A Randomized Placebo-controlled Multicenter Trial to Evaluate the Efficacy and Safety of JTR-161, Allogeneic Human Dental Pulp Stem Cell, in Patients With Acute Ischemic stRoke (J-REPAIR)

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and efficacy of a single intravenous administration of JTR-161 (allogeneic stem cell product derived from the dental pulp of healthy adult humans) to patients with acute ischemic stroke. This study is comprised of 3 cohorts and conducted in the order of Cohort 1, Cohort 2 and Cohort 3. Cohort 1 Arm-1: JTR-161, 1 × 10^8 cells/subject, 6 subjects Arm-2: Placebo, 2 subjects The Data and Safety Monitoring Board (DSMB) and the Sponsor will decide whether Cohort 2 can be initiated or not. Cohort 2 Arm-1: JTR-161, 3 × 10^8 cells/subject, 6 subjects Arm-2: Placebo, 2 subjects DSMB and the Sponsor will decide whether Cohort 3 can be initiated or not and the dose of JTR-161 in Cohort 3. Cohort 3 Arm-1: JTR-161, 1 × 10^8 cells/subject or 3 × 10^8 cells/subject, 30 subjects Arm-2: Placebo, 30 subjects

Official Title
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An Exploratory, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate Safety and Efficacy of JTR-161 in Patients With Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Biological: JTR-161
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have ischemic strokes in the anterior circulation Patients whose mRS is 0 or 1 prior to the onset of ischemic stroke Patients whose NIHSS score of ≥5 to ≤20 at screening Patients who can be administered dosing solutions within 48 h of stroke onset Exclusion Criteria: Patients who have new ischemic lesion in the cerebellum or brainstem Patients whose consciousness level drops severely Patients whose infarct area is widespread Patients who have a clinically significant hemorrhagic transformation Patients who had seizures after onset of ischemic stroke Patients who have medical history of a neurological event such as stroke or clinically significant head trauma within 180 days prior to giving informed consent Patients who have poor blood pressure control Patients who have poor glycaemic control Patients who have one of the following complications Severe liver dysfunction Severe kidney dysfunction Severe heart failure Severe pulmonary dysfunction Patients who have severe infections Patients who have any neurological disorder affecting informed consent or study assessments Patients who have the malignant tumor, or medical history of malignant tumor within 2 years prior to the onset of ischemic stroke Patients who have a contraindication for MRI Patients who have thrombocytopenia Patients who have medical history of allergy to products derived from human tissues, bovine or porcine Patients who have medical history of allergy to streptomycin Patients who have undergone splenectomy in the past Patients who have a possibility of transient ischemic attack Patients who are scheduled to undergo revascularization (carotid endarterectomy, stent placement etc.)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JTR-161<br> | Biological: JTR-161<br>* JTR-161 (1 or 3 × 10^8 cells/subject) will be suspended and administered in an intravenously infusion.<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Placebo will be suspended and administered in an intravenously infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients who achieved Excellent outcome (modified Rankin Scale [mRS] ≤1 and National Institutes of Health Stroke Scale [NIHSS] ≤1 and Barthel Index [BI] ≥95) on Day 91 in Cohort 3. |  | 91 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who achieved mRS ≤ 1 or mRS ≤ 2 |  | 366 days | 
| Percentage of patients who achieved BI ≥ 95 |  | 366 days | 
| Percentage of patients who achieved NIHSS ≤ 1, who achieved improvement of ≥ 75%, and who achieved improvement of ≥ 10 points |  | 91 days | 
| Changes in EQ-5D-5L scores | The EuroQOL 5 dimension 5-level (EQ-5D-5L) consists of 2 parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. | 366 days | 
| Percentage of patients who achieved excellent outcome (mRS ≤ 1, NIHSS ≤ 1, and BI ≥ 95) |  | 91 days | 
| Percentage of patients who showed overall improvement (mRS ≤ 2, NIHSS improvement of ≥ 75%, and BI ≥ 95) |  | 91 days | 
| Incidence of Adverse events (signs and symptoms) |  | 366 days | 
| Changes in Laboratory tests (hematology, blood chemistry, blood coagulation test, urinalysis) | Number of participants with clinical laboratory abnormalities for each parameter hematology Red blood cell count, Hemoglobin, Hematocrit, Platelet count, Leukocyte count, Leukocyte formula (neutrophils, lymphocytes, monocytes, eosinophils, basophils) blood chemistry Total protein, Albumin, Total bilirubin, Aspartate aminotransferase , Alanine aminotransferase, Alkaline phosphatase , Lactate dehydrogenase , γ-Glutamyltransferase, Blood urea nitrogen , Creatinine, Uric acid, Sodium, Potassium, Calcium, Chloride, Creatine kinase , C-reactive protein blood coagulation Prothrombin time (International normalized ratio) , Activated partial thromboplastin time urinalysis Urine Protein, Urine Glucose | 366 days | 
| Changes in Vital signs (blood pressure [systolic/diastolic], pulse rate, body temperature) | Number of participants of the vital signs abnormalities for each parameter: blood pressure (mmHg), pulse rate (bpm) and body temperature (℃). | 366 days | 
| Changes in Oxygen saturation (SpO2) |  | 366 days | 
| Changes in findings of imaging examination by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). |  | 31 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke