Investigation of Neural Stem Cells in Ischemic Stroke

NCT ID: NCT03629275

Last Updated: 2021-08-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-31
• Study Completion Date: 2021-03-02

Brief Summary

A study of stereotactic, intracerebral injection of CTX0E03 neural stem cells into patients with moderate to moderately severe disability as a result of an ischemic stroke.

Detailed Description

This is a randomized, placebo-controlled, multi-center study. Patients with persistent disability 6-24 months following an ischemic stroke will be enrolled following confirmation of eligibility. Patients will be randomized 2:1 to undergo a stereotactic surgery and receive a single administration of CTX0E03 Drug Product by intracerebral implantation or undergo sham surgery only (placebo). Patients will be followed for 12 months after surgery with follow-up assessments occurring at various time points over the 12 months. All eligible patients will be assigned a standardized Physical Therapy (PT) program. Patients will complete their daily PT exercises at home for 12 weeks after their surgery.

Conditions

Ischemic Stroke; Chronic Stroke; Hemiparesis; Arm Paralysis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CTX0E03 Drug Product and delivery device

20 million neural stem cells

Group Type: EXPERIMENTAL

CTX0E03 Drug Product and delivery device

Intervention Type: COMBINATION_PRODUCT

Includes stereotactic surgery and a burr hole drilled through the skull to allow for a one time intracerebral injection of 20 million CTX0E03 Drug Product stem cells into an area of the brain adjacent to the area affected by the stroke.

Placebo

Sham Surgery

Group Type: SHAM_COMPARATOR

Placebo

Intervention Type: DRUG

Sham surgical comparator includes stereotactic surgery and a partial thickness burr hole drilled into the skull. No injection of any kind is made into the brain, and no other intervention is given.

Interventions

CTX0E03 Drug Product and delivery device

Includes stereotactic surgery and a burr hole drilled through the skull to allow for a one time intracerebral injection of 20 million CTX0E03 Drug Product stem cells into an area of the brain adjacent to the area affected by the stroke.

Intervention Type: COMBINATION_PRODUCT

Placebo

Sham surgical comparator includes stereotactic surgery and a partial thickness burr hole drilled into the skull. No injection of any kind is made into the brain, and no other intervention is given.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ischemic stroke that includes the supratentorial region as confirmed by CT or MRI, occurring within 6 to 24 months of the time that surgical intervention will be performed (Qualifying Stroke Event)
• Modified Rankin Score of 3 or 4 due to the Qualifying Stroke Event
• Some residual upper limb movement
• Sufficient cognitive and language abilities to comprehend verbal commands and to carry out the study assessments
• No medical conditions that would preclude neurosurgery with appropriate preparation and management.
• Ability to attend study visits and complete all study assessments including ability to provide informed consent

Exclusion Criteria

• Modified Rankin Score of >1 prior to the Qualifying Stroke Event
• Stroke due to hemorrhage or stroke known or suspected of being caused by, or related to, connective tissue disorder, congenital disorder of the cerebral vessels or a disorder of thrombosis; patients with atrial fibrillation as a suspected cause of stroke are NOT excluded
• Neurosurgical pathway obstructed by vascular malformation or cavity
• History of neurological or other disease resulting in significant functional impairment (e.g. Parkinson's disease, motor neuron disease, moderate dementia, arthritis, contractures or fixed anatomical abnormality)
• Inability to stop or transition off valproic acid or other demethylating agents or Histone deacetylases (HDAC) inhibitors for 1 week before and 4 weeks after surgery
• Use of selective serotonin reuptake inhibitors (SSRI), unless the subject is on a stable dose that has been started at least 2-months before screening (V1)
• Use of antispasticity medications (excluding oral antispasticity medications if they have been taken regularly for at least one month prior to surgery)The use of Botox® or similar is allowed if the last dose was ≥3 months prior to screening; however, its use will be prohibited until following the 12 month visit
• Inability to discontinue anticoagulation therapy for a required interval
• History of malignant disease within the last 5 years, or any history of primary or secondary brain malignant disease
• Patients who have previously participated in a cell-based therapy study at any time or in any other study involving an investigational product or rehabilitation study within the last 30 days
• Patients with clinically significant lab values, including positive Class I human leukocyte antigen (HLA) antibodies specific for CTX0E03
• Planned initiation of any new PT regimen within 6-months of surgery

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ReNeuron Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Beckman, MD

Role: STUDY_DIRECTOR

ReNeuron Ltd.

Locations

University of Arkansas

Little Rock, Arkansas, United States

University of California, Irvine

Irvine, California, United States

University of California, Los Angeles

Los Angeles, California, United States

University of Southern California Neurorestoration Center

Los Angeles, California, United States

Stanford University

Palo Alto, California, United States

University of California, San Diego

San Diego, California, United States

University of Miami

Coral Gables, Florida, United States

University of South Florida

Tampa, Florida, United States

Emory

Atlanta, Georgia, United States

Augusta University

Augusta, Georgia, United States

Shirley Ryan Ability Lab

Chicago, Illinois, United States

MedStar Health Research Institute

Hyattsville, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

JFK Neuroscience Institute

Edison, New Jersey, United States

Albany Medical College

Albany, New York, United States

Duke University School of Medicine

Durham, North Carolina, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, United States

University of Texas Health Science Center

Houston, Texas, United States

University of Texas Health Science Center

San Antonio, Texas, United States

Countries

United States

References

Kolls BJ, Muir KW, Savitz SI, Wechsler LR, Pilitsis JG, Rahimi S, Beckman RL, Holmes V, Chen PR, Albers DS, Laskowitz DT. Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III). Trials. 2024 Feb 28;25(1):150. doi: 10.1186/s13063-024-07988-z.

Reference Type: DERIVED

PMID: 38419030 (View on PubMed)

Olmsted ZT, Petersen EA, Pilitsis JG, Rahimi SY, Chen PR, Savitz SI, Laskowitz DT, Kolls BJ, Staudt MD. Toward Generalizable Trajectory Planning for Human Intracerebral Trials and Therapy. Stereotact Funct Neurosurg. 2022;100(4):214-223. doi: 10.1159/000521916. Epub 2022 Feb 7.

Reference Type: DERIVED

PMID: 35130557 (View on PubMed)

Other Identifiers

RN01-CP-0003

Identifier Type: -

Identifier Source: org_study_id