ESOC 2022 | ACTIMIS: Glenzocimab add-on therapy reduces hemorrhage and mortality in ischemic stroke
Mikael Mazighi, MD, Université de Paris, Paris, France, reports the findings of the ACTIMIS study (NCT03803007): a Phase Ib/IIa randomized trial assessing the safety of glenzocimab as an add-on therapy to alteplase, with or without mechanical thrombectomy, in patients with acute ischemic stroke. Glenzocimab is a first in class anti-platelet therapy targeting glycoprotein VI. The Phase I dose escalation portion of the trial included 60 patients who were treated with doses from 125 to 1000 mg. The subsequent Phase IIa portion randomized 106 patients to a 1000mg dose of glenzocimab or placebo, under a 1:1 parallel group design. There was no significant difference in the occurrence of serious adverse events between the treatment and the placebo arm. Glenzocimab was found to significantly reduce symptomatic and asymptomatic intracranial hemorrhage rates, compared to placebo (symptomatic ICH 1% vs. 8%, asymptomatic ICH 29% vs. 47%, respectively). Mortality rates were also significantly reduced in the treatment arm. The ongoing ACTISAVE (NCT05070260) and upcoming GREEN trials will aim to confirm to benefits of glenzocimab as an add on therapy to standard-of-care reperfusion approaches. This interview took place at European Stroke Organisation Conference 2022 in Lyon, France.
Transcript (edited for clarity)
The ACTIMIS trial was a safety trial, which aims to evaluate the safety of a first-in-class, antithrombotic therapy. It’s an antiplatelet agent targeting glycoprotein GPVI, platelet GPVI, from 4.5 hours of acute ischemic stroke in addition to alteplase plus/minus mechanical thrombectomy. And this agent glenzocimab is a fragment of antibody targeting the GPVI glycoprotein and this agent has an antithrombotic activity, but very interestingly has no effect on hemostasis, so no expected increase in bleeding risk...
The ACTIMIS trial was a safety trial, which aims to evaluate the safety of a first-in-class, antithrombotic therapy. It’s an antiplatelet agent targeting glycoprotein GPVI, platelet GPVI, from 4.5 hours of acute ischemic stroke in addition to alteplase plus/minus mechanical thrombectomy. And this agent glenzocimab is a fragment of antibody targeting the GPVI glycoprotein and this agent has an antithrombotic activity, but very interestingly has no effect on hemostasis, so no expected increase in bleeding risk.
This trial was the association of a Phase Ib escalating dose trial, including 60 patients with a dose ranging from 125 to 1000 milligram of glenzocimab, and a Phase IIa study, including 106 patients, randomized to receive either placebo or glenzocimab at the dose of 1000 milligram. So the primary endpoint was safety, including serious adverse events, intracerebral hemorrhage, and death, and there were some key secondary endpoints, including NIH at 24 hours, Rankin scale at 90 days.
So regarding the results and the serious adverse events, well, there were no significant difference between the placebo and the glenzocimab group. And the other results were the striking difference between the intracranial hemorrhage rates, which were of 1% for symptomatic ICH in the glenzocimab group versus 8% in the placebo group for symptomatic ICH. Regarding non-symptomatic ICH, we had the rate of 29% for the glenzocimab group and 47% for the placebo group. Regarding mortality, the mortality rate was 8% for glenzocimab group and 19% for the placebo group. So a significant difference between those two groups.
So I may summarize by saying that the administration of this antiplatelet therapy, glenzocimab add on to alteplase reduced intracranial hemorrhagic events and reduced mortality. These very interesting results are preliminary and we need to confirm these results in larger samples of patients. So there are two studies, one which is already ongoing, which is the ACTISAVE study. And this study will include, or is currently including, patients with acute ischemic stroke on intravenous thrombolysis plus/minus mechanical thrombectomy. And we have another study, the GREEN study that should be starting later this year. The GREEN study will include only patients eligible for mechanical thrombectomy and included with mismatch profile on perfusion imaging.
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Disclosures
Prof. Mazighi reports the following disclosures:
Consulting activities for: Acticor Biotech, Air liquid, Boerhinger Ingelheim, & Novonordisk.
