Abstract Body: Introduction: Approved thrombolytic agents are currently only recommended for acute ischemic stroke (AIS) within 4.5 hours from the last known well (LKW). Hence, there remains an unmet need in the treatment of AIS for safer and more effective thrombolytics, which can also be administered to a broader population with an extended treatment window. JX10 is a novel thrombolytic that works by inducing conformational changes in plasminogen to increase downstream fibrin affinity and promote physiological fibrinolysis instead of direct plasminogen activation like that of tissue plasminogen activators (t-PA). JX10 also exerts anti-inflammatory activity through inhibition of soluble epoxide hydrolase, which may suppress hemorrhagic changes associated with cerebral infarction. In a randomized, double-blind, placebo-controlled, dose-escalation phase 2a study conducted in Japan, JX10 increased vessel recanalization and improved neurologic outcomes. This subgroup analysis evaluated the safety and efficacy of JX10 in participants who presented with acute lacunar infarct.
Methods: JX10 or placebo was administered as a single intravenous infusion at a dose of 1, 3, or 6 mg/kg to AIS patients who were ineligible for tissue plasminogen activator or thrombectomy within 12 h of LKW. Safety and Efficacy outcomes were assessed at 90 days.
Results: Among the 90 patients enrolled in the trial, a total of 25 patients with acute lacunar infarct were dosed (JX10 1 mg/kg group: 1 subject; 3 mg/kg group: 3 subjects; 6 mg/kg group: 7 subjects; and placebo group: 14 subjects). In the JX10 1, 3, 6 mg/kg, pooled groups, and the placebo group, the rates of mRS 0–1 were 0 subject out of 1 (0.0%), 1 subject out of 3 (33.3%), 3 subjects out of 7 (42.9%), 4 subjects out of 11 (36.4%), and 1 subject out of 14 (7.1%), respectively, and those of mRS 0–2 were 0 subjects out of 1 (0.0%), 3 subjects out of 3 (100.0%), 4 subject out of 7 (57.1%), 7 subjects out of 11 (63.6%), and 2 subjects out of 14 (14.3%), respectively. Despite small numbers, patients with acute lacunar infarct who were treated with JX10 showed trend of improved neurologic function at 90 days, as measured by mRS. Symptomatic intracranial hemorrhage was not observed in any JX10 treated patients.
Conclusions: JX10 improved functional outcome in patients who presented with lacunar infarct, as measured by mRS at day 90 vs placebo. Findings support further testing of JX10 in larger and broader patient populations.