A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase II Clinical Study to Evaluate the Efficacy and Safety of ALT001 in Patients With Ischemic Stroke in the Sequelae Stage
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change from baseline in Fugl-Meyer Assessment (FMA) motor score
研究概览
简要总结
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.
详细描述
Ischemic stroke (IS) is the most common type of stroke, yet for patients with persistent neurological deficits beyond 6 months (sequelae stage) there is no widely accepted effective therapy. ALT001 is an allogeneic unrelated human umbilical cord mesenchymal stem cell-derived protein complex intended to promote neurological repair. This phase II study enrolls adults (18-80 years) with unilateral limb weakness (FMA motor score ≤90) and modified Ashworth spasticity ≤2, at least 180 days but no more than 5 years after the most recent ischemic stroke. Participants are randomized to one of three ALT001 dose groups (65, 130, or 260 μg/day) or matching placebo. Study drug is reconstituted in 100 mL normal saline and given by IV infusion once daily over ~60 minutes, 14 days on / 14 days off per cycle, for 3 cycles in the DB period. Eligible participants may then enter a 3-cycle OLE period (placebo group re-randomized to an active dose). Efficacy is assessed by FMA (primary, Week 12), mRS, NIHSS, Barthel Index, and modified Ashworth scale; safety by AE/SAE monitoring; exploratory outcomes include new vascular events and immunologic/cytokine changes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
A double-blind design is employed. The investigational product and placebo should be identical in appearance, packaging, labeling, post-reconstitution characteristics, and the appearance of the final infused product. The investigator, participant, efficacy assessor, and sponsor remain blinded. Independent unblinded pharmacists/pharmacy staff are responsible for preparing the study drug in accordance with the randomization system assignment.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria to be eligible for enrollment in this study:
- •Male or female participants aged 18 to 80 years, inclusive (determined at the time of signing the informed consent form);
- •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;
- •Unilateral limb weakness, with a total Fugl-Meyer Motor score ≤90;
- •Modified Ashworth Scale score ≤2;
- •Premorbid mRS ≤1 (i.e., independence in daily living prior to the most recent stroke);
- •On a stable-dose standard treatment for secondary prevention of ischemic stroke (antiplatelet agents, statins, etc.) for at least 1 month prior to enrollment;
- •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.
排除标准
- •Participants who meet any of the following criteria will be excluded from this study:
- •The culprit lesion of the most recent stroke is a posterior circulation infarct on imaging;
- •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);
- •A cerebrovascular or cardiovascular event within the past 3 months, such as transient ischemic attack (TIA) or acute coronary syndrome (ACS);
- •History of recurrent seizures or epilepsy;
- •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);
- •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;
- •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;
- •Poorly controlled blood glucose or blood pressure despite systematic treatment (HbA1c ≥8.5%; systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg);
- •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;
- •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;
- •Women who are pregnant or breastfeeding, or participants planning to conceive during the treatment period or within 3 months after treatment discontinuation;
- •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;
- •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;
- •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;
- •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).
研究组 & 干预措施
ALT001 65 μg/day
A total of 50 participants in the active treatment arm. ALT001 65 μg/day (~1.0 μg/kg), reconstituted in 100 mL normal saline, IV infusion once daily over ~60 minutes; 14 days on / 14 days off per cycle; 3 cycles in DB period.
干预措施: ALT001 (Drug)
Placebo
ALT001 matching placebo (simulator) without active ingredient, same administration schedule; in the OLE period, placebo-group participants are re-randomized to one of the three active dose groups for 3 cycles (12 weeks).
干预措施: Placebo (ALT001 matching placebo) (Other)
ALT001 130 μg/day
A total of 50 participants in the active treatment arm. ALT001 130 μg/day (~2.0 μg/kg), same administration schedule as Arm 1.
干预措施: ALT001 (Drug)
ALT001 260 μg/day
A total of 50 participants in the active treatment arm. ALT001 260 μg/day (~4.0 μg/kg), same administration schedule as Arm 1.
干预措施: ALT001 (Drug)
结局指标
主要结局
Change from baseline in Fugl-Meyer Assessment (FMA) motor score
时间窗: 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.
次要结局
- Change from baseline in the Fugl-Meyer Assessment (FMA) Motor score(After 4 and 8 weeks of treatment during the double-blind treatment period)
- Change from baseline in modified Rankin Scale (mRS) distribution / proportion of patients by mRS grade(Weeks 4, 8, and 12)
- Change from baseline in National Institutes of Health Stroke Scale (NIHSS) score(Weeks 4, 8, and 12)
- Change from baseline in Barthel Index (BI) score(Weeks 4, 8, and 12)
- Change from baseline in the Modified Ashworth Scale (MAS) score(Weeks 4, 8, and 12)
- Incidence of adverse events (AEs) and serious adverse events (SAEs)(Through study completion, up to approximately 28 weeks (up to 24 weeks of treatment, comprising the 12-week double-blind period and the 12-week open-label extension period, plus a 28-day safety follow-up after the last dose).)