Back to resultsCNS10-NPC-GDNF Delivered to the Motor Cortex for ALS
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CNS10-NPC-GDNF
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS, Stem cells, Growth Factor, Regenerative, Neural Progenitor Cells, NPC, Transplantation
Eligibility Criteria
Inclusion:
- Confirmed diagnosis of ALS (Possible, Lab-supported Probable, Probable or Definite El Escorial Criteria)
- Duration of ALS symptoms ≤ 36 months
- Progressive weakness in upper extremities, with EMG supported evidence of denervation in both upper extremities
- Forced Vital Capacity ≥50% of predicted normal in supine
- Age: 18 years or older
- Able to provide Informed Consent
- Be geographically accessible to the study site and able to travel to study site for required visits
- Have caregiver to assist in the transportation and care required by participation in the study
- Not taking riluzole and/or edaravone or on a stable dose for ≥ 30 day
- For women of child bearing capacity, negative pregnancy test prior to surgery and willingness to use birth control for the duration of the trial.
- Medically able to undergo craniotomy as determined by the site PI and/or investigators
- Medically able to tolerate the immunosuppression regimen as determined by the site PI
Exclusion:
- Using invasive ventilatory assistance
- Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI
Presence of any of the following conditions:
- Current drug or alcohol abuse
- Any known immunodeficiency syndrome
- Unstable medical condition
- Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
- Persons of child bearing capacity not willing to practice birth control
- Receiving any investigational device/biologic/drug in the past 30 days or any previous exposure to stem cell therapy
- Any condition in the upper extremities that precludes serial strength or coordination testing
- Any condition that the investigators feel may pose complications for the surgery
- Any condition or ALS disease phenotype that the site PI feels may interfere with participation in the study or in the interpretation of study endpoints
- Allergy to Beta-Lactam antibiotics
- Donor Specific Antibodies (DSA) ≥ 2500MFI or CPRA ≥ 20%
- Contraindications to MRI
Sites / Locations
- Cedars-Sinai Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
CNS10-NPC-GDNF - Group A
CNS10-NPC-GDNF - Group B
CNS10-NPC-GDNF - Group C
Arm Description
Unilateral, Motor Cortex, 0.25x10^6 cells in 10 µL/site, 21 sites (5.25x10^6 total cells) - Motor cortex corresponding to the non-dominant hand
Unilateral, Motor Cortex, 0.5x10^6 cells in 10 µL/site, 21 sites (10.5x10^6 total cells) - Motor cortex corresponding to the non-dominant hand
Unilateral Motor Cortex, 0.5x10^6 cells in 10 µL/site, 21 sites (10.5x10^6 total cells) - Motor cortex corresponding to the dominant hand
Outcomes
Primary Outcome Measures
Safety, as evaluated by the incidence of Adverse Events and Serious Adverse Events and their relationship to the treatment
Safety, as evaluated by changes from baseline in the brain MRI
Secondary Outcome Measures
Force Generation via Accurate Test of Limb Isometric Strength (ATLIS) testing
Change from baseline for force generation by ATLIS
Pinch Strength
Change from baseline for pinch strength
Hand/Wrist Strength
Change from baseline for Hand/Wrist strength using Hand-held dynamometer
Compound Motor Action Potential (CMAP)
Change from baseline for CMAP
Functional Hand assessments using 9-hole peg test
Change from baseline for 9-hole peg test
Penn Upper Motor Neuron Score (PUMNS)
Change from baseline for Penn Upper Motor Neuron Score. (Scale of 0-32, where 0 is normal)
Hand Knob - Functional MRI (fMRI)
Changes from baseline in brain activity in the hand knob area evaluated by fMRI
Full Information
NCT ID
NCT05306457
First Posted
December 21, 2021
Last Updated
January 19, 2023
Sponsor
Cedars-Sinai Medical Center
Collaborators
California Institute for Regenerative Medicine (CIRM)
1. Study Identification
Unique Protocol Identification Number
NCT05306457
Brief Title
CNS10-NPC-GDNF Delivered to the Motor Cortex for ALS
Official Title
Human Neural Progenitor Cells Secreting Glial Cell Line-Derived Neurotrophic Factor (CNS10-NPC-GDNF) Delivered to the Motor Cortex for the Treatment of Amyotrophic Lateral Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 8, 2022 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cedars-Sinai Medical Center
Collaborators
California Institute for Regenerative Medicine (CIRM)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The investigator is examining the safety of transplanting cells, that have been engineered to produce a growth factor, into the motor cortex (brain) of patients with Amyotrophic Lateral Sclerosis (ALS). The cells are called neural progenitor cells, which are a type of stem cell that can become several different types of cells in the nervous system. These cells have been derived to specifically become astrocytes, which is a type of neural cell. The growth factor is called glial cell line-derived neurotrophic factor, or GDNF. GDNF is a protein that promotes the survival of many types of neural cells. Therefore, the cells are called "CNS10-NPC-GDNF." The investigational treatment has been tested in people by delivering it to the spinal cord. However, it has only been delivered to the motor cortex of animals. In this study, we want to learn if CNS10-NPC-GDNF cells are safe to transplant into the motor cortex (brain) of people.
Detailed Description
This study will be the first to use a genetically modified progenitor cell line delivered to the motor cortex to treat a neurodegenerative disease. This is a Phase 1/2a, single-center, safety study of two escalating doses of human neural progenitor cells expressing GDNF (CNS10-NPC-GDNF) delivered unilaterally to the "hand-knob" area of the motor cortex of patients with ALS.
Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of three sequential dosing groups. Subjects will be treated sequentially with a minimum of one month interval between surgeries for the first three subjects in each dosing cohort. The remaining subjects in the cohort will be treated with a minimum interval of at least one week between surgeries.
Primary Outcome:
Safety, as evaluated by:
Adverse Events and Serious Adverse Events
Post-op MRI and/or CT (with contrast) and as clinically indicated
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
ALS, Stem cells, Growth Factor, Regenerative, Neural Progenitor Cells, NPC, Transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CNS10-NPC-GDNF - Group A
Arm Type
Experimental
Arm Description
Unilateral, Motor Cortex, 0.25x10^6 cells in 10 µL/site, 21 sites (5.25x10^6 total cells) - Motor cortex corresponding to the non-dominant hand
Arm Title
CNS10-NPC-GDNF - Group B
Arm Type
Experimental
Arm Description
Unilateral, Motor Cortex, 0.5x10^6 cells in 10 µL/site, 21 sites (10.5x10^6 total cells) - Motor cortex corresponding to the non-dominant hand
Arm Title
CNS10-NPC-GDNF - Group C
Arm Type
Experimental
Arm Description
Unilateral Motor Cortex, 0.5x10^6 cells in 10 µL/site, 21 sites (10.5x10^6 total cells) - Motor cortex corresponding to the dominant hand
Intervention Type
Biological
Intervention Name(s)
CNS10-NPC-GDNF
Intervention Description
Unilateral injections of CNS10-NPC-GDNF into the motor cortex
Primary Outcome Measure Information:
Title
Safety, as evaluated by the incidence of Adverse Events and Serious Adverse Events and their relationship to the treatment
Time Frame
12 months post-operatively
Title
Safety, as evaluated by changes from baseline in the brain MRI
Time Frame
12 months post-operatively
Secondary Outcome Measure Information:
Title
Force Generation via Accurate Test of Limb Isometric Strength (ATLIS) testing
Description
Change from baseline for force generation by ATLIS
Time Frame
ATLIS testing will be performed 7 times over 15 months
Title
Pinch Strength
Description
Change from baseline for pinch strength
Time Frame
Pinch Strength testing will be performed 7 times over 15 months
Title
Hand/Wrist Strength
Description
Change from baseline for Hand/Wrist strength using Hand-held dynamometer
Time Frame
Hand/Wrist strength testing will be performed 7 times over 15 months
Title
Compound Motor Action Potential (CMAP)
Description
Change from baseline for CMAP
Time Frame
CMAP will be performed 7 times over 15 months
Title
Functional Hand assessments using 9-hole peg test
Description
Change from baseline for 9-hole peg test
Time Frame
9-hole peg testing will be performed 7 times over 15 months
Title
Penn Upper Motor Neuron Score (PUMNS)
Description
Change from baseline for Penn Upper Motor Neuron Score. (Scale of 0-32, where 0 is normal)
Time Frame
PUMNS will be performed 7 times over 15 months
Title
Hand Knob - Functional MRI (fMRI)
Description
Changes from baseline in brain activity in the hand knob area evaluated by fMRI
Time Frame
fMRI will be performed up to 4 times over 15 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion:
Confirmed diagnosis of ALS (Possible, Lab-supported Probable, Probable or Definite El Escorial Criteria)
Duration of ALS symptoms ≤ 36 months
Progressive weakness in upper extremities, with EMG supported evidence of denervation in both upper extremities
Forced Vital Capacity ≥50% of predicted normal in supine
Age: 18 years or older
Able to provide Informed Consent
Be geographically accessible to the study site and able to travel to study site for required visits
Have caregiver to assist in the transportation and care required by participation in the study
Not taking riluzole and/or edaravone or on a stable dose for ≥ 30 day
For women of child bearing capacity, negative pregnancy test prior to surgery and willingness to use birth control for the duration of the trial.
Medically able to undergo craniotomy as determined by the site PI and/or investigators
Medically able to tolerate the immunosuppression regimen as determined by the site PI
Exclusion:
Using invasive ventilatory assistance
Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI
Presence of any of the following conditions:
Current drug or alcohol abuse
Any known immunodeficiency syndrome
Unstable medical condition
Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening
Persons of child bearing capacity not willing to practice birth control
Receiving any investigational device/biologic/drug in the past 30 days or any previous exposure to stem cell therapy
Any condition in the upper extremities that precludes serial strength or coordination testing
Any condition that the investigators feel may pose complications for the surgery
Any condition or ALS disease phenotype that the site PI feels may interfere with participation in the study or in the interpretation of study endpoints
Allergy to Beta-Lactam antibiotics
Donor Specific Antibodies (DSA) ≥ 2500MFI or CPRA ≥ 20%
Contraindications to MRI
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pablo Avalos
Phone
310-248-8584
Email
Pablo.avalos@cshs.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Lewis, MD
Organizational Affiliation
Cedars-Sinai Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pablo Avalos
Phone
310-248-8584
First Name & Middle Initial & Last Name & Degree
Richard Lewis, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
CNS10-NPC-GDNF Delivered to the Motor Cortex for ALS
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