Starting soon
Phase 2
ALT001 in Patients With Ischemic Stroke in the Sequelae Stage
Condition(s) studied
Ischemic Stroke in the Sequelae Stage
Investigational drug(s) / intervention(s)
ALT001 →Placebo (ALT001 matching placebo)
ALT001: A total of 150 participants in the active treatment arm were randomized in a 1:1:1 ratio to the 65 μg/day ALT001 treatment group, the 130 μg/day ALT001 treatment group, or the 260 μg/day ALT001 treatment group, with 50 participants in each group. For each treatment group, according to the assigned dose, ALT001 was dissolved in 100 mL of normal saline injection and administered by intravenous infusion once daily, completed within approximately 60 minutes.
Dosing schedule: Fourteen days of continuous dosing followed by 14 days off constituted one cycle. The DB period consisted of 3 consecutive cycles, Participants who complete the DB period will enter the OLE treatment period, using the same administration method as in the DB period. The active treatment groups will continue to receive the dose level of their assigned dose group, and the OLE period consisted of 3 consecutive cycles.
Placebo (ALT001 matching placebo): The placebo group consisted of 50 participants. The placebo was dissolved in 100 mL of normal saline injection and administered by intravenous infusion once daily, completed within approximately 60 minutes.
Dosing schedule: Fourteen days of continuous dosing followed by 14 days off constituted one cycle. The DB period consisted of 3 consecutive cycles, and the OLE period consisted of 3 consecutive cycles.
Participants who complete the DB period will enter the OLE treatment period. The placebo group will be randomly assigned to the 3 dose groups and receive treatment for 3 consecutive cycles (12 weeks).
Study summary
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.
Eligibility
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 \[eGFR\] \<30 mL/min/1.73 m²); severe heart failure (New York Heart Association \[NYHA\] class III-IV); or coagulation disorders or a history of systemic bleeding;
8. Poorly controlled blood glucose or blood pressure despite systematic treatment (HbA1c ≥8.5%; systolic blood pressure \>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).
Primary outcome measure(s)
- Change from baseline in Fugl-Meyer Assessment (FMA) motor score — Week 12 (double-blind period)
The Fugl-Meyer Assessment (FMA) is used to evaluate the motor function of patients with ischemic stroke. It comprises an upper-extremity motor function subscore (66 points) and a lower-extremity motor function subscore (34 points), for a total of 100 points. Total-score grading: 0-49 = severe motor impairment; 50-84 = marked motor impairment; 85-95 = moderate motor impairment; 96-99 = mild motor impairment.
Trial sites (1)
| Facility | City | Region | Status |
| Capital Medical University Affiliated Beijing Tiantan Hospital |
Beijing |
Beijing Municipality |
|
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