Safety and Preliminary Efficacy of Allogeneic Endothelial Progenitor Cells (EPCs) in Patients With Acute Ischemic Stroke

Phase I Clinical Study on the Safety and Preliminary Efficacy of Allogeneic Endothelial Progenitor Cells (EPCs) Injection in Patients With Acute Ischemic Stroke

This is a multicenter, randomized, double-blind, placebo-controlled, dose-Escalation clinical study to investigate the safety and efficacy of EPCs transplantation in Acute ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: iEPCs; Drug: Placebo

Detailed Description

Acute ischemic stroke (AIS) occurs when blood flow to the brain is blocked by a clot or mechanical event and is the most common type of stroke. However, due to the limitation of time and contraindications, only a few patients with AIS are eligible candidates. Endothelial progenitor cells (EPCs) have the potential to reduce brain damage from AIS. They can effectively repair endothelial cells with vascular injuries by directly differentiating into endothelial cells or releasing corresponding regulatory factors, which is a potentially important means for the prevention and treatment of a series of vascular system disorders. The introduction of induced pluripotent stem cells (iPSCs) technology provides a highly feasible option for clinical application of EPCs. Allogeneic iPSC-EPCs can be produced on a large scale to provide enough cells, fundamentally solving the problem of insufficient dosage, and making them a feasible clinical option for treatment of AIS.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Allife
    • Beijing, Beijing, China, 100053
      • Allife Medicine （Beijing） Limitied

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1.Able to provide consent to study or consent is obtained from the patient's legal representative
• 2.Male or females,aged 18 to 80 years
• 3. Subjects with acute ischemic stroke:1) Onset time ≤ 7 days; 2) Imaging confirmed infarction in the blood-supplying area of the internal carotid artery; 3) treated with thrombolysis and/or thrombolysis, or without the above treatment;
• 4.Subjects with NIHSS score between≥6 points and≤24 points at the time of screening
• 5.Eligible patients of childbearing potential(both men and women)if sexually active must agree to use a reliable method of contraception with their partners

Exclusion Criteria:

1. Impaired consciousness (NIHSS score Ia ≥ 2);
2. Disease progression or fluctuation in the subject after the first visit to the screening enrollment, which in the judgment of the investigator has a poor prognosis and will not benefit from this clinical study;
3. Those who have bleeding conversion as assessed by imaging after thrombolysis and/or thrombolysis;
4. History of previous intracranial hemorrhage (within 1 year), arteriovenous malformations, arterial entrapment, aneurysm (≥3 mm in maximum diameter), epilepsy, and history of brain tumor;
5. Abnormalities in major organ function

7. severe respiratory disease that, as assessed by the investigator, may have an impact on the subject's determination of test results (active tuberculosis, chronic obstructive pulmonary disease, interstitial lung disease, severe or critical pneumonia); 8. Uncontrolled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg) after treatment, which in the judgment of the investigator carries a high risk of bleeding and has a poor prognosis; 9. Those with malignant tumors or a history of malignant tumors; 10. Have an autoimmune disease or are undergoing immunotherapy; 11. Being pregnant or breastfeeding; 12. Allergic to multiple drugs (≥2) or allergic to human albumin; 13. have been alcohol- or drug-dependent in the 6 months prior to the onset of illness or have had an episode of acute alcoholism in the 24 h prior to the onset of illness or have had an episode of Those with acute alcohol intoxication within 24 h; 14. History of psychiatric illness or severe cognitive impairment that may affect the evaluation of neurologic function; 15. Positive for Hepatitis B surface antigen, positive for Hepatitis C virus antibody, positive for syphilis serum antibody or positive for HIV antibody; 16. Being enrolled in a clinical study of another drug; 17. Patients who, in the opinion of the investigator, are not suitable for participation in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Cohort 1; 1X level dose of iEPCs	Drug: iEPCs; Patients receive iEPCs IV with the single dose; Other Names: iPSC EPCs
Experimental: Experimental: Cohort 2; 3X level dose of iEPCs or placebo	Drug: iEPCs; Patients receive iEPCs IV with the single dose; Other Names: iPSC EPCs; Drug: Placebo; Patients receive placebo IV with a single dose; Other Names: iEPCs excipients
Experimental: Experimental: Cohort 3; 6X level dose iEPCs or Placebo	Drug: iEPCs; Patients receive iEPCs IV with the single dose; Other Names: iPSC EPCs; Drug: Placebo; Patients receive placebo IV with a single dose; Other Names: iEPCs excipients
Experimental: Experimental: Cohort 4; 10X level dose of iEPCs or placebo	Drug: iEPCs; Patients receive iEPCs IV with the single dose; Other Names: iPSC EPCs; Drug: Placebo; Patients receive placebo IV with a single dose; Other Names: iEPCs excipients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Incidence and severity of adverse events after iEPCs infusion	Incidence and severity of adverse events assessed by CTCAE V5.0 during the twelve-month study period after iEPCs infusion.	baseline to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HLA matching	the level of HLA matching pairs of donor/recipient	From enrollment to the end of treatment at 1 year
plasma HLA antibody	The change from the baseline of plasma HLA antibody will be calculated at Day 14，month 1, month 3 post infusion, as available.	From enrollment to the end of treatment at 14 days, 1 month and 3 months
plasma T lymphocytes	The change from the baseline in plasma T lymphocytes will be calculated at day 1, day 3, day 7, day 14, day 21, month 1, month 3, month 6, month 9, month 12 post infusion, as available.	From enrollment to the end of treatment at 1 day , 3 days, 7 days, 14 days, 21 days, 1 month , 3 months, 6 months, 9 months, 12 months
plasma iEPCs	The change from the baseline in plasma iEPCs will be calculated at 30~40 min, day 1, day 3, day 7, day 14, day 21, month 1, month 2, month 3 post infusion, as available.	From enrollment to the end of treatment at 30~40 mins, 1 day, 3 days, 7 days, 14 days, 21 days, 1 month, 2 months, 3 months
Modified Rankin Scale, mRS	The change from the baseline in mRS will be calculated at month 1, month 3, month 6, as available. The scale is divided into 7 degrees, from 0 (no deficit) to 6 (dead).	From enrollment to the end of treatment at 1 month, 3 months, 6 months
National Institute of Health stroke scale, NIHSS	The change from the baseline in NIHSS will be calculated at month 1, month 3, month 6 post-treatment, as available. The range of scores is from 0 (normal) to 42.	From enrollment to the end of treatment at 1 month, 3 months, 6 months
activity of daily living, ADL	The change from the baseline in ADL will be calculated at month 1, month 3, month 6 post-treatment, as available. Every activity will be scored 5 and the range of scores is from 0 (normal) to 5.	From enrollment to the end of treatment at 1 month, 3 months, 6 months
cerebral infarct volume	The change from baseline in cerebral infarct volume using MRI will be calculated at day 7, month 6 post-treatment, as available.	From enrollment to the end of treatment at 7 days and 6 months
vascular endothelial growth factor, VEGF	Changes of concentration of vascular endothelial growth factor（VEGF）in the serum from the baseline will be calculated at day 1, day 3, day 7, day 14, day 21, month 1, month 3, month 6, month 9, month 12 post-treatment, as available.	From enrollment to the end of treatment at 1 day , 3 days, 7 days, 14 days, 21 days, 1 month , 3 months, 6 months, 9 months, 12 months
brain derived neurotrophic factor，BDNF	Changes of concentration of brain derived neurotrophic factor (BDNF) in the serum from the baseline will be calculated at day 1, day 3, day 7, day 14, day 21, month 1, month 3, month 6, month 9, month 12 post-treatment, as available.	From enrollment to the end of treatment at 1 day , 3 days, 7 days, 14 days, 21 days, 1 month , 3 months, 6 months, 9 months, 12 months

Collaborators and Investigators

• Sponsor: Allife Medical Science and Technology Co., Ltd.
• Collaborators: Beijing Tiantan Hospital; Peking University Third Hospital; Xuanwu Hospital, Beijing; Linyi People's Hospital; Linfen Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Actual): April 15, 2025
• Study Completion (Actual): April 15, 2025

Study Registration Dates

• First Submitted: April 27, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke; EPCs; phase Ⅰ
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia
• Other Study ID Numbers: CNYX-2020-003

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