XY03-EA片治疗急性缺血性脑卒中的研究 (XY03-EA)

Study Background and Rationale Acute ischemic stroke (AIS) is a leading cause of death and long-term disability worldwide. Despite advances in reperfusion therapies, including intravenous thrombolysis and endovascular thrombectomy, a substantial proportion of patients still experience poor functional outcomes, highlighting an unmet need for effective neuroprotective strategies that can salvage ischemic brain tissue and improve neurological recovery.

XY03-EA is a novel oral neuroprotective agent developed for the treatment of AIS. Preclinical pharmacodynamic and pharmacological studies have demonstrated that XY03-EA exerts neuroprotective effects by promoting reactive oxygen species (ROS) clearance and modulating autophagy-related proteins and signaling pathways in neural cells. These mechanisms significantly improve neurological function impaired by cerebral ischemia, with low toxicity and high activity observed in non-clinical studies.

Study Design This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase Ⅱb/Ⅲ clinical study conducted to evaluate the efficacy and safety of XY03-EA tablets in the treatment of acute ischemic stroke and to explore the dose-response relationship. The study was designed as a seamless Phase Ⅱb/Ⅲ trial; the Phase Ⅱb stage served as a dose-exploration phase to provide data support for the subsequent Phase Ⅲ stage.

Eligible patients were aged 18 to 80 years, diagnosed with acute ischemic stroke according to the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023), classified as total or partial anterior circulation infarction by the Oxfordshire Community Stroke Project (OCSP) classification, with a National Institutes of Health Stroke Scale (NIHSS) score of 6 to 20, and enrolled within 48 hours from the time they were last seen normal.

In the Phase Ⅱb stage, 360 eligible subjects were enrolled and randomly assigned in a 1:1:1:1:1 ratio to four XY03-EA dose groups or one placebo group. Study treatment was administered for up to 90 days, with follow-up assessments conducted at scheduled time points.

Endpoints The primary efficacy endpoint was the proportion of patients with a modified Rankin Scale (mRS) score ≤ 1 at Day 90 after the start of study treatment. Secondary efficacy endpoints included the proportion of patients with mRS ≤ 2 at Day 14 (discharge), Day 30, and Day 90; the proportion of patients with mRS ≤ 1 at Day 30; the change from baseline in NIHSS score at Day 14 (discharge), Day 30, and Day 90; the proportion of patients with NIHSS ≤ 1 or a decrease of ≥ 4 points from baseline at Day 30 and Day 90; the proportion of patients with a Barthel Index (BI) ≥ 95 at Day 90; the change from baseline in Mini-Mental State Examination (MMSE) score at Day 90; and the proportion of patients with new vascular events (ischemic stroke, hemorrhagic stroke, transient ischemic attack, myocardial infarction, or vascular death) within 90 days after treatment. Safety was assessed throughout the study by monitoring adverse events, laboratory tests, vital signs, and physical examinations.