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

NCT03280056 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: BCT-002-US
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 6

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

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

MSC; Autologous; Neurotrophic factors

Outcome Measures

Primary Outcomes (1)

• The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo

  The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.

  28 weeks following the first intrathecal injection

Secondary Outcomes (3)

• Number of Participants Whose Disease Progression is Halted or Improved as Measured by a 100% or Greater Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score of NurOwn® Treatment vs. Placebo

  28 weeks following the first intrathecal injection

• Score of NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by Change From Baseline in ALSFRS-R Score at Week 28

  28 weeks following the first intrathecal injection

• NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks

  28 weeks following the first intrathecal injection

Study Arms (2)

NurOwn® (MSC-NTF cells)

ACTIVE COMPARATOR

Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals

Biological: NurOwn® (MSC-NTF cells); Other: Bone Marrow aspiration

Placebo

PLACEBO COMPARATOR

Three Intrathecal administrations of Placebo at bi-monthly intervals

Other: Placebo; Other: Bone Marrow aspiration

Interventions

NurOwn® (MSC-NTF cells) BIOLOGICAL

NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10\^6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors

NurOwn® (MSC-NTF cells)

Placebo OTHER

One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection

Placebo

Bone Marrow aspiration OTHER

Bone Marrow aspiration

NurOwn® (MSC-NTF cells); Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brainstorm-Cell Therapeutics: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (6)

University of California Irvine Alpha Stem Cell Clinic

Irvine, California, 92697, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

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

Limitations and Caveats

This trial had a unique and atypical trial population that included more participants than anticipated with advanced ALS, who had a low ALSFRS-R score. As compared with recent large ALS clinical trials, this study population is an outlier, with a mean overall ALSFRS-R score at baseline lower than other studies, and this impacted the power of this study.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Brainstorm Cell Therapeutics

ClinicalTrial@brainstorm-cell.com

+1-201-488-0460

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled Multicenter Study

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 12, 2017
• Study Start: August 28, 2017
• Primary Completion: September 29, 2020
• Study Completion: September 29, 2020
• Last Updated: February 29, 2024
• Results First Posted: February 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)