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)

Phase 1

Completed

• Conditions: Acute Ischemic Stroke

• Registration Number: NCT04608838
• Lead Sponsor: Teijin Pharma Limited

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-30
• Study First Submitted: 2020-09-08
• Study First Submitted QC: 2020-10-28
• Study First Posted: 2020-10-29
• Primary Completion: 2021-02-15
• Study Completion: 2021-11-24
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-28
• Last Update Posted: 2022-06-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Changes in Oxygen saturation (SpO2)	366 days
Percentage of patients who achieved BI ≥ 95	366 days
Percentage of patients who achieved excellent outcome (mRS ≤ 1, NIHSS ≤ 1, and BI ≥ 95)	91 days
Percentage of patients who achieved mRS ≤ 1 or mRS ≤ 2	366 days
Percentage of patients who achieved NIHSS ≤ 1, who achieved improvement of ≥ 75%, and who achieved improvement of ≥ 10 points	91 days
Incidence of Adverse events (signs and symptoms)	366 days
Percentage of patients who showed overall improvement (mRS ≤ 2, NIHSS improvement of ≥ 75%, and BI ≥ 95)	91 days
Changes in Laboratory tests (hematology, blood chemistry, blood coagulation test, urinalysis)	366 days	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
Changes in findings of imaging examination by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).	31 days
Changes in Vital signs (blood pressure [systolic/diastolic], pulse rate, body temperature)	366 days	Number of participants of the vital signs abnormalities for each parameter: blood pressure (mmHg), pulse rate (bpm) and body temperature (℃).
Changes in EQ-5D-5L scores	366 days	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'.

Trial Locations

Locations (1)

Nippon Medical School Hospital; 🇯🇵 Bunkyo-ku, Tokyo, Japan