Clinical trial NCT06759753: Aleeto in Acute ISchemic Stroke：A RandomISed Controlled Clinical Trial
Official title: Aleeto in Acute ISchemic Stroke：A RandomISed Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Keywords: Aleeto
Placebo parallel-controlled
Double Blind Study
Randomized Controlled Trial
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2025-01-06
Enrollment: 192
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is a prospective, double-blind, 1:1:1 randomized controlled study. 192 patients will be randomly assigned to 3 groups. Two dose groups are set 130μg/day and 260μg/day and one placebo group.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in NIH Stroke Scale
timeFrame: At 14 days after randomization
Secondary outcomes:
measure: Change from baseline in NIH Stroke Scale
timeFrame: At 7±1 days after randomization.
measure: Change from baseline in Modified Rankin Scale
timeFrame: At 90±7days after randomization
measure: Change from baseline in Fugl-Meyer Assessment
timeFrame: At 14±2 and 90±7days after randomization.
measure: Change from baseline in Ashworth scale
timeFrame: At 14±2 and 90±7days after randomization.
measure: The ratio of modified Barthel index ≥95 points
timeFrame: At 90±7days after randomization.
measure: Change from baseline in Visual Analogue Scale
timeFrame: At 14±2 and 90±7days after randomization.
measure: Change from baseline in Montreal Cognitive Assessment
timeFrame: At 90±7days after randomization.
measure: Combined vascular events
timeFrame: From randomization to the end of treatment at 90±7days
measure: New-onset Stroke Events
timeFrame: From randomization to the end of treatment at 90±7days
measure: All-cause Mortality
timeFrame: From randomization to the end of treatment at 90±7 days
Other outcomes:
measure: Imaging markers of brain tissue edema
timeFrame: At 14±2 days post-randomization or before discharge
measure: Neurocellular metabolic markers
timeFrame: At 14±2 days post-randomization or before discharge
measure: Hypersensitivity events
timeFrame: From randomization to the end of treatment at 90±7days weeks
measure: Serious adverse events
timeFrame: From randomization to the end of treatment at 90±7days weeks
measure: Other adverse/serious adverse events
timeFrame: From randomization to the end of treatment at 90±7days weeks
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
Study officials:
affiliation: Beijing Tiantan Hospital
name: YiLong Wang
role: PRINCIPAL_INVESTIGATOR
References: