This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03280056
Recruitment Status : Completed
First Posted : September 12, 2017
Results First Posted : February 29, 2024
Last Update Posted : February 29, 2024
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Brainstorm-Cell Therapeutics

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 196 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 : September 29, 2020
Actual Study Completion Date : September 29, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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)

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


Other: Bone Marrow aspiration
Bone Marrow aspiration
Placebo Comparator: Placebo
Three Intrathecal administrations of Placebo at bi-monthly intervals
 Other: Placebo

One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks

Placebo: liquid solution in syringe for injection


Other: Bone Marrow aspiration
Bone Marrow aspiration


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  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 [ Time Frame: 28 weeks following the first intrathecal injection ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: 28 weeks following the first intrathecal injection ]
    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.

  2. 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 [ Time Frame: 28 weeks following the first intrathecal injection ]
    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.

  3. NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks [ Time Frame: 28 weeks following the first intrathecal injection ]

    The combined Assessment of Function and Survival (CAFS) is a composite endpoint based on (1) the change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score and (2) time to death.

    On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time the better outcome.

    A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to death to all other patients in the study in a pairwise fashion. The ranked scores range from 001 to 189 (the number of subjects in the mITT population) with larger rank score numbers associated with a better outcome. The reported values are the mean rank scores in each group for the composite endpoint.



Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03280056


Locations
Layout table for location information
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
Layout table for investigator information
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
  Study Documents (Full-Text)

Documents provided by Brainstorm-Cell Therapeutics:
Study Protocol  [PDF] March 1, 2020
Statistical Analysis Plan  [PDF] June 19, 2020

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Brainstorm-Cell Therapeutics
ClinicalTrials.gov Identifier: NCT03280056    
Other Study ID Numbers: BCT-002-US
First Posted: September 12, 2017    Key Record Dates
Results First Posted: February 29, 2024
Last Update Posted: February 29, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for 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