Clinical Plan of Ischemic Stroke

A Multicenter, Blind, Randomized, Placebo-controlled Phase I / IIA Study to Evaluate the Safety, Tolerability, and Initial Efficacy of a Single Injection of Ischemia Tolerant Human Allogeneic Bone Marrow Mesenchymal Stem Cells in Patients With Ischemic Stroke

Stroke is the main cause of adult health damage. 20% of stroke survivors need institutional care after 3 months, and up to 30% of them have severe or permanent disability. Stem cells are a kind of pluripotent cells with the ability of self replication. The self-renewal and differentiation characteristics of mesenchymal stem cells, as well as cytokine secretion effect and immune characteristics, provide the possibility for mesenchymal stem cells to treat ischemic stroke. After the infusion of mesenchymal stem cells, the secretion of soluble media including growth factors and cytokines may be the main mechanism of mesenchymal stem cells.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Biological: it-hMSC

Detailed Description

Stroke is the main cause of adult health damage. 20% of stroke survivors need institutional care after 3 months, and up to 30% of them have severe or permanent disability. Stem cells are a kind of pluripotent cells with the ability of self replication. The self-renewal and differentiation characteristics of mesenchymal stem cells, as well as cytokine secretion effect and immune characteristics, provide the possibility for mesenchymal stem cells to treat ischemic stroke. After the infusion of mesenchymal stem cells, the secretion of soluble media including growth factors and cytokines may be the main mechanism of mesenchymal stem cells. The main purpose of this study was to evaluate the safety and tolerance of intravenous injection of ischemia tolerant human allogeneic bone marrow mesenchymal stem cells in patients with ischemic stroke. The secondary objective was to evaluate the clinical efficacy of ischemic tolerant human allogeneic bone marrow mesenchymal stem cells in the treatment of ischemic stroke patients with neurological dysfunction.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijin, China
    • Recruiting
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female ≥ 18 years old;
2. The history showed that the last clinical diagnosis of ischemic stroke was more than 6 months;
3. The results of MRI at the first diagnosis and at the time of selection indicated that there was ischemic stroke and dysfunction;
4. There was no significant improvement in neurological function or functional defect 2 months before the study;
5. There is serious neurological dysfunction related to the diagnosis in Article 2, which leads to the subjects need the assistance of others to walk, or cannot complete the general activities of daily living independently;
6. NIHSS score was 6-20;
7. The life expectancy is more than 12 months;
8. Before treatment, the patient received standard medical care for secondary prevention of ischemic stroke, including but not limited to appropriate blood pressure and cholesterol control measures, use of antiplatelet drugs or anticoagulants (except prohibited cases);
9. Be able to understand and provide the signed informed consent, or ask the designated legal guardian or spouse to make the above decision voluntarily on behalf of the subjects;
10. It is reasonable to expect that patients will receive standard medical care for secondary prevention of ischemic stroke and participate in safety follow-up of all plans;
11. Organ function determined according to the following criteria:

Serum AST ≤ 2.5 × Upper normal limit (ULN);

Serum alanine aminotransferase (ALT) ≤ 2.5 × Normal upper limit;

Total serum bilirubin ≤ 1.5 × Normal upper limit;

In subjects without antithrombotic therapy, prothrombin time (PT) and partial thrombokinase time (PTT) ≤ 1.25 × Normal upper limit;

Serum albumin ≥ 3.0g/dl;

Absolute neutrophil count (ANC) ≥ 1500/ μ L；

Platelets ≥ 150000/ μ L；

Hemoglobin ≥ 9.0g/dl;

Serum creatinine ≤ 1.5 × Normal upper limit;

Serum amylase or lipase were in normal range.

Exclusion Criteria:

1. History of epilepsy;
2. History of tumor;
3. History of brain tumor and brain trauma;
4. hepatitis B, five surface antigens, e antigens, e antibodies and core antibodies were positive for any one, positive for hepatitis C virus antibody, positive for syphilis serum antibody or HIV positive.
5. Myocardial infarction occurred within 6 months before the trial;
6. Suffering from any other medical disease with clinical significance, or with abnormal mental or laboratory results, the researcher or the sponsor determines that participating in the trial will bring safety risks to the subjects;
7. Imaging examination showed subarachnoid hemorrhage or intracerebral hemorrhage in the past 12 months;
8. Participate in another study on the use of test drug or equipment within 3 months before treatment;
9. Participated in other stem cell therapy related research;
10. History of drug or alcohol abuse in the past year;
11. Women who are known to be pregnant, breast-feeding or have a positive pregnancy test (to be tested during the screening process) or plan to be pregnant during the trial;
12. Allergic to cattle and pork products.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo group; placebo	Biological: it-hMSC; Different doses of it-hMSC
Experimental: Low dose group; 0.5 × 10 ^ 6 / kg (body weight) of it-hMSC per person	Biological: it-hMSC; Different doses of it-hMSC
Experimental: Middle dose group; 1 × 10 ^ 6 / kg (body weight) of it-hMSC per person	Biological: it-hMSC; Different doses of it-hMSC
Experimental: High dose group; 2 × 10 ^ 6 / kg (body weight) of it-hMSC per person	Biological: it-hMSC; Different doses of it-hMSC
Experimental: Highest dose cell group; Highest dose of it-hMSC	Biological: it-hMSC; Different doses of it-hMSC
Experimental: Sub high dose cell group; Sub high dose of it-hMSC	Biological: it-hMSC; Different doses of it-hMSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events and serious adverse events rate	Safety and tolerability of it-hMSC treatment	In 12 months
Rate of clinical significant changes in laboratory	Safety and tolerability of it-hMSC treatment	In 12 months
Rate of abnormal neurological physical examination results	Safety and tolerability of it-hMSC treatment	In 12 months
Rate of imaging changes	Safety and tolerability of it-hMSC treatment	In 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of NIHSS scores	The improvement of neurological function was evaluated by neurological	1、3、6、9、12 months after treatment
Change of BI scores	The improvement of neurological function was evaluated by neurological	1、3、6、9、12 months after treatment
Change of mRS scores	The improvement of neurological function was evaluated by neurological	1、3、6、9、12 months after treatment
Change of MMSE scores	The improvement of neurological function was evaluated by neurological	1、3、6、9、12 months after treatment
Change of GDS scores	The improvement of neurological function was evaluated by neurological	1、3、6、9、12 months after treatment

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: June 27, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 8, 2021

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 1, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: D2020093

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