018.11.008 PMID: 30580130

pubmed: 30580130

pii: S0002-8703(18)30324-7

doi: 10.1016/j.ahj.2018.11.008

pii:

doi:

Substances chimiques

Apolipoprotein A-I 0

Biomarkers 0

CSL112 0

Lipoproteins, HDL 0

Cholesterol 97C5T2UQ7J

Creatinine AYI8EX34EU

Banques de données

ClinicalTrials.gov

['NCT02742103']

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

81-90

Subventions

Organisme : NCATS NIH HHS

ID : UL1 TR000064

Pays : United States

Organisme : NHGRI NIH HHS

ID : U01 HG007269