Phase III Clinical Trial of SHPL-49 Injection in the Treatment of Acute Ischemic Stroke

Phase III Clinical Trial to Evaluate the Efficacy and Safety of SHPL-49 Injection in the Treatment of Acute Ischemic Stroke（SAIL）- a Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase III Clinical Trial

This study is designed to determine the efficacy and safety of SHPL-49 intravenous infusion in acute ischemic stroke patients.

The objective of this study is to determine the efficacy and safety of SHPL-49 intravenous infusion for 7 consecutive days in acute ischemic stroke patients within 8hours after onset. This study is a Phase III, multicenter, randomized, double-blind, placebo-controlled parallel design. Participants receive twice daily dosing for 7 consecutive days, or once on Day 1 and Day 8 and twice daily on Days 2 to 7, with each participant scheduled to receive 14 doses throughout the clinical trial. 1096 participants will be randomized 1:1 to SHPL-49 injection treated group and placebo group.

Inclusion Criteria:

1. Age 18-80 years old (including upper and lower limits);
2. Clinically diagnosed as acute ischemic stroke according to the latest guidelines;
3. Patients diagnosed as acute ischemic stroke who plan to receive or have received standard intravenous thrombolysis in hospital (this research center) within 8hours of symptom onset;
4. Patients who have NIHSS score≥5 and ≤ 22 before thrombolysis;
5. Pre-stroke mRS score ≤1;
6. Patients or legally authorized representatives who are able and willing to sign informed consent.

Exclusion Criteria:

1. Complicated with intracranial hemorrhagic diseases, including hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc.;
2. Severe disturbance of consciousness: patients with NIHSS 1a consciousness level item score ≥2;
3. Cerebral Computed tomography (CT) or Magnetic resonance imaging (MRI) indicated a large anterior circulation cerebral infarction (infarct area greater than 1/3 of the middle cerebral artery blood supply area);
4. Stroke with rapid improvement of symptoms before intravenous thrombolysis, or acute ischemic symptoms suspected to be caused by other causes;
5. Patients who are ready to receive or have received endovascular therapy;
6. After the onset of the disease, the drugs with neuroprotective effects which have been used: commercially available Edaravone, Edaravone and Dexborneol, Butylphthalide, Citicoline, Nimodipine, Ganglioside, Human Urinary Kallidinogenase, Cinepazide, Cattle Encephalon Glycoside and Ignotin, Fasudil, Compound Porcine Cerebroside and Ganglioside, Piracetam, Oxiracetam, Mouse Nerve Growth Factor For Injection, Cerebrolysin, Deproteinised Calf Blood Serum Injection, Deproteinised Calf Blood Extractives Injection, Ginkgolides Injection, Ginkgolides Diterpene Lactone Meglumine Injection, Ginkgo Leaf Extract and Dipyridamole Injection, Extract of Ginkgo Biloba Leaves Injection, Safflower Extract and Aceglutamide Injection, Xuesaitong Injection, Xuesaitong Soft Capsules, and injections containing any single eXtract of Chuanxiong (Chuanxiong Rhizoma), Danshen (Salviae Miltiorrhizae Radix ET Rhizoma), Hongjingtian (Rhodiolae Crenulatae Radix Et Rhizoma),or several of these Chinese herbal ingredients;
7. Patients with a history of atrial fibrillation, deep vein thrombosis of the lower extremities, pulmonary embolism or other conditions that require the use of anticoagulant drugs during administration;
8. Severe hypertension: systolic blood pressure ≥180mmHg or diastolic blood pressure ≥100mmHg after taking antihypertensive drugs before thrombolysis;
9. Severe renal insufficiency: serum creatinine >2 times upper limit of normal or creatinine clearance (CLcr) < 30mL/min (Cockcroft-Gault formula), or with other known severe renal insufficiency such as renal failure and uremia ; (Note: Cockcroft Gault formula: (1) Male: CLcr (mL/min) = [140 - age (yrs)]× body weight (kg) / [0.814 × serum creatinine (μmol/L)]; (2) female: CLcr (mL/min) = {[140 - age (years old)] by weight (kg) / [0.814 x serum creatinine (μmol/L)]} x 0.85);
10. Severe hepatic function impairment: Alanine aminotransferase (ALT) or Aspartate aminotransferase(AST) 3 times upper limit of normal, or with other known hepatic diseases such as hepatic failure, hepatic cirrhosis, portal hypertension (with esophageal varices), active hepatitis, etc.;
11. Patients with a heart function rating above Class II (according to the New York Heart Association (NYHA) heart function rating) or a history of congestive heart failure;
12. Patients with malignant tumors or undergoing anti-tumor therapy;
13. Allergic to experimental drugs or similar ingredients or materials used in imaging examinations;
14. Patients during pregnancy, lactation or planning pregnancy;
15. Patients who have a history of epilepsy or have had seizure-like symptoms at the onset of stroke, or suffer from serious mental disorders, intellectual disabilities or dementia;
16. Alcohol dependence, or drinking more than 3 units (male) or 2 units (female) of alcohol within 24 hours prior to onset (1 unit =360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine);
17. Patients have participated in other drug or non-drug clinical studies, or are participating in another clinical study within 3 months before signing informed consent form;
18. Patients have a history of severe head trauma or stroke within the past 3 months;
19. Patients are suffering from severe systemic diseases, with a life expectancy of less than 90 days;
20. Patients who are judged unsuitable for participation by the investigators in the study.