Investigation of Neural Stem Cells in Ischemic Stroke

NCT03629275 | Terminated Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: RN01-CP-0003
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 23

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.

Conditions

Ischemic Stroke; Chronic Stroke; Hemiparesis; Arm Paralysis

Keywords

Efficacy; Neural Stem cells; Intracerebral; Cerebral Infarction; Cerebrovascular disorders; Brain diseases; Stereotactic surgery

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects in which Modified Rankin Scale (mRS) improves by ≥1 point at Month 6 from Baseline

  The mRS is an ordinal scale from 0-6, where 0 represents no disability, and each grade above 0 represents a subject's increased level of disability and dependence upon others to perform daily activities.

  6 months

Secondary Outcomes (13)

• Change from baseline in a subject's ability to execute activities of daily living using the Barthel Index (BI).

  6 months

• Change from baseline in a subject's basic mobility and balance using the Timed Up and Go Test (TUG).

  6 months

• Change from baseline in the function of subject's paretic limb using the Chedoke Arm and Hand Activity Inventory (CAHAI).

  6 months

• Change from baseline in a subject's executive processing speed, language skills and memory using the Symbol Digit Modalities Test.

  6 months

• Change from baseline in a subject's executive processing speed, language skills and memory using Controlled Oral Word Association tasks.

  6 months

Study Arms (2)

CTX0E03 Drug Product and delivery device

EXPERIMENTAL

20 million neural stem cells

Combination Product: CTX0E03 Drug Product and delivery device

Placebo

SHAM COMPARATOR

Sham Surgery

Drug: Placebo

Interventions

CTX0E03 Drug Product and delivery device 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.

CTX0E03 Drug Product and delivery device

Placebo 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.

Placebo

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ReNeuron Limited: lead

Study Sites (23)

University of Arkansas

Little Rock, Arkansas, 72205, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of Southern California Neurorestoration Center

Los Angeles, California, 90095, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of California, San Diego

San Diego, California, 92093-0706, United States

Location

University of Miami

Coral Gables, Florida, 33146, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Emory

Atlanta, Georgia, 30322, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Shirley Ryan Ability Lab

Chicago, Illinois, 60611, United States

Location

MedStar Health Research Institute

Hyattsville, Maryland, 20782, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63130, United States

Location

JFK Neuroscience Institute

Edison, New Jersey, 08820, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37403, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229-3900, United States

Location

Related Publications (3)

• Laskowitz DT, Muir KW, Savitz SI, Wechsler LR, Pilitsis JG, Rahimi SY, Beckman RL, Holmes V, Chen PR, Juel L, Koltai D, Kolls BJ. Methodological considerations in PISCES 3: a randomized, placebo-controlled study of intracerebral stem cells in subjects with disability following an ischemic stroke. Front Stroke. 2023 Jul 4;2:1182537. doi: 10.3389/fstro.2023.1182537. eCollection 2023.

  PMID: 41541089 DERIVED

• 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.

  PMID: 38419030 DERIVED

• 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.

  PMID: 35130557 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Paresis; Cerebral Infarction; Cerebrovascular Disorders; Brain Diseases

Condition Hierarchy (Ancestors)

Stroke; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Infarction; Brain Ischemia; Infarction; Ischemia; Pathologic Processes; Necrosis

Study Officials

• Richard Beckman, MD

  ReNeuron Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: August 14, 2018
• Study Start: August 31, 2018
• Primary Completion: September 9, 2020
• Study Completion: March 2, 2021
• Last Updated: August 13, 2021

Record last verified: 2021-08

Locations

US (23)