Aleeto in Acute ISchemic Stroke：A RandomISed Controlled Clinical Trial

Overview

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.

Interventions

• 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.
• Drug Placebo
  Placebo with the same dosage form, odor and color as Aleeto was administered in the same way and course of treatment.

Primary outcome measures

• Change from baseline in NIH Stroke Scale [Time frame: At 14 days after randomization]

Secondary outcome measures (10)

• Change from baseline in NIH Stroke Scale [Time frame: At 7±1 days after randomization.]
• Change from baseline in Modified Rankin Scale [Time frame: At 90±7days after randomization]
• Change from baseline in Fugl-Meyer Assessment [Time frame: At 14±2 and 90±7days after randomization.]
• Change from baseline in Ashworth scale [Time frame: At 14±2 and 90±7days after randomization.]
• The ratio of modified Barthel index ≥95 points [Time frame: At 90±7days after randomization.]
• Change from baseline in Visual Analogue Scale [Time frame: At 14±2 and 90±7days after randomization.]
• Change from baseline in Montreal Cognitive Assessment [Time frame: At 90±7days after randomization.]
• Combined vascular events [Time frame: From randomization to the end of treatment at 90±7days]
• New-onset Stroke Events [Time frame: From randomization to the end of treatment at 90±7days]
• All-cause Mortality [Time frame: From randomization to the end of treatment at 90±7 days]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Intracranial hemorrhagic diseases identified by head CT: cerebral hemorrhage, extradural hemorrhage, subarachnoid hemorrhage, intraventricular hemorrhage, etc.
• Combined with other active and major neurological diseases (such as induced seizures, poor drug control of recurrent seizures, multiple sclerosis, intracranial tumors, etc.).
• 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).
• 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).
• Resistant Hypertension, systolic pressure ≥220mmHg or diastolic pressure ≥120mmHg.
• 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.
• History of severe anemia within the past 1 month (hemoglobin < 90g/L).
• Body Mass Index (BMI) < 16kg/m2 or BMI> 35kg/m2.
• Severe organic diseases with expected survival time <5 years, such as malignant tumor.
• Women of child bearing potential, pregnant or breastfeeding.
• 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.
• Combined with alcohol and drug abuse history.
• Known history of allergy to biological agents such as proteins and cell products.
• History of intracranial or spinal surgery, major surgery, or severe physical trauma within the past 4 weeks.
• Received any vaccinations within the past 28 days.
• Use of other investigational drugs within 30 days or 5 drug half-lives.
• Unable to complete follow-up due to geographical or other reasons.
• The researchers believe that the patient is not suitable to participate in this study.
• Participated in other clinical trials.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital — Beijing

Identifiers

NCT: NCT06759753 · HX-A-2024088

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗