Evaluation of Safety, Tolerability, and Efficacy of TGD001 in Acute Ischemic Stroke Patients with or without Endovascular Thrombectomy

The primary objective is to evaluate the Acute Ischemic Stroke safety and tolerability profile of single intravenous doses of TGD001 in participants diagnosed by neuroimaging who either undergo endovascular thrombectomy or receive neither thrombectomy nor standard intravenous thrombolysis, with the clinical relevance of establishing a tolerable dosing range and preliminary efficacy signals to inform subsequent development stages.

The trial enrolled 50 participants diagnosed with Acute Ischemic Stroke confirmed by neuroimaging, all of whom were functionally independent (modified Rankin Scale score 0‑2) prior to stroke onset. Eligible individuals were aged 18 to < 80 years, included both females and males, and met a baseline National Institutes of Health Stroke Scale score of ≥5 that remained ≥5 immediately before enrollment. Selection required imaging evidence of a visible occlusion or an ischemic lesion with an ASPECTS score of 6‑10 and a target mismatch profile. Participants were stratified according to treatment pathway: (A) those meeting local criteria for endovascular thrombectomy and undergoing the procedure, or (B) those not receiving endovascular thrombectomy or standard‑of‑care intravenous thrombolysis. General health status was limited to patients without prior disabling deficits, and no specific lifestyle restrictions such as diet or physical activity were stipulated in the inclusion parameters.

The study comprises an open‑label, dose‑finding Phase 1b/2a segment followed by a randomized, double‑blind, placebo‑controlled expansion phase to evaluate safety, tolerability, and preliminary efficacy of TGD001 in participants with Acute Ischemic Stroke. Eligible adults (18‑<80 years) with pre‑stroke functional independence (mRS 0‑2), a baseline NIHSS ≥ 5, and neuroimaging evidence of an occlusion or ASPECTS 6‑10 undergo a screening visit to confirm eligibility, including assessment of EVT eligibility. In the dose‑finding portion, participants receive a single intravenous infusion of TGD001; safety outcomes such as symptomatic intracranial hemorrhage and treatment‑emergent adverse events are monitored. After dose escalation, participants meeting inclusion criteria are randomized 1:1 to TGD001 or placebo (0.9 % sodium chloride) and remain blinded to treatment. Follow‑up visits occur at 24 hours, 7 days, 30 days, and 90 days post‑dose, each assessing neurological status, imaging, and adverse events. The end‑of‑study visit at Day 90 concludes participant involvement, which therefore spans approximately three months. Early termination may occur if a participant experiences a predefined safety event, withdraws consent, or is lost to follow‑up. The overall recruitment period is planned from October 2025 to October 2027.

The investigational product, urokinase, catalytic domain, fused with a single‑chain antibody against von Willebrand factor, is provided as a sterile solution for injection for intravenous administration. Single doses are delivered via a peripheral or central venous line, with the volume and infusion rate defined by the dose‑escalation cohort. Dosing is performed once per participant during the study visit, and the amount administered is adjusted according to the predefined dose levels evaluated in the Phase 1b/2a portion of the trial.

The control intervention consists of sodium chloride solution 0.9 %, administered intravenously in an identical volume and infusion schedule to maintain blinding. This placebo solution contains no active therapeutic agent and is used to match the appearance and administration characteristics of the investigational product.

All intravenous infusions are prepared under aseptic conditions and administered by qualified clinical personnel. Participants are observed for a minimum of 24 hours post‑infusion for safety assessments, including vital signs, laboratory parameters, and neurological examinations. Compliance with the dosing protocol is documented through infusion logs, medication accountability records, and electronic case report forms to ensure accurate capture of the administered dose and timing.