ALT001 in Patients With Ischemic Stroke in the Sequelae Stage

This is a phase II, randomized, double-blind, placebo-controlled, multicentre clinical study to evaluate the efficacy and safety of ALT001 in patients with ischemic stroke in the sequelae stage (≥180 days and ≤5 years after the most recent event). A total of 200 participants will be randomized 1:1:1:1 to receive ALT001 at 65 μg/day, 130 μg/day, or 260 μg/day, or matching placebo, by intravenous infusion once daily (over \~60 minutes) using a 14-day-on / 14-day-off cycle for 3 cycles (12 weeks) in the double-blind (DB) period, followed by an optional open-label extension (OLE) period of 3 additional cycles. The primary endpoint is the change from baseline in the Fugl-Meyer Assessment (FMA) motor score at Week 12.

Inclusion Criteria: Participants must meet all of the following criteria to be eligible for enrollment in this study: 1. Male or female participants aged 18 to 80 years, inclusive (determined at the time of signing the informed consent form); 2. A history of acute ischemic stroke confirmed by CT or MRI, with the most recent stroke occurring ≥180 days and no more than 5 years prior to enrollment; 3. Unilateral limb weakness, with a total Fugl-Meyer Motor score ≤90; 4. Modified Ashworth Scale score ≤2; 5. Premorbid mRS ≤1 (i.e., independence in daily living prior to the most recent stroke); 6. On a stable-dose standard treatment for secondary prevention of ischemic stroke (antiplatelet agents, statins, etc.) for at least 1 month prior to enrollment; 7. Participants must be willing and able to participate in the study, sign the informed consent form, and commit to completing all study-related procedures and visits in accordance with the protocol. Exclusion Criteria: Participants who meet any of the following criteria will be excluded from this study: 1. The culprit lesion of the most recent stroke is a posterior circulation infarct on imaging; 2. Baseline head CT or MRI showing malformations, tumors, abscesses, or other major non-vascular brain diseases (e.g., multiple sclerosis, dementia, Parkinson's disease, and other neurodegenerative diseases); 3. A cerebrovascular or cardiovascular event within the past 3 months, such as transient ischemic attack (TIA) or acute coronary syndrome (ACS); 4. History of recurrent seizures or epilepsy; 5. Allergic constitution (allergies to multiple drugs and foods), history of severe allergic/hypersensitivity reactions, or, in the investigator's judgment, potential allergy to the investigational drug or any of its components (e.g., history of allergy to protein-based drugs); 6. At screening: positive for hepatitis B surface antigen (HBsAg) with HBV-DNA above the upper limit of normal (ULN) (if HBsAg is negative, HBV-DNA testing is not required); positive for hepatitis C antibody (anti-HCV) with HCV-RNA above the ULN (if anti-HCV is negative, HCV-RNA testing is not required); positive for human immunodeficiency virus (HIV) antibody; or positive for Treponema pallidum antibody; 7. Severe hepatic impairment (defined as ALT ≥3 × ULN or AST ≥3 × ULN); severe renal impairment (estimated glomerular filtration rate \[eGFR\] \180 mmHg or diastolic blood pressure \>110 mmHg); 9. At screening, severe autoimmune diseases, myeloproliferative disorders, leukemia or lymphoma, malignant tumors, fractures, or severe scoliosis that, in the investigator's judgment, would affect the study evaluation; 10. Significant cognitive impairment (per MMSE: ≤19 for the illiterate group, ≤22 for the primary school group, ≤26 for the junior high school and above group \[\>8 years of education\]), or other unstable psychiatric conditions that, in the investigator's judgment, render the participant unsuitable for the study (including suicidal ideation, untreated major depression, etc.), or aphasia (aphasia severity grade 0) such that the participant cannot understand and/or comply with the study procedures; 11. Women who are pregnant or breastfeeding, or participants planning to conceive during the treatment period or within 3 months after treatment discontinuation; 12. Alcohol dependence or a history of drug abuse within 6 months prior to screening that, in the investigator's judgment, renders the participant unsuitable for this study; 13. Use of neuroprotective agents within 14 days prior to randomization, such as butylphthalide, edaravone, edaravone dexborneol, urinary kallidinogenase, citicoline, cerebroprotein hydrolysate, etc., or use of traditional Chinese medicine preparations with an indication of stroke; 14. Participation in another clinical trial with use of any other investigational drug or device within 3 months prior to screening; or prior receipt of stem cell therapy or gene therapy; 15. Patients who, in the investigator's judgment, are unsuitable for participation in this study (e.g., clinically significant abnormalities on physical examination or laboratory tests).