Clinical trial NCT04608838: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Ischemic Stroke
Keywords: Acute Ischemic Stroke
Lead sponsor: Teijin Pharma Limited
Sponsor class: INDUSTRY
First posted: 2020-10-29
Enrollment: 79
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.)

Primary outcomes:
measure: 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.
timeFrame: 91 days
Secondary outcomes:
measure: Percentage of patients who achieved mRS ≤ 1 or mRS ≤ 2
timeFrame: 366 days
measure: Percentage of patients who achieved BI ≥ 95
timeFrame: 366 days
measure: Percentage of patients who achieved NIHSS ≤ 1, who achieved improvement of ≥ 75%, and who achieved improvement of ≥ 10 points
timeFrame: 91 days
measure: Changes in EQ-5D-5L scores
timeFrame: 366 days
measure: Percentage of patients who achieved excellent outcome (mRS ≤ 1, NIHSS ≤ 1, and BI ≥ 95)
timeFrame: 91 days
measure: Percentage of patients who showed overall improvement (mRS ≤ 2, NIHSS improvement of ≥ 75%, and BI ≥ 95)
timeFrame: 91 days
measure: Incidence of Adverse events (signs and symptoms)
timeFrame: 366 days
measure: Changes in Laboratory tests (hematology, blood chemistry, blood coagulation test, urinalysis)
timeFrame: 366 days
measure: Changes in Vital signs (blood pressure [systolic/diastolic], pulse rate, body temperature)
timeFrame: 366 days
measure: Changes in Oxygen saturation (SpO2)
timeFrame: 366 days
measure: Changes in findings of imaging examination by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).
timeFrame: 31 days
Other outcomes:
Locations:
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
Study officials:
References:
citation: 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.