Aleeto in Acute ISchemic Stroke：A RandomISed Controlled Clinical Trial (ASSIST)

This study is a prospective, double-blind, 1:1:1 randomized controlled study aimed at evaluating the efficacy and safety of Aleeto treatment compared to placebo in improving the NIHSS score at 14 days in patients with moderate to severe acute ischemic stroke. It also aims to explore the neuroprotective effects of Aleeto in moderate to severe acute ischemic stroke and provide data support and evidence for future clinical trials and evidence-based medicine.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Aleeto; Drug: Placebo

Detailed Description

Stroke is the second leading cause of death worldwide, associated with high rates of morbidity, mortality, and disability. As a result, it places a significant social and economic burden on societies. Stroke is generally classified into two types: ischemic stroke and hemorrhagic stroke. Acute ischemic stroke (AIS) accounts for approximately 87% of all stroke cases, characterized by the sudden cessation of oxygen and blood supply to local cerebral tissue due to arterial occlusion.

According to the Global Burden of Disease study, in 2019, there were 28.76 million stroke patients in China, including 3.94 million new cases and 2.19 million deaths due to stroke. The burden of ischemic stroke (IS) in China has increased dramatically, with the Disability-Adjusted Life Years (DALYs) for IS rising by 138.6% from 1990 to 2019. This burden is expected to grow further due to the aging population, the persistently high incidence of stroke risk factors (such as hypertension), and inadequate management. Although significant advances have been made in the diagnosis and treatment of ischemic stroke in recent years-resulting in a notable reduction in recurrence rates-effective, targeted treatments to reduce disability and improve neurological recovery remain limited.

Aleeto, derived from cellular exosomes, is a group of specific protein polymers secreted by stem cells under stress. These exosomes possess several advantages, including selective assembly, targeted delivery, efficient tissue repair, high safety, stable chemical properties, and ease of preservation. Moreover, Aleeto has demonstrated strong potential for nerve repair.

This study is a single-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of Aleeto in patients with acute ischemic stroke. The trial also aims to determine the appropriate dosage for future clinical studies.

A total of 192 patients will be enrolled and randomly assigned to three groups. All participants will receive standardized treatment according to clinical guidelines, along with ginkgo ester dropping pills (4 pills per dose, 3 times per day, for 90 days of oral treatment). The dosage and type of drugs used will remain consistent throughout the trial.

Experimental Group 1: Intravenous administration of Aleeto at 130 μg/day for 14 ± 2 days (130 μg Aleeto dissolved in 100 mL sodium chloride injection).

Experimental Group 2: Intravenous administration of Aleeto at 260 μg/day for 14 ± 2 days (260 μg Aleeto dissolved in 100 mL sodium chloride injection).

Placebo Group: A placebo with the same appearance, odor, and color as Aleeto will be administered in the same manner and for the same duration as the experimental groups.

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yilong Wang; Phone Number: 59975885; Email: yilong528@gmail.com
• Study Contact Backup: Name: WeiQi Chen; Email: weiqichen@aliyun.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tiantan Hospital
    • Contact: Yilong Wang; Phone Number: 59975885; Email: yilong528@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 30 and 80 years (30 ≤ age ≤ 80).
2. Diagnosis of acute ischemic stroke confirmed by CT or MRI, according to the "Key Points for Diagnosis of Major Cerebrovascular Diseases in China 2019."
3. Time from symptom onset ≤ 72 hours.
4. NIHSS score between 6 and 24, with a score of ≥ 1 on items 5 and 6 of the NIHSS.
5. Pre-stroke mRS (modified Rankin Scale) < 2, indicating independent activities of daily living.
6. Signed informed consent.

Exclusion Criteria:

1. Intracranial hemorrhagic diseases identified by head CT: cerebral hemorrhage, extradural hemorrhage, subarachnoid hemorrhage, intraventricular hemorrhage, etc.
2. Combined with other active and major neurological diseases (such as induced seizures, poor drug control of recurrent seizures, multiple sclerosis, intracranial tumors, etc.).
3. History of infectious diseases (HIV positive or positive test history, HCV antibody positive or positive test history, HBV surface antigen positive and/or serum HBV DNA positive or serum HBV DNA > 2 × 10^8 IU/ml).
4. Severe renal or hepatic insufficiency. (Severe hepatic insufficiency is defined as alanine aminotransferase (ALT) value>3 times normal upper limit or Aspartate aminotransferase (AST)>3 times normal upper limit; Severe renal insufficiency is defined as creatinine>1.5 times normal upper limit or creatinine clearance < 50 ml/min, or over stage 3 of chronic kidney disease), severe heart failure (New York Heart Association grades III - IV).
5. Resistant Hypertension, systolic pressure ≥220mmHg or diastolic pressure ≥120mmHg.
6. History of Hemostatic disorder, systemic bleeding, thrombocytopenia or neutropenia, drug-induced hematology or liver dysfunction, white blood cell count <2×10^9/L or platelet count <100×10^9/L.
7. History of severe anemia within the past 1 month (hemoglobin < 90g/L).
8. Body Mass Index (BMI) < 16kg/m2 or BMI> 35kg/m2.
9. Severe organic diseases with expected survival time <5 years, such as malignant tumor.
10. Women of child bearing potential, pregnant or breastfeeding.
11. Individual who have difficulty communicating verbally to the extent that they are unable to communicate, understand or follow instructions normally, and are unable to cooperate with treatment and evaluation.
12. Combined with alcohol and drug abuse history.
13. Known history of allergy to biological agents such as proteins and cell products.
14. History of intracranial or spinal surgery, major surgery, or severe physical trauma within the past 4 weeks.
15. Received any vaccinations within the past 28 days.
16. Use of other investigational drugs within 30 days or 5 drug half-lives.
17. Unable to complete follow-up due to geographical or other reasons.
18. The researchers believe that the patient is not suitable to participate in this study.
19. Participated in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group 1; Intravenous administration of Aleeto at 130μg/day for 14±2 days (130μg Aleeto with 100 ml sodium chloride injection), along with Ginkgo Ester Dropping Pills, 4 pills per dose, 3 times/day, orally, for 90 days.	Drug: Aleeto; According to the groups, patients would be treated with Aleeto via intravenous injection, and the specific dosage of Aleeto will depend on the grouping.
Experimental: Experimental group 2; Intravenous administration of Aleeto at 130μg/day for 14±2 days (260μg Aleeto with 100 ml sodium chloride injection), along with Ginkgo Ester Dropping Pills, 4 pills per dose, 3 times/day, orally, for 90 days.	Drug: Aleeto; According to the groups, patients would be treated with Aleeto via intravenous injection, and the specific dosage of Aleeto will depend on the grouping.
Placebo Comparator: Placebo group; Placebo with the same dosage form, odor and color as Aleeto was administered in the same way and course of treatment, along with Ginkgo Ester Dropping Pills, 4 pills per dose, 3 times/day, orally, for 90 days.	Drug: Placebo; Placebo with the same dosage form, odor and color as Aleeto was administered in the same way and course of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in NIH Stroke Scale	NIH Stroke Scale (NIHSS) scores from 0 to 42. A higher score indicates worse neural function.	At 14 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in NIH Stroke Scale	NIH Stroke Scale (NIHSS) scores from 0 to 42. A higher score indicates worse neural function.	At 7±1 days after randomization.
Change from baseline in Modified Rankin Scale	Modified Rankin Scale (mRS) ranks from 0 to 5. A higher rank indicates worse neural function.	At 90±7days after randomization
Change from baseline in Fugl-Meyer Assessment	Fugl-Meyer Assessment (FMA) socres from 0 to 226. A higher score indicates better motor function.	At 14±2 and 90±7days after randomization.
Change from baseline in Ashworth scale	Ashworth scale ranks from 0 to 5. A higher rank indicates worse motor function.	At 14±2 and 90±7days after randomization.
The ratio of modified Barthel index ≥95 points	Modified Barthel index socres from 0 to 100. A higher score indicates better self-care ability.	At 90±7days after randomization.
Change from baseline in Visual Analogue Scale	Visual Analogue Scale (VAS) ranks from 0 to 10. A higher rank indicates higher pain level.	At 14±2 and 90±7days after randomization.
Change from baseline in Montreal Cognitive Assessment	Montreal Cognitive Assessment (MoCA) socres from 0 to 30. A higher score indicates better cognitive function.	At 90±7days after randomization.
Combined vascular events	Including stroke (including ischemic and hemorrhagic stroke), myocardial infarction and cardiovascular death	From randomization to the end of treatment at 90±7days
New-onset Stroke Events	Including hemorrhagic and ischemic strokes	From randomization to the end of treatment at 90±7days
All-cause Mortality		From randomization to the end of treatment at 90±7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Imaging markers of brain tissue edema	Assessed by MRI Diffusion Tensor Imaging (DTI) and SPICE (SPectroscopic Imaging by exploiting Spatiospectral Correlation) rapid high-resolution 3D magnetic resonance spectroscopic imaging technique.	At 14±2 days post-randomization or before discharge
Neurocellular metabolic markers	Assessed by MRI Diffusion Tensor Imaging (DTI) and SPICE (SPectroscopic Imaging by exploiting Spatiospectral Correlation) rapid high-resolution 3D magnetic resonance spectroscopic imaging technique.	At 14±2 days post-randomization or before discharge
Hypersensitivity events	Including skin reactions (rash, urticaria), eosinophilia, and one or more of the following: pulmonary lesions, hepatitis, tubular-interstitial nephritis, myocarditis, pericarditis, arthralgia, possibly accompanied by fever and lymphadenopathy	From randomization to the end of treatment at 90±7days weeks
Serious adverse events	Resulting in death; Immediately life-threatening(Life-threatening means that the event was immediately endangering the patient's life at the time it occurred, rather than the potential risk of death if the event worsens.); Requires hospitalization or prolongation of hospitalization; Leads to lifelong or severe disability/functional impairment, or the loss of essential abilities to maintain normal daily living functions; Congenital anomalies, congenital defects, birth defects, or reproductive disorders; Major medical events that may endanger the subject, or require medical intervention to prevent any of the above outcomes.	From randomization to the end of treatment at 90±7days weeks
Other adverse/serious adverse events	A. Laboratory tests: Safety tests include complete blood count, urine analysis, liver function, kidney function, coagulation, etc. Attention should be given to abnormal changes in laboratory results, and further testing may be required to assess their relevance to the study. B. Vital signs: The occurrence of abnormal temperature (≥38°C or ≤35°C), blood pressure (systolic BP ≥180 mmHg or <90 mmHg), respiratory rate (>24 breaths/min or other rhythm abnormalities), heart rate (>100 bpm or <60 bpm).	From randomization to the end of treatment at 90±7days weeks

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: YiLong Wang, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2025
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: December 29, 2024
• First Submitted That Met QC Criteria: December 29, 2024
• First Posted (Actual): January 6, 2025

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: September 1, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Double Blind Study; Placebo parallel-controlled; Aleeto
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: HX-A-2024088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No