Clinical trial NCT05993884: Safety and Preliminary Efficacy of Allogeneic Endothelial Progenitor Cells (EPCs) in Patients With Acute Ischemic Stroke
Official title: Phase I Clinical Study on the Safety and Preliminary Efficacy of Allogeneic Endothelial Progenitor Cells (EPCs) Injection in Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Acute Ischemic Stroke
Keywords: Acute Ischemic Stroke
EPCs
phase Ⅰ
Lead sponsor: Allife Medical Science and Technology Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Linfen Central Hospital
name: Peking University Third Hospital
name: Xuanwu Hospital, Beijing
name: Beijing Tiantan Hospital
name: Linyi People's Hospital
First posted: 2023-08-15
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the Incidence and severity of adverse events after iEPCs infusion
timeFrame: baseline to 1 year
Secondary outcomes:
Other outcomes:
measure: HLA matching
timeFrame: From enrollment to the end of treatment at 1 year
measure: plasma HLA antibody
timeFrame: From enrollment to the end of treatment at 14 days, 1 month and 3 months
measure: plasma T lymphocytes
timeFrame: 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
measure: plasma iEPCs
timeFrame: 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
measure: Modified Rankin Scale, mRS
timeFrame: From enrollment to the end of treatment at 1 month, 3 months, 6 months
measure: National Institute of Health stroke scale, NIHSS
timeFrame: From enrollment to the end of treatment at 1 month, 3 months, 6 months
measure: activity of daily living, ADL
timeFrame: From enrollment to the end of treatment at 1 month, 3 months, 6 months
measure: cerebral infarct volume
timeFrame: From enrollment to the end of treatment at 7 days and 6 months
measure: vascular endothelial growth factor, VEGF
timeFrame: 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
measure: brain derived neurotrophic factor，BDNF
timeFrame: 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
Locations:
city: Beijing
country: China
facility: Allife Medicine （Beijing） Limitied
state: Beijing
city: Beijing
country: China
facility: Allife
state: Beijing
Study officials:
References: