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)

Teijin Pharma Limited79 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Acute Ischemic Stroke

Interventions

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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 1. Severe liver dysfunction 2. Severe kidney dysfunction 3. Severe heart failure 4. 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.)

Outcomes

Primary Outcomes

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.

Time frame: 91 days

Secondary Outcomes

Percentage of patients who achieved mRS ≤ 1 or mRS ≤ 2

Time frame: 366 days

Percentage of patients who achieved BI ≥ 95

Time frame: 366 days

Percentage of patients who achieved NIHSS ≤ 1, who achieved improvement of ≥ 75%, and who achieved improvement of ≥ 10 points

Time frame: 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'.

Time frame: 366 days

Percentage of patients who achieved excellent outcome (mRS ≤ 1, NIHSS ≤ 1, and BI ≥ 95)

Time frame: 91 days

Percentage of patients who showed overall improvement (mRS ≤ 2, NIHSS improvement of ≥ 75%, and BI ≥ 95)

Time frame: 91 days

Incidence of Adverse events (signs and symptoms)

Time frame: 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

Time frame: 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 (℃).

Time frame: 366 days

Changes in Oxygen saturation (SpO2)

Time frame: 366 days

Changes in findings of imaging examination by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).

Time frame: 31 days

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)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes