O02 First in man study of OTR4132, a heparan sulfate mimetic neuroprotector, injected intra-arterially after endovascular thrombectomy in patients with acute ischemic stroke: the matriss trial

<h3>Introduction</h3> There is an important need for the development of neuroprotective therapeutic agents that could be combined to reperfusion strategies in acute ischemic stroke to further improve functional outcome. OTR4132 is a polymer of glucose engineered to mimic heparan sulphate (HS), which demonstrated neuroprotective effects in animal models. <h3>Aim of Study</h3> To assess the safety, tolerability of OTR4132 and to identify the highest, well-tolerated, and safest single dose in acute stroke patients <h3>Methods</h3> The MATRISS study is a multi-center, first-in-man, open label, dose-escalation study. OTR4132 was administered intra-arterially at a rate of 1mL/min over 10 minutes, following endovascular thrombectomy recanalization (TICI score 2b - 3). The primary endpoint was the rate of investigational treatment-related severe adverse events occurring from baseline to 7 days after inclusion. All other safety and efficacy endpoints were exploratory. <h3>Results</h3> Nineteen patients were recruited in the study between March 2022 and March 2024 and 6 different doses of OTR4132 were tested (from 0.2 mg to 2.5 mg). No serious adverse event attributable to the investigational treatment was noticed at any of the 6 tested doses. Although, the study was not powered to demonstrate efficacy, in the highest dose groups, the rate of severe intracranial hemorrhages at 24 hours was lower, better functional recovery was noticed, and MRI volumetric analyses suggested a dose effect in the reduction of stroke volume at 3 months. <h3>Conclusion</h3> These encouraging results need to be confirmed in a placebo-controlled clinical study. <h3>Disclosure of Interest</h3> yes Frederic Sedel, Martin Inizan and Denis Barritault are employees and shareholders of OTR3.