Novel Antiplatelet May Offer Antithrombotic Effect Without Bleeding Risk
ACT017, a novel antiplatelet agent, has consistent pharmacokinetic and pharmacodynamic properties and appears to be safe and tolerable, according to results of a first-in-human, randomized, placebo-controlled phase 1 study.1
ACT017 is a first-in-class, therapeutic antibody to platelet glycoprotein VI agent with potent and selective antiplatelet effects. By targeting a protein that is critical for clot formation but not in regulating bleeding, the drug can safely inhibit the clumping of platelets without increasing the risk for bleeding.
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To evaluate its safety and tolerability when administered as a 6-hour intravenous infusion, the researchers studied the effect of ACT017 in 36 healthy men and women aged 22 to 65 years with a body mass index between 18 kg/m2 and 30 kg/m2.
The study was composed of 6 cohorts, each with 8 participants. Within each cohort, 6 participants received ascending single doses of ACT017 and 2 received a placebo. A quarter of the total dose was administered within 15 minutes, while the rest of the dose was given within 5 hours and 45 minutes.
The 6 dosages that were studied ranged from 62.5 to 2000.0 mg, all of which were well-tolerated, and none of which led to any serious adverse event or infusion site reaction.
At none of the dosage levels was there a clinically significant effect on template bleeding time.
Plasma concentrations, as well as the established pharmacokinetics values, increased linearly with the dose received. Further, the extent and duration of the therapeutic effect was dose-dependent and reached its maximum effectiveness and duration at 2000.0 mg.
“Our results are quite encouraging because they show the candidate compound is well-tolerated at doses even twice as high as the ones targeted for a future treatment and without any signs of bleeding,” said study senior author Martine Jandrot-Perrus, MD, PhD. “Another encouraging finding is the fact that the drug’s action on platelets is rapid, specific, and largely reversible within 24 hours.”2
The next phases of the study will determine the effectiveness and safety in participants with acute ischemic strokes.2
—Colleen Murphy
References:
1. Voors-Pette C, Lebozec K, Dogterom P, et al. Safety and tolerability, pharmacokinetics, and pharmacodynamics of ACT017, an antiplatelet GPVI (glycoprotein VI) fab [published online April 18, 2019]. Arterioscler Thromb Vasc Biol. doi:10.1161/ATVBAHA.118.312314.
2. Experimental antiplatelet compound for acute stroke shows promise [press release]. Dallas, TX; April 18, 2019. www.newsroom.heart.org/news/experimental-antiplatelet-compound-for-acute-stroke-shows-promise. Accessed April 18, 2019.