Allogeneic Mesenchymal Stem Cells for the Survivors of Ischemic Stroke Trial (ASSIST)

A Phase I/IIa Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of a Multicenter, Blind, Randomized, Placebo Controlled Single Injection of It-hMSC in Patients With Ischemic Stroke

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of single injection of it-hMSC in patients with ischemic stroke in a multicenter, blind, randomized, placebo controlled trial

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: it-hMSC; Drug: Placebo

Detailed Description

Stroke is a leading cause of disability. According to the comprehensive standardized prevalence estimation in 2016, 12.42 million people older than 40 years in China are currently suffering from stroke or have ever suffered from stroke. The overall prevalence rate of stroke in China was 1,596 per 100,000 people in 2016, 4.6 times higher than the rate of 345.1 per 100,000 people in 2013 and 70% of the survivors have disabilities in varying degrees. In addition to rehabilitation therapy, there is no therapeutic drugs of remarkable curative effect for the treatment of ischemic stroke patients. The latest data show that the annual recurrence rate of ischemic stroke in China is as high as 17.7%.

Allogeneic mesenchymal stem cells have been used in many clinical studies for different diseases. In addition to differentiating into multiple cell types and promoting the recovery and repair of the brain by replacing damaged cells, mesenchymal stem cells also secrete cytokines and neurotrophic factors to support and stimulate the growth of other endogenous cells. Meanwhile, mesenchymal stem cells also have anti-inflammatory and immunomodulatory functions. These characteristics of mesenchymal stem cells provide a new therapy for the treatment of stroke.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100070
    • Recruiting
    • Beijing Tiantan Hospital, Capital Medical University
    • Contact: Yongjun Wang, MD; Phone Number: 010-59978538; Email: yongjunwang1962@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older.
• Clinical diagnosis of ischemic stroke for more than 6 months.
• Imaging findings suggestive of ischemic stroke with functional deficits at initial diagnosis and enrollment.
• Severe neurological impairment associated with the diagnosis of ischemic stroke that resulted in the subject needing assistance to walk or not being able to perform general daily activities independently.
• No substantial improvement in neurologic or functional deficits for the 2 months prior to enrollment.
• NIHSS score between 6-20.
• Life expectancy longer than 12 months.
• Prior to treatment, the patient received standard medical care for secondary prevention of ischemic stroke, including but not limited to appropriate blood pressure and cholesterol control measures, use of antiplatelet agents or anticoagulants (except when prohibited).
• Understand and provide signed informed consent, or have a designated legal guardian or spouse make such decision voluntarily on behalf of the subject.
• Expected that the patient will receive standard medical care for secondary prevention of ischemic stroke and participate in all planned safe follow-up visits reasonably.
• Organ function as defined by the following criteria:

AST ≤ 2.5×ULN ALT ≤ 2.5×ULN TSB ≤1.5×ULN PT ≤1.25×ULN and PTT ≤1.25×ULN in subjects who did not receive antithrombotic therapy Serum albumin ≥ 3.0g/dL ANC ≥ 1,500/μL Platelets ≥ 150,000/μL Hemoglobin ≥ 9.0g/dL Serum creatinine ≤ 1.5×ULN Serum amylase or lipase ≤ 1.0×ULN

Exclusion Criteria:

• History of epilepsy.
• History of cancer.
• History of brain trauma and brain tumor.
• Positive for hepatitis B surface antigen, E antigen, E antibody, core antibody, hepatitis C, HIV or RPR.
• Myocardial infarction occurred within six months of study entry.
• Any other medical problems of clinical significance, abnormal mental or test results that the investigator or sponsor determined participating in the study pose a safety risk to the subject.
• Imaging findings suggestive of subarachnoid hemorrhage or intracerebral hemorrhage in the past 12 months.
• Participation in any study of experimental drug or device within 3 months.
• Participation in other study related to stem cell-therapy.
• History of drug or alcohol abuse within 1 year.
• Pregnant, lactating or planning to become pregnant during the trial.
• Allergic to cattle or pork products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: it-hMSC; Single intravenous infusion of 0.5×10^6, 1×10^6, 2×10^6 it-hMSC/kg	Drug: it-hMSC; Single intravenous infusion of it-hMSC for ischemic stroke patients
Placebo Comparator: Placebo-controlled: Placebo; Single intravenous infusion of 1 ml/kg placebo	Drug: Placebo; Single intravenous infusion of 1 ml/kg placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events assessed by CTCAE V5.0 during the twelve-month study period after it-hMSC infusion.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale	The change from the baseline in Modified Rankin Scale will be calculated at month 1, month 3, month 6, month 9, month 12 post-treatment, as available. The scale is divided into 7 degrees, from 0 (no deficit) to 6 (dead).	month 1, month 3, month 6, month 9, month 12
National Institute of Health stroke scale	The change from the baseline in National Institute of Health stroke scale will be calculated at month 1, month 3, month 6, month 9, month 12 post-treatment, as available. The range of scores is from 0 (normal) to 42.	month 1, month 3, month 6, month 9, month 12
Mini-mental State Examination	The change from the baseline in Mini-mental State Examination will be calculated at month 1, month 3, month 6, month 9, month 12 post-treatment, as available. The range of scores is from 0 to 30 (normal).	month 1, month 3, month 6, month 9, month 12
Barthel Index	The change from the baseline in Barthel Index will be calculated at month 1, month 3, month 6, month 9, month 12 post-treatment, as available. The range of scores is from 0 to 100 (normal).	month 1, month 3, month 6, month 9, month 12
Geriatric Depression Scale	The change from the baseline in Geriatric Depression Scale will be calculated at month 1, month 3, month 6, month 9, month 12 post-treatment, as available. The range of scores is from 0 (normal) to 10.	month 1, month 3, month 6, month 9, month 12

Collaborators and Investigators

• Sponsor: Jiuzhitang Maker (Beijing) Cell Technology Co.,Ltd.
• Collaborators: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: September 7, 2020
• First Submitted That Met QC Criteria: October 10, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: STCMSC-CT-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No