CNS10-NPC-GDNF for the Treatment of ALS

NCT ID: NCT02943850

Last Updated: 2020-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-01
• Study Completion Date: 2019-10-18

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.

Detailed Description

This study will be the first to use a genetically modified progenitor cells to treat a neurodegenerative disease. This is a Phase 1/2a, single-center, blinded (as to side of injection), safety study of two escalating doses of human neural progenitor cells expressing GDNF (CNS10-NPC-GDNF) delivered unilaterally to the lumbar region in ALS subjects with moderate leg involvement.

Subjects meeting all Eligibility Criteria and providing Informed Consent will be enrolled in one of two 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 two weeks between surgeries.

Specific aims:

Safety, as evaluated by:

• Adverse Events and Serious Adverse Events
• Clinical laboratory assessments, as clinically indicated (hematology, chemistry, immunology)

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stem cell implantation

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.

Group Type: EXPERIMENTAL

Stem cell (HPC) implantation

Intervention Type: BIOLOGICAL

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

Stereotactic surgical device

Intervention Type: DEVICE

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

Interventions

Stem cell (HPC) implantation

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

Intervention Type: BIOLOGICAL

Stereotactic surgical device

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Confirmed diagnosis of ALS (Lab-supported Probable, Probable or Definite EI Escorial Criteria)

2. Duration of symptoms ≤ 36 months

3. Progressive weakness in lower extremities, with EMG supported evidence of denervation in both lower extremities.

4. Forced Vital Capacity >60% of predicted normal in supine.

5. Male/Female; Age: 18 and older

6. Able to provide Informed Consent

7. Be geographically accessible to the study site and able to travel to study site for required visits

8. Have caregiver to assist in the transportation and care required by participation in the study

9. Not taking riluzole or on a stable dose for ≥ 30 days

10. For women of child bearing capacity, negative pregnancy test prior to surgery

11. Medically able to undergo thoracolumbar laminectomy or laminoplasty as determined by the site PI and Neurosurgeon

12. Medically able to tolerate the immunosuppression regimen as determined by the site PI

Exclusion Criteria

1. Using invasive ventilatory assistance

2. Diagnosis of another active or unstable medical illness that may interfere with study participation at discretion of PI

3. Presence of any of the following conditions:

1. Current drug or alcohol abuse

2. Any known immunodeficiency syndrome

3. Unstable medical condition

4. Unstable psychiatric illness including psychosis and untreated major depression within 90 days of screening

4. Persons of child bearing capacity not willing to practice birth control

5. Receiving any investigational device/biologic/drug in past 30 days or any previous exposure to stem cell therapy

6. Any condition in the lower extremities which precludes serial strength testing

7. Any condition that the Neurosurgeon feels may pose complications for the surgery

8. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

California Institute for Regenerative Medicine (CIRM)

OTHER

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Robert H. Baloh

Director of Neuromuscular Medicine, ALS Program Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert H. Baloh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36064599 (View on PubMed)

Other Identifiers

Pro00042350

Identifier Type: -

Identifier Source: org_study_id