Evaluation of potential antiplatelet effects of CSL112 (Apolipoprotein A-I [Human]) in patients with atherosclerosis: results from a phase 2a study.

Published

Journal Article

CSL112 (Apolipoprotein A-I [Human]), an infusible, plasma-derived apolipoprotein A-I, is being developed to reduce cardiovascular events following acute myocardial infarction (AMI). A predecessor compound (CSL111) demonstrated a potential antiplatelet effect. A phase 2a multicentre, randomised, single-ascending dose study in patients with stable atherosclerotic disease receiving dual antiplatelet therapy (DAPT) assessed the potential additive effects of CSL112 administration on platelet function and increase bleeding risk in the subacute period after AMI. Patients (n = 44) on aspirin (75-325 mg/day) and either clopidogrel (75 mg/day, n = 37) or prasugrel (10 mg/day, n = 7) for > 30 days alongside standard-of-care therapy were randomised to a single dose of placebo or CSL112: 1.7, 3.4, or 6.8 g. Light transmission aggregometry was used to assess platelet aggregation in response to 2 mM arachidonic acid, 5 and 20 µM adenosine diphosphate, and 4 µg/mL collagen, pre-dose (baseline) and up to 48 h post-dosing. Compared to placebo, CSL112 had no clinically meaningful time- or dose-dependent effects on maximum platelet aggregation in response to any agonist, by either dose or renal function subgroup (p > 0.05). Coagulation parameters showed little variation over time or between treatment groups (p > 0.05). CSL112, when co-administered with standard DAPT, did not significantly influence platelet aggregation in response to agonists and is, therefore, not expected to significantly increase bleeding risk when administered with antiplatelet therapies.

Full Text

Duke Authors

Cited Authors

  • Gurbel, PA; Tantry, US; D'Andrea, D; Chung, T; Alexander, JH; Bliden, KP; Wright, SD; Tricoci, P

Published Date

  • May 2018

Published In

Volume / Issue

  • 45 / 4

Start / End Page

  • 469 - 476

PubMed ID

  • 29582212

Pubmed Central ID

  • 29582212

Electronic International Standard Serial Number (EISSN)

  • 1573-742X

Digital Object Identifier (DOI)

  • 10.1007/s11239-018-1644-z

Language

  • eng

Conference Location

  • Netherlands