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) (J-REPAIR)

• ClinicalTrials.gov Identifier: NCT04608838
• Recruitment Status: Completed
• First Posted: October 29, 2020
• Last Update Posted: June 30, 2022
• Sponsor: Teijin Pharma Limited
• Information provided by (Responsible Party): Teijin Pharma Limited

Tracking Information

• First Submitted Date: September 8, 2020
• First Posted Date: October 29, 2020
• Last Update Posted Date: June 30, 2022
• Actual Study Start Date: January 30, 2019
• Actual Primary Completion Date: February 15, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 28, 2020): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 28, 2020)

• 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 [ Time Frame: 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'.
• 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) [ Time Frame: 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 Vital signs (blood pressure [systolic/diastolic], pulse rate, body temperature) [ Time Frame: 366 days ]
  Number of participants of the vital signs abnormalities for each parameter: blood pressure (mmHg), pulse rate (bpm) and body temperature (℃).
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Some care providers who involved in the preparation or administration of dosing solutions are unblinded.

Primary Purpose: Treatment

• Condition: Acute Ischemic Stroke

Intervention

• Biological: JTR-161
  JTR-161 (1 or 3 × 10^8 cells/subject) will be suspended and administered in an intravenously infusion.
• Biological: Placebo
  Placebo will be suspended and administered in an intravenously infusion.

Study Arms

• Experimental: JTR-161
  Intervention: Biological: JTR-161
• Placebo Comparator: Placebo
  Intervention: Biological: Placebo

• Publications *: Suda S, Nito C, Ihara M, Iguchi Y, Urabe T, Matsumaru Y, Sakai N, Kimura K; J- REPAIR trial group. Randomised placebo-controlled multicentre trial to evaluate the efficacy and safety of JTR-161, allogeneic human dental pulp stem cells, in patients with Acute Ischaemic stRoke (J-REPAIR). BMJ Open. 2022 May 24;12(5):e054269. doi: 10.1136/bmjopen-2021-054269.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 23, 2020): 79
• Original Estimated Enrollment (submitted: October 28, 2020): 76
• Actual Study Completion Date: November 24, 2021
• Actual Primary Completion Date: February 15, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04608838
• Other Study ID Numbers: JTR-161-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Teijin Pharma Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Teijin Pharma Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Teijin Pharma Limited
• Verification Date: June 2022