CNS10-NPC-GDNF for the Treatment of ALS

NCT02943850 | Completed Phase 1 FDA Drug FDA Device

• 1 other identifier: Pro00042350
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator is examining the safety of transplanting cells that have been engineered to produce a growth factor into the spinal cord 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 neuronal 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 neuronal cells. Therefore, the cells are called "CNS10-NPC-GDNF." The investigational treatment has been tested in animals, but it has not yet been tested in people. In this study, we want to learn if CNS10-NPC-GDNF cells are safe to transplant into the spinal cords of people.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

stem cells; growth factor; ALS

Outcome Measures

Primary Outcomes (1)

• Safety evaluated by Adverse Events and Serious Adverse Events, post-operative MRI, and clinical laboratory assessments

  Safety, as evaluated by: * Adverse Events and Serious Adverse Events * Post-op MRI * Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)

  Patients will be followed postoperatively for 12 months

Secondary Outcomes (5)

• Compound Motor Action Potential (CMAP)

  CMAP will be performed 7 times over 15 months

• Force Generation via ATLIS testing

  ATLIS testing will be performed 7 times over 15 months

• Quantitative Muscle MRI

  Muscle MRI will be performed 6 times over 15 months

• Electrical Impedance Myography (EIM)

  EIM will be performed 7 times over 15 months

• Assessment of glial cell line derived neurotrophic factor (GDNF) in the cerebral spianl fluid (CSF)

  CSF will be collected at 3 time points over 12 months

Study Arms (1)

Stem cell implantation

EXPERIMENTAL

Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two sequential dosing groups (Group A and B). 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. There will be 9 subjects in each group. No control group is included. All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.

Biological: Stem cell (HPC) implantation; Device: Stereotactic surgical device

Interventions

Stem cell (HPC) implantation BIOLOGICAL

All patients will received unilateral lumbar spinal cord injections of CNS10-NPC-GDNF cells.

Stem cell implantation

Stereotactic surgical device DEVICE

A newly developed stereotactic frame is being evaluated as a part of this trial

Stem cell implantation

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of ALS (Lab-supported Probable, Probable or Definite EI Escorial Criteria)
• Duration of symptoms ≤ 36 months
• Progressive weakness in lower extremities, with EMG supported evidence of denervation in both lower extremities.
• Forced Vital Capacity \>60% of predicted normal in supine.
• Male/Female; Age: 18 and 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 or on a stable dose for ≥ 30 days
• For women of child bearing capacity, negative pregnancy test prior to surgery
• Medically able to undergo thoracolumbar laminectomy or laminoplasty as determined by the site PI and Neurosurgeon
• Medically able to tolerate the immunosuppression regimen as determined by the site PI

You may not qualify if:

• 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 past 30 days or any previous exposure to stem cell therapy
• Any condition in the lower extremities which precludes serial strength testing
• Any condition that the Neurosurgeon feels 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• Baloh RH, Johnson JP, Avalos P, Allred P, Svendsen S, Gowing G, Roxas K, Wu A, Donahue B, Osborne S, Lawless G, Shelley B, Wheeler K, Prina C, Fine D, Kendra-Romito T, Stokes H, Manoukian V, Muthukumaran A, Garcia L, Banuelos MG, Godoy M, Bresee C, Yu H, Drazin D, Ross L, Naruse R, Babu H, Macklin EA, Vo A, Elsayegh A, Tourtellotte W, Maya M, Burford M, Diaz F, Patil CG, Lewis RA, Svendsen CN. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial. Nat Med. 2022 Sep;28(9):1813-1822. doi: 10.1038/s41591-022-01956-3. Epub 2022 Sep 5.

  PMID: 36064599 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Drug Implants

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Robert H. Baloh, MD, PhD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neuromuscular Medicine, ALS Program Director

Study Record Dates

• First Submitted: October 20, 2016
• First Posted: October 25, 2016
• Study Start: April 1, 2017
• Primary Completion: October 18, 2019
• Study Completion: October 18, 2019
• Last Updated: July 15, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)