Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients

• ClinicalTrials.gov Identifier: NCT03280056
• Recruitment Status: Completed
• First Posted: September 12, 2017
• Last Update Posted: October 6, 2021
• Sponsor: Brainstorm-Cell Therapeutics
• Collaborator: California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): Brainstorm-Cell Therapeutics

Study Description

Brief Summary:

This study will evaluate the safety and efficacy of repeated administration of NurOwn® (MSC-NTF cells) therapy, which is based on transplantation of autologous bone marrow derived mesenchymal stromal cells (MSC), which are enriched from the patient's own bone marrow, propagated ex vivo and induced to secrete Neurotrophic factors (NTFs).

The autologous NurOwn® (MSC-NTF cells) are back-transplanted into the patient intrathecally by standard lumbar puncture where neurons and glial cells are expected to take up the neurotrophic factors secreted by the transplanted cells

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Biological: NurOwn® (MSC-NTF cells); Other: Placebo; Other: Bone Marrow aspiration	Phase 3

Detailed Description:

Neurotrophic factors (NTFs) are potent survival factors for embryonic, neonatal, and adult neurons and are considered potential therapeutic candidates for ALS. Delivery of multiple NTFs to the immediate environment of afflicted neurons in ALS patients is expected to improve their survival and thus slow down disease progression and alleviate symptoms. NTF-secreting mesenchymal stromal cells (MSC-NTF cells) are a novel cell-therapeutic approach aimed at effectively delivering NTFs directly to the site of damage in ALS patients.

Participants meeting the inclusion and exclusion criteria will be randomized and will undergo bone-marrow aspiration. MSC of the participants randomized to the treatment group will be induced into MSC-NTF cells. Participants will undergo a total of three intrathecal (IT) transplantations with NurOwn® (MSC-NTF cells) or matching placebo at three bi-monthly intervals

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 263 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, Double-Blind, Placebo-Controlled Multicenter Study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: This is a double-blind study where the investigators, participants and all sponsor and CRO personnel involved in the conduct, data management or analysis of the study will remain blinded to the treatment assignments
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized Double-Blind, Placebo-Controlled Multicenter Study to Evaluate Efficacy and Safety of Repeated Administration of NurOwn® (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors) in Participants With ALS
• Actual Study Start Date: August 28, 2017
• Actual Primary Completion Date: October 30, 2020
• Actual Study Completion Date: October 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: NurOwn® (MSC-NTF cells); Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals	Biological: NurOwn® (MSC-NTF cells); Autologous transplantation of bone marrow derived mesenchymal stem cells propagated ex vivo and induced to secrete neurotrophic factors; Other: Bone Marrow aspiration; Bone Marrow aspiration
Placebo Comparator: Placebo; Three Intrathecal administrations of Placebo at bi-monthly intervals	Other: Placebo; Placebo; Other: Bone Marrow aspiration; Bone Marrow aspiration

Outcome Measures

Primary Outcome Measures :

1. To evaluate the efficacy and safety of NurOwn® (autologous MSC-NTF cells) as compared to placebo as measured by the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) [ Time Frame: 28 weeks following the first treatment ]
   To determine efficacy and safety of repeat intrathecal injections of NurOwn® as compared to Placebo given three times two months apart to participants with Amyotrophic Lateral Sclerosis

Secondary Outcome Measures :

1. Biomarkers [ Time Frame: Through selected post-treatment time points up to 20 weeks post transplant ]
   To evaluate biomarkers (such as cell-secreted neurothrophic factors, inflammatory factors, and cytokines in pg/ml) in the cerebrospinal fluid (CSF) as well as in serum samples throughout the study to evaluate their relationship to treatment with NurOwn® (MSC-NTF cells)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
• Having onset of ALS disease symptoms, including limb weakness within 24 months at the Screening Visit.
• ALSFRS-R ≥ 25 at the screening Visit.
• Upright slow vital capacity (SVC) measure ≥ 65% of predicted for gender, height, and age at the screening Visit.
• Rapid progressors
• Participants taking a stable dose of Riluzole are permitted in the study
• Citizen or permanent resident of the United States or Canadian citizen able to travel to a US site for all follow-up study visits

Exclusion Criteria:

• Prior stem cell therapy of any kind
• History of autoimmune or other serious disease (including malignancy and immune deficiency) that may confound study results
• Current use of immunosuppressant medication or anticoagulants (per Investigator discretion)
• Exposure to any other experimental agent or participation in an ALS clinical trial within 30 days prior to Screening Visit
• Use of RADICAVA (edaravone injection) within 30 days of screening or intent to use edaravone at any time during the course of the study including the follow up period
• Use of non-invasive ventilation (BIPAP), diaphragm pacing system or invasive ventilation (tracheostomy)
• Feeding tube
• Pregnant women or women currently breastfeeding

Contacts and Locations

Locations

United States, California

University of California Irvine Alpha Stem Cell Clinic

Irvine, California, United States, 92697

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

California Pacific Medical Center

San Francisco, California, United States, 94115

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02115

University of Massachusetts Medical School

Worcester, Massachusetts, United States, 01655

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Brainstorm-Cell Therapeutics

California Institute for Regenerative Medicine (CIRM)

Investigators

• Principal Investigator: Merit E. Cudkowicz, MD; Massachusetts General Hospital
• Principal Investigator: Robert H. Brown, MD, PhD; UMass Medical School
• Principal Investigator: Anthony J. Windebank, MD; Mayo Clinic
• Principal Investigator: Namita A. Goyal, MD; UC Irvine
• Principal Investigator: Robert G. Miller, MD; California Pacific Medical Center (CPM) Research Institute
• Principal Investigator: Robert Baloh, MD, Ph.D.; Cedars-Sinai Medical Center

More Information

• Responsible Party: Brainstorm-Cell Therapeutics
• ClinicalTrials.gov Identifier: NCT03280056
• Other Study ID Numbers: BCT-002-US
• First Posted: September 12, 2017
• Last Update Posted: October 6, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Brainstorm-Cell Therapeutics:

MSC; Autologous; Neurotrophic factors

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases